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Archive
Vaccines: The Week in Review
4 November 2008
Center for Vaccine Ethics & Policy
http://www.centerforvaccineethicsandpolicy.org/
A program of
- Center for Bioethics, University of Pennsylvania
- The Wistar Institute Vaccine Center
- Children’s Hospital of Philadelphia, Vaccine Education Center
This weekly summary targets news and events in the global vaccines field gathered from key governmental, NGO and company
announcements, key journals and events. This summary provides support for ongoing initiatives of the Center for Vaccine Ethics
& Policy, and is not intended to be exhaustive in its coverage. This summary is also posted at http://www.
centerforvaccineethicsandpolicy.org/ Comments and suggestions should be directed to David Curry, Executive Director of the
Center, at david.r.curry@drcurryassociates.net. We also invite you to visit VaccineEthics.org www.vaccineethics.org/ which
complements this weekly review and is edited by Jason Schwartz, MBE, Center for Bioethics.
[Editor’s Note: In Journal Watch below we note an important special issue of Vaccine, celebrating the journal’s
25th anniversary year of publication. The issue carries thoughtful editorials reflecting on vaccines, their development,
and their deployment in global public health going forward.]
The Washington Global Health Alliance (WGHA), which “strives to connect, organize, and motivate
Washington groups that share the goal of improving health conditions for people around the world,”
marked its official launch on 24 October 2008 at the Greater Seattle Chamber of Commerce’s Regional Leadership
Conference in Cle Elum, Washington. Lisa Cohen, director of WGHA, introduced the Alliance to 275 business and
global health leaders from the Seattle area who attended the conference. The Alliance describes its mission as “to
facilitate creative global health collaboration and initiatives with its partners and promote efforts to expand research,
education, and training opportunities with the goal of improving health worldwide.” Throughout the past year, the
Alliance has been identifying the critical components to a successful global health sector in Washington State. From
these components, the organization created a global health framework that “focuses on four areas: education,
training, and mentoring; research, technology, and programming; public-private partnerships; and marketing,
outreach, and recruitment.”
PATH is the hosting secretariat for WGHA staff and “has been instrumental in laying the groundwork over the
past year for this official launch.” PATH’s president and CEO, Dr. Christopher Elias serves as the president of the
Alliance executive board, which includes members from the Bill & Melinda Gates Foundation, Fred Hutchinson Cancer
Research Center, the Infectious Disease Research Institute, PATH, Seattle Biomedical Research Institute, Seattle
Children’s Hospital Global Alliance to Prevent Prematurity and Stillbirth, the University of Washington’s Department of
Global Health, and Washington State University’s School for Global Animal Health.
Washington Global Health Alliance website: http://www.wghalliance.org/
This month’s Bulletin of the World Health Organization (BLT) is a special WHO 60th anniversary
commemorative volume and is a special theme issue around health financing. Volume 86, Number 11,
November, 817-908
http://www.who.int/bulletin/volumes/86/11/en/index.html
The WHO introduced a new WHO/UNICEF brochure introducing the Global Immunization Vision and
Strategy. The brochure is targeted for the general public and “captures the essence of GIVS which aims to protect
more people against more diseases. Illustrated with photos and the brand new visual identity for GIVS, it describes
achievements in immunization and the benefits of this key and cost-effective health intervention. Needs, challenges,
the cost of immunization programmes and resource requirements are given. The document provides the four
strategic areas of GIVS and immunization goals established therein.”
http://whqlibdoc.who.int/hq/2008/WHO_IVB_08.13_eng.pdf
The Weekly Epidemiological Record (WER)7 November 2008, vol. 83, 45 (pp 401–412) includes: WHO external
quality assessment project for the detection of subtype influenza A viruses by polymerase chain reaction – summary
analysis, 2007 and 2008; and an overview on global influenza
http://www.who.int/wer/2008/wer8345.pdf
Journal Watch
[Editor’s Note]
Vaccines: The Week in Review continues a new feature, scanning key journals to identify and cite articles, comment
and editorials, books reviews and other content supporting our focus on vaccine ethics and policy. Journal Watch is
not intended to be exhaustive, but indicative of themes and issues the center is actively tracking. We selectively
provide full text of some editorial and comment articles that are specifically relevant to our work. Successful access to
some of the links provided may require subscription or other access arrangement unique to the publisher. Our initial
scan list includes the journals below. If you would like to suggest other titles, please write to David Curry at david.r.
curry@centerforvaccineethicsandpolicy.org
JAMA
Vol. 300 No. 17, pp. 1969-2084, November 5, 2008
http://jama.ama-assn.org/current.dtl
[No relevant content]
Journal of Infectious Disease
15 November 2008 Volume 198, Number 10
http://www.journals.uchicago.edu/toc/jid/current
[Reviewed last week}
The Lancet
Nov 08, 2008 Volume 372 Number 9650 Pages 1607 – 1706
http://www.thelancet.com/journals/lancet/issue/current
“A global movement to address the social determinants of health has been gathering pace. This week's issue of The
Lancet contributes to this campaign by publishing evidence on actions that can reduce the startling health
inequalities that persist within and between countries.”
Globalisation and health: the need for a global vision
Ted Schrecker, Ronald Labonté, Roberto De Vogli
“The reduction of health inequities is an ethical imperative, according to the WHO Commission on Social
Determinants of Health (CSDH). Drawing on detailed multidisciplinary evidence assembled by the Globalization
Knowledge Network that supported the CSDH, we define globalisation in mainly economic terms. We consider and
reject the presumption that globalisation will yield health benefits as a result of its contribution to rapid economic
growth and associated reductions in poverty. Expanding on this point, we describe four disequalising dynamics by
which contemporary globalisation causes divergence: the global reorganisation of production and emergence of a
global labour-market; the increasing importance of binding trade agreements and processes to resolve disputes; the
rapidly increasing mobility of financial capital; and the persistence of debt crises in developing countries.”
Global health equity and climate stabilisation: a common agenda
Sharon Friel, Michael Marmot, Anthony J McMichael, Tord Kjellstrom, Denny Vågerö
“Although health has improved for many people, the extent of health inequities between and within countries is
growing. Meanwhile, humankind is disrupting the global climate and other life-supporting environmental systems,
thereby creating serious risks for health and wellbeing, especially in vulnerable populations but ultimately for
everybody. Underlying determinants of health inequity and environmental change overlap substantially; they are
signs of an economic system predicated on asymmetric growth and competition, shaped by market forces that
mostly disregard health and environmental consequences rather than by values of fairness and support.
Addressing social determinants of health inequities: what can the state and civil society do?
Erik Blas, Lucy Gilson, Michael P Kelly, Ronald Labonté, Jostacio Lapitan, Carles Muntaner, Piroska Östlin, Jennie
Popay, Ritu Sadana, Gita Sen, Ted Schrecker, Ziba Vaghri
“In this Health Policy article, we selected and reviewed evidence synthesised by nine knowledge networks established
by WHO to support the Commission on the Social Determinants of Health. We have indicated the part that national
governments and civil society can play in reducing health inequity. Government action can take three forms: (1) as
provider or guarantor of human rights and essential services; (2) as facilitator of policy frameworks that provide the
basis for equitable health improvement; and (3) as gatherer and monitor of data about their populations in ways that
generate health information about mortality and morbidity and data about health equity.”
Nature
Volume 455 Number 7214 pp707-834 (9 October 2008)
http://www.nature.com/nature/journal/v455/n7214/
Editorial
Malaria's watershed
Nature 455, 707 (9 October 2008) | doi:10.1038/455707a; Published online 8 October 2008
[Full text; bolding added]
A Global Malaria Action Plan, announced at the UN Millennium Development Goals Malaria Summit in New York on 25
September, has the ambitious goals of both reducing the malaria burden and eradicating the disease entirely.
Eradication any time soon might seem hopelessly optimistic, given the failure so far to make a serious dent in the
number of malaria deaths. But much of the 274-page plan makes good sense. It calls for scaling up the use of
existing tools, such as bednets, drugs and spraying, to near universal coverage, and then sustaining this effort for
decades. True, this won't come cheaply. Funds for control have already grown from US$250 million annually in 2004
to an estimated US$1.1 billion this year; the plan calls for increasing that to $5 billion annually until at least 2020.
Likewise, total spending on malaria-related research has risen from $265 million in 2003 to $422 million in 2007; the
plan would see that figure double to between $750 million and $900 million annually until 2018. Whether donors will
rise to the challenge is a big question, given current economic woes. Still, it is heartening that at the summit, donors
from governments, industry and philanthropic organizations pledged US$3 billion.
Striking the right balance between basic and applied research is also critical. For example, the sequencing in 2002 of
the genome of Plasmodium falciparum, the main parasite that causes malaria, has stimulated the hunt for new drug
and vaccine candidates. This week's issue of Nature sees the addition of two more parasite sequences: P. vivax,
which is less deadly than P. falciparum, and P. knowlesi, which mainly infects monkeys. These new sequences show
how much more there is to learn: more than half of P. falciparum's encoding genes still have no known function.
Basic research is also needed to stay ahead of drug resistance in the parasite and insecticide resistance in mosquitoes,
and to get a better understanding of natural infection in humans. One surprise from P. falciparum's genome is
evidence that it evades the human immune system mainly by genomic and gene-expression diversity. Plasmodium
seems to have different metabolic and physiological states, and can reprogram its gene expression. These findings
could alter the way researchers think about both drug and vaccine development.
The malaria drug and vaccine pipelines are healthier now than they have been for decades, but they are in urgent
need of new candidates and approaches. So it was welcome news when the Bill & Melinda Gates Foundation, already
the largest donor in malaria research, announced at the UN summit that it would spend US$168 million to develop
next-generation malaria vaccines. Moreover, this initiative will include early-stage laboratory research — most of the
Gates Foundation's funding has so far focused on translational and clinical research.
Many scientists would like to see the foundation fund even more basic research, but this cannot be the foundation's
responsibility alone. Its support of translational work has rejuvenated the field over the past decade, and has helped
get tools into the field. In the process, the malaria research community has become excessively and undesirably
dependent on this one entity. Other research organizations would do well to step up to the plate and match the
Gates Foundation's spending with their own basic-research funds. That would also go some way to addressing what
scientists say is an unfortunate consequence of the emphasis on translational research: that scientists entering
malaria research are less likely to choose basic science.
Any massive increase in research funding means that the malaria community must think about how to coordinate
research across funding agencies. It is encouraging that the main research funders and scientists are to sit down as a
group — called MalERA — over the next year to thrash out a research agenda for eradication. One lesson of the
malaria and human genome projects is that consortia are a key route to delivery, focusing resources wisely, and
avoiding duplication and excessive bureaucracy. It is also essential that international research recognizes the maturity
of the malaria research community in the poorer countries where the disease is endemic — they should be on board
as equals and not, as is too often the case, afterthoughts.
New England Journal of Medicine
Volume 359 — November 6, 2008 — Number 19
http://content.nejm.org/current.shtml
Perspective
Drug Development for Neglected Diseases — The Trouble with FDA Review Vouchers
Aaron S. Kesselheim, M.D., J.D., M.P.H.
[Full text]
September 2008 marked the beginning of a new federal program intended to promote the development of
pharmaceutical products for so-called neglected diseases — infectious diseases that disproportionately affect poor
populations in developing countries. Implemented by the Food and Drug Administration (FDA) Amendments Act of
2007, this program will give the sponsor of a drug for a tropical disease a "voucher" entitling the company to
expedited FDA review of a new drug application for any other product it makes.1
The need to encourage additional research in this field is clear. Diseases such as tuberculosis, malaria, leishmaniasis,
and trypanosomiasis affect millions of people each year, but these people live primarily in resource-poor settings with
underdeveloped health care systems. As a result, the for-profit pharmaceutical industry has invested little in
treatments for these conditions. One study found that of the 1393 new chemical entities marketed between 1975
and 1999, only 16 were for such diseases.2
The new program links the development of drugs targeting tropical diseases to accelerated approval of a company's
other, more profitable drugs for conditions prevalent in wealthier countries. A voucher obtained after the approval of
a drug for a tropical disease can be used to require accelerated regulatory review (in 6 months or less) of a
cholesterol-lowering drug or an antidepressant, for example, that the sponsor might sell in the United States for
thousands of dollars per year of treatment. According to the arrangement's proponents, vouchers could speed up
FDA evaluation time by an average of 12 months, providing domestic patients with more rapid access to the latter
types of drugs.3 A voucher could be worth more than $300 million, thanks to the earlier period of market exclusivity
afforded by decreasing the time a drug spends in FDA review.
As enacted, however, priority-review vouchers represent an inefficient and potentially dangerous way of encouraging
research into tropical diseases. It is inefficient because the program does not directly connect the incentive with the
innovation. Large pharmaceutical companies traditionally have not conducted effective research programs on
tropical diseases. These manufacturers will be unlikely to start such a program merely because of the prospect of
earning a voucher some years in the future, since the voucher's value depends on the success of potential
"blockbuster" drugs that are currently in their pipelines, which is far from assured. In fact, tropical-disease research is
predominantly conducted by small pharmaceutical companies with limited drug portfolios. Such companies will often
be unable to use their vouchers, although the law permits voucher rights to be sold to a large manufacturer. Relying
on these sorts of transactions to spur innovation is speculative as well, and the deals between small and large
pharmaceutical companies affecting agents of great importance to global health will lack transparency. Such deals
may include other payments or exchanges of intellectual property that raise the cost or restrict the future availability
of the products.
Another source of inefficiency is that a voucher's value will bear no relation to the usefulness of the drug whose
development it is intended to reward. For example, the law stipulates that no voucher will be earned for a product
whose "active ingredient" was previously approved. As a result, an effective novel antimalarial drug that degrades in
the heat and must be taken six times a day would earn its sponsor a voucher, but no voucher would be granted for
a follow-on formulation that might be more useful in resource-poor settings. Even more problematically, a sponsor
rewarded with a voucher for FDA approval of a product for a neglected disease will have no incentive to follow
through with implementation of the therapy. After an innovative product is approved in the United States, there can
be significant delays before it reaches patients in developing countries, and drug-company ownership of its intellectual
property may make it unaffordable. The human papillomavirus vaccine, for example, could be useful in combating
cervical cancer in developing countries, but while it remains under patent protection, intellectual property rights and
logistic problems have hindered its dissemination in resource-poor settings.4
In addition, too-speedy FDA review may lead to bad regulatory decision making. The "priority review" designation
was meant to shorten the review time of products that represent major advances in treatment or that treat
conditions for which no adequate therapy exists, such as certain types of cancer and infection with the human
immunodeficiency virus (HIV). In such circumstances, accelerating the review process is reasonable, given the serious
problems faced by patients. But the voucher program will allow drugs for which there is little or no clinical urgency to
be subject to accelerated deadlines and may lead to approval of products without adequate consideration by the
FDA.
The program reflects a growing trend in health policy toward reliance on substantial financial incentives to achieve a
socially desirable outcome. Such initiatives may achieve short-term gains, but they do not consistently lead to
sustained improvement and may have important unintended consequences. It is especially problematic to rely on
pharmaceutical companies' profit motive as the key to developing drugs for resource-poor settings. Effectively
conducting research into treatments for neglected diseases involves a more sustained commitment than can be
achieved simply by rationalizing the revenue that arises from it. If any changes in the drug-development
marketplace, such as initiation of federal drug-reimbursement guidelines in the United States, diminish the perceived
value of these vouchers, then any research started solely in anticipation of voucher revenue will again cease, to the
detriment of public health.
Though Congress should reconsider the usefulness of the voucher program, there are more direct ways to
encourage drug development for medical conditions for which current incentives have proven inadequate. For
example, wealthier countries could, in concert with international public health groups, set up independent funds that
award reasonable compensation for the development of a safe and useful drug or vaccine and then continue to
compensate companies for the appropriate implementation of treatment programs. The level of payment could be
adjusted according to the degree of success in controlling the disease in question.5
Another alternative would be for governments to work with nonprofit foundations to develop treatments for
neglected diseases. The drugs could then be licensed to for-profit pharmaceutical manufacturers for dissemination.
Incentives for the manufacturers to become involved could take the form of advance-purchasing promises or grants
of extended periods of market exclusivity for such drugs, with accompanying price restrictions to ensure affordability
and modest but predictable profits. Precedents exist for such partnerships, including the combined efforts by
GlaxoSmithKline and the Bill and Melinda Gates Foundation to create a malaria vaccine and the work of Institute for
OneWorld Health, a nonprofit drug-development firm that has produced a treatment for visceral leishmaniasis and
implemented a program to distribute it.
Over the past few decades, the patent system has provided the primary incentive structure for drug development,
with the result that needed drugs have not been developed for certain diseases affecting people in resource-poor
settings. At the same time, many patients in these environments continue to have inadequate access to important
products for more widely prevalent conditions, such as routine immunizations and drugs for cardiovascular disease,
cancer, and HIV. It is encouraging to see Congress addressing neglected diseases and taking an interest in an area in
which the market has been unable to provide sufficient results. But as the patent system's limitations have shown us,
incentives in this field must be narrowly tailored to the desired result and tied to implementation to avoid misuse and
to have the greatest effect on global health.
No potential conflict of interest relevant to this article was reported. Source Information
Dr. Kesselheim is a patent attorney and an instructor in medicine in the Division of Pharmacoepidemiology and
Pharmacoeconomics at Brigham and Women's Hospital, Harvard Medical School, Boston.
References
Food and Drug Administration Amendments Act of 2007, 1102 (codified at 21 U.S.C. 524) (2007).
Trouiller P, Olliaro P, Torreele E, Orbinski J, Laing R, Ford N. Drug development for neglected diseases: a deficient
market and a public-health policy failure. Lancet 2002;359:2188-2194.
Ridley DB, Grabowski HG, Moe JL. Developing drugs for developing countries. Health Aff (Millwood) 2006;25:313-
324. [Free Full Text]
Outterson K, Kesselheim AS. Market-based licensing for HPV vaccines in developing countries. Health Aff (Millwood)
2008;27:130-139. [Free Full Text]
Love J, Hubbard T. The big idea: prizes to stimulate R&D for new medicines. Chic-Kent Rev 2007;82:1519-54.
PLoS Medicine
[Accessed 10 November 2008)
http://medicine.plosjournals.org/perlserv/?request=browse&issn=1549-
1676&method=pubdate&search_fulltext=1&order=online_date&row_start=1&limit=10&document_count=1533&ct
=1&SESSID=aac96924d41874935d8e1c2a2501181c#results
[No new content]
Science
7 November 2008 Vol 322, Issue 5903, Pages 805-1008
http://www.sciencemag.org/current.dtl
[No relevant content]
Vaccine
Volume 26, Issue 49, Pages 6173-6292 (18 November 2008)
http://www.sciencedirect.com/science/journal/0264410X
[This issue celebrates 25 years of publication and leads with a series of editorials on that milestone. Vaccine requires
an individual or institutional subscription for access]
“Vaccine”; 25 years on
Pages 6173-6176
Ray Spier
The end of the beginning: Vaccines for the next 25 years
Pages 6179-6182
J.S. Oxford
New vaccine approaches for seasonal and pandemic influenza
Pages 6232-6236
Bram Palache
Abstract
“Inactivated influenza vaccines have been available since the late 1940s for the prevention of influenza disease. Based
on the available scientific evidence, many public health authorities, including the World Health Organization,
recommend annual use of these vaccines for specific populations, including the elderly. Despite these
recommendations, actual vaccination uptake rates are very limited in many countries. Influenza vaccine research is
confounded by the variable nature of the influenza viruses and annual influenza epidemics and by non-specific clinical
diagnostic criteria. These confounding factors complicate evaluation not only of overall vaccine effectiveness, but also
of the relative efficacy and effectiveness of different vaccine formulations. This paper summarizes recent advances in
the development of seasonal and (pre-)pandemic vaccines, discusses the methodologic constraints on influenza
vaccine research, and proposes measures to reduce the level of potential bias and confounding in influenza vaccine
research.”
Cost-effectiveness of HPV vaccination compared with Pap smear screening on a national scale: A literature review
Pages 6258-6265
Win Techakehakij, Roger D. Feldman
Abstract
“Recommendations for worldwide use of human papillomavirus (HPV) vaccine are increasing. This study conducted a
systematic review of articles related to cost-effectiveness analysis of wide-range HPV vaccination programs compared
with Pap smear screening published before August 2007. Eight articles were identified using predefined inclusion and
exclusion criteria. After excluding two outliers, the range of incremental cost-effectiveness ratios (ICERs) from six
articles is between $16,600 and $27,231 per quality-adjusted life year (QALY) gained. The World Health Organization’
s guideline that compares incremental cost-effectiveness ratios (ICERs) with per capita Gross Domestic Product
(GDP) was used to determine whether nation-wide application of HPV vaccine would be cost-effective. The HPV
vaccination program is cost-effective in only 46 countries where per capita GDP is high. Further cost-effectiveness
studies in developing and third-world countries are needed for making policy decisions.
______________________________________________________________________________________________________
4 November 2008
The GAVI Alliance announced that former President of Ireland and High Commissioner for Human
Rights Mary Robinson will lead its new executive board “to strengthen the organisation’s ability to meet global
health challenges.” President Robinson commented, “I feel humbled and honored to be elected. Over these past few
years, I have witnessed GAVI achieve extraordinary success through its unique public and private approach to
improving the health of the world’s poor, especially children. The new board structure embodies this approach and
will enable us to meet the challenges ahead...As the global economy enters into a period of recession, it will be our
challenge to stay focused on reaching the Millennium Development Goals through increasing the positive impact that
immunisation provides on people’s lives.”
The 28-member board has representatives from developing countries, donor governments, UNICEF, WHO and the
World Bank, private institutions like the Gates Foundation, civil society, and the vaccine industry, plus independent
experts. A 10-member executive committee and five committees for programme and policy, audit and finance,
governance, investment, and fundraising will provide support. WHO Assistant Director-General Denis Aitken was
elected as the board’s Vice Chairman. Graça Machel, former first lady of Mozambique and a GAVI founding member,
will retain a board seat. The new body replaces a two board structure that was created when the alliance was
launched and will help support the establishment of the alliance as an international institution in Switzerland.
http://www.gavialliance.org/media_centre/statements/2008_10_30_Board_MaryRobinson.php
The Washington Post of 30 October 2008 carried the followed opinion piece, carried in turn on the GAVI Alliance site
[link below]:
Our Vote to End Cervical Cancer
By Lance Armstrong and John Seffrin
Preventing, treating and defeating cancer are among the greatest scientific challenges and personal triumphs of our
time. And right now, we have the power to save our mothers, sisters and daughters from a type of cancer that
claims a life every two minutes globally.
Cervical cancer progresses over decades, attacking women who might never know they are sick until it is too late. It
often hits women in their prime, when they're raising children, working hard and fully engaged in family, community
and economic life, making these unnecessary deaths especially tragic.
Cervical cancer is unique among cancers because we know one of the main causes for it: certain strains of the
human papilloma virus (HPV). We also know how to prevent it. There are now vaccines available that, when given to
girls before they become sexually active, will later protect them from the potentially deadly strains of HPV.
In the United States and other wealthy countries, HPV vaccines, along with screening and early detection
technologies, have become the standard. Yet cervical cancer remains the number one cause of cancer death among
women in the developing world, because they do not have access to these technologies.
It's hard to stop all HPV strains from spreading, but we can stop certain ones from killing.
Today in Geneva, the Board of the Global Alliance for Vaccines and Immunization (GAVI), which includes a U.S.
representative, will decide whether to commit to making HPV vaccines available to girls in the 72 poorest countries.
GAVI is an international alliance of governments, international agencies and nongovernmental organizations that helps
bring needed vaccines to countries that can't otherwise afford them. Once GAVI commits to a vaccine, it works with
leaders in the public and private sectors to deliver its promise. But without a GAVI commitment, this lifesaving vaccine
will remain the privilege of the few, rather than being deployed on the front lines of this terrible disease.
We have the data to prove that providing HPV vaccines to the poorest regions of the world is feasible, affordable and
necessary. GAVI calculates that the cost of HPV vaccine at $10 per dose is possible, and in all likelihood, far less. The
purchase price for GAVI-eligible countries will be $.30 per dose, which even the poorest of countries can pay. The
difference will be covered through international financing and dramatic discounts from the pharmaceutical companies
that make the vaccine. This combination of need, and a simple, affordable solution, makes the path forward clear.
To be sure, no new innovation or technology is without some controversy, and the HPV vaccine is no exception.
Some concerns have been raised over the impact the vaccine may have on sexual behavior; however, there is no
evidence that the introduction of this or any other effective vaccine leads to changes in human behavior, including
sexual activity.
At the same time, we recognize that HPV vaccine alone is not enough to eradicate cervical cancer in the coming
decades. We need to bring simple new screening technologies to women for whom the vaccine is not appropriate.
Vaccines are most effective when they are given to girls before they become sexually active and contract the virus.
For all other women, screening tools, as well as treatments for both precancerous cervical abnormalities and cancer
itself, must be made more widely available. In places where screening and treatment may always be out of reach,
vaccination is paramount.
Indeed, it is one of the miracles of our young century that cervical cancer prevention now comes in a vial. The HPV
vaccine is built on Nobel-recognized science. It is effective. It is safe. It is affordable. And it is needed most in the
places where it is hardest to get it.
The United States has another opportunity to show our belief and leadership in the powers of innovation and
technology, by this commitment to improve lives of families, communities and nations. We urge our delegation to
GAVI to vote "yes" on the commitment today in Geneva.
Lance Armstrong is a champion cyclist, cancer survivor and chairman of the Lance Armstrong Foundation . John
Seffrin is chief executive officer of the American Cancer Society.
http://www.gavialliance.org/media_centre/news/WashPost___HPV.php
WHO’s Global Immunization News for 30 0ctober 2008 includes reports on endorsement of a new regional
strategy in the Americas to “prevent cervical cancer using new technologies.” The endorsement came as
part of recent 48th Directing Council of the Pan-American Health Organization held 29 Sep – 3 Oct 2008. The action
“will give priority to cervical cancer prevention and control treatment and palliative care, and evidence-based policy
decisions on whether and how to introduce HPV vaccines...” The issue also notes that PATH launched a new Vaccine
Resource Library (VRL) which “seeks to gather the leading immunization resources in a single, easy-to-use website”
available at www.path.org/vaccineresources/
http://www.who.int/immunization/GIN_October2008.pdf
Journal Watch
[Editor’s Note]
Vaccines: The Week in Review continues a new feature, scanning key journals to identify and cite articles, comment
and editorials, books reviews and other content supporting our focus on vaccine ethics and policy. Journal Watch is
not intended to be exhaustive, but indicative of themes and issues the center is actively tracking. We selectively
provide full text of some editorial and comment articles that are specifically relevant to our work. Successful access to
some of the links provided may require subscription or other access arrangement unique to the publisher. Our initial
scan list includes the journals below. If you would like to suggest other titles, please write to David Curry at david.r.
curry@centerforvaccineethicsandpolicy.org
JAMA
Vol. 300 No. 16, pp. 1845-1962, October 22/29, 2008
http://jama.ama-assn.org/current.dtl
Research Letters
Upper Income Limit for SCHIP and Forgone Care Among Uninsured US Children
Laura P. Shone; Jonathan D. Klein; Aaron K. Blumkin; Peter G. Szilagyi
JAMA. 2008;300(16):1882-1884.
Journal of Infectious Disease
15 November 2008 Volume 198, Number 10
http://www.journals.uchicago.edu/toc/jid/current
p 1427
Cross-Protection between Successive Waves of the 1918–1919 Influenza Pandemic: Epidemiological
Evidence from US Army Camps and from Britain
John M. Barry, Cécile Viboud, and Lone Simonsen
“…Conclusion. Exposure to influenza in the spring and summer of 1918 provided mortality and morbidity protection
during the fall pandemic wave. The intensity of the first wave may have differed across US cities and countries and
may partly explain geographical variation in pandemic mortality rates in the fall. Pandemic preparedness plans should
consider that immune protection could be naturally acquired during a first wave of mild influenza illnesses.”
The Lancet
Nov 01, 2008 Volume 372 Number 9649 Pages 1519 - 1606
http://www.thelancet.com/journals/lancet
The Lancet, Volume 372, Issue 9649, Pages 1563 - 1569, 1 November 2008
WHO's budgetary allocations and burden of disease: a comparative analysis
David Stuckler MPH, Lawrence King PhD, Helen Robinson MPhil, Prof Martin McKee MD
Summary
Background
Ministers of health, donor agencies, philanthropists, and international agencies will meet at Bamako, Mali, in November,
2008, to review global priorities for health research. These individuals and organisations previously set health priorities
for WHO, either through its regular budget or extra-budgetary funds. We asked what insights can be gained as to
their priorities from previous decisions within the context of WHO.
Methods
We compared the WHO biennial budgetary allocations with the burden of disease from 1994—95 to 2008—09. We
obtained data from publicly available WHO sources and examined whether WHO allocations varied with the burden of
disease (defined by death and disability-adjusted life years) by comparing two WHO regions—Western Pacific and
Africa—that are at differing stages of epidemiological transition. We further assessed whether the allocations differed
on the basis of the source of funds (assessed and voluntary contributions) and the mechanism for deciding how
funds were spent.
Findings
We noted that WHO budget allocations were heavily skewed toward infectious diseases. In 2006—07, WHO allocated
87% of its total budget to infectious diseases, 12% to non-communicable diseases, and less than 1% to injuries and
violence. We recorded a similar distribution of funding in Africa, where nearly three-quarters of mortality is from
infectious disease, and in Western Pacific, where three-quarters of mortality is from non-communicable disease. In
both regions, injuries received only 1% of total resources. The skew towards infectious diseases was substantially
greater for the WHO extra-budget, which is allocated by donors and has risen greatly in recent years, than for the
WHO regular budget, which is decided on by member states through democratic mechanisms and has been held at
zero nominal growth.
Interpretation
Decision makers at Bamako should consider the implications of the present misalignment of global health priorities and
disease burden for health research worldwide. Funds allocated by external donors substantially differ from those
allocated by WHO member states. The meeting at Bamako provides an opportunity to consider how this disparity
might be addressed.”
Nature
Volume 455 Number 7217 pp1149-1278 (30 October 2008)
http://www.nature.com/nature/journal/v455/n7214/
[No relevant content]
New England Journal of Medicine
Volume 359 — October 30, 2008 — Number 18
http://content.nejm.org/current.shtml
[No relevant content]
PLoS Medicine
[Accessed 4 November 2008)
http://medicine.plosjournals.org/perlserv/?request=browse&issn=1549-
1676&method=pubdate&search_fulltext=1&order=online_date&row_start=1&limit=10&ct=1
The Effects of Influenza Vaccination of Health Care Workers in Nursing Homes: Insights from a
Mathematical Model
Carline van den Dool, Marc J. M. Bonten, Eelko Hak, Janneke C. M. Heijne, Jacco Wallinga
“Annual influenza vaccination of institutional health care workers (HCWs) is advised in most Western countries, but
adherence to this recommendation is generally low. Although protective effects of this intervention for nursing home
patients have been demonstrated in some clinical trials, the exact relationship between increased vaccine uptake
among HCWs and protection of patients remains unknown owing to variations between study designs, settings,
intensity of influenza seasons, and failure to control all effect modifiers. Therefore, we use a mathematical model to
estimate the effects of HCW vaccination in different scenarios and to identify a herd immunity threshold in a nursing
home department.
Methods and Findings
We use a stochastic individual-based model with discrete time intervals to simulate influenza virus transmission in a 30-
bed long-term care nursing home department. We simulate different levels of HCW vaccine uptake and study the
effect on influenza virus attack rates among patients for different institutional and seasonal scenarios. Our model
reveals a robust linear relationship between the number of HCWs vaccinated and the expected number of influenza
virus infections among patients. In a realistic scenario, approximately 60% of influenza virus infections among
patients can be prevented when the HCW vaccination rate increases from 0 to 1. A threshold for herd immunity is
not detected. Due to stochastic variations, the differences in patient attack rates between departments are high and
large outbreaks can occur for every level of HCW vaccine uptake.
Conclusions
The absence of herd immunity in nursing homes implies that vaccination of every additional HCW protects an
additional fraction of patients. Because of large stochastic variations, results of small-sized clinical trials on the effects
of HCW vaccination should be interpreted with great care. Moreover, the large variations in attack rates should be
taken into account when designing future studies.”
Science
31 October 2008 Vol 322, Issue 5902, Pages 633-804
http://www.sciencemag.org/current.dtl
[No relevant content]
Vaccine
Volume 26, Issue 46, Pages 5775-5896 (29 October 2008)
http://www.sciencedirect.com/science/journal/0264410X\
[Reviewed last week]
________________________________________________________________________________________
27 October 2008
The WHO released “The global burden of disease: 2004 update,” describing it as “a comprehensive
assessment of the health of the world's population. It provides detailed global and regional estimates of premature
mortality, disability and loss of health for 135 causes by age and sex, drawing on extensive WHO databases and on
information provided by Member States.” The update is available at: http://www.who.
int/healthinfo/global_burden_disease/2004_report_update/en/index.html
THE REPORT IN SECTIONS
Part 1: Introduction [pdf 577kb]
Part 2: Causes of death [pdf 635kb]
Part 3: Disease incidence, prevalence and disability [pdf 247kb]
Part 4: Burden of disease: DALYs [pdf 395kb]
Annex A: Deaths and DALYs 2004 Annex tables [pdf 581kb]
Annex B: Data sources and methods [pdf 300kb]
Annex C: Analysis categories and mortality data sources [pdf 224kb]
References [pdf 144kb]
STATISTICS FROM THE REPORT
Regional estimates of YLL, YLD, and DALYs, deaths, incidence and prevalence for 2004
Regional projections of deaths and DALYs for 2008, 2015, and 2030
The Bill & Melinda Gates Foundation announced 104 grants “to explore bold and largely unproven ways
to improve global health.” The grants of US$100,000 each will be made to scientists from 22 countries and five
continents, and mark the first round of funding from Grand Challenges Explorations, an initiative to help lower the
barriers for testing innovative ideas in global health. Gates said the initial set of grants will “inject fresh perspective into
research for preventing or curing infectious diseases such as HIV/AIDS and TB, and limiting the emergence of drug
resistance. Successful applicants showed how their project falls outside current scientific paradigms and could lead to
significant advances if successful—in just two pages.” Dr. Tachi Yamada, president of global health at the Gates
Foundation, who announced the grants at the fourth annual meeting of the Grand Challenges in Global Health
initiative in Bangkok, said, “We were hoping this program would level the playing field so anyone with a
transformational idea could more quickly assess its potential for the benefit of global health. The quality of the
applications exceeded all of our expectations. It was so hard for reviewers to champion just one great idea that we
selected almost twice as many projects for funding as we had initially planned.” The 104 grants were selected from
nearly 4,000 proposals, “with the geographic distribution of applicants largely matching the geographic distribution of
awards.” A complete list of the funded projects is available at the Grand Challenges Explorations web site.
(Gates Foundation Media Release, 22 October 2008)
http://www.gatesfoundation.org/press-releases/Pages/grand-challenges-explorations-recipients-081022.aspx
The WHO issued a request for comments on a new draft document: Guidance on Pandemic Influenza
Preparedness and Response. The request “…invites Member States, technical institutions, sub-regional, regional
and international organizations, whether governmental or nongovernmental, and all experts concerned with
pandemic influenza preparedness to participate in a web-based review of draft WHO guidance on Pandemic Influenza
Preparedness and Response (2008). Comments will be accepted online from 15 October through 3 November.”
WHO Guidance on Pandemic Influenza Preparedness and Response- Explanation of the revision process
Contact
WHO Global Influenza Programme
avenue Appia 20
CH-1211 Geneva 27
Switzerland
E-mail: WHOInfluenza@who.int
http://www.who.int/csr/disease/influenza/EN_guidancereview/en/index.html
The Weekly Epidemiological Record (WER) 24 October 2008, vol. 83, 43 (pp 385–392) includes:
- Evaluating clinical trial data and guiding future research for rotavirus vaccines
- Worldwide progress in introducing pneumococcal conjugate vaccine, 2000–2008
http://www.who.int/wer/2008/wer8343.pdf
Journal Watch
[Editor’s Note]
Vaccines: The Week in Review continues a new feature, scanning key journals to identify and cite articles, comment
and editorials, books reviews and other content supporting our focus on vaccine ethics and policy. Journal Watch is
not intended to be exhaustive, but indicative of themes and issues the center is actively tracking. We selectively
provide full text of some editorial and comment articles that are specifically relevant to our work. Successful access to
some of the links provided may require subscription or other access arrangement unique to the publisher. Our initial
scan list includes the journals below. If you would like to suggest other titles, please write to David Curry at david.r.
curry@centerforvaccineethicsandpolicy.org
JAMA
Vol. 300 No. 16, pp. 1845-1962, October 22/29, 2008
http://jama.ama-assn.org/current.dtl
[No relevant content]
Journal of Infectious Disease
1 November 2008 Volume 198, Number 9
http://www.journals.uchicago.edu/toc/jid/current
[Reviewed last week]
The Lancet
Volume 372, Number 9648, 25 October 2008
The Lancet 2008; 372:1438
DOI:10.1016/S0140-6736(08)61603-7
Editorial [full text]
Raising the profile of pneumococcal disease
Pneumococcal disease has never received the high-level, international attention that it deserves. Developments such
as the formation of the Global Fund to Fight AIDS, Malaria, and Tuberculosis and the advent of Integrated
Management of Childhood Illnesses, which moved attention away from programmes for acute respiratory infections,
have inadvertently contributed to this situation. But now efforts are being made to shine a spotlight on this neglected
disease. The latest is a report by the All-Party Parliamentarian Group on Pneumococcal Disease Prevention in the
Developing World—a group formed in January, 2007, to raise awareness about the disease.
The report, compiled from expert evidence, makes a welcome series of recommendations, including a request to the
UK Government to give equal standing and prominence to pneumococcal disease in its statements and policies as to
HIV/AIDS, tuberculosis, and malaria. There is also a call for developing countries to increase their commitments to
treating and preventing pneumonia and meningitis—the two most common manifestations of serious pneumococcal
disease.
Launched at the House of Lords in London, the report's recommendations are likely to be taken seriously by the UK
Government. Douglas Alexander, the UK Secretary of State for International Development, has written the report's
foreword, and the UK already contributes financially to the Advanced Market Commitment—an innovative financing
mechanism to improve access to effective vaccines against pneumococcal disease in developing countries. The
report might also influence some Members of the European Parliament. But whether its impact will be felt any further
than Brussels is uncertain.
The Global Action Plan for the Prevention and Control of Pneumonia, launched by WHO and UNICEF in 2007, also
seems to have fizzled out. Perhaps what is needed to kick-start a campaign against the disease is for all interested
parties—parliamentarians, UN agencies, and those outside the UN system—to form a powerful advocacy group,
similar to the Roll Back Malaria partnership. Such a development would form a united front and would be more
effective than individual attempts to push this major killer higher up the global-health agenda.
The Lancet
Nature
Volume 455 Number 7216 pp1007-1148 (23 October 2008)
http://www.nature.com/nature/journal/v455/n7214/
[No relevant content]
New England Journal of Medicine
Volume 359 — October 23, 2008 — Number 17
http://content.nejm.org/current.shtml
[No relevant content]
PLoS Medicine
[Accessed 27 October 2008]
http://medicine.plosjournals.org/perlserv/?request=browse&issn=1549-
1676&method=pubdate&search_fulltext=1&order=online_date&row_start=1&limit=10&ct=1
[No relevant content]
Science
24 October 2008 Vol 322, Issue 5901, Pages 501-608
http://www.sciencemag.org/current.dtl
ETHICS: Clinical Trials Guidelines at Odds With U.S. Policy
Dennis Normile
Science 24 October 2008: 516
Summary: The World Medical Association last week reaffirmed its opposition to the use of placebos in clinical trials and
urged trial sponsors to provide care for participants after studies are done.
Vaccine
Volume 26, Issue 46, Pages 5775-5896 (29 October 2008)
http://www.sciencedirect.com/science/journal/0264410X\
[Reviewed last week]
____________________________________________________________________________________________________
20 October 2008
BIO Ventures for Global Health (BVGH) announced that the Bill & Melinda Gates Foundation expanded
its support of the organization with a US$7 million grant, “so it can further engage biotechnology industry
innovation to create new medicines for infectious diseases of the developing world.” The new support “will help BVGH
build the market case for biotechnology industry investment through market-based incentives and to create new
opportunities for R&D collaborations.” Christopher D. Earl, PhD, President and CEO of BVGH, commented, "We are
thrilled by the Bill & Melinda Gates Foundation's support for expanding the BVGH mission. Biotechnology industry
resources are integral to the discovery of new solutions for the millions of patients suffering from diseases such as
malaria, tuberculosis and African sleeping sickness." Tachi Yamada, MD, President of the Gates Foundation's Global
Health Program, said "The biotech industry has an exceptional opportunity to apply its innovative skills to create new
global health solutions. BVGH designs economic incentives and partnerships that help make this industry commitment
possible."
(BVGH Media Release, 14 October 2008)
The GAVI Alliance said it welcomes a new report released in the United Kingdom by the All Party Group
on Pneumococcal Disease Prevention (APPG) “which highlights the devastating global health burden
caused by Streptococcus pneumoniae, a group of bacteria that kills up to one million children every
year.” The APPG report – Improving Global Health by Preventing Pneumococcal Disease – “provides strong
evidence from governments, multilateral agencies, NGOs, pharmaceutical companies and funding organizations about
the human and economic burden of pneumococcal disease. It points to the interventions available to prevent and
treat pneumonia and meningitis, and calls for them to be made a top health priority along with HIV, malaria and TB.”
According to the World Health Organisation, at least one child dies of pneumococcal disease every minute, making it
the leading cause of childhood pneumonia deaths in the developing world and the number one vaccine-preventable
cause of death in children worldwide.
The new report endorses the Advance Market Commitment (AMC) pilot mechanism to accelerate
pneumococcal vaccines launched by the Governments of Italy, the United Kingdom, Canada, Russia, and Norway
and the Bill & Melinda Gates Foundation. Julian Lob Levyt, Executive Director, GAVI Alliance, commented, “The GAVI
Alliance applauds the work of the APPG in highlighting pneumococcal as an unrecognized global health tragedy. The
report is a wakeup call to the international community that increased attention and commitment are vital. Innovative
initiatives such as the AMC and the strengthening of health systems are vital to bolster efforts to prevent this disease
and save more children’s lives, faster.”
(GAVI Media Release, 16 October 2008)
A new internal World Bank study assessing the potential impacts of an avian flu pandemic is reported on
by Bloomberg News. The study suggests that severe pandemic could kill 71 million people worldwide and push the
global economy into a “major global recession” cost the world economy up to US$3 trillion.
http://www.bloomberg.com/apps/news?pid=newsarchive&sid=ashmCPWATNwU# and
Separately, Lloyd’s Bank Emerging Risks Team released a new report: "Pandemic: Potential Insurance
Impact"
http://www.lloyds.com/NR/rdonlyres/08B1357D-AD59-4C48-8064-
599AF6F4F340/0/ER_Pandemic_InsuranceImpacts.pdf
The International Vaccine Institute (IVI) announced that Madame Kim Yoon-ok, First Lady of the
Republic of Korea, was inaugurated as the Honorary President of the Korea Support Committee (KSC)
for IVI on October 6. IVI describes itself as “a Seoul-based international organization exclusively devoted to the
accelerated development and introduction of new vaccines for children, and the only international organization
headquartered in Korea.” The KSC for the IVI is “a non-profit organization committed to improving the welfare of
humanity and to enhancing science and technology by supporting IVI´s humanitarian research. The Committee has
70 members, including prominent figures such as former prime ministers.” Madame Kim was appointed as the KSC’s
third Honorary President during a ceremony marking the IVI’s 11th Anniversary held at the IVI’s headquarters. In her
acceptance remarks, Madame Kim said, “Despite advances in medicine, 7 million children are dying from infectious
diseases. I will make my utmost efforts to ensure that children will no longer die needlessly from preventable diseases
because vaccines are unavailable to them.” She also urged more countries of the world to join in these global
humanitarian efforts by becoming signatories to the IVI’s charter.
(IVI Media Release, 6 October 2008)
The Weekly Epidemiological Record (WER) 7 October 2008, vol. 83, 42 (pp 373–384) includes: “23-valent
pneumococcal polysaccharide vaccine: WHO position paper.”
http://www.who.int/wer/2008/wer8342.pdf
Journal Watch
[Editor’s Note]
Vaccines: The Week in Review continues a new feature, scanning key journals to identify and cite articles, comment
and editorials, books reviews and other content supporting our focus on vaccine ethics and policy. Journal Watch is
not intended to be exhaustive, but indicative of themes and issues the center is actively tracking. We selectively
provide full text of some editorial and comment articles that are specifically relevant to our work. Successful access to
some of the links provided may require subscription or other access arrangement unique to the publisher. Our initial
scan list includes the journals below. If you would like to suggest other titles, please write to David Curry at david.r.
curry@centerforvaccineethicsandpolicy.org
JAMA
Vol. 300 No. 15, pp. 1729-1836, October 15, 2008
http://jama.ama-assn.org/current.dtl
[No relevant content]
Journal of Infectious Disease
1 November 2008 Volume 198, Number 9
http://www.journals.uchicago.edu/toc/jid/current
EDITORIAL COMMENTARY
Human Genetics and Malaria: Relevance for the Design of Clinical Trials
Sunil Parikh and Philip J. Rosenthal
Department of Medicine, San Francisco General Hospital, University of California, San Francisco
Received 1 July 2008; accepted 7 July 2008; electronically published 27 August 2008.
MAJOR ARTICLE
Sickle Cell Trait Is Associated with a Delayed Onset of Malaria: Implications for Time-to-Event Analysis in
Clinical Studies of Malaria
Peter D. Crompton,1; Boubacar Traore,5; Kassoum Kayentao,5; Safiatou Doumbo,5; Aissata Ongoiba,5; Seidina A.
S. Diakite,5; Michael A. Krause,3; Didier Doumtabe,5
Younoussou Kone,5; Greta Weiss,1; Chiung-Yu Huang,2; Seydou Doumbia,5; Aldiouma Guindo,5; Rick M. Fairhurst,
3; Louis H. Miller,4; Susan K. Pierce,1 and
Ogobara K. Doumbo5
1Laboratory of Immunogenetics, 2Biostatistics Research Branch, 3Laboratory of Malaria and Vector Research, and
4Malaria Vaccine Development Branch, National Institute of Allergy and Infectious Diseases, National Institutes of
Health, Bethesda, Maryland; 5Malaria Research and Training Centre, Department of Epidemiology of Parasitic
Diseases, Faculty of Medicine, Pharmacy, and Odonto-Stomatology, University of Bamako, Mali
“Background. The World Health Organization (WHO) recently recommended that the time to first malaria episode
serve as the primary end point in phase III malaria vaccine trials—the first of which will be held in Africa. Although
common red blood cell (RBC) polymorphisms such as sickle hemoglobin (HbS) are known to protect against malaria
in Africa, their impact on this end point has not been investigated.
Methods. A longitudinal study of 225 individuals aged 2–25 years was conducted in Mali. The association between
common RBC polymorphisms and the time to first malaria episode was evaluated.
Results. Among children aged 2–10 years, sickle cell trait (HbAS) was associated with a 34-day delay in the median
time to first malaria episode ( ). Cox regression analysis showed that greater age (hazard ratio [HR], 0.87 [95% CI,
0.80–0.94]; ), HbAS (HR, 0.48 [95% CI, 0.26–0.91]; ), and asymptomatic parasitemia at enrollment (HR, 0.35
[95% CI, 0.14–0.85]; ) were associated with decreased malaria risk.
Conclusion. Given the delay in the time to first malaria episode associated with HbAS, it would be advisable for clinical
trials and observational studies that use this end point to include Hb typing in the design of studies conducted in
areas where HbAS is prevalent.”
The Lancet
Volume 372, Number 9647, 18 October 2008
http://www.thelancet.com/journals/lancet
World Report
HIV discoverers awarded Nobel Prize for medicine
Stephen Pincock, page 1373
Virologist wins Nobel for cervical cancer discovery
Stephen Pincock, page 1374
Nature
Volume 455 Number 7215 pp835-1006 (16 October 2008)
http://www.nature.com/nature/journal/v455/n7214/
[No relevant content]
New England Journal of Medicine
Volume 359 — October 16, 2008 — Number 16
http://content.nejm.org/current.shtml
Monovalent Oral Poliovirus Vaccines — A Good Tool but Not a Total Solution
Ellie Ehrenfeld, Ph.D., and Konstantin Chumakov, Ph.D.
Partial text as available via online access
“The polio eradication campaign initiated in 1988 by the World Health Organization (WHO) led to an impressive
decline in cases of paralytic poliomyelitis around the world. The eradication strategy involved highly organized mass
immunization campaigns, relying solely on the trivalent oral polio vaccine developed by Albert Sabin and licensed in
the United States in 1963. Monovalent versions of oral polio vaccine had been licensed earlier but were abandoned in
favor of the trivalent combination oral polio vaccine to simplify immunization schedules. Efficacy was not considered
to be a significant issue, and differences between monovalent and trivalent vaccines were never formally…”
Monovalent Type 1 Oral Poliovirus Vaccine in Newborns
Nasr El-Sayed, M.D., M.P.H., Yehia El-Gamal, M.D., Ph.D., Ahmed-Amr Abbassy, M.D., Ph.D., Iman Seoud, M.D., Ph.
D., Maha Salama, M.D., Amr Kandeel, M.D., M.P.H., Elham Hossny, M.D., Ph.D., Ahmed Shawky, M.D., Heba Abou
Hussein, M.D., Ph.D., Mark A. Pallansch, Ph.D., Harrie G.A.M. van der Avoort, Ph.D., Anthony H. Burton, B.S.,
Meghana Sreevatsava, M.P.H., Pradeep Malankar, M.D., Mohamed H. Wahdan, M.D., Ph.D., and Roland W. Sutter, M.
D., M.P.H.T.M.
ABSTRACT
“Background: In 1988, the World Health Assembly resolved to eradicate poliomyelitis. Although substantial progress
toward this goal has been made, eradication remains elusive. In 2004, the World Health Organization called for the
development of a potentially more immunogenic monovalent type 1 oral poliovirus vaccine.
Methods: We conducted a trial in Egypt to compare the immunogenicity of a newly licensed monovalent type 1 oral
poliovirus vaccine with that of a trivalent oral poliovirus vaccine. Subjects were randomly assigned to receive one
dose of monovalent type 1 oral poliovirus vaccine or trivalent oral poliovirus vaccine at birth. Thirty days after birth,
a single challenge dose of monovalent type 1 oral poliovirus vaccine was administered in all subjects. Shedding of
serotype 1 poliovirus was assessed through day 60.
Results: A total of 530 subjects were enrolled, and 421 fulfilled the study requirements. Thirty days after the study
vaccines were administered, the rate of seroconversion to type 1 poliovirus was 55.4% in the monovalent-vaccine
group, as compared with 32.1% in the trivalent-vaccine group (P<0.001). Among those with a high reciprocal titer
of maternally derived antibodies against type 1 poliovirus (>64), 46.0% of the subjects in the monovalent-vaccine
group underwent seroconversion, as compared with 21.3% in the trivalent-vaccine group (P<0.001). Seven days
after administration of the challenge dose of monovalent type 1 vaccine, a significantly lower proportion of subjects
in the monovalent-vaccine group than in the trivalent-vaccine group excreted type 1 poliovirus (25.9% vs. 41.5%,
P=0.001). None of the serious adverse events reported were attributed to the trial interventions.
Conclusions: When given at birth, monovalent type 1 oral poliovirus vaccine is superior to trivalent oral poliovirus
vaccine in inducing humoral antibodies against type 1 poliovirus, overcoming high preexisting levels of maternally
derived antibodies, and increasing the resistance to excretion of type 1 poliovirus after administration of a challenge
dose. (Current Controlled Trials number, ISRCTN76316509)”
Effectiveness of Immunization against Paralytic Poliomyelitis in Nigeria
Helen E. Jenkins, M.Sc., R. Bruce Aylward, M.D., Alex Gasasira, M.B., Ch.B., Christl A. Donnelly, Sc.D., Emmanuel A.
Abanida, M.P.H., Titi Koleosho-Adelekan, Ph.D., and Nicholas C. Grassly, D.Phil.
ABSTRACT
“Background: The number of cases of paralytic poliomyelitis has declined in Nigeria since the introduction of newly
licensed monovalent oral poliovirus vaccines and new techniques of vaccine delivery. Understanding the relative
contribution of these vaccines and the improved coverage to the decline in incident cases is essential for future
planning.
Methods: We estimated the field efficacies of monovalent type 1 oral poliovirus vaccine and trivalent oral poliovirus
vaccine, using the reported number of doses received by people with poliomyelitis and by matched controls as
identified in Nigeria's national surveillance database, in which 27,379 cases of acute flaccid paralysis were recorded
between 2001 and 2007. Our estimates of vaccine coverage and vaccine-induced immunity were based on the
number of doses received by children listed in the database who had paralysis that was not caused by poliovirus.
Results: The estimated efficacies per dose of monovalent type 1 oral poliovirus vaccine and trivalent oral poliovirus
vaccine against type 1 paralytic poliomyelitis were 67% (95% confidence interval [CI], 39 to 82) and 16% (95% CI,
10 to 21), respectively, and the estimated efficacy per dose of trivalent oral poliovirus vaccine against type 3
paralytic poliomyelitis was 18% (95% CI, 9 to 26). In the northwestern region of Nigeria, which reported the majority
of cases during the study period, coverage with at least one dose of vaccine increased from 59 to 78%. Between
2005 and 2007, vaccine-induced immunity levels among children under the age of 5 years more than doubled, to
56%.
Conclusions: The higher efficacy of monovalent type 1 oral poliovirus vaccine (four times as effective as trivalent oral
poliovirus vaccine) and the moderate gains in coverage dramatically increased vaccine-induced immunity against
serotype 1 in northern Nigeria. Further increases in coverage in Nigerian states with infected populations are required
to achieve the levels of vaccine-induced immunity associated with the sustained elimination achieved in other parts of
the country.”
PLoS Medicine
[Accessed 20 October 2008]
http://medicine.plosjournals.org/perlserv/?request=browse&issn=1549-
1676&method=pubdate&search_fulltext=1&order=online_date&row_start=1&limit=10&ct=1
[No relevant content]
Science
17 October 2008 Vol 322, Issue 5900, Pages 329-488
http://www.sciencemag.org/current.dtl
[No relevant content]
Vaccine
Volume 26, Issue 46, Pages 5775-5896 (29 October 2008)
http://www.sciencedirect.com/science/journal/0264410X\
Air travel as a risk factor for introduction of measles in a highly vaccinated population
Pages 5775-5777
Robert S. van Binnendijk, Susan Hahné, Aura Timen, Gijs van Kempen, Robert H.G. Kohl, Hein J. Boot, Katja C.
Wolthers, José C.F.M. Wetsteijn, Anne de Vries, Krista Westert, Kevin E. Brown, Rik L. de Swart
Abstract
“Epidemiological and molecular investigation of two small measles clusters in The Netherlands in July/August 2007
revealed an association with travel by air of the index cases and nosocomial spread in the first cluster. Although these
importations did not result in an outbreak among unvaccinated subjects, the observations illustrate the challenges
for measles control in a country with high measles vaccination coverage (>95%) but with pockets of low coverage.”
Internationally adopted children: What vaccines should they receive?
Pages 5784-5790
M.J. Cilleruelo, F. de Ory, J. Ruiz-Contreras, R. González-González, M.J. Mellado, M. García-Hortelano, J. Villota, M.
García-Ascaso, R. Piñeiro, P. Martín-Fontelos, R. Herruzo
Abstract
“It is of paramount importance to know the vaccination status in internationally adopted children, so that they can
be correctly immunized. This study ascertains the seroprotection rate for vaccine-preventable diseases and the
validity of the immunization cards in 637 adopted children. The absence of the immunization card (13% of children)
correlated with a poor global vaccine protection. Children with immunization records (87%) had a better global
seroprotection but the information obtained from the card did not accurately predict seroprotection for each
particular antigen. The best variable to predict the status of seroprotection was the country of origin. The highest
rate of protection was found in children from Eastern Europe and, in descending order, India, Latin America, China
and Africa. General recommendations for immunization of internationally adopted children are difficult to establish.
Actions for vaccination have to be mainly implemented on the basis of the existence of the immunization card and of
the country of origin.”
_____________________________________________________________________________________________________
13 October 2008
The MMWR for October 10, 2008 / 57(40);1100-1103 includes: Vaccination Coverage Among Adolescents
Aged 13--17 Years --- United States, 2007. The media release notes that “The nation’s immunization coverage
rates for preteens and teens are increasing for routinely recommended vaccines, but most still do not have all of the
recommended immunizations. Dr. Lance Rodewald, director of the Division of Immunization Services at the CDC′s
National Center for Immunization and Respiratory Diseases, commented, “The overall trends are good news. We are
seeing more preteens and teenagers being protected against serious, sometimes deadly diseases. But we remain
short of our goals—for almost all of these vaccines we want at least 90 percent of adolescents to be fully immunized.
As such, we have much work to do to get many more adolescents protected.”
The survey provides estimates for three vaccines recommended at 11 or 12 years of age: the tetanus-diphtheria-
acellular pertussis (Tdap) vaccine, the meningococcal conjugate vaccine (MCV4), and the human papillomavirus
(HPV4) vaccine for girls and young women. It also includes estimates of the percentage of 13- through 17-year-old
teens who should have received the recommended immunizations for measles, mumps and rubella vaccine (MMR),
hepatitis B (HepB) vaccine, and varicella vaccine (VAR) earlier in life.
Specific findings included:
- Vaccination coverage levels for three or more doses of hepatitis B (HepB) and two or more doses of measles,
mumps and rubella vaccine (MMR) were over 80 percent;
- Coverage with one dose of varicella vaccine (VAR) was high at 75.7 percent but coverage with two doses was low
at 18.8 percent among preteens and teens without a previous history of disease;
- 32.4 percent of preteens and teens surveyed had received MCV4 vaccination, up from 11.7 percent in 2006 (a
20.7 percentage point increase);
- 30.4 percent had received Tdap vaccination, up from 10.8 percent in 2006 (a 19.6 percentage point increase);
- 25.1 percent of adolescent females had received at least one dose of HPV vaccine
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5740a2.htm
The Association for Professionals in Infection Control and Epidemiology (APIC) announced its support
for requiring flu immunization for healthcare workers who have direct patient contact as well as ancillary
staff. APIC further recommended that healthcare facilities “obtain informed statements acknowledging the risk to
patients from employees who decline the vaccine for reasons other than medical.” APIC states that healthcare
facilities should implement a comprehensive strategy incorporating all of the guidelines for influenza vaccination of
healthcare personnel from the Centers for Disease Control and Prevention’s (CDC) Healthcare Infection Control
Practices Advisory Committee (HICPAC) and the Advisory Committee on Immunization Practices (ACIP). Linda R.
Greene, RN, MPS, CIC, lead author of APIC’s position paper, noted, “We must do a better job of immunizing
healthcare workers every year to ensure patient safety and protect those individuals at high risk of developing
complications of influenza. Despite longstanding recommendations by government agencies and national healthcare
organizations, only 42 percent of healthcare workers receive yearly flu vaccines. Voluntary efforts are clearly not
effective – it’s time for hospitals and other healthcare facilities to require influenza immunization.”
http://www.apic.org/AM/Template.cfm?Section=Featured_News_and_Events&TEMPLATE=/CM/ContentDisplay.
cfm&CONTENTID=11963
Merck announced that ROTATEQ (rotavirus vaccine, live, oral, pentavalent) was awarded pre-
qualification status by the WHO, which “allows for expanded access to ROTATEQ and provides a
greater opportunity to help protect millions of babies from rotavirus gastroenteritis.” This pre-
qualification means that the vaccine is now eligible for procurement by the Pan American Health Organization (PAHO),
UNICEF and other United Nations agencies for use in national vaccination programs. Merck noted that rotavirus
infects nearly all children worldwide by age 5 and causes approximately 1.9 million hospitalizations each year in
developing countries, and that ROTATEQ is the only ready-to-use oral liquid rotavirus vaccine to receive WHO pre-
qualification. Mark Feinberg, M.D., Ph.D., vice president, Medical Affairs and Policy, Merck Vaccines and Infectious
Diseases, said “WHO pre-qualification of ROTATEQ is an important milestone in expanding the global availability of
ROTATEQ, and importantly, for facilitating efforts to accelerate the introduction of the vaccine in the world's poorest
countries. Merck's pledge to provide ROTATEQ to GAVI-eligible countries at prices at which we do not profit is
another step to make this vaccine accessible to all who need it in every part of the world.”
(BUSINESS WIRE, 9 October 2008)
Journal Watch
[Editor’s Note]
Vaccines: The Week in Review continues a new feature, scanning key journals to identify and cite articles, comment
and editorials, books reviews and other content supporting our focus on vaccine ethics and policy. Journal Watch is
not intended to be exhaustive, but indicative of themes and issues the center is actively tracking. We selectively
provide full text of some editorial and comment articles that are specifically relevant to our work. Successful access to
some of the links provided may require subscription or other access arrangement unique to the publisher. Our initial
scan list includes the journals below. If you would like to suggest other titles, please write to David Curry at david.r.
curry@centerforvaccineethicsandpolicy.org
JAMA
Vol. 300 No. 14, pp. 1621-1718, October 8, 2008
http://jama.ama-assn.org/current.dtl
[No relevant content]
Journal of Infectious Disease
15 October 2008 Volume 198, Number 8
http://www.journals.uchicago.edu/toc/jid/current
[Reviewed last week (no relevant content)]
The Lancet
Volume 372, Number 9646, 11 October 2008
http://www.thelancet.com/journals/lancet
The Lancet 2008; 372:1287-1290
DOI:10.1016/S0140-6736(08)61534-2
Special Report
Nigeria struggles to contain poliomyelitis
Margaret Harris Cheng
“Nigeria has had several setbacks in its bid to control poliomyelitis, including false rumours about vaccine safety. Now
public anger over the failure of the ailing health system to deliver for its people threatens to derail the country's
eradication campaign. Margaret Harris Cheng reports.”
Nature
Volume 455 Number 7214 pp707-834 (9 October 2008)
http://www.nature.com/nature/journal/v455/n7214/
Editorial
Malaria's watershed
Nature 455, 707 (9 October 2008) | doi:10.1038/455707a; Published online 8 October 2008
Abstract [Full text]
Malaria's moment has come, but success in control, let alone eradication, demands a renewed commitment to basic
research.
A Global Malaria Action Plan, announced at the UN Millennium Development Goals Malaria Summit in New York on 25
September, has the ambitious goals of both reducing the malaria burden and eradicating the disease entirely.
Eradication any time soon might seem hopelessly optimistic, given the failure so far to make a serious dent in the
number of malaria deaths. But much of the 274-page plan makes good sense. It calls for scaling up the use of
existing tools, such as bednets, drugs and spraying, to near universal coverage, and then sustaining this effort for
decades. True, this won't come cheaply. Funds for control have already grown from US$250 million annually in 2004
to an estimated US$1.1 billion this year; the plan calls for increasing that to $5 billion annually until at least 2020.
Likewise, total spending on malaria-related research has risen from $265 million in 2003 to $422 million in 2007; the
plan would see that figure double to between $750 million and $900 million annually until 2018. Whether donors will
rise to the challenge is a big question, given current economic woes. Still, it is heartening that at the summit, donors
from governments, industry and philanthropic organizations pledged US$3 billion.
Striking the right balance between basic and applied research is also critical. For example, the sequencing in 2002 of
the genome of Plasmodium falciparum, the main parasite that causes malaria, has stimulated the hunt for new drug
and vaccine candidates. This week's issue of Nature sees the addition of two more parasite sequences: P. vivax,
which is less deadly than P. falciparum, and P. knowlesi, which mainly infects monkeys (pages 751, 757 and 799).
These new sequences show how much more there is to learn: more than half of P. falciparum's encoding genes still
have no known function.
Basic research is also needed to stay ahead of drug resistance in the parasite and insecticide resistance in mosquitoes,
and to get a better understanding of natural infection in humans. One surprise from P. falciparum's genome is
evidence that it evades the human immune system mainly by genomic and gene-expression diversity. Plasmodium
seems to have different metabolic and physiological states, and can reprogram its gene expression. These findings
could alter the way researchers think about both drug and vaccine development.
The malaria drug and vaccine pipelines are healthier now than they have been for decades, but they are in urgent
need of new candidates and approaches. So it was welcome news when the Bill & Melinda Gates Foundation, already
the largest donor in malaria research, announced at the UN summit that it would spend US$168 million to develop
next-generation malaria vaccines. Moreover, this initiative will include early-stage laboratory research — most of the
Gates Foundation's funding has so far focused on translational and clinical research.
Many scientists would like to see the foundation fund even more basic research, but this cannot be the foundation's
responsibility alone. Its support of translational work has rejuvenated the field over the past decade, and has helped
get tools into the field. In the process, the malaria research community has become excessively and undesirably
dependent on this one entity. Other research organizations would do well to step up to the plate and match the
Gates Foundation's spending with their own basic-research funds. That would also go some way to addressing what
scientists say is an unfortunate consequence of the emphasis on translational research: that scientists entering
malaria research are less likely to choose basic science.
Any massive increase in research funding means that the malaria community must think about how to coordinate
research across funding agencies. It is encouraging that the main research funders and scientists are to sit down as a
group — called MalERA — over the next year to thrash out a research agenda for eradication. One lesson of the
malaria and human genome projects is that consortia are a key route to delivery, focusing resources wisely, and
avoiding duplication and excessive bureaucracy. It is also essential that international research recognizes the maturity
of the malaria research community in the poorer countries where the disease is endemic — they should be on board
as equals and not, as is too often the case, afterthoughts.”
Article
Comparative genomics of the neglected human malaria parasite Plasmodium vivax
Nature 455, 757-763 (9 October 2008) | doi:10.1038/nature07327; Received 18 January 2008; Accepted 8 August
2008
Jane M. Carlton et al
[First paragraph full text] “The human malaria parasite Plasmodium vivax is responsible for 25–40% of the 515
million annual cases of malaria worldwide. Although seldom fatal, the parasite elicits severe and incapacitating clinical
symptoms and often causes relapses months after a primary infection has cleared. Despite its importance as a major
human pathogen, P. vivax is little studied because it cannot be propagated continuously in the laboratory except in
non-human primates. We sequenced the genome of P. vivax to shed light on its distinctive biological features, and as
a means to drive development of new drugs and vaccines. Here we describe the synteny and isochore structure of
P. vivax chromosomes, and show that the parasite resembles other malaria parasites in gene content and metabolic
potential, but possesses novel gene families and potential alternative invasion pathways not recognized previously.
Completion of the P. vivax genome provides the scientific community with a valuable resource that can be used to
advance investigation into this neglected species….”
New England Journal of Medicine
Volume 359 — October 9, 2008 — Number 15
http://content.nejm.org/current.shtml
[No relevant content]
PLoS Medicine
[Accessed 13 October 2008]
[No relevant content]
Science
10 October 2008 Vol 322, Issue 5899, Pages 161-290
http://www.sciencemag.org/current.dtl
Special Issue on Clinical Trials
Science 10 October 2008:
Vol. 322. no. 5899, p. 209
DOI: 10.1126/science.322.5899.209
[Full text]
Introduction to special issue:
Lemons, Oranges, and Complexity
Eliot Marshall
“Faced with an epidemic of scurvy, British surgeon James Lind decided to test some cures in 1747. In a legendary
trial, he put 12 sickly sailors on a fixed diet and divided the group into twos. Each pair received a different
supplement--cider, seawater, dilute acid, and so on. The result: After 6 days, the two who ate lemons and oranges
improved so much that they were sent back on duty. The navy was slow to recognize the significance of Lind's work
but eventually decreed that citrus (a source of vitamin C that prevents scurvy) must be in all sailors' rations.
By modern standards, Lind's test was weak. It had no control group. No placebo. No blinding of data. But it worked.
By controlling the environment and varying treatments, it made possible an accurate reading of the human body's
response. This idea, with many refinements, drives the modern clinical trial. But now the clinical trial itself is facing an
epidemic--of rising costs and blurred objectives.
On page 210, David Malakoff reports on the view, as one U.S. researcher puts it, that the "system isn't working."
Malakoff describes factors that are driving inflation. Among them are complex rules for reporting, the proliferation of
required tests, the difficulty of recruiting and keeping volunteers, and waste in the design and management of trials.
But there is an encouraging note, too: Public and private organizations are aware of these problems and are pushing
for reform.
One counterpoint to problems in the West is a boom in the East. Dennis Normile describes the expansion of clinical
studies in Asia on page 214. A desire to cut costs is only part of this trend; China and India see clinical trials as a
means of growing their economies and developing skills.
Jocelyn Kaiser reports on page 217 about ongoing efforts to make Western trial data more accessible. A mandate
requiring disclosure of results from all trials of drugs approved by the U.S. Food and Drug Administration takes effect
this fall, for example.
On page 219, Constance Holden gives an update on efforts to ensure that U.S. government-sponsored trials are
balanced by gender. And Jennifer Couzin dissects an important series of interventions designed to prevent heart
disease by controlling cholesterol (p. 220). The results raise fundamental questions about how cholesterol functions in
the body--and about the usefulness of certain biomarkers as surrogates for health outcomes.
A video report by Robert Frederick on progress in testing drugs for children, "Pediatric Medicines: Prescribing Off-
Label," appears online at www.sciencemag.org/clinicaltrials.
The subtlety and cost of these modern clinical trials would amaze James Lind.”
Vaccine
Volume 26, Issue 45, Pages 5669-5774 (23 October 2008)
http://www.sciencedirect.com/science/journal/0264410X\
[Reviewed last week]
_____________________________________________________________________________________________________
6 October 2008
Wyeth Pharmaceuticals announced the initiation of the Community Acquired Pneumonia Immunization
Trial in Adults, described as a major study in adults of an investigational 13-valent conjugate vaccine
designed to help prevent pneumococcal pneumonia, the leading cause of bacterial pneumonia in adults.
Wyeth noted that in Europe and the United States, pneumococcal pneumonia is the most common community-
acquired bacterial pneumonia, for which the adult mortality rate averages between 10 to 20 percent, and that rate
may exceed 50 percent in high-risk groups worldwide. The Community Acquired Pneumonia Immunization Trial in
Adults is a double-blind, placebo-controlled study expected to enroll approximately 85,000 participants 65 years of
age and older. The study is being conducted by the Julius Center for Health Sciences and Primary Care at the
University Medical Center Utrecht in the Netherlands. Participants in the trial will receive either Wyeth's investigational
13-valent pneumococcal conjugate vaccine or placebo.
(PRNewswire, 26 September 2008)
HHS Secretary Mike Leavitt announced two new actions in the department’s “ongoing activities to
bolster the nation’s preparedness for a potential outdoor anthrax attack.” The first action “focuses on
United States Postal Service letter carriers who volunteer to deliver medicines directly to residences in their
communities during an emergency.” Homeland Security Secretary Michael Chertoff and HHS Secretary Leavitt “have
invoked their authority under section 564 of the Federal Food, Drug, and Cosmetic Act to make the determination
and declaration of emergency required by law in order for HHS’ Food and Drug Administration (FDA) to consider
issuing an Emergency Use Authorization (EUA) allowing eligible letter carriers to receive kits containing small quantities
of antibiotics for future use by them and other members of their households during an anthrax emergency.” These
antibiotics “would help protect volunteers against contracting anthrax if, following an outdoor anthrax attack, the
Postal Service was called upon to deliver the same life-saving antibiotics directly to homes across their community
where people may have been exposed to the bacterium that causes anthrax. Although no imminent threat
currently exists, these legal actions would enable FDA to issue a EUA.”
Secretary Leavitt commented, “In an anthrax attack, time is of the essence in preventing illness and death by getting
antibiotics to those who may have been exposed. By providing advance protection to letter carriers who volunteer
to deliver antibiotics in an affected community, we can gain the benefits of the unique capabilities of the Postal
Service to get much needed medicines to those who need it quickly. This is one part of our strategy to encourage
preparedness at all levels of government to enable our nation to respond effectively in the event of an anthrax
emergency.”
HHS said that over the past several years, under the Cities Readiness Initiative (CRI), HHS and the Postal Service
“have successfully developed and tested in three U.S. cities -- Seattle, Philadelphia and Boston --the ability of letter
carriers to quickly deliver door-to-door quantities of antibiotics from the Strategic National Stockpile to residential
addresses. This quick-strike capability is intended to buy time for local and State public health authorities to set up
points of dispensing for further provision of antibiotics across the community.”
“The letter carrier has long been a reliable presence in America's neighborhoods. This important and potentially life
saving undertaking is a natural extension of what the carriers see as a service to their community,” Postmaster
General John E. Potter said.
Begun in 2004, CRI is a federally funded effort to prepare 72 major U.S. cities and metropolitan areas to effectively
respond to a large scale bioterrorist event by dispensing antibiotics to their entire identified population within 48 hours
of the decision to do so. With today’s actions, CRI cities will now have another distribution tool at their disposal when
crafting their plans to protect their populations. Such innovations have been encouraged by the National Academy
of Sciences’ Institute of Medicine, which earlier this year conducted an evaluation of medical countermeasure
distribution capabilities.
In a related action, HHS said Secretary Leavitt issued a declaration under the Public Readiness and Emergency
Preparedness Act (PREP Act) that “provides liability protection for activities related to developing, manufacturing,
distributing, prescribing, dispensing, administering and using anthrax countermeasures in preparation for, and in
response to, a potential anthrax attack. This includes entities, such as large “big-box” retail stores, retail pharmacies,
and other private sector businesses, that help to deliver and distribute medicines.” Secretary Leavitt said,
“Preparedness is a shared responsibility that must involve all sectors of society, including the private sector,
community groups, families and individuals. We are using the authorities available to us to do all we can to support
preparedness at all levels.”
The DHS Determination of an Emergency (under Section 564(b) of the Federal Food, Drug and Cosmetic Act) is
available at http://www.dhs.gov/xlibrary/assets/ofsec_signed_determination092308.pdf; the HHS Declaration of an
Emergency (under Section 564(b) of the Federal Food, Drug and Cosmetic Act) is available at http://www.hhs.
gov/disasters/emergency/manmadedisasters/bioterorism/564anthrax-declaration.html; and the HHS PREP Act
Declaration available at http://www.hhs.gov/disasters/emergency/manmadedisasters/bioterorism/prepact-081001.
html.
(HHS Media Release, 1 October 2008)
Emergent BioSolutions announced it signed a new, multi-year, firm fixed price contract to supply an
additional 14.5 million doses of BioThrax (Anthrax Vaccine Adsorbed), its FDA licensed anthrax vaccine,
from the U.S. Department of Health and Human Services (HHS)for inclusion in the Strategic National Stockpile (SNS).
The total value of this follow-on contract is between US$364 million and US$404 million, with the higher amount tied
to the delivery of product having four-year expiry dating. Fuad El-Hibri, chairman and CEO of Emergent BioSolutions,
commented, “This follow-on contract with HHS is continuing evidence of the government’s steadfast commitment to
procure critical countermeasures to protect against the threat of bioterrorism in our country,”
(BUSINESS WIRE, 1 October 2008)
GenVec said the National Institutes of Health (NIH) executed its second option period (year three)
under a previously announced, five-year contract with GenVec valued at up to US$52 million for the
production of HIV vaccines. GenVec will receive up to $3.8 million for the third year of activities, and said the
funds will continue to support the development of new HIV vaccine candidates based on its proprietary adenovirus
vector and production cell line technologies. Dr. Rick King, GenVec’s Senior Vice President of Research and
Development, said, “We appreciate NIAID’s decision to execute its renewal option under our contract. This renewal
will help fund the development of new HIV vaccine candidates, which are based on multiple serotypes of adenovirus.
GenVec’s adenovector technology platform now includes six distinct serotypes that can be used singly or in
combination.”
(BUSINESS WIRE, 2 October 2008)
VGX Pharmaceuticals announced that the National Institute of Allergy and Infectious Diseases (NIAID)
awarded the company a contract to develop a preventive HIV DNA vaccine candidate in conjunction
with VGX’s constant current electroporation technology for intradermal delivery of DNA vaccines. The
contract is part of the NIAID’s HIV Vaccine Design and Development Teams program, and brings together HIV
vaccine experts from the University of Pennsylvania School of Medicine and VGX. The contract, titled “Development
of Improved DNA Vaccines and Electroporation Delivery Devices for Prophylactic HIV Vaccines”, provides US$23.5
million of funding over seven years, including a base period and follow-on option years. VGX’s vaccine candidate,
PENNVAX-G (targeting HIV clades A, C, and D), was developed in the laboratory of Professor David B. Weiner at the
University of Pennsylvania School of Medicine and licensed to VGX. The DNA-based vaccine will be delivered using VGX’
s intradermal electroporation (ID-EP) technology.
(BUSINESS WIRE, 1 October 2008)
Novavax announced that it was recognized at the annual meeting of the Clinton Global Initiative
("CGI") “for developing affordable methods of producing an H5N1 avian influenza vaccine and a
seasonal influenza vaccine using the company's proprietary recombinant virus-like particles ("VLPs").”
Novavax said it is working “to create novel vaccines and manufacturing solutions for producing avian and seasonal
influenza vaccines with portable equipment that can be deployed worldwide,” and that it believes its vaccine initiatives
“have the potential to impact millions of people affected by infectious diseases each year by creating novel vaccines
that can be produced in a cost effective and timely manner within the same scalable manufacturing platform
worldwide.”
(PRNewswire-FirstCall, 29 September 2008)
Journal Watch
[Editor’s Note]
Vaccines: The Week in Review continues a new feature, scanning key journals to identify and cite articles, comment
and editorials, books reviews and other content supporting our focus on vaccine ethics and policy. Journal Watch is
not intended to be exhaustive, but indicative of themes and issues the center is actively tracking. We selectively
provide full text of some editorial and comment articles that are specifically relevant to our work. Successful access to
some of the links provided may require subscription or other access arrangement unique to the publisher. Our initial
scan list includes the journals below. If you would like to suggest other titles, please write to David Curry at david.r.
curry@centerforvaccineethicsandpolicy.org
JAMA
Vol. 300 No. 13, pp. 1489-1610, October 1, 2008
http://jama.ama-assn.org/current.dtl
[No relevant content]
Journal of Infectious Disease
15 October 2008 Volume 198, Number 8
http://www.journals.uchicago.edu/toc/jid/current
[No relevant content]
The Lancet
Volume 372, Number 9645, 4 October 2008
http://www.thelancet.com/journals/lancet
The Lancet 2008; 372:1193
DOI:10.1016/S0140-6736(08)61494-4
Editorial
Rolling back malaria—the next 10 years
The Roll Back Malaria (RBM) partnership is 10 years old this month. What started out in 1998 as an alliance of four UN
agencies, to facilitate and coordinate implementation of malaria control, has grown exponentially to become a
coalition of more than 500 partners. In the early years, RBM faced several problems: uncertainty around its role, four
leadership changes in 5 years, and a catalogue of missed opportunities and failures to make any substantial headway
to tackle malaria. But last week, the partnership launched their Global Malaria Action Plan to a huge fanfare at the high-
level UN Millennium Development Goal meeting in New York. The promise of US$3 billion, new technologies, increased
awareness, and political will to fight this ancient scourge signals a new era of confidence and support for the
previously beleaguered partnership.
The plan lays out three goals to reduce malaria: in the short-term, to reduce mortality and morbidity by half from
2000 levels by scaling up the available methods of prevention and treatment for all those in need by 2010; in the
medium term, to reduce the number of malaria deaths to near zero by 2015 through sustained coverage of these
tools; and in the long-term, to maintain near zero deaths worldwide, while eliminating malaria transmission in feasible
countries and moving towards eradication of malaria with new tools and approaches.
The plan is far more comprehensive than previous versions. It provides an evidence-informed approach to deliver
effective prevention and treatment to those at risk. It also estimates the annual funding needed to achieve the goals
of the partnership, with at least US$62 billion being required by 2020. Having been sent for wide consultation to
countries, experts, and institutions, it is perhaps the closest the malaria community has got to a consensus-based
plan. RBM estimates that if the plan is successfully implemented, 4.2 million lives could be saved by 2015 in the 20
highest-burden African countries alone. What makes the plan ambitious is the focus on elimination and ultimately
eradication. These terms are attractive and hold much political weight, but one only has to look at the poliomyelitis
eradication programme to know in reality that such ambition can turn out to be a great deal more complex. There
are dangers in setting the bar too high.
To date the actual burden of malaria has been difficult to be sure of. The second WHO Malaria Report 2008
(containing data up to 2006) estimates a substantial decrease in the number of cases and deaths compared with
previous years. But these numbers are disputed by experts. Without proper baseline assessments of what the
current burden was in 2000, it is unclear how exactly the partnership will know when it has reached its 50% target.
Furthermore, changes in malaria epidemiology and transmission make it vital that success is measured properly in
terms of health outcomes, infection rates, and intervention coverage. Monitoring, evaluation, and surveillance must
be prioritised, funded properly, and put in place at the country level. Progress in achieving these goals should be
reviewed regularly and independently.
A major challenge in countries with high malaria mortality is the lack of human capacity and health systems to deliver
interventions. It is encouraging to see capacity building and health system strengthening being included in the plan,
but these commitments, so often given before, need to translate into practice. Too frequently, donors tend to be
commodity-driven and would rather invest in bednets and medicines. The returns on health-system strengthening
are enormous and provide the opportunity of integration with broader global-health initiatives.
One threat to progress is the commitment to long-term funding. Just to reach the 2010 coverage targets will require
four times the funds currently available. Along-side continued donor contributions, increased funding by malaria-
endemic countries, monitoring financial commitments against actual needs, and a formal external evaluation of
impact and progress of the plan over time are imperative. Partners, donors, and country leaders should all be held to
account; here an independent and transparent scientific evaluation would be most useful.
RBM has raised the profile of malaria, taking the disease from being grossly under funded and largely neglected to
being widely recognised as an exemplary investment opportunity in the development agenda. It has achieved this
through stronger leadership, better cooperation between its partners, and responding to country needs by
improved coordination around their national strategic and implementation plans. During the next decade, RBM has
huge challenges. But for the first time, we sense these challenges might be met. The decisions taken in New York last
week have created an unprecedented opportunity, one that must be grasped firmly by all parties.
The Lancet
The Lancet 2008; 372:1203-1205
DOI:10.1016/S0140-6736(08)61499-3
Comment
Blocking humanitarian assistance: a crime against humanity?
John D Kraemer, Dhrubajyoti Bhattacharya and Lawrence O Gostin
In May, Cyclone Nargis left nearly 140,000 people dead or missing in Burma, while the Government severely
restricted international assistance.1 More recently, Zimbabwean President Robert Mugabe cut off international
assistance, apparently to manipulate an election but leaving millions without food aid or medical care.2 The global
community has a long and sad history of exalting human rights in the abstract but failing to protect them in practice.
When political leaders willfully block vital humanitarian aid to their people, they violate international human rights and
potentially commit a crime against humanity. Such violations give the international community a legal right of
intervention, with force if necessary. While intervention is best pursuant to authorisation from the UN Security
Council, without such authorisation regional organisations or individual nations should prioritise the survival of large
populations over the sovereignty claims of despotic leaders.
Can a right to health overcome barriers of national sovereignty? Human rights prevent states from claiming that
systematic maltreatment of their nationals is exclusively a domestic concern. International law holds the state
accountable for safeguarding the human rights of its people, and legitimises the actions of the international
community to monitor and redress violations. This view was affirmed in the UN Charter, which proclaimed the UN's
mission as solving international humanitarian concerns through international cooperation.3
The International Covenant on Civil and Political Rights guarantees the right to life, and the International Covenant on
Economic, Social, and Cultural Rights codifies the right to health. Neither has been signed by Burma, although
Zimbabwe has signed both but respected neither. Nonetheless, the rights to life and health are so widely accepted
that they are part of international customary law. WHO's Constitution also requires nations to seek to attain the
highest possible level of health for all peoples.4 But it stops short of mandating countries to accept international aid
during crises.
The right to health requires states to respect, protect, and fulfill basic health needs. This demands, at the least, the
bare minimums to ensure survival, including medical aid and supplies, potable water, and food for the most
vulnerable populations.5 During crises, countries have limited capacity to secure these public goods, but international
law requires cooperation with the international community to meet these obligations. Additionally, the right to life is a
non-derogable right, and even the most hardened isolationist regimes must respect it.
Even governments as repressive as Burma and Zimbabwe have ratified the Convention on the Rights of the Child
(CRC), which recognises the rights to health and life, and demands international cooperation. The CRC requires
states to ensure to the maximum extent possible children's survival and development, including access to basic
determinants of health. Moreover, signatories must “promote and encourage international cooperation with a view to
achieving progressively the full realization of the right”.6 Consequently, they cannot invoke sovereignty to belie
obligations to secure the health and wellbeing of their children. Humanity knows no borders and, though imperfect,
human-rights laws should be applied vigorously to secure health and life during intentionally exacerbated public-
health emergencies.
International crimes—which include genocide, war crimes, and crimes against humanity—are breaches of international
norms that result in individual liability. The primary purpose of international criminal law is to bring the perpetrators of
international crimes to justice. But when officials commit atrocities, the international community should not remain
idle. If leaders act, or fail to act, in ways that will lead to widespread death—and then block those who seek to
prevent it—they commit a crime against humanity and intervention is appropriate.
Assessing a county's response to crises under a lens of preventing potential crimes against humanity proffers a useful
and pragmatic standard. Generally, crimes against humanity are particularly serious attacks on human dignity. A
finding of such crimes rests solely on the widespread or systematic practice of atrocities. Unlike war crimes, crimes
against humanity may be committed during times of peace. And unlike genocide, crimes against humanity do not
require a special intent to kill on account of group status. Perpetrators need only act with the wilful intent to inflict
widespread or systematic harm on their victims—a bar that is readily met when officials block assistance to large
populations with vital need.
Crimes against humanity require the infliction of “great suffering, or serious injury to body or to mental or physical
health”—or extermination.7 Both acts that directly inflict injury and refusals to act can constitute a crime. In 2003,
the International Criminal Tribunal for the Former Yugoslavia found a physician guilty of extermination for the
treatment of prisoners during the 1990s' Bosnian–Serb conflict, including for “conditions imposed on a [prisoner]
whose health was fragile, [which] alone would inevitably cause his death”.8 The Court held that it was not only the
resultant deaths but also the creation of conditions leading to a large number of deaths that justified a conviction.
Accordingly, where governments block food, medical supplies, and health care to meet basic survival needs,
preventing atrocities is consonant with securing the right to health.
Does international law permit humanitarian intervention? During humanitarian crises, the desire for assistance by the
affected country almost invariably exceeds its available resources. Thus the normal crisis model is to request
assistance from donor countries. However, when official conduct constitutes a crime against humanity, either by
refusing aid to those in need (as in Burma) or actively creating a humanitarian emergency (Zimbabwe), ameliorating
the emergency may require foreign intervention without host-country consent.
The UN Charter prohibits countries from intervening “in matters which are essentially within the domestic jurisdiction”
of another state.3 However, under modern conceptions, sovereignty inheres in the people, not the government, so
a government's sovereign authority is conditional on refraining from grievous violations of human dignity.9 Thus
sovereignty yields to human rights when a government has wilfully taken steps to cause death or widespread
suffering.
Non-consensual intervention to relieve grave humanitarian need would likely require military force or its threat if relief
efforts were resisted or endangered. This point subjects humanitarian intervention to the body of use-of-force law
that prohibits the use or threat of force “against the territorial integrity or political independence of any state, or in
any other manner inconsistent with the purposes of the United Nations.”3
Intervention sanctioned by the UN Security Council to ameliorate a crime against humanity would be legal. The
Charter permits the Council to authorise intervention if a crisis poses a “threat to the peace, breach of the peace, or
act of aggression”.3 Threats to the peace extend beyond armed attack and include widespread suffering and crimes
against humanity. This was the basis of the Council's determination in 1992 that the “human tragedy” of famine in
Somalia, exacerbated by deteriorations in that country's stability, posed a “threat to international peace and
security” even though the effects of the crisis were not significantly felt outside of Somalia.10 Upon a subsequent
finding that non-forcible measures were unlikely to succeed, the Council authorised an American-led contingent to
ensure delivery of humanitarian aid to starving Somalis.10
A 2005 resolution of the UN General Assembly reiterated the Council's power to act when governments “manifestly
fail to protect their populations from…crimes against humanity” if peaceful means cannot avert the crisis.11 This
authority would permit limited interventions, such as airdrops, but, if necessary, would permit broader Somalia-style
“boots on the ground” interventions.
Unfortunately, the Council is often paralysed by its five permanent members' ability to veto initiatives, necessitating
examination of the legality of unilateral or coalition interventions. Notably, the Charter prohibits force only where
“inconsistent” with UN purposes and when used against the “territorial integrity or political independence of any
state”. “Territorial integrity” refers to shifting international borders, and “political independence” to states gaining
control of other's political machinations. Intervention solely to stop a crime against humanity infringes on neither of
these, so it does not fall within the Charter's force prohibition. Furthermore, humanitarian intervention is within the
principles of the UN, because the Charter's dual purposes are preserving peace and promoting human rights.12
Additionally, international law requires the existence of grave violations of human rights, an exhaustion of non-forcible
responses, and the unavailability of UN-sanctioned action. The response must be proportionate—no more than
necessary to achieve humanitarian ends—and it must not interfere unnecessarily with a country's self-determination.
Finally, the interveners must disengage upon securing fundamental rights and report their actions to the Security
Council.13
Nations should be justifiably cautious about using or threatening intervention to stop crimes against humanity. Policy
makers must carefully consider risks to relief workers, civilians, and troops, as well as the danger of complicating
future health-promotion activities. Forced intervention is a complex policy question, but blanket rejection may
condemn innocent civilians and prevent deterrence of crimes against humanity. Where leaders engage in intentional
acts of cruelty toward their populations, wealthy nations should be prepared to intervene beyond their borders to
safeguard health and human rights.
We declare that we have no conflict of interest.
References
1. Ohmar K. Burma aid efforts press on despite blocks. UPI Asia Online. June 26, 2008:
http://www.upiasiaonline.com/Politics/2008/06/26/burma_...
(accessed July 3, 2008)..
2. Rotberg RI. Who will have the courage to save Zimbabwe?. Boston Globe June 25 2008; A15.
3. UN. Charter of the United Nations. June 26, 1945:
http://www.un.org/aboutun/charter
4. WHO. Constitution of the World Health Organization. October, 2006:
http://www.who.int/governance/eb/who_constitution_en.pd...
(accessed July 3, 2008)..
5. UN Economic and Social Council. The right to the highest attainable standard of health. Aug 11, 2000:
http://www.unhchr.ch/tbs/doc.nsf/(symbol)/E.C.12.2000.4...
(accessed July 3, 2008)..
6. Office of the United Nations High Commissioner for Human Rights. Convention on the rights of the child, article 24
(4). Sept 2, 1990
http://www2.ohchr.org/english/law/crc.htm
(accessed July 8, 2008)..
7. International Criminal Court. Rome Statute of the International Criminal Court, article 7(1). July 1, 2002
http://untreaty.un.org/cod/icc/statute/romefra.htm
(accessed July 3, 2008)..
8. Prosecutor v, Milomir Stakić, Case No. IT-97-24-T, International Criminal Tribunal for the Former Yugoslavia. July
31, 2003
http://www.un.org/icty/stakic/trialc/judgement/index.ht...
(accessed July 8, 2008)..
9. Saechao TR. Natural disasters and the responsibility to protect: from chaos to clarity. Brookland J Int Law 2007;
32: 663-707.
10. Hutchinson MR. Restoring hope: UN Security Council resolutions for Somalia and an expanded doctrine of
humanitarian intervention. Harvard Int Law J 1993; 34: 624-640.
11. UN General Assembly. 2005 World Summit outcome. Oct 24, 2005:
http://unpan1.un.org/intradoc/groups/public/documents/U...
(accessed July 8, 2008)..
12. Mertus J. The imprint of Kosovo on the law of humanitarian intervention. ILSA J Int Comparative Law 2000; 6:
527-540.
13. Terry JP. Rethinking humanitarian intervention after Kosovo: legal reality and political pragmatism. Army Lawyer
2004; 8: 36-46.
Nature
Volume 455 Number 7213 pp565-706 (2 October 2008)
http://www.nature.com/nature/journal/v455/n7212/
[No relevant content]
New England Journal of Medicine
Volume 359 — October 2, 2008 — Number 14
http://content.nejm.org/current.shtml
[No relevant content]
PLoS Medicine
Week of 30 September 2008
Informed Consent in the Genomics Era
Deborah Mascalzoni, Andrew Hicks, Peter Pramstaller, Matthias Wjst
Since the Nuremberg trials, informed consent (IC) has been recognized as a basic ethical requirement for research
involving human participants. Such consent encompasses two distinct elements: (1) researchers communicate
detailed information about study procedures, outcomes, risks, and benefits for the participating individual or
community, and (2) after understanding and careful consideration, the participants consent to take part under these
conditions. However, the suitability of IC for genomic studies has been recently challenged. Because the research
protocol for such studies may evolve over time, the condition in IC of providing detailed information for a well-defined
protocol is not easily satisfied.
Large amounts of data stored as electronic records allow multiple post-hoc analyses, which in many cases were not
foreseen at the beginning of a study. The potential for analysis is constantly growing and recently has increased
dramatically with the development of high-throughput sequencing and genotyping technologies. More than one
million genetic variants of an individual may be determined within hours—and even the full genetic sequence within
weeks. Such technical advances expose participants to a new class of risk different from the physical harm usually
considered in ethical reviews. Release of genetic information could lead to uninsurability, unemployability,
discrimination, and the breakdown of family relationships by unintentionally demonstrating missing or unknown
relatedness. Moreover, participants usually do not get any direct benefit from the research. All of these concerns raise
the question: are IC procedures still in accordance with the currently accepted ethical standards of autonomy,
beneficence, and non-maleficence?
Summary Points
- Genetic cohort studies storing biological materials hold great promise for medical research, but also present new
problems that are profoundly different from the classical clinical trial for which informed consent was developed.
- The classical risk/benefit analysis of physical harm doesn't take into account new threats to the individual such as
uninsurability, unemployability, genetic discrimination, or disruption of family relationships.
- Traditional informed consent may therefore no longer be appropriate when dealing with long-term studies using
biological materials.
- Informed consent should be seen as an ongoing process between researcher and participant, and not just as a
once-and-for-all decision.
- Research following the initial storage of samples needs to be likewise explained and may be announced using new
communication methods.
There is pressure to harmonize different views, since a shared ethical and legal framework is still missing and
approaches vary greatly. A wide spectrum of opinions exists: Some researchers believe that available sample
collections do not need any further consent, even for large-scale genotyping, while some institutional review boards
recommend the destruction of samples immediately after testing (MW, personal observation).
Citation: Mascalzoni D, Hicks A, Pramstaller P, Wjst M (2008) Informed Consent in the Genomics Era. PLoS Med 5(9):
e192 doi:10.1371/journal.pmed.0050192
Published: September 16, 2008
Deborah Mascalzoni, Andrew Hicks, Peter Pramstaller, and Matthias Wjst are at the Institute of Genetic Medicine,
EURAC Research, Bozen, Italy. Matthias Wjst is also at the Helmholtz Zentrum München, German Research Center
for Environmental Health, Neuherberg, Germany.
Science
3 October 2008 Vol 322, Issue 5898, Pages 1-148
http://www.sciencemag.org/current.dtl
Science 3 October 2008:
Vol. 322. no. 5898, pp. 26 - 27
DOI: 10.1126/science.322.5898.26
News of the Week
INFECTIOUS DISEASE:
New Malaria Plan Called Ambitious By Some, Unrealistic by Others
Leslie Roberts
It was standing room only last week at U.N. headquarters in New York City when a star-studded cast, including
philanthropist Bill Gates, U2 rocker Bono, and British Prime Minister Gordon Brown, kicked off the latest in a string of
grand plans to conquer malaria, the mosquito-transmitted scourge that kills some 1 million people a year, mostly
African children.
The goals of the Global Malaria Action Plan (GMAP) are stunningly ambitious: Reduce malaria deaths to near zero by
2015, then progressively eliminate the disease from countries and regions until it is eradicated from the planet. That
will take mosquito- and parasite-foiling technologies that have yet to be invented, along with billions of new dollars a
year that the plan's architects hope generous donors will provide. GMAP, assembled over the past year with input
from more than 250 experts, is the creation of the Roll Back Malaria (RBM) partnership, a coalition of international
agencies, public and private donors, and malaria-affected countries.
Regina Rabinovich, head of infectious diseases at the Bill and Melinda Gates Foundation and one of the key forces
behind the plan, calls the goals "ambitious but achievable." But many malaria experts say it's unlikely that GMAP will
meet its targets--even with abundant funding--although they applaud the renewed commitment. Several also
caution that donors and agencies should be careful in what they promise, given the humbling outcomes of previous
grand plans (see table, above).
Scientists and the World Health Organization (WHO) also exuded confidence in the 1950s when they vowed to
eradicate malaria, for instance. After that initiative's spectacular demise in the 1960s, malaria cases surged worldwide,
and support for malaria control and research essentially dried up.
After a long hiatus, international health and development agencies reentered the fight against malaria in the late
1990s, setting a series of increasingly ambitious targets. They culminated in Bill and Melinda Gates' unexpected call
last year to again attempt to eradicate the disease, a word that hadn't been uttered in the context of malaria for
some 40 years (Science, 7 December 2007, p. 1544).
"We set year after year new goals and never meet any of them," says Christian Lengeler, a malaria researcher at the
Swiss Tropical Institute. Lengeler, who has worked extensively in Tanzania, calls GMAP's 2015 target of zero deaths
"totally unrealistic." "Silly," says another scientist. As for the eventual eradication of malaria, "maybe, but not in my
lifetime," seems to be the general consensus.
This time it is different, insist Rabinovich and Awa Marie Coll-Seck, executive director of RBM. For one, coffers are
flush. Thanks to contributions from the Gates Foundation, the Global Fund to Fight AIDS, Tuberculosis and Malaria,
the World Bank, the President's Malaria Initiative, and others, international funding for malaria control jumped from
$51 million in 2003 to an estimated $1.1 billion in 2008. Last week, the Global Fund announced that it will award
$1.62 billion over the next 2 years to help poor countries fight malaria, and the World Bank pledged $1.1 billion to
expand its Malaria Booster Program. These and other smaller contributions unveiled last week still fall significantly
short of the $5 billion or $6 billion a year GMAP says is needed.
Also in the past few years, malaria interventions, such as long-lasting insecticide-treated bed nets and a new class of
drugs known as artemisinin-based combination therapies (ACTs), have proved their mettle (Science, 26 October
2007, p. 556). A half-dozen African countries with committed leadership and a lot of outside support have scaled up
these interventions rapidly--Ethiopia, for instance, distributed 20 million bed nets in just 18 months. A few of these
countries or areas, those with small populations and high access to prevention and treatment, have seen roughly a
50% decline in malaria cases and deaths since 2000, WHO notes in its 2008 World Malaria Report. Ensuring universal
access to these and other tools such as indoor insecticide spraying and preventive treatments in pregnant women
can halve deaths by 2010, says GMAP, and then reduce them to near zero 5 years out.
But none of the countries has reached the target of 80% coverage with existing interventions, set just a few years
ago, much less the 90% called for by GMAP. Across the continent, just 23% of children slept under a bed net in
2006, and only 3% of patients were treated with ACTs, according to WHO estimates.
The challenges facing big countries like the Democratic Republic of the Congo (DRC) and Nigeria are especially
daunting. They account for about 20% to 25% of malaria deaths, although hard data are scarce, and are plagued
by civil unrest and weak health systems. "That it can be done in Zambia, with a population of 10 million and a
dynamic minister of health, does not say a thing about what to do in DRC," agrees Rabinovich.
To develop the radical types of new vaccines, drugs, and insecticides needed for the toughest areas--as well as for
eradication many decades from now--GMAP calls for pumping $750 million to $900 million a year into research. A
working group is already hammering out a detailed research and development plan, which Rabinovich says should be
ready in 15 months.
To prime the pump, Gates announced $168 million for research on the next generation of malaria vaccines. The
award is going to the Bethesda, Maryland-based PATH Malaria Vaccine Initiative, which will try to build off the
experience gained from vaccine candidates already in the pipeline, says MVI Director Christian Loucq.
GlaxoSmithKline's RTS,S, which targets the malaria parasite form that infects the liver, for instance, is about to enter
phase III trials--the first malaria vaccine candidate to get that far. MVI is investigating additional antigens that target
different stages in the parasite's life cycle that could be used in combination, as well as novel adjuvants to boost
vaccine power. Although expected to be significantly more efficacious, such second-generation vaccines won't be
available until well after 2015 and, like RTS,S, will still be only partially protective.
Another intriguing possibility is a transmission- blocking vaccine that would be administered to humans but that
would target the parasite after it is taken up by the mosquito in her blood meal. Loucq calls the approach "elegant,"
the equivalent of an "immunological bed net," but cautions that it is early days.
Whether the exact targets are met is beside the point, says RBM leader Coll-Seck. "I am a glass-half-full person," she
says. If GMAP leads to a significant reduction in malaria cases and deaths--even if the plan promised much more--who
would call that a failure, she asks.
Vaccine
Volume 26, Issue 45, Pages 5669-5774 (23 October 2008)
http://www.sciencedirect.com/science/journal/0264410X\
Community perspectives on the ethical issues surrounding adolescent HIV vaccine trials in South Africa
Pages 5679-5683
Heather B. Jaspan, Nosiphiwo F. Soka, Ann E. Strode, Catherine Mathews, Daniella Mark, Alan J. Flisher, Robin Wood,
Linda-Gail Bekker
Abstract
“Adolescents globally are at high risk for HIV acquisition and are the targets of HIV prevention interventions such as
HIV vaccines. In order to understand stakeholders’ attitudes towards the ethical issues of adolescent involvement in
HIV vaccine trials, we conducted focus group discussions with key members of a semi-urban, informal Cape Town
community with high HIV prevalence in which HIV vaccine trials are taking place. Themes were identified from focus
group transcripts by four researchers, and included necessity of guardian consent, age of independent consent, and
confidentiality of in-trial medical results. In general, ethical adolescent HIV vaccine trials will be feasible in this
community.”
Epidemiology of poliomyelitis—Options and update
Pages 5767-5773
Anil Dutta
Abstract
“Poliomyelitis is a disease of major public health importance. Since the launch of the Global Poliomyelitis Eradication
Initiative in 1988, considerable progress has been achieved globally. At present, the causative agent for the disease –
poliovirus – remains endemic in only four countries (Afghanistan, India, Nigeria and Pakistan). The poliovirus
eradication plan, as outlined in the WHO strategic plan for 2004–2008, incorporates priority activities for each phase
of the plan: (i) polio eradication certification for regions, (ii) oral poliovirus vaccine (OPV) cessation phase, and (iii) post-
OPV phase. The ultimate goal to eventually stop all vaccination is, however, jeopardized by the emergence of
vaccine-derived polioviruses and the risk of bioterrorism. In the post-eradication era, individual countries will be
presented with guidelines on OPV cessation and inactivated poliovirus vaccine (IPV) usage. This paper, presented
during the Asian Pacific Pediatric Association (APPA) meeting in Pattaya, Thailand from 20 to 22 July 2006, provides
an update on the current global situation, focusing on the progress and challenges faced by different countries in
their quest for
____________________________________________________________________________________________________
29 September 2008
The Bill & Melinda Gates Foundation announced that it will provide US$168.7 million to PATH for its
Malaria Vaccine Initiative. The PATH Malaria Vaccine Initiative (MVI) is “working with GlaxoSmithKline Biologicals to
develop a first-generation vaccine candidate, known as RTS,S, which could become the first-ever approved malaria
vaccine. With the new grant announced today, MVI will support the development of next-generation vaccines that
could provide even greater and longer-lasting protection.” Bill Gates, co-chair of the Gates Foundation, commented,
"I'm very hopeful that the malaria vaccine currently in advanced testing will be proven effective, but that will just be
the first step. Now it's time to develop a new generation of vaccines that are even more effective, and could
someday help eradicate malaria altogether." Mr. Gates announced the new funding at the UN Millennium
Development Goals Malaria Summit. The event included launch of the Global Malaria Action Plan by the Roll Back
Malaria Partnership.
The Gates Foundation grant will “support MVI's efforts to expand its vaccine R&D pipeline with projects ranging from
early-stage laboratory research to advanced clinical testing. MVI will work with partners to discover new antigens and
adjuvants that could lead to more effective vaccines, and develop new tools to select the most promising candidates
for further development. MVI will also work to foster a more competitive vaccine marketplace and help ensure that
future vaccines will be affordable and accessible in developing countries. They will conduct market assessments,
demand forecasting, and modeling studies to guide policymakers and vaccine manufacturers, and partner with
vaccine makers in developing countries to keep costs low,: the media release noted.
Dr. Christian Loucq, Director of MVI, said, "These new funds are recognition that we have a solid research and
development strategy, and the team to deliver on it. This commitment should signal to potential research partners
that the time is ripe to work with us to help defeat this horrible disease. Already, we have added to our roster of
partners and entered into collaborative agreements on vaccine components, ways to boost their potency, and
methods for testing their biological activity." Dr. Christopher J. Elias, president and CEO of PATH, commented, "Our
strategy for developing a malaria vaccine follows the PATH approach to neglected diseases, which has shown that
investment in core areas of research and development, particularly vaccine technology, does yield important
advances. The PATH Malaria Vaccine Initiative is now ready to accelerate further the development of what the world
urgently needs: safe, effective, and affordable vaccines that reduce the suffering caused by malaria."
(Gates Foundation Media Release, 25 September 2008)
http://www.gatesfoundation.org/GlobalHealth/Pri_Diseases/Malaria/Announcements/Announce-080925.htm
The Centers for Disease Control and Prevention (CDC) said it awarded US$24 million to fund 55
projects in 29 state and local public health departments “that could serve as innovative approaches for
influenza pandemic preparedness.” Richard Besser, MD, Director of CDC′s Coordinating Office for Terrorism
Preparedness and Emergency Response, commented, “What is learned from these projects can benefit everyone
because it could improve national, regional and local public health detection and response to a pandemic involving
influenza.” A total of 184 funding applications were submitted by state and local health departments in a competitive
application process. Eligible applicants for the awards were limited to the 62 state, local and territorial public health
departments that currently receive federal funding through CDC′s Public Health Emergency Preparedness (PHEP)
Cooperative Agreement.
The projects focus on seven key areas and include:
- Use of public engagement as part of the public health decision-making process
- Electronic laboratory data exchange to support influenza pandemic monitoring
- Integration of state-based immunization information systems to track distribution of influenza pandemic
countermeasures.
- Development of statewide electronic death reporting systems compliant with Public Health Information Network
(PHIN) requirements
- Collaborative planning among healthcare providers to ensure the delivery of essential services during an influenza
pandemic
- Development of interventions that promote preparedness for pandemic disease among identified vulnerable
populations
- Distribution and dispensing of antiviral drugs to self-isolated or self-quarantined persons in an influenza pandemic
event
A list of the 29 award recipients and their projects can be found at: http://emergency.cdc.
gov/cotper/coopagreement/07/funding-schedule-pan-flu.asp.
Media Release: http://www.cdc.gov/media/pressrel/2008/r080924.htm
UNICEF Executive Director Ann M. Veneman, speaking on a panel on the opening day of the United
Nations General Assembly session, said “there is a long way to go” to reach the Millennium
Development Goals by their 2015 target date. And the challenges are greatest in countries dealing with conflict
and post-conflict situations, as well as those most affected by HIV/AIDS. Ms. Veneman highlighted the progress that
UNICEF and its partners have made towards achieving the MDG target on rates of mortality for children under the
age of five. According to data released last week, she noted, the number of children under five who died in 2007
dropped to 9.2 million, compared to 12.7 million in 1990. Since 1960, the global under-five mortality rate has
declined more than 60 per cent, and the new data show that downward trend continuing, Ms. Veneman added.
The panelists agreed that one intervention – immunisation – “has proven highly successful and cost-effective in
saving children’s lives throughout the developing world. Childhood immunisation coverage for the six major vaccine-
preventable diseases – diphtheria, measles, pertussis, polio, tetanus and tuberculosis – rose from less than 5 per cent
in 1974 to more that 75 per cent in 2006.” As the world’s largest purchaser of vaccines for developing countries,
UNICEF is a key partner in global immunisation efforts. In the last decade, immunisation is the only public health
intervention that has consistently reached over 70 per cent of children under five. And there is the potential for an
even greater impact. The panel called for an increased level of access to life-saving resources – including vaccines, as
well as anti-retroviral drugs for HIV infection, bed nets to prevent malaria, and more health information – for millions
of people in developing countries. Of particular concern, they said, are children and families who are the hardest to
reach, the most impoverished and the most marginalized. To make achievement of the MDGs possible, Ms. Veneman
concluded, humanitarian and development partners must focus on integrated approaches using solid data and good
mechanisms for evaluation of their work.
GAVI Media release, 23 September 2008)
The Weekly Epidemiological Record (WER) 26 September 2008, vol. 83, 39 (pp 349–356) includes:
- Outbreak news: Cholera, Iraq
- Melamine-contaminated powdered infant formula, China
- Progress towards eliminating measles in Japan, 2008
- WHO web sites on infectious diseases
http://www.who.int/wer/2008/wer8339.pdf
Journal Watch
[Editor’s Note]
Vaccines: The Week in Review continues a new feature, scanning key journals to identify and cite articles, comment
and editorials, books reviews and other content supporting our focus on vaccine ethics and policy. This scan is not
intended o be exhaustive, but indicative of themes and issues the center is actively tracking. Successful access to
some of the links provided may require subscription or other access arrangement unique to the publisher. Our initial
scan list includes the journals below. If you would like to suggest other titles, please write to David Curry at david.r.
curry@centerforvaccineethicsandpolicy.org
JAMA
Vol. 300 No. 12, pp. 1383-1480, September 24, 2008
http://jama.ama-assn.org/current.dtl
[No relevant content]
Journal of Infectious Disease
15 October 2008 Volume 198, Number 8
http://www.journals.uchicago.edu/toc/jid/current
[No relevant content]
The Lancet
Volume 372, Number 9644, 27 September 2008
http://www.thelancet.com/journals/lancet
The Lancet 2008; 372:1135-1136
DOI:10.1016/S0140-6736(08)61462-2
World Report
The global fight against rabies
Talha Burki
[Editor’s Summary] This report is occasioned by World Rabies Day (28 September), spearheaded by the Alliance for
Rabies Control. The author notes that rabies kills at least 55,000 people every year worldwide (under-reporting and
misdiagnosis may mean that the actual figure is higher). In Asia, the death toll numbers around 30,000. But reliable
information for many geographic areas is scant. WHO has endorsed several vaccines and issued directives for
treating potentially dangerous animal bites. If followed correctly, these post-exposure prophylaxis (PEP) guidelines
are virtually 100% effective—PEP is thought to prevent around 280,000 deaths per year. The author notes that
human rabies vaccines need multiple applications, so it is not usually practical for developing populations to vaccinate
the entire population. Hence it is crucial that canine-rabies is controlled—dog bites account for over 99% of human
rabies. For this to happen, 75% of dogs must be vaccinated. Malaysia is an excellent example, says Wilde, of a
country that eliminated rabies by concerted culling, neutering, and vaccination of the dog population. The report
focuses on some of the unique challenges in addressing this disease in India and Pakistan, and other perspectives on
strategies employed in China and other selected geographies.
The Lancet 2008; 372:1150
DOI:10.1016/S0140-6736(08)61480-4
Correspondence
The right to health and accountability
Peter Hall
[Editor’s Summary] The author speaks to the right to the highest attainable standard of health and state
accountability embodied in the International Covenant on Economic, Social and Cultural Right, ratified by more than
80% of the world's countries. A new publication (3 below) from the office of the Special Rapporteur on the right to
the highest attainable standard of health emphasises the importance of accountability. Five broad types of
accountability mechanism are discussed in the publication: (1) judicial—e.g., judicial review of executive acts and
omissions, constitutional redress, statutory interpretation, and public interest litigation; (2) quasijudicial—e.g., national
human rights institutions, and regional and international human rights treaty bodies; (3) administrative—e.g., human
rights impact assessment; (4) political—e.g., parliamentary committee review of budgetary allocations and the use of
public funds, and democratically elected health councils and health-care commissions; and (5) social—e.g., the
involvement of civil society (independently or in collaboration with government) in budget monitoring, health-centre
monitoring, public hearings, and social audits.
The author notes that “the right to the highest attainable standard of health is the entitlement to an optimum health
outcome that takes into account a patient's pre-existing health status and national resources.” General Comment 14,
(4 below) in defining governments' responsibilities for health in a structured way within a human rights framework,
“has galvanised and empowered human rights activists and health professionals alike to use health rights as a vehicle
with which to promote health,” the author argues.
References
1. Horton R. What does a National Health Service mean in the 21st century?. Lancet 2008; 371: 2213-2218.
http://www.thelancet.com/journals/lancet/article/PIIS0140673608609563/fulltext
2. Office of the High Commissioner for Human Rights. International covenant on economic, social and cultural rights.
Geneva: Office of the High Commissioner for Human Rights, 1966:
http://www.unhchr.ch/html/menu3/b/a_cescr.htm
(accessed Aug 13, 2008)..
3. Potts H. Accountability and the right to the highest attainable standard of health. Colchester: University of Essex,
2008:
http://www2.essex.ac.uk/human_rights_centre/rth/project...
(accessed Aug 13, 2008)..
4. Office of the High Commissioner for Human Rights. Substantive issues arising in the implementation of the
International Covenant on Economic, Social and Cultural Rights. General comment no. 14: the right to the highest
attainable standard of health (article 12 of the International Covenant on Economic, Social and Cultural Rights).
Geneva: Office of the High Commissioner for Human Rights, 2000:
http://www.unhchr.ch/tbs/doc.nsf/(symbol)/E.C.12.2000.4...
(accessed Aug 13, 2008)..
Nature
Volume 455 Number 7212 pp431-564 (25 September 2008)
http://www.nature.com/nature/journal/v455/n7212/
[No relevant content]
New England Journal of Medicine
Volume 359 — September 25, 2008 — Number 13
http://content.nejm.org/current.shtml
[No relevant content]
Science
26 September 2008 Vol 321, Issue 5897, Pages 1737-1860
http://www.sciencemag.org/current.dtl
[No relevant content]
Vaccine
Volume 26, Issue 44, Pages 5547-5668 (16 October 2008)
http://www.sciencedirect.com/science/journal/0264410X\
The ethics of mandatory vaccination against influenza for health care workers
Pages 5562-5566
J.J.M. van Delden, R. Ashcroft, A. Dawson, G. Marckmann, R. Upshur, M.F. Verweij
Abstract
“Vaccination of health care workers (HCW) in long-term care results in indirect protection of patients who are at high-
risk for influenza. The voluntary uptake of influenza vaccination among HCW is generally low. We argue that
institutions caring for frail elderly have the responsibility to implement voluntary programmes for vaccination against
influenza of HCW. When uptake falls short a mandatory programme may be justified. The main justification stems
from the duty of care givers not to harm one's patient when one knows there is a significant risk of harm and the
intervention to reduce this chance has a favourable balance of benefit over burdens and risks.”
Decline in influenza-associated mortality among Dutch elderly following the introduction of a nationwide
vaccination program
Pages 5567-5574
Angelique G.S.C. Jansen, Elisabeth A.M. Sanders, Kristin L. Nichol, Anton M. van Loon, Arno W. Hoes, Eelko Hak
Abstract
“With a retrospective nationwide cohort study in the Netherlands over 1992–2003, using mortality and viral
surveillance data, the aim was to assess by means of rate difference methods the influenza-associated mortality in the
elderly before and after the introduction of a nationwide influenza vaccination program in 1996 (vaccination
coverage raised from below 50 to 80%). The average annual influenza-associated mortality declined in the years
before and after the introduction from 131 to 105 per 100,000 persons (relative risk 0.80). The decline was largest in
the age group 65–69 years (relative risk 0.54) and less in those aged 75 years and older. Validation by Serfling-type
regression analysis revealed similar results. In conclusion, routine influenza vaccination among Dutch elderly was
associated with a significant decrease in influenza-associated mortality, notably in those aged 65–69 years.”
Cost-effectiveness of human papillomavirus vaccine in reducing the risk of cervical cancer in Ireland due
to HPV types 16 and 18 using a transmission dynamic model
Pages 5654-5661
Cara Usher, Lesley Tilson, Jens Olsen, Martin Jepsen, Cathal Walsh, Michael Barry
Abstract
“We evaluated the cost-effectiveness of combining a cervical cancer screening programme with a national HPV
vaccination programme compared to a screening programme alone to prevent cervical dysplasia and cervical cancer
related to HPV types 16 and 18 in the Irish healthcare setting. The incremental cost effectiveness of vaccination
strategies for 12-year-old females (base-case) and 12–26-year-old catch-up vaccination strategies were examined.
The base-case incremental cost-effectiveness ratio was €17,383/LYG. Using a probabilistic sensitivity analysis about
the base-case, the 95% CI for cost per LYG was (€3400 to €38,400). This suggests that vaccination against HPV
types 16 and 18 would be cost-effective from the perspective of the Irish healthcare payer.”
_____________________________________________________________________________________________________
22 September 2008
The American Academy of Pediatrics announced formation of a new coalition – The Immunization
Alliance – involving “the nation’s leading medical and advocacy groups…to raise the public’s confidence
in vaccines…(calling) on policymakers, public health agencies, physicians, and the public to work together to
preserve the health of the nation’s children through immunization.” Renee Jenkins, MD, FAAP, president of the
American Academy of Pediatrics, said, “We do not want to become a nation of people who are vulnerable to diseases
that are deadly or that can have serious complications, especially if those diseases can be prevented. The groups in
this Alliance have made a commitment to pool our resources and expertise, and to ask the government to help avert
what could become a national emergency. We want to impress upon the public the possible consequences—safety,
medical, personal, and economic issues—of having a population that is not adequately protected against measles,
whooping cough, meningitis, and many other diseases.”
The Alliance stated its commitment to “ensure adequate levels of immunization in the United States,” and jointly
endorsed a Call to Action to enlist health professionals, the public, the media and the government in supporting
immunizations and their importance to the public’s health. Included are “requests for a public information campaign
by the government; a commitment to ongoing research to ensure the continued safety, efficacy and development
of vaccines; balanced reporting by the media; continued efforts from doctors in working with parents; and
confidence from parents themselves.” The group noted that although the Centers for Disease Control and
Prevention (CDC) announced that 2007 immunization rates were adequate, recent data show that approximately
one-fourth of toddlers are not properly immunized, and that recent outbreaks of measles in several cities, the worst
in a decade, are just one example of how the decision not to vaccinate can affect individual children and the public’s
health. Most cases have been among the unvaccinated.
The Alliance also said that adolescents and adults should receive immunizations and vaccine boosters according to
recommendations from the CDC, the American Academy of Family Physicians, the American Academy of Pediatrics,
the American College of Physicians, the American Medical Association, and the American College of Obstetricians and
Gynecologists “in order to protect themselves and to do their part to keep infectious diseases at bay in their
communities.”
The Immunization Alliance, which comprises the groups listed below, sets forth the following
Call to Action for public health organizations, government, health care professionals, the media and the
public:
What the Alliance commits to:
We commit to continued partnerships with policy makers to ensure that:
- children receive recommended immunizations on time (according to the schedule of the Centers for Disease Control
and Prevention/Advisory Committee on Immunization Practices, the American Academy of Family Physicians and the
American Academy of Pediatrics) to protect them against vaccine-preventable diseases and to protect the public’s
health;
- vaccines are as safe as possible and vaccine safety research is adequately funded;
- the vaccine supply is sufficient and equitably distributed;
- parents and caregivers have the knowledge and information they need to make fully-informed decisions in the best
interests of their child.
What the Alliance asks:
- We ask the U.S. Department of Health and Human Services to undertake a public information campaign reinforcing
the value and importance of immunization to empower parents to make informed decisions about vaccinating their
children.
- We ask physicians and other health care professionals to work closely with parents and patients to foster an
understanding of the need for, and timing of, recommended vaccines, and to assess what is needed to earn or
regain the trust of some parents. The goal is to work as a team to fully protect infants and children against diseases
that can result in death or life-long disability.
- We ask medical professional organizations and public health agencies to provide support and guidance to physicians
in counseling parents about the importance and safety of vaccines. The goal is to facilitate informed decision-making
by parents and caregivers.
- We encourage parents to ask questions at the doctor’s office, and to expect answers based on the best scientific
information available. We ask them to rely on credible sources for their information about vaccine safety and
effectiveness, and to take the time to understand the evidence on which immunization recommendations are based
in order to make fully informed decisions about their children’s health.
- We ask the federal government to dedicate funding for continued research into vaccine safety and effectiveness.
- We ask the media to take the time to understand vaccine science and the evidence on which immunization
recommendations are based. We also ask the media to keep the public interest foremost in their treatment of this
subject, and to consider the potential consequences of lending credence to various publicity efforts and
spokespersons without a complete and critical review of the scientific merit of these sources.
- We ask that, given the importance of communicating scientifically based and trustworthy information, all editors of
Internet content, publications and blogs should ensure that appropriate efforts are made to comply with the high
standards associated with responsible journalism.
List of Participating Organizations
American Academy of Family Physicians
American Academy of Pediatrics
American Academy of Physician Assistants
American College of Preventive Medicine
American College of Obstetricians and Gynecologists
American College of Osteopathic Pediatricians
American Medical Association
American Public Health Association
America’s Health Insurance Plans
Association of State and Territorial Health Officials
California Immunization Coalition
Every Child By Two
Immunization Action Coalition
Infectious Diseases Society of America
March of Dimes
National Foundation for Infectious Diseases
Parents of Kids with Infectious Diseases
Pediatric Infectious Diseases Society
Sabin Vaccine Institute
UnitedHealth Group
Vaccine Education Center at The Children's Hospital of Philadelphia
Voices for Vaccines
(Sept. 18, 2008)
http://www.aap.org/advocacy/releases/sept08Immunizationalliance.htm
The WHO reported that progress is being made in malaria control, but the overall disease burden is still
enormous, and that new methods estimate that the number of malaria cases in 2006 was 247 million,
substantially lower than previous estimates. Access to malaria control interventions, especially bednets in Africa,
increased sharply between 2004 and 2006, says the WHO report [link below]. WHO Director-General Dr Margaret
Chan said, "With dramatic increases in funding and intense momentum towards reducing the malaria burden in
recent years, we have a greater need for reliable information and analysis. This report begins to answer that need.
Progress in malaria control has accelerated dramatically since 2006, especially in the wake of the UN Secretary-
General’s call for universal malaria control coverage by the end of 2010. We expect these expanded efforts to be
reflected in future reports."
Overall, the report finds that recent increases in malaria funding were beginning to translate into coverage of key
malaria interventions, especially bednets, by 2006. The percentage of children protected by insecticide-treated nets
increased almost eightfold, from 3% in 2001 to 23% in the 18 African countries where surveys were held in 2006.
Procurement of antimalarial medicines also increased sharply between 2001 and 2006. About 100 million people,
including 22 million in Africa, were protected by indoor spraying of insecticide, the report notes. In Africa, only 125
million people were protected by bednets in 2007, while 650 million are at risk.
(18 September 2008)
http://www.who.int/mediacentre/news/releases/2008/pr32/en/index.html
Report: http://www.who.int/malaria/wmr2008/
The Weekly Epidemiological Record (WER) for 12 September 2008, vol. 83, 37 (pp 333 348) includes:
- Global programme to eliminate lymphatic filariasis;
- Conclusions of the meeting of the Technical Advisory Group on the Global Elimination of Lymphatic Filariasis,
November 2007;
- WHO web sites on infectious diseases
http://www.who.int/wer/2008/wer8337.pdf
Journal Watch
[Editor’s Note]
Vaccines: The Week in Review continues a new feature, scanning key journals to identify and cite articles, comment
and editorials, books reviews and other content supporting our focus on vaccine ethics and policy. This scan is not
intended o be exhaustive, but indicative of themes and issues the center is actively tracking. Successful access to
some of the links provided may require subscription or other access arrangement unique to the publisher. Our initial
scan list includes the journals below. If you would like to suggest other titles, please write to David Curry at david.r.
curry@centerforvaccineethicsandpolicy.org
JAMA
Vol. 300 No. 11, pp. 1273-1374, September 17, 200808
http://jama.ama-assn.org/current.dtl
[No relevant content]
Journal of Infectious Disease
1 October 2008 Volume 198, Number 7
http://www.journals.uchicago.edu/toc/jid/current
[reviewed earlier]
The Lancet
Volume 372, Number 9643, 20 September 2008
http://www.thelancet.com/journals/lancet
The Lancet 2008; 372:1025-1026
DOI:10.1016/S0140-6736(08)61425-7
[Editor’s Note: We present this report in full text due to its importance and as a courtesy to our project team]
World Report
Predicting the next pandemic
Eliza Barclay
“Even as HIV/AIDS and avian influenza remain unresolved threats to human health, increasingly attention is shifting
to the next pandemic, and how to predict and prevent the disastrous consequences of wide-spread transmission of
a new disease. That undiscovered viruses and pathogens are evolving with the potential to infect the human
population is not under dispute. According to an analysis published in Nature in February, 2008, 335 emerging
infectious disease events occurred between 1940 and 2004. Of those, 60·3% were zoonoses, and most originated in
wildlife, including the virus that causes severe acute respiratory syndrome (SARS) and the Ebola virus. Vectorborne
diseases made up 22·8% of the total. The analysis also found that the threat of emerging infectious diseases to
global health has been increasing over time. As international travel and trade have proliferated, disease-causing
agents now have the ability to move around the globe at faster rates. Human beings and animals are also finding
themselves in increasingly closer contact with each other from deforestation and higher demand for animal products
in local and international markets.
Google.org—the philanthropic arm of the technology giant—has surfaced as one of the champions of intercepting
emerging diseases before they become pandemics with its Predict and Prevent initiative. “Zoonoses have only come
to our attention when people start dying in the USA”, said Frank Rijsberman, Google.org’s director of water and
climate adaptation initiatives. “We want to move surveillance to the places of origin and the current hotspots to find
out when people get sick.” At the moment “there are few systematic ways to do that”.
Predict and Prevent has a special interest in two regional hot spots: southeast Asia—where animals and human
beings coexist more intimately than anywhere else in the world—and sub-Saharan Africa—which has the greatest
burden of infectious diseases and worst public-health infrastructure in the world. Poverty makes both regions
exceptionally vulnerable to new diseases. Until recently scientists' understanding of the process of disease emergence
was poor. But with viral genetics, researchers can now follow the evolution of a virus at a molecular level and estimate
its ability to infect large numbers of human beings.
Many infectious-disease experts believe widespread transmission of HIV/AIDS could have been prevented if the
proper surveillance systems had been in place in the 1970s and 80s as the disease emerged. Nathan Wolfe, professor
of epidemiology at the University of California, Los Angeles and the founder and director of the Global Viral
Forecasting Initiative, says the failure of the “wait-and-respond” approach to HIV/AIDS and the lack of an early
warning system cost millions of lives. Wolfe's work on prediction of zoonosis emergence has shown that the global
emergence of a zoonotic pathogen such as SARS or HIV/AIDS depends on three steps. First, the pathogen must be
successfully transmitted between a wild reservoir and human beings or their domestic animals. Second, the pathogen
must be directly transmitted between humans. Finally, the pathogen must move from a local epidemic into the global
population. “We work with bushmeat hunters and other people who [often come into contact with] wild animals
because these people are highly exposed to viral agents that could be emerging diseases”, said Wolfe. “We also look
at animal die-offs as important indicators of an emerging disease.”
According to Wolfe, samples from human beings in close contact with animals can reveal patterns of viral chatter,
where viruses bubbling up in animal populations are constantly crossing into human populations. “These viruses are
pinging humans, or chattering. In the same way we monitor cellphone conversations for key words, we are
monitoring viral chatter, and looking for viruses that are transmissible and cause disease”, said Wolfe. “Not all of the
chatter will be real; we'll have to understand patterns of chatter to improve our ability to predict a pandemic.” As
scientists like Wolfe gather samples from human beings on potentially threatening new viruses, other scientists
interested in emerging infectious diseases are trying to cull data gathered by wildlife biologists and veterinarians on
zoonoses.
The Wild Bird Global Avian Influenza Network for Surveillance (GAINS) is a mapping and data sharing initiative of the
Wildlife Conservation Society with partners in 34 countries. The project was launched during the avian influenza scare
in 2006 and currently has over 100 million birds with their Global Positioning System [GPS] locations logged into the
system, along with other relevant data. “We can't begin to predict and prevent until we have information on what's
going on and where”, said William Karesh, vice president for global-health programmes at the Wildlife Conservation
Society. “The information has to be readily available so that people can look in the right place.” Although data are
currently available only for wild birds, GAINS has the technological capacity to make data for other animal species
available in the future. GAINS also counts on an unusual relationship with scientists—that they will share their data
before they are published in a journal in hopes that they will be useful to other researchers interested in or working
on similar issues.
With systems like GAINS and other resources, the world took one step closer to anticipating the potential of avian flu
to become a pandemic. “Avian influenza helped a lot of people get mobilised but so far it is a relatively isolated event”,
said Rijsberman. “We would like to use some of the tools developed for avian flu for other emerging infectious
diseases.” What Rijsberman foresees is a broad, international community of people bringing data together to build
early warning systems covering various diseases. Thus far, most of the scientific and surveillance effort has focused
on developed countries from where the next emerging infectious disease is least likely to originate.
Several web-based tracking initiatives are attempting to broaden the scope of available information on outbreaks and
emerging diseases by culling information from news reports around the world. The best developed of these initiatives
are HealthMap, ProMED-mail, and the Public Health Agency of Canada's Global Public Health Intelligence Network
(GPHIN). GPHIN helped establish the credibility and need for online tracking systems when it helped to capture and
disseminate initial reports of SARS in China.
HealthMap is a free, web-based program that searches news and other non-traditional or informal web information
sources to assist and publicise early outbreaks using Google Maps. John Brownstein, co-creator of HealthMap and an
assistant professor of paediatrics at Harvard Medical School, says HealthMap is one of the few systems tracking
outbreaks in real time with respect to when news gets posted, whereas official government sites usually confirm
outbreaks before posting them online. One of the challenges for HealthMap is filling in the gaps between what is
happening on the ground in disease hot spots and what information is making it into the news. HealthMap says it is
on the cusp of integrating text messages into its system as cellphone usage is increasing at a more dramatic pace
than is internet use. “As we roll out the system eventually we want to build in ways to allow anyone to input
information”, said Brownstein. Clark Freifeld, co-creator of HealthMap, says HealthMap is also looking at ways to build
in data from scientists like Wolfe and those who are contributing to GAINS. “We are building up a database of
infectious disease reports, which we will catalogue in a way to look at different pathogens” he said.
ProMED-mail is one key source of relevant news reports for HealthMap and another web-based surveillance system
that is helping to monitor disease emergence. The service is daily report, monitored and edited by public health
experts affiliated with the International Society for Infectious Diseases.
Although HealthMap and ProMED-mail are the free, multilingual programs accessible to anyone, GPHIN is available by
subscription only and is limited to officials and institutions that are involved in public-health surveillance.
As existing systems for disease surveillance develop and integrate, Google.org is looking at creating new ways to
share information globally using the internet. “We would love to see something like an eBay or a virtual marketplace
for samples where demand, supply, and knowledge would come together, where people doing research on diseases
in Africa collaborate with sites in Asia”, said Rijsberman. “The current systems are very far behind the power of the
internet, and Google has the ability to build new platforms for researchers. In a couple of years we could see real
concrete outputs that allow us to predict and prevent in new ways.”
Nature
Volume 455 Number 7211 pp263-430 (18 September 2008)
http://www.nature.com/nature/journal/v455/n7209/
[No relevant content]
New England Journal of Medicine
Volume 359 — September 18, 2008 — Number 12
http://content.nejm.org/current.shtml
[No relevant content]
Science
19 September 2008 Vol 321, Issue 5896, Pages 1589-1724
http://www.sciencemag.org/current.dtl
[No relevant content]
Vaccine
Volume 26, Issue 42, Pages 5331-5434 (3 October 2008)
http://www.sciencedirect.com/science/journal/0264410X\
(reviewed last week)
______________________________________________________________________________________________________
15 September 2008
GAVI said that some 2,2 million people were successfully vaccinated in Abidjan, Cote d'Ivoire following
an urban yellow fever outbreak. The national Ministry of Health, WHO, UNICEF, NGOs and others in the Yellow
Fever Partnership combined their forces to vaccinate people in the Ivorian capital in a campaign which lasted 14 days
and finished on Friday 5 September, GAVI said. Vaccine financed by the GAVI Alliance was distributed to points across
the capital, and administered by trained health teams. GAVI said that “by ensuring that over 2.2 million non-
vaccinated people out of a total population of approximately 5 million in the capital received their Yellow Fever (YF)
vaccination, YF vaccination coverage rates were brought up to levels in the city where the entire population can be
expected to be protected against epidemics.” It is estimated that at least 60-80% of a given population has to be
vaccinated for epidemics to be obviated in the entire population. Prior to this vaccination campaign, the last YF
vaccination campaign in Abidjan had taken place in 2001, achieving a coverage rate above 90%. But vaccination
coverage rates were estimated to have slipped down to 60% in the intervening years, due to population movements
and births.
GAVI noted that this emergency campaign comes as the Yellow Fever Initiative, with $58 million worth of support
from GAVI, is continuing its mass vaccination programmes across West Africa aimed at drastically reducing the
numbers at risk from Yellow Fever. So far, three countries - Mali, Senegal and Togo - have undertaken national
preventive vaccination campaigns as part of the Initiative, with other countries due to follow suit as soon as sufficient
vaccine is available. The ministries of Health of these 12 countries are being supported financially and technically by a
Yellow Fever partnership which was launched in February 2006 and now includes WHO, UNICEF, GAVI, Médecins
Sans Frontières, IFRC, the Association pour la Médecine Préventive (AMP), the Programme for Appropriate
Technology (PATH), the European Union Humanitarian Aid Office (ECHO), the United States Centers for Disease
Control and Prevention (CDC), the Global Outbreak Alert and Response Network (GOARN) and the Institut Pasteur.
The partnership continues to take on new members.
http://www.gavialliance.org/media_centre/press_releases/2008_09_09_WHO_pr_Abidjan_yellow_fever.php
The International Federation of Pharmaceutical Manufacturers & Associations (IFPMA) said it created a
special Pediatric Task Force “to enhance the contribution of industry expertise to the important task of
improving the availability of medicines and vaccines for children.” The IFPMA Pediatric Task Force “will work
with relevant intergovernmental organizations, non-governmental organizations and other key stakeholders to
identify and address opportunities for the systematic expansion of medicine development for younger age groups.”
IFPMA Director General Alicia Greenidge said, “The IFPMA Pediatric Task Force will enable more focused work between
the industry and other stakeholders, to address effectively and concretely the various obstacles to developing more
medicines adapted for children, especially for the developing world. This new task force will serve as a catalyst for that
process, inspired by regulatory, World Health Organization and other initiatives -- principally, the critical needs of the
world's children.”
IFPMA said the Task Force “will build on the industry’s existing range of pediatric medicine and vaccine development
and access activities, and work to address specific concerns highlighted by the WHO(1) and other organizations.
These include identifying appropriate dosage forms and strengths of medicines for children (starting with HIV/AIDS,
tuberculosis, malaria and chronic diseases), encouraging R&D of appropriate medicines for diseases that specifically
affect children, and ensuring high quality and ethical standards in clinical trials involving children, including informed
consent.”
The new body will also serve as an industry discussion forum, “to ensure pediatric medicine R&D and related topics
have a prominent position in the industry’s agenda.” It will also provide a global complement to existing regional and
national industry association pediatric medicine groups, such as those set up by the European Federation of
Pharmaceutical Industries and Associations (EFPIA) in the European Union, the Japan Pharmaceutical Manufacturers
Association (JPMA) in Japan and the Pharmaceutical Research and Manufacturers of America (PhRMA) in the USA.
( IFPMA Media Release, 15 September 2008)
The Fogarty International Center of the National Institutes of Health, said it will award $4.6 million over
three years “to expand its network of global health education programs to include 12 additional
campuses in the United States, China and Mexico” through its Framework Programs for Global Health.
The initiative aims “to raise awareness of global health within the academic community and support development of
new curricula and degree programs that cut across departments and schools to create a pipeline for the next
generation of global health researchers.” NIH Director Elias A. Zerhouni, M.D., said,
"As the world becomes increasingly interconnected, there is a compelling need for novel, multidimensional
approaches to global health research. By removing the existing academic silos and working across disciplines, we can
better leverage our knowledge and skills to tackle difficult global health challenges and save lives around the world."
Each site will receive approximately $400,000 over three years “…to develop a structure and activities that best suit
its existing strengths and research capabilities.” NIH said the new awardees will join the existing network of 19 sites
that have received Framework grants since the program’s inception in 2005. Within these institutions, faculty from
more than 17 different disciplines have participated including those from schools of medicine, public health,
anthropology, law, engineering, environmental sciences, journalism, business and others, NIH said
2008 Framework Awards:
Brown University, Providence, R.I.
Duke University, Durham, N.C.
Fudan University, Shanghai, China
Harvard University, Cambridge, Mass.
National Institute of Public Health, Cuernavaca, Mexico
Northwestern University, Evanston, Ill.
Ohio State University, Columbus, Ohio
Oregon Health and Science University, Portland, Ore.
Tulane University, New Orleans
University of California, San Francisco
University of Pittsburgh
University of Texas Medical Branch at Galveston, Texas
(NIH Media Release, 10 September 2008)
http://www.nih.gov/news/health/sep2008/fic-10.htm
The Heinz Foundation honored five Americans with 14th Annual Human Achievement Prize. The
$250,000 awards recognize significant accomplishments in five distinct categories – the arts and humanities; the
environment; human condition; public policy; and technology, the economy and employment. Each area was of
particular interest to John Heinz, the late U.S. Senator for whom the awards are named. The recipient in the
Technology, the Economy and Employment category is Joseph DeRisi, Ph.D., 38, a molecular biologist,
researcher and inventor, from San Francisco.
The award media release noted:
“An innovative, selfless and generous researcher whose breakthrough creation of a viral detection platform for
malaria and other infectious diseases has helped advance biomedicine’s ability to detect both existing and new
viruses, Dr. Joseph DeRisi stands at the intersection of the disciplines driving the life sciences – genomics,
bioinformatics, virology, materials science and computer engineering. His pioneering invention – the ViroChip, a band-
aid-sized glass wafer that contains a microarray of 22,000 DNA sequences from more than 1,300 viral families –
provides “diagnostics on a chip,” enabling scientists to not only quickly and accurately identify existing viruses, but
also to detect new viruses that could emerge as pandemic threats. In 2003, the ViroChip identified the SARS virus
within 24 hours.
“Notwithstanding his work in virus detection, Dr. DeRisi’s primary focus has been on finding a cure for malaria, a
disease that infects up to 500 million people annually, killing between 700,000 and 2.7 million, mostly children. Dr.
DeRisi, together with his longtime collaborator, Dr. Don Ganem, and his team at the University of California, San
Francisco developed a malaria-specific DNA chip, similar to the ViroChip, that enabled them to characterize the
parasite’s distinctive 48-hour life cycle, a breakthrough that could pave the way for potential drug and vaccine
therapy. He also has taken on a number of other challenges, from investigating a cure for the common cold to an
analysis of the disappearance of a half-million honeybee colonies in the United States. Driven by scientific discovery
alone, Dr. DeRisi has distinguished himself within the highly competitive world of biomedicine by giving most of his
research and knowledge away for free.”
(Business Wire, 9 September 2008)
The U.S. Food and Drug Administration approved “expanded uses” of Gardasil vaccine for the
prevention of vaginal and vulvar cancer caused by Human Papillomavirus (HPV) types 16 and 18 in girls
and women ages 9 to 26. These two HPV types cause 70 percent of cervical cancers, and are known to also
cause some vulvar and vaginal cancers, but the percentages are not well defined. Jesse L. Goodman, M.D., M.P.H.,
director of the FDA’s Center for Biologics Evaluation and Research, commented, “There is now strong evidence
showing that this vaccine can help prevent vulvar and vaginal cancers due to the same viruses for which it also helps
protect against cervical cancer. While vulvar and vaginal cancers are rare, the opportunity to help prevent them is
potentially an important additional benefit from immunization against HPV.” The FDA originally approved Gardasil in
2006 for girls and women ages 9 to 26 for the prevention of cervical cancer caused by HPV types 16 and 18,
precancerous genital lesions caused by HPV types 6, 11, 16, and 18 and genital warts caused by HPV types 6 and
11. HPV includes more than 100 related viruses and more than 30 types can be transmitted via sexual contact.
According to the U.S. Centers for Disease Control and Prevention, HPV is the most common sexually transmitted
infection in the United States with 6.2 million Americans becoming infected with genital HPV each year.
(FDA Media Release, 12 September 2008)
http://www.fda.gov/bbs/topics/NEWS/2008/NEW01885.html
WHO: Avian influenza – situation in Indonesia – update 44
10 September 2008 -- The Ministry of Health of Indonesia has retrospectively announced two confirmed cases of
human infection with the H5N1 avian influenza virus. The first case, a 38 year old male from Tangerang Municipality,
Banten Province developed symptoms on 4 July 2008, was hospitalized on 9 July and died on 10 July. There were
free roaming poultry throughout his neighbourhood, including a commercial poultry pen owned by a neighbour. The
second case, a 20 year old male from Tangerang District, Banten Province developed symptoms on 20 July, was
hospitalized on 29 July, and died on 31 July. Reports indicate that chickens from the case's household had died in
the week preceding the onset of his symptoms and that he had slaughtered and consumed some of his stock during
this period. Of the 137 cases confirmed to date in Indonesia, 112 have been fatal.
The Weekly Epidemiological Record (WER) 12 September 2008, vol. 83, 37 (pp 333–348) includes:
- Global programme to eliminate lymphatic filariasi
- Conclusions of the meeting of the Technical Advisory Group on the Global Elimination of Lymphatic Filariasis,
November 2007
- WHO web sites on infectious diseases
http://www.who.int/wer/en/
Journal Watch
[Editor’s Note]
Vaccines: The Week in Review continues a new feature, scanning key journals to identify and cite articles, comment
and editorials, books reviews and other content supporting our focus on vaccine ethics and policy. This scan is not
intended o be exhaustive, but indicative of themes and issues the center is actively tracking. Successful access to
some of the links provided may require subscription or other access arrangement unique to the publisher. Our initial
scan list includes the journals below. If you would like to suggest other titles, please write to David Curry at david.r.
curry@centerforvaccineethicsandpolicy.org
JAMA
Vol. 300 No. 10, pp. 1115-1262, September 10, 2008
http://jama.ama-assn.org/current.dtl
[No relevant content]
Journal of Infectious Disease
1 October 2008 Volume 198, Number 7
http://www.journals.uchicago.edu/toc/jid/current
[reviewed last week]
The Lancet
Volume 372, Number 9642, 13 September 2008
http://www.thelancet.com/journals/lancet
[This issue of The Lancet focuses on the state of global primary health care. The Editorial on this theme is presented
in full text below as a courtesy to our working group.]
Editorial
“30 years ago, in the midst of the Cold War, health experts and policy makers from 134 WHO member states
convened in the former USSR to attend a conference on international primary health care. On Sept 12, 1978, the
Alma-Ata Declaration was signed, with the ambitious target of achieving “Health for All by 2000”.
“In 1978, 2000 million people were estimated to have no access to adequate health care. There were vast inequalities
between rich and poor countries, and between rich and poor populations within countries. The Alma-Ata Declaration
revolutionised the world's interpretation of health. Its message was that inadequate and unequal health care was
unacceptable: economically, socially, and politically. Unfortunately, the goal of “health for all”, while a rallying call to
action, was not met. Theories for this failure abound: the vision for primary health care was politically unacceptable to
some nations and so was marginalised; emerging health threats took precedence (no one imagined the global disease
burden that HIV/AIDS would bring); and health priorities shifted (to the Millennium Development Goals [MDGs]).
“30 years on, what is the relevance of the Alma-Ata Declaration in 2008? In short, primary health care is now offering
global health a lifeline. Progress towards the MDGs has stalled. Weak health systems have restricted the success of
efforts to improve maternal, newborn, and child health, and to reduce the disease burden from malaria and
tuberculosis. New epidemics of chronic disease threaten to reverse what small gains have been achieved. To get back
on track, and to meet the MDGs by 2015, countries need to strengthen their health systems through the
implementation of effective primary health care.
“Now is the right moment to proclaim the urgent need for a renaissance in primary health care. The continuing
relevance of this 30-year-old Declaration is remarkable. Many of the challenges faced in 1978 remain, such as
infectious diseases (e.g., the ongoing threat of H5N1 avian influenza and HIV/AIDS), political instability and conflict
(most recently seen in Iraq and Zimbabwe), and worsening poverty (the World Bank last month estimated that 1•4
billion people now live in poverty).
“In recognition of this timely reawakening of interest in primary health care, this week's Lancet revisits, updates, and
relaunches the key messages from Alma-Ata. A series of eight papers begins with an analysis of modern primary
health care, and issues such as implementing cost-effective interventions in low-resource settings and tackling the
growing burden of chronic diseases. We publish an analysis of individual country progress since 1978, with possible
lessons for those who have shown the least advance. Involvement of communities in planning and implementation of
health care (one of the main tenets of the Alma-Ata Declaration) is explored in the context of maternal, newborn,
and child health, as are the roles of national policies and effective service integration, all foundations of a successful
primary health care service. The final paper in the series looks to the future and provides a series of action points to
revitalise primary health care, both nationally and globally.
“WHO's vision for health—complete physical, mental, and social wellbeing—is the key to achieving Alma-Ata's prime
goal of “health for all”. This week's research articles also focus on these three principles. Stephen Tollman and
colleagues discuss the challenges in managing chronic diseases in primary health care and the importance of
providing adequate services to ensure physical wellbeing. Atif Rahman and co-workers tackle mental health in
Bangladesh, with a psychological intervention that can be delivered within communities to treat mothers with
perinatal depression. And the importance of social development is shown by Luis Huicho and authors who present
data from four countries highlighting the importance of health workers with shorter durations of training in providing
vital care to people in low-resource settings.
“Importantly, WHO, under Margaret Chan's effective leadership and together with her regional directors, has
reaffirmed its commitment to primary health care. This revisioning of the principles of Alma-Ata is welcome and
illustrates a new unity of purpose across global health institutions. Political progress is also encouraging. Following the
G8 meeting earlier this year, Japan has announced its own commitment to lead international initiatives to strengthen
health systems. Such renewed global interest in primary health care is promising. The need remains great and there
are no shortcuts to success. But with refined international relationships, new and emerging technologies, and 30
years of experience, “health for all” need not be a dream buried in the past. The right to the highest attainable
standard of health can be a reality within our grasp.”
Nature
Volume 455 Number 7210 pp137-262 (11 September 2008)
http://www.nature.com/nature/journal/v455/n7209/
[No relevant content]
New England Journal of Medicine
Volume 359 — September 11, 2008 — Number 11
http://content.nejm.org/current.shtml
[No relevant content]
Science
12 September 2008 Vol 321, Issue 5895, Pages 1401-1588
http://www.sciencemag.org/current.dtl
[No relevant content]
Vaccine
Volume 26, Issue 42, Pages 5331-5434 (3 October 2008)
http://www.sciencedirect.com/science/journal/0264410X\
The role of economic information in decision-making by the Advisory Committee on Immunization
Practices
Pages 5389-5392
Amanda F. Dempsey, Anne E. Cowan, Shannon Stokley, Mark Messonnier, Sarah J. Clark, Matthew M. Davis
Abstract
“With cost of vaccines steadily increasing, recommendations of the Advisory Committee on Immunization Practices
(ACIP) have growing economic implications for the public. We used semi-structured telephone interviews to assess
the knowledge, attitudes, and practices of the 15 voting members of the 2006–2007 ACIP regarding the use of
economic information by the committee in their deliberations about new vaccine recommendations. These interviews
demonstrated the importance of economic information in ACIP deliberations, but also revealed that many members
felt economic information should not be outweighed by the more important issues of vaccine efficacy, disease
burden, and safety. In addition, though members had variable levels of expertise in analyzing economic data, there
was a general concern that assumptions inherent in the development of cost-effectiveness models made
interpretation of the data resulting from these models difficult. To counteract this concern, several ACIP members
suggested standardizing the process of how economic data are presented to the committee so that a more uniform
consideration of consequential information might be undertaken by the ACIP in their deliberations.”
H5N1 VLP vaccine induced protection in ferrets against lethal challenge with highly pathogenic H5N1
influenza viruses
Pages 5393-5399
Kutubuddin Mahmood, Rick A. Bright, Nutan Mytle, Donald M. Carter, Corey J. Crevar, Jenna E. Achenbach, Penny
M. Heaton, Terrence M. Tumpey, Ted M. Ross
Abstract
“In this study, recombinant virus-like particles (VLPs) were evaluated as a candidate vaccine against emerging
influenza viruses with pandemic potential. The VLPs are composed of the hemagglutinin (HA), neuraminidase (NA),
and matrix 1 (M1) proteins of the H5N1 A/Indonesia/05/2005 (clade 2.1; [Indo/05]) virus, which were expressed
using baculovirus in Spodoptera frugiperda (Sf9) cells. Ferrets received either 2 injections of the VLP vaccine at
escalating doses (based on HA content), recombinant HA, or were mock vaccinated. Vaccinated ferrets were then
challenged with either H5N1 Indo/05 or H5N1 A/Viet Nam 1203/2004 (VN/04) wild-type viruses. All ferrets that
received the VLP vaccine survived regardless of the VLP dose or challenge strain, whereas seven of eight mock
vaccinated ferrets died. The VLP vaccine induced HAI antibodies against the homologous H5N1 clade 2.1 strain, as
well as heterologous strains from H5N1 clades 1, 2.2, and 2.3. The magnitude of the HAI titers correlated with VLP
dose. Neutralizing antibody responses against the Indo/05 and VN/04 strains showed a similar pattern. Affinity of the
anti-HA antibodies raised by the H5N1 Indo/05 VLPs had a higher association rate to the homologous clade 2.1 HA
than to the clade 1 (VN/04) HA; however, once bound, antibodies had similar slow disassociation rates. These results
provide support for continued development of the H5N1 VLPs as a candidate vaccine against pandemic influenza.
Exploration of immunologic correlates of protection for H5N1 vaccines beyond HAI and neutralizing antibody
responses is warranted.”
______________________________________________________________________________________________________
8 September 2008
A new UN report – “Delivering on the Global Partnerships for Achieving the Millennium Development
Goals” – highlights “the existence of large gaps in the availability of medicines in both the public and
private sectors, as well as a wide variation in prices which render essential medicines unaffordable to
poor people.” Launched on September 4th by the UN Secretary-General, the report describes progress towards
achieving MDG 8 (Develop a global partnership for development) and its related targets in the areas of essential
medicines, official development assistance, trade, external debt and technology.
[MDG 8, Target 8.E: In cooperation with pharmaceutical companies, provide access to affordable essential
medicines in developing countries was measured using nine indicators for measuring access to
medicines using data collected by WHO and its partners.]
The report found that “in the public sector, generic medicines are only available in 34.9% of facilities, and on average
cost 250% more than the international reference price. In the private sector, those same medicines are available in
63.2% of facilities, but cost on average about 650% more than the international reference price. While policies that
promote access such as generic substitution are in place in many countries, additional national and international
efforts are required to improve the availability and affordability of medicines.”
http://www.who.int/medicines/mdg/en/index.html
The WHO reported that health ministers from countries of the African meningitis belt have “committed
themselves to introduce a highly promising candidate meningitis vaccine,” designed to prevent periodic
epidemics. The ministers were meeting at the 58th session of the WHO Regional Committee for Africa, held in
Yaoundé from 1 to 5 September, and the ministers adopted the Yaoundé Declaration, committing themselves to ”
…prepare comprehensive meningitis control plans, including the introduction of the new vaccine once available; to
implement meningitis control strategies; to undertake joint action vis-à-vis the threat; to improve information
exchange for epidemic response; and to contribute financially to epidemic control activities.”
Professor Avocksouma Djona, Minister of Public Health, Chad, said, "Several hundred million people are at risk of
meningitis in 25 African countries. Many generations have suffered. On behalf of all affected countries in Africa, today
we are collectively committing ourselves to put an end to devastating outbreaks of this disease. We will ensure that
this effective new vaccine is made available to populations throughout the Meningitis belt." WHO Director-General, Dr
Margaret Chan noted that WHO will provide technical support for introduction of the vaccine. The meningitis
prevention and control strategy was reviewed and endorsed by WHO's Strategic Advisory Group of Experts on
Immunization in April 2008 and by the GAVI Alliance Board in June 2008.
The new product, conjugate meningococcal A vaccine ("MenAfriVac"), was developed through the Meningitis Vaccine
Project, a product development partnership between WHO and the Program for Appropriate Technology in Health
(PATH), a non-governmental organization. The project was set up in 2001 with core funding from the Bill & Melinda
Gates Foundation. The new vaccine is expected to be introduced starting 2009-10 in Burkina Faso and will be phased
into an additional 24 countries between 2010 and 2015, with GAVI support. GAVI funding will also go towards
ensuring sufficient stocks of the current vaccines are available for epidemic response during the introduction of
MenAfriVac.
http://www.who.int/mediacentre/news/releases/2008/pr31/en/index.html
GAVI Alliance Executive Secretary Julian Lob-Levyt GAVI, speaking at the opening plenary of the Third
High-Level Forum on Aid Effectiveness in Accra, Ghana, “highlighted the experience of GAVI and other
global partnerships, saying that the strong focus on country ownership to achieve results had proved
effective.” He observed, “Country ownership has to be the starting point of aid effectiveness. The challenge is
genuinely to put the country in charge, to listen, adjust priorities, and measure results…” The conference involved
some 1,300 delegates, including more than 100 government ministers and heads of development agencies, donor
organisations and civil society organisations (CSOs) “committed to making aid more transparent, accountable and
results-oriented.” Julian Lob-Levyt also underlined GAVI’s commitment to the principles of aid effectiveness by
endorsing the International Aid Transparency Initiative, http://www.dfid.gov.uk/news/files/pressreleases/aid-
transparency-intiative.asp which is being launched in Accra. The initiative commits donors and agencies to improve
public access to information on aid flows.
http://www.gavialliance.org/media_centre/statements/2008_09_03_Accra_statement.php
The Bill & Melinda Gates Foundation said it is now accepting grant proposals for Round 2 of Grand
Challenges Explorations, described as a five-year US$100 million initiative “to encourage bold and
unconventional research on new global health solutions.” Proposals for six topics will be accepted online
through November 2, 2008 and “…follows on the heels of the initiative's first funding round, which closed in May of
this year, and generated nearly 4,000 applications from scientists in more than 100 countries.” The Gates Foundation
noted that one of the primary objectives of Grand Challenges Explorations is “to involve scientists around the world
who do not typically work in global health. This includes those with innovative ideas in Africa, Asia, and other parts of
the developing world; people working in the private sector; and young investigators.” Gates said the topic areas for
which proposals will be accepted in Round 2 are:
- Create new vaccines for diarrhea, HIV, malaria, pneumonia, and TB.
- Create new tools to accelerate the eradication of malaria.
- Create new ways to protect against infectious diseases, including alternatives to traditional vaccination.
- Create new drugs and delivery systems to limit the emergence of resistance in the disease-causing agent.
- Create new ways to prevent or cure HIV infection that fall outside current research on vaccines and other
biomedical and behavior-change strategies.
- Explore the basis for latency in TB, with the goal of discovering new ways to identify and eliminate latent infection.
The foundation and an independent group of reviewers will select the most innovative proposals, and grants will be
awarded within approximately three months from the proposal submission deadline. Initial grants will be $100,000
each. Projects showing success will have the opportunity to receive additional funding of $1 million or more. Round 1
grants are expected to be announced in October, the foundation said.
(Gates Media Release, 3 September 2008)
http://www.gatesfoundation.org/GlobalHealth/Announcements/Announce-080903.htm?version=print
Murdoch Children’s Research Institute (MCRI) and PATH announced a new partnership to support the
further development of the MCRI rotavirus vaccine candidate, RV3. PATH will provide up to US$350,000 to
assist MCRI in the production of clinical trial lots of RV3 under Good Manufacturing Practices (GMP) at Meridian Life
Science in Memphis, Tennessee, in preparation for Phase 1 and 2 clinical trials to be conducted by MCRI. Dr. Georges
Thiry, director of PATH’s Advancing Rotavirus Vaccine Development project, said, ”PATH is pleased to collaborate
with MCRI on the further development of the RV3 vaccine. RV3 represents a promising approach in the fight against
rotavirus, and MCRI’s clinical trials will provide critical evidence to advance the development of this potential tool.” The
organizations said the RV3 vaccine candidate was developed from a strain of rotavirus that was discovered in babies
at a newborn nursery in Melbourne, Australia. Babies who were naturally infected with the RV3 strain had no
symptoms and were protected from contracting rotavirus disease in the first three years of life. Professor Julie Bines
of the University of Melbourne and MCRI, commented, “This vaccine candidate was created from a strain of the
natural infection found in healthy babies, but provides protection from disease due to rotavirus infection later in life,
making it an ideal vaccine candidate to provide protection from birth. Our vaccine could offer a major boost for
global efforts to reduce death and suffering due to rotavirus gastroenteritis in children worldwide.”
Murdoch Childrens Research Institute describes itself as “Australia’s largest and most prestigious child health institute.
Its staff work side by side with the doctors and nurses at Melbourne’s Royal Children’s Hospital and have a unique
opportunity to make discoveries and translate them into real benefits for children. The team of 1,100 passionate
researchers conduct innovative, world class research into a wide range of conditions affecting children, including
asthma, premature birth, cancer, depression, genetic conditions, obesity, and infectious diseases.”
(PATH Media release, 2 September 2008)
http://www.path.org/news/pr080901-mcri.php
MMWR News Synopsis for September 4, 2008
National, State, and Local Area Vaccination Coverage Among Children Aged 19–35 Months – United
States, 2007
According to the CDC′s 2007 National Immunization Survey (NIS), childhood immunization rates remain at or near
record levels with at least 90 percent coverage for all but one of the vaccines in the recommended series for young
children. More than 77 percent of children were fully vaccinated for the complete series of recommended vaccines,
and there were no differences in coverage among any racial or ethnic group for the complete series. Importantly,
less than one percent of children had received no vaccines by age 19 to 35 months. The NIS coverage data includes
children born between January 2004 and July 2006. There were no statistically significant decreases in individual
vaccine coverage from 2006 to 2007. For the first time in 2007, there was 90% coverage for varicella vaccine and
for the third dose of PCV. One dose of varicella vaccine increased in 2007 to 90 percent compared to the 2006
coverage rate of 89.2 percent. There were also significant increases for pneumococcal conjugate vaccine. Coverage
of three or more doses of increased from 86.9 percent in 2006 to 90.0 percent in 2007, and coverage four or more
doses rose from 68.4 percent in 2006 to 75.3 percent in 2007. Varicella vaccine and pneumococcal conjugate
vaccine coverage among American Indian and Alaska Native children increased significantly. Varicella coverage
increased from 85.4 percent in 2006 to 94.9 percent in 2007 and coverage with the fourth dose of PCV7 increased
from 64.8 percent to 80.4 percent.
http://www.cdc.gov/media/mmwrnews/2008/n080904.htm
The Weekly Epidemiological Record (WER), 5 September 2008, vol. 83, 36 (pp 321–332), includes:
- 321 Laboratory surveillance for wild and vaccine-derived polioviruses, January 2007–June 2008
- 328 Performance of acute flaccid paralysis (AFP) surveillance and incidence of poliomyelitis, 2008
http://www.who.int/wer/2008/wer8336/en/index.html
Journal Watch
[Editor’s Note]
Vaccines: The Week in Review continues a new feature, scanning key journals to identify and cite articles, comment
and editorials, books reviews and other content supporting our focus on vaccine ethics and policy. This scan is not
intended o be exhaustive, but indicative of themes and issues the center is actively tracking. Successful access to
some of the links provided may require subscription or other access arrangement unique to the publisher. Our initial
scan list includes the journals below. If you would like to suggest other titles, please write to David Curry at david.r.
curry@centerforvaccineethicsandpolicy.org
JAMA
Vol. 300 No. 9, pp. 995-1104, September 3, 2008
http://jama.ama-assn.org/current.dtl
[No relevant content]
Journal of Infectious Disease
1 October 2008 Volume 198, Number 7
http://www.journals.uchicago.edu/toc/jid/current
Editorial Commentary
Planning for an Influenza Pandemic: Thinking beyond the Virus
Jonathan A. McCullers
[Excerpt; citation indicators removed]
“…A shift in focus is required. Pandemic planning must take into account the possibility that secondary bacterial
pneumonia will be a frequent complication of pandemic influenza. Basic research into the interactions between
influenza viruses and bacteria is needed. Modeling studies extrapolating the breadth of potential risk should be
undertaken. Planning for prevention of disease must include pneumococcal vaccines as well as influenza vaccines. A
comprehensive survey of the sources, supply, and surge capacity of important antibiotics should be undertaken.
This should include analysis of distribution patterns, as has been done for influenza vaccines; it is likely that many of
the countries in the developing world, where complications of pandemic influenza are likely to be worst, will have little
to no access to appropriate antimicrobials in this scenario. Planners should consider strengthening and diversifying
these pipelines—in the United States alone in the last 3 years, there have been shortages of more than a dozen
antibiotics. Included among these is vancomycin, an important drug used in the treatment of antibiotic-resistant
infections due to Streptococcus pneumoniae and Staphylococcus aureus, the 2 most common secondary
pathogens in the infections that follow influenza. If these shortages are occurring in times of constant demand, it
seems likely that worse will occur when there is a surge in demand.
Since the 1997 H5N1 outbreak in Hong Kong, a tremendous amount of work has been done to understand influenza
viruses and prepare for the next pandemic. As Morens et al. have reminded us, however, the virus is only half of the
story, and the bacterial superinfections may be the more deadly half [3]. Harry S. Truman may have summed it up
best, “The only thing new in the world is the history you don't know” [13]. This timely reminder of our past should
act as an impetus to help prevent the history of the 1918 pandemic from repeating itself.”
Predominant Role of Bacterial Pneumonia as a Cause of Death in Pandemic Influenza: Implications for
Pandemic Influenza Preparedness
David M. Morens, Jeffery K. Taubenberger, and Anthony S. Fauci
[Excerpt from Abstract at http://www.journals.uchicago.edu/doi/abs/10.1086/591708]
“Conclusions. The majority of deaths in the 1918–1919 influenza pandemic likely resulted directly from secondary
bacterial pneumonia caused by common upper respiratory–tract bacteria. Less substantial data from the subsequent
1957 and 1968 pandemics are consistent with these findings. If severe pandemic influenza is largely a problem of viral-
bacterial copathogenesis, pandemic planning needs to go beyond addressing the viral cause alone (e.g., influenza
vaccines and antiviral drugs). Prevention, diagnosis, prophylaxis, and treatment of secondary bacterial pneumonia,
as well as stockpiling of antibiotics and bacterial vaccines, should also be high priorities for pandemic planning.”
Persistence of Genital Human Papillomavirus Infection in a Long-Term Follow-Up Study of Female
University Students
Laura K. Sycuro, Long Fu Xi, James P. Hughes, Qinghua Feng, Rachel L. Winer, Shu-Kuang Lee, Sandra O'Reilly,
Nancy B. Kiviat, and Laura A. Koutsky
http://www.journals.uchicago.edu/doi/abs/10.1086/591625
The Lancet
Volume 372, Number 9641, 6 September 2008
http://www.thelancet.com/journals/lancet
Childhood pneumonia deaths: a new role for health workers?
Igor Rudan, Harry Campbell
pages 781-782
[Excerpt; citation indicators removed]
“Pneumonia is the leading cause of child death worldwide, causing the deaths of more than 2 million children every
year. Deaths from pneumonia, more than any other major childhood disease, affect mainly underprivileged and poor
children who have limited or no access to health systems. Most of these deaths are potentially avoidable through
application of existing interventions. However, highly cost-effective interventions are neither being adequately
implemented in local settings, nor being implemented at a scale that reaches all children nationwide….In today's
Lancet, Enayet Chowdhury and colleagues show the importance of implementation research. The investigators
found that many sick children who were referred for hospital care by health workers in first-level facilities in
Bangladesh never actually received treatment. They proposed a modification to WHO's Integrated Management of
Childhood Illness (IMCI) guidelines in response to this problem. Chowdhury evaluated an extension of the role of
health workers from simple triage and hospital referral of very sick children to include treatment of children with
severe pneumonia (IMCI classification) with oral amoxicillin at home. Allowing health workers to give antibiotic
treatment was both safe and effective in this study setting, and the investigators recommended adoption of the
modified guideline by IMCI national programmes…”
Care at first-level facilities for children with severe pneumonia in Bangladesh: a cohort study
Enayet K Chowdhury, Shams El Arifeen, Muntasirur Rahman, DM Emdadul Hoque, M Altaf Hossain, Khadija Begum,
Ashraf Siddik, Nazma Begum, Qazi Sadeq-ur Rahman, Tasnima Akter, Twaha M Haque, ZA Motin Al-Helal, Abdullah H
Baqui, Jennifer Bryce, Robert E Black
pages 822-830
Nature
Volume 455 Number 7209 pp1-136
http://www.nature.com/nature/journal/v455/n7209/
[No relevant content]
New England Journal of Medicine
Volume 359 — September 4, 2008 — Number 10
http://content.nejm.org/current.shtml
[No relevant content]
Science
5 September 2008 Vol 321, Issue 5894, Pages 1268-1374
http://www.sciencemag.org/current.dtl
[No relevant content]
Vaccine
Volume 26, Issue 41, Pages 5239-5338 (26 September 2008)
http://www.sciencedirect.com/science/journal/0264410X\
Seroepidemiology as basis for design of a human papillomavirus vaccination program
Pages 5263-5268
J. Ryding, K.M. French, P. Naucler, R.V. Barnabas, G.P. Garnett, J. Dillner
Preview:
“We have performed a serological survey of HPV type 16-antibody prevalence by age and sex in Sweden and used it
as a basis for modelling the optimal vaccination strategies in this population. Samples of 3317 subjects were tested
for HPV16-specific antibodies. The observed age-specific seroprevalences along with sexual behaviour data were used
to infer parameter values for a mathematical model representing Sweden and the preventive effect of possible
strategies estimated. By the year 2055, vaccination of females starting at age 12 in 2008 was most efficient,
estimated to prevent 5.8 million cumulative HPV16 infections. Catch-up programs had a strong additional preventive
effect. Vaccination also targeting males increased protective effect by about 4%, but had lower preventive effect per
vaccination given. Addition of an HPV serosurvey to existing models and data has enabled us to estimate effect of
different vaccination strategies, optimized to the HPV epidemiology in our population.”
The GAVI Financing Task Force: One model of partner collaboration
Pages 5296-5302
Julie B. Milstien, Lidija Kamara, Patrick Lydon, Violaine Mitchell, Steve Landry
Abstract
Preview:
“The Global Alliance for Vaccines and Immunization, now called the GAVI Alliance, was launched in 2000 as a coalition
of partners, including countries, international organizations, bilateral donors, the vaccine production industry, and
nongovernmental organizations; most activities were to be implemented through these partner organizations. Four
task forces were established at the outset to define issues relevant to GAVI Alliance goals and to recommend actions.
This paper describes the innovations and outputs of the Financing Task Force (FTF), which worked in three areas:
country support to sustainably finance vaccines and immunization programs in the context of introducing new
vaccines; vaccine supply and demand issues as they impact vaccine choice, production costs and price/dose;
innovative financing mechanisms for vaccines and immunization programs through, for example, capital markets.
This analysis particularly focuses on the FTF's work on financial sustainability. Through its partnership, the FTF was
able to leverage organizational change in its participating organizations, in the countries supported by the GAVI
Alliance, and in the policies of GAVI itself. These achievements, along with areas where the desired outcome was not
achieved, are summarized with lessons that may be useful to other multi-partner health alliances.”
_________________________________________________________________
1 September 2008
The World Health Organization's Commission on the Social Determinants of Health presented its
findings to WHO Director-General Dr Margaret Chan. These "social determinants of health" have been the
focus of a three-year investigation by the Commission, “an eminent group of policy makers, academics, former
heads of state and former ministers of health.” The report – Closing the Gap in a Generation: Health Equity through
Action on the Social Determinants of Health – states ”(The) toxic combination of bad policies, economics, and politics
is, in large measure responsible for the fact that a majority of people in the world do not enjoy the good health that
is biologically possible. Social injustice is killing people on a grand scale."
Sir Michael Marmot, Commission Chair said, “Central to the Commission’s recommendations is creating the conditions
for people to be empowered, to have freedom to lead flourishing lives. Nowhere is lack of empowerment more
obvious than in the plight of women in many parts of the world. Health suffers as a result. Following our
recommendations would dramatically improve the health and life chances of billions of people.” Health inequities,
defined as “unfair, unjust and avoidable causes of ill health,” have long been measured between countries but the
Commission documents "health gradients" within countries as well. The Commission found evidence that
“demonstrates in general the poor are worse off than those less deprived, but they also found that the less deprived
are in turn worse than those with average incomes, and so on. This slope linking income and health is the social
gradient, and is seen everywhere – not just in developing countries, but all countries, including the richest. The slope
may be more or less steep in different countries, but the phenomenon is universal.”
The Commission makes three overarching recommendations to tackle the "corrosive effects of inequality of life
chances”:
- Improve daily living conditions, including the circumstances in which people are born, grow, live, work and age.
- Tackle the inequitable distribution of power, money and resources – the structural drivers of those conditions –
globally, nationally and locally.
- Measure and understand the problem and assess the impact of action.
The report also highlights how “over 100 million people are impoverished due to paying for health care – a key
contributor to health inequity.” The Commission thus calls for health systems to be “based on principles of equity,
disease prevention and health promotion with universal coverage, based on primary health care.” WHO will now
make the report available to Member States which will determine how the health agency is to respond.
http://www.who.int/mediacentre/news/releases/2008/pr29/en/index.html
(WHO Media Release, 28 August 2008)
[Editor’s Note: The Commission Report Executive Summary is available at http://whqlibdoc.who.
int/hq/2008/WHO_IER_CSDH_08.1_eng.pdf. The document does not address vaccines or immunization to any
substantial degree.]
The University of Pittsburgh’s Graduate School of Public Health said it received a $10 million grant from
the Gates Foundation for the Vaccine Modeling Initiative, which will create computer simulations of epidemics,
showing worst- and best-case outbreak scenarios, and be used to evaluate new vaccine technologies and modes of
vaccine delivery.” The Vaccine Modeling Initiative is a research partnership among infectious disease modeling teams
at the University of Pittsburgh, The Pennsylvania State University and Imperial College London, and is headquartered
at Pitt’s Graduate School of Public Health. The project also involves collaborations with leading infectious disease
experts, computational modelers and public health officials at Johns Hopkins University, the Pittsburgh
Supercomputing Center, Médecins Sans Frontières Epicentre, University of Georgia, Resources for the Future, and
the World Health Organization. The models they develop “will be designed to fit the prevalence, incidence and
geographic spread patterns of past epidemics in developing countries worldwide, and will help prevent future
infectious disease epidemics by optimizing vaccine strategies for particular diseases and regions.” Initially, the project
will focus on evaluation of new vaccine technologies for influenza, measles and dengue. Later, the project will develop
vaccine models of epidemic pertussis, rotavirus, polio, pneumococcus, malaria and tuberculosis.
Donald S. Burke, MD, principal investigator of the grant and dean of GSPH, said, “Infectious diseases create an
enormous burden on the world’s population, from both a human suffering and an economic development
perspective. One of the major challenges we face in stopping infectious disease outbreaks is predicting how control
strategies, such as vaccines, will work. By using computer models to conduct ‘epidemiology in silicon,’ we will be able
to test the impact of new candidate vaccine technologies and select the most effective strategies.”
http://www.publichealth.pitt.edu/news.php?id=45
(UP Media Release, 20 August 2008)
CDC’s National Center for Immunization and Respiratory Diseases launched a public service
announcement (PSA)campaign to “encourage parents to protect their 11-and 12-year-olds from
meningitis, whooping cough, and the virus that causes cervical cancer." The three pre-teen vaccines
involved in the campaign include MCV4, which protects against meningitis and its complications, Tdap, a booster
against tetanus, diphtheria, and pertussis or “whooping cough,” and for girls, HPV vaccine. The PSAs, available in
both English and Spanish and at lengths of 60, 30 and 15 seconds, are available for download and broadcast at www.
countingonyoupsas.com.
The MMWR August 29, 2008 / Vol. 57 / No. 34 includes:
Progress Toward Poliomyelitis Eradication --- Nigeria, January 2007--August 12, 2008
“Nigeria is one of only four countries that have never interrupted poliovirus transmission (the others are Afghanistan,
India, and Pakistan). A resurgence in wild poliovirus (WPV) transmission occurred in Nigeria during 2003--2004 after a
loss of public confidence in oral poliovirus vaccine (OPV) and suspension of supplementary immunization activities
(SIAs) in several northern states. Subsequently, WPV spread within Nigeria and ultimately into 20 previously polio-free
countries during 2003--2006. Even after national SIAs resumed, limited acceptance and ongoing operational
problems resulted in low polio vaccination coverage and continued WPV transmission. Beginning in 2006, health
authorities in Nigeria introduced new initiatives to control the spread of WPV, including a focus on interrupting type 1
WPV (WPV1) transmission and use of monovalent type 1 OPV (mOPV1) for most of the SIAs to increase vaccine
effectiveness.
Nigeria also instituted changes in SIA implementation to increase community acceptance of vaccination.
Subsequently, 285 polio cases were reported in Nigeria in 2007, the lowest number since sensitive surveillance has
been in place. As of August 12, 2008, confirmed polio cases reported in Nigeria totaled 556 (including 511 WPV1
cases), compared with 176 cases (53 WPV1) reported during the same period in 2007. This report updates overall
progress toward polio eradication in Nigeria during 2007--2008. Given the increase in WPV transmission thus far in
2008, urgent measures are needed to reach all children during SIAs to bring WPV under control in Nigeria.
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5734a4.htm
EndoBiologics and PATH said they formed a new research partnership “to investigate novel conjugate
vaccine candidates against enteric bacteria that cause dysentery and severe diarrhea.” PATH will fund
EndoBiologics to complete preclinical research into process development, mucosal immunization, and evaluation of
novel antigens for potential protection in animal models. EndoBiologics will focus on vaccines against Shigella bacteria
that cause more than 165 million episodes of severe dysentery and diarrhea and kill more than 600,000 children
each year. Since many forms of Shigella mediate disease, “the challenge is to produce a vaccine that provides broad-
spectrum protection.” EndoBiologics said it believes that the unique composition of its new conjugate vaccine
candidates “holds special promise in meeting this challenge.” The Shigella vaccines are part of a pipeline of subunit
vaccines that EndoBiologics said it is developing to provide broad protection against diarrhea, fever, and septic
symptoms caused by enteric bacteria.
(BUSINESS WIRE, 19 August 2008)
Novavax announced “favorable results” from the second stage of the Phase I/IIa human clinical trial of
its pandemic influenza virus-like particle (VLP) vaccine candidate. The vaccine, which does not contain an
adjuvant, “induced robust neutralizing antibody responses” and is directed against the H5N1 A/Indonesia/05/2005
avian influenza strain. VLPs “are recombinant structures mimicking the size and shape of the virus but lack genetic
material and are therefore incapable of replication. Because they resemble actual infectious particles presenting
proteins in the same conformation as on the wild-type virus, they are able to induce a potent immune response,”
Novavax said. Dr. Rahul Singhvi, president and CEO of Novavax. Commented, "These data are exciting because
they demonstrate that recombinant VLPs are a valid and potent vaccine approach against influenza. Combined with
our innovative manufacturing approach, our VLP vaccine candidate has the potential to address an unmet need in
pandemic influenza preparedness efforts being planned by health authorities around the world."
(PRNewswire-FirstCall, 26 August 2008)
Journal Watch
[Editor’s Note]
Vaccines: The Week in Review continues a new feature, scanning key journals to identify and cite articles, comment
and editorials, books reviews and other content supporting our focus on vaccine ethics and policy. This scan is not
intended o be exhaustive, but indicative of themes and issues the center is actively tracking. Successful access to
some of the links provided may require subscription or other access arrangement unique to the publisher. Our initial
scan list includes the journals below. If you would like to suggest other titles, please write to David Curry at david.r.
curry@centerforvaccineethicsandpolicy.org
JAMA
Vol. 300 No. 8, pp. 875-986, August 27, 2008
http://jama.ama-assn.org/current.dtl
Special Communication
Opt-Out Testing for Human Immunodeficiency Virus in the United States
Progress and Challenges
John G. Bartlett, MD; Bernard M. Branson, MD; Kevin Fenton, MD, PhD; Benjamin C. Hauschild, MPH; Veronica Miller,
PhD; Kenneth H. Mayer, MD
JAMA. 2008;300(8):945-951.
“The Centers for Disease Control and Prevention (CDC) has recommended human immunodeficiency virus (HIV)
testing for all persons aged 13 to 64 years in all health care settings. Signed consent would not be required and
counseling with referral would be managed as it is for other serious conditions. The goal of the recommendations is to
promote earlier entry into care to reduce unnecessary mortality and facilitate prevention by behavioral changes that
accompany knowledge of serostatus. Concerns about the change include laws in some states that mandate signed
consent and counseling, a perception that counseling is an effective prevention strategy, variability in payment
coverage for the test, concerns about the stigma and discrimination that may accompany the HIV diagnosis, and the
possibility that other testing policies would be more effective. Eleven of 16 states have changed legislation to reduce
barriers to testing, 35 of 74 national professional societies have endorsed the new recommendations, and multiple
demonstration projects have shown feasibility. Metrics to evaluate the health outcomes of the CDC's
recommendations for HIV testing have been defined, but the data necessary to determine the effects on early entry
into care, the actual reduction in disease incidence, and the unanticipated consequences are not yet available.”
Book Review
Biomedical Ethics: A Multidisciplinary Approach to Moral Issues in Medicine and Biology
Edited by David Steinberg
346 pp, $40
Lebanon, NH, University Press of New England, 2007
ISBN-13: 978-1-5846-5643-2
“Biomedical Ethics contains more than 100 essays previously published in the journal Medical Ethics, many with
commentaries and responses. Overall, the book is a satisfying read that presents many different complex ethical
problems in an engaging manner. Many of the dilemmas highlight just how complicated bioethics and medical science
have become in the 21st century…”
Stephen Workman, MD, MSc, Reviewer
Queen Elizabeth II Health Sciences Center
Halifax, Nova Scotia, Canada
Journal of Infectious Disease
Volume 198, Number 6, 15 September 2008 http://www.journals.uchicago.edu/toc/jid/current
[This issue reviewed last week]
The Lancet
Volume 372, Number 9640, 30 August 2008
http://www.thelancet.com/journals/lancet
[No relevant content]
Nature
Volume 454 Number 7208 pp1029-1150, 28 August 2008
http://www.nature.com/nature/journal/v454/n7205/
[No relevant content]
New England Journal of Medicine
Volume 359 — August 28, 2008 — Number 9
http://content.nejm.org/current.shtml
Perspective
An HIV Vaccine — Challenges and Prospects
Margaret I. Johnston, Ph.D., and Anthony S. Fauci, M.D.
The authors conclude:
”… We may not be able to develop an HIV vaccine that is highly effective in the classic sense of successful viral
vaccines. If we do, it will be in the face of enormous scientific challenges. To tackle these challenges we must turn to
fundamental research to a degree that has not been required in the development of vaccines for other viral diseases.
We remain cautiously optimistic that a substantial increase in our understanding of HIV infection and disease will lead
to creative ideas about how to design an effective HIV vaccine.
Selected Obstacles to HIV-Vaccine Development and Their Implications
Obstacles
- The window of opportunity for the immune system to clear the initial infection is narrow, since HIV integrates and
establishes latent infection within days or weeks.
- Destruction of CD4+ T cells begins early after infection.
- Enormous genetic diversity and mutations that occur with replication enable HIV to avoid immune surveillance.
- Conserved antibody targets on the outer envelope protein are "hidden" from immune recognition.
Implications
- Rational, empirical approaches to vaccine development have not been successful to date.
- Fundamental questions regarding HIV disease and the host response to the virus need to be answered.”
Fresh new ideas beyond the scope of classic vaccinology are urgently needed.”
http://content.nejm.org/cgi/content/full/359/9/888
Book Review
The Oxford Textbook of Clinical Research Ethics
Edited by Ezekiel J. Emanuel, Christine Grady, Robert A. Crouch, Reidar K. Lie, Franklin G. Miller, and David Wendler.
827 pp., illustrated. New York, Oxford University Press, 2008. $150. ISBN 978-0-19-516865-5.
“The Oxford Textbook of Clinical Research Ethics is a resource suitable for a course in research ethics and would also
be helpful for those starting a career in clinical research. It is an accessible synthesis and discussion of the many facets
of research ethics — a massive undertaking, as its size indicates. Scholars and students will find the book valuable, but
it is also an important resource for those already conducting clinical research as investigators (or those contemplating
becoming investigators), as well as for research team members, reviewers, sponsors, research advocacy groups, and
regulators…” http://content.nejm.org/cgi/content/extract/359/9/982
Science
29 August 2008 Vol 321, Issue 5893, Pages 1129-1232
http://www.sciencemag.org/current.dtl
[No relevant content]
Vaccine
Volume 26, Issue 38, Pages 4877-4974 (8 September 2008)
http://www.sciencedirect.com/science/journal/0264410X\
Impact of the introduction of pneumococcal conjugate vaccine on rates of community acquired
pneumonia in children and adults
Pages 4947-4954
Jennifer C. Nelson, Michael Jackson, Onchee Yu, Cynthia G. Whitney, Lora Bounds, Rachel Bittner, Ann Zavitkovsky,
Lisa A. Jackson
Abstract
“Pneumococcal conjugate vaccine use among young children has led to significant declines in invasive
pneumococcal disease in the United States, but the impact on community-acquired pneumonia is unknown. We
conducted population-based pneumonia surveillance among 794,282 Group Health members before and after infant
vaccine introduction in 2000. We presumptively identified pneumonia episodes using diagnosis codes assigned to
medical encounters and confirmed 17,513 outpatient and 6318 hospitalized events by reviewing chest radiograph
reports or hospitalization records. There was evidence for a decline in rates of both outpatient and hospitalized
pneumonia in children less than 1 year of age following vaccine introduction but there were no consistent reductions
in pneumonia rates among older children and adults.”
Vaccines: The Week in Review
4 November 2008
Center for Vaccine Ethics & Policy
http://www.centerforvaccineethicsandpolicy.org/
A program of
- Center for Bioethics, University of Pennsylvania
- The Wistar Institute Vaccine Center
- Children’s Hospital of Philadelphia, Vaccine Education Center
This weekly summary targets news and events in the global vaccines field gathered from key governmental, NGO and company
announcements, key journals and events. This summary provides support for ongoing initiatives of the Center for Vaccine Ethics
& Policy, and is not intended to be exhaustive in its coverage. This summary is also posted at http://www.
centerforvaccineethicsandpolicy.org/ Comments and suggestions should be directed to David Curry, Executive Director of the
Center, at david.r.curry@drcurryassociates.net. We also invite you to visit VaccineEthics.org www.vaccineethics.org/ which
complements this weekly review and is edited by Jason Schwartz, MBE, Center for Bioethics.
[Editor’s Note: In Journal Watch below we note an important special issue of Vaccine, celebrating the journal’s
25th anniversary year of publication. The issue carries thoughtful editorials reflecting on vaccines, their development,
and their deployment in global public health going forward.]
The Washington Global Health Alliance (WGHA), which “strives to connect, organize, and motivate
Washington groups that share the goal of improving health conditions for people around the world,”
marked its official launch on 24 October 2008 at the Greater Seattle Chamber of Commerce’s Regional Leadership
Conference in Cle Elum, Washington. Lisa Cohen, director of WGHA, introduced the Alliance to 275 business and
global health leaders from the Seattle area who attended the conference. The Alliance describes its mission as “to
facilitate creative global health collaboration and initiatives with its partners and promote efforts to expand research,
education, and training opportunities with the goal of improving health worldwide.” Throughout the past year, the
Alliance has been identifying the critical components to a successful global health sector in Washington State. From
these components, the organization created a global health framework that “focuses on four areas: education,
training, and mentoring; research, technology, and programming; public-private partnerships; and marketing,
outreach, and recruitment.”
PATH is the hosting secretariat for WGHA staff and “has been instrumental in laying the groundwork over the
past year for this official launch.” PATH’s president and CEO, Dr. Christopher Elias serves as the president of the
Alliance executive board, which includes members from the Bill & Melinda Gates Foundation, Fred Hutchinson Cancer
Research Center, the Infectious Disease Research Institute, PATH, Seattle Biomedical Research Institute, Seattle
Children’s Hospital Global Alliance to Prevent Prematurity and Stillbirth, the University of Washington’s Department of
Global Health, and Washington State University’s School for Global Animal Health.
Washington Global Health Alliance website: http://www.wghalliance.org/
This month’s Bulletin of the World Health Organization (BLT) is a special WHO 60th anniversary
commemorative volume and is a special theme issue around health financing. Volume 86, Number 11,
November, 817-908
http://www.who.int/bulletin/volumes/86/11/en/index.html
The WHO introduced a new WHO/UNICEF brochure introducing the Global Immunization Vision and
Strategy. The brochure is targeted for the general public and “captures the essence of GIVS which aims to protect
more people against more diseases. Illustrated with photos and the brand new visual identity for GIVS, it describes
achievements in immunization and the benefits of this key and cost-effective health intervention. Needs, challenges,
the cost of immunization programmes and resource requirements are given. The document provides the four
strategic areas of GIVS and immunization goals established therein.”
http://whqlibdoc.who.int/hq/2008/WHO_IVB_08.13_eng.pdf
The Weekly Epidemiological Record (WER)7 November 2008, vol. 83, 45 (pp 401–412) includes: WHO external
quality assessment project for the detection of subtype influenza A viruses by polymerase chain reaction – summary
analysis, 2007 and 2008; and an overview on global influenza
http://www.who.int/wer/2008/wer8345.pdf
Journal Watch
[Editor’s Note]
Vaccines: The Week in Review continues a new feature, scanning key journals to identify and cite articles, comment
and editorials, books reviews and other content supporting our focus on vaccine ethics and policy. Journal Watch is
not intended to be exhaustive, but indicative of themes and issues the center is actively tracking. We selectively
provide full text of some editorial and comment articles that are specifically relevant to our work. Successful access to
some of the links provided may require subscription or other access arrangement unique to the publisher. Our initial
scan list includes the journals below. If you would like to suggest other titles, please write to David Curry at david.r.
curry@centerforvaccineethicsandpolicy.org
JAMA
Vol. 300 No. 17, pp. 1969-2084, November 5, 2008
http://jama.ama-assn.org/current.dtl
[No relevant content]
Journal of Infectious Disease
15 November 2008 Volume 198, Number 10
http://www.journals.uchicago.edu/toc/jid/current
[Reviewed last week}
The Lancet
Nov 08, 2008 Volume 372 Number 9650 Pages 1607 – 1706
http://www.thelancet.com/journals/lancet/issue/current
“A global movement to address the social determinants of health has been gathering pace. This week's issue of The
Lancet contributes to this campaign by publishing evidence on actions that can reduce the startling health
inequalities that persist within and between countries.”
Globalisation and health: the need for a global vision
Ted Schrecker, Ronald Labonté, Roberto De Vogli
“The reduction of health inequities is an ethical imperative, according to the WHO Commission on Social
Determinants of Health (CSDH). Drawing on detailed multidisciplinary evidence assembled by the Globalization
Knowledge Network that supported the CSDH, we define globalisation in mainly economic terms. We consider and
reject the presumption that globalisation will yield health benefits as a result of its contribution to rapid economic
growth and associated reductions in poverty. Expanding on this point, we describe four disequalising dynamics by
which contemporary globalisation causes divergence: the global reorganisation of production and emergence of a
global labour-market; the increasing importance of binding trade agreements and processes to resolve disputes; the
rapidly increasing mobility of financial capital; and the persistence of debt crises in developing countries.”
Global health equity and climate stabilisation: a common agenda
Sharon Friel, Michael Marmot, Anthony J McMichael, Tord Kjellstrom, Denny Vågerö
“Although health has improved for many people, the extent of health inequities between and within countries is
growing. Meanwhile, humankind is disrupting the global climate and other life-supporting environmental systems,
thereby creating serious risks for health and wellbeing, especially in vulnerable populations but ultimately for
everybody. Underlying determinants of health inequity and environmental change overlap substantially; they are
signs of an economic system predicated on asymmetric growth and competition, shaped by market forces that
mostly disregard health and environmental consequences rather than by values of fairness and support.
Addressing social determinants of health inequities: what can the state and civil society do?
Erik Blas, Lucy Gilson, Michael P Kelly, Ronald Labonté, Jostacio Lapitan, Carles Muntaner, Piroska Östlin, Jennie
Popay, Ritu Sadana, Gita Sen, Ted Schrecker, Ziba Vaghri
“In this Health Policy article, we selected and reviewed evidence synthesised by nine knowledge networks established
by WHO to support the Commission on the Social Determinants of Health. We have indicated the part that national
governments and civil society can play in reducing health inequity. Government action can take three forms: (1) as
provider or guarantor of human rights and essential services; (2) as facilitator of policy frameworks that provide the
basis for equitable health improvement; and (3) as gatherer and monitor of data about their populations in ways that
generate health information about mortality and morbidity and data about health equity.”
Nature
Volume 455 Number 7214 pp707-834 (9 October 2008)
http://www.nature.com/nature/journal/v455/n7214/
Editorial
Malaria's watershed
Nature 455, 707 (9 October 2008) | doi:10.1038/455707a; Published online 8 October 2008
[Full text; bolding added]
A Global Malaria Action Plan, announced at the UN Millennium Development Goals Malaria Summit in New York on 25
September, has the ambitious goals of both reducing the malaria burden and eradicating the disease entirely.
Eradication any time soon might seem hopelessly optimistic, given the failure so far to make a serious dent in the
number of malaria deaths. But much of the 274-page plan makes good sense. It calls for scaling up the use of
existing tools, such as bednets, drugs and spraying, to near universal coverage, and then sustaining this effort for
decades. True, this won't come cheaply. Funds for control have already grown from US$250 million annually in 2004
to an estimated US$1.1 billion this year; the plan calls for increasing that to $5 billion annually until at least 2020.
Likewise, total spending on malaria-related research has risen from $265 million in 2003 to $422 million in 2007; the
plan would see that figure double to between $750 million and $900 million annually until 2018. Whether donors will
rise to the challenge is a big question, given current economic woes. Still, it is heartening that at the summit, donors
from governments, industry and philanthropic organizations pledged US$3 billion.
Striking the right balance between basic and applied research is also critical. For example, the sequencing in 2002 of
the genome of Plasmodium falciparum, the main parasite that causes malaria, has stimulated the hunt for new drug
and vaccine candidates. This week's issue of Nature sees the addition of two more parasite sequences: P. vivax,
which is less deadly than P. falciparum, and P. knowlesi, which mainly infects monkeys. These new sequences show
how much more there is to learn: more than half of P. falciparum's encoding genes still have no known function.
Basic research is also needed to stay ahead of drug resistance in the parasite and insecticide resistance in mosquitoes,
and to get a better understanding of natural infection in humans. One surprise from P. falciparum's genome is
evidence that it evades the human immune system mainly by genomic and gene-expression diversity. Plasmodium
seems to have different metabolic and physiological states, and can reprogram its gene expression. These findings
could alter the way researchers think about both drug and vaccine development.
The malaria drug and vaccine pipelines are healthier now than they have been for decades, but they are in urgent
need of new candidates and approaches. So it was welcome news when the Bill & Melinda Gates Foundation, already
the largest donor in malaria research, announced at the UN summit that it would spend US$168 million to develop
next-generation malaria vaccines. Moreover, this initiative will include early-stage laboratory research — most of the
Gates Foundation's funding has so far focused on translational and clinical research.
Many scientists would like to see the foundation fund even more basic research, but this cannot be the foundation's
responsibility alone. Its support of translational work has rejuvenated the field over the past decade, and has helped
get tools into the field. In the process, the malaria research community has become excessively and undesirably
dependent on this one entity. Other research organizations would do well to step up to the plate and match the
Gates Foundation's spending with their own basic-research funds. That would also go some way to addressing what
scientists say is an unfortunate consequence of the emphasis on translational research: that scientists entering
malaria research are less likely to choose basic science.
Any massive increase in research funding means that the malaria community must think about how to coordinate
research across funding agencies. It is encouraging that the main research funders and scientists are to sit down as a
group — called MalERA — over the next year to thrash out a research agenda for eradication. One lesson of the
malaria and human genome projects is that consortia are a key route to delivery, focusing resources wisely, and
avoiding duplication and excessive bureaucracy. It is also essential that international research recognizes the maturity
of the malaria research community in the poorer countries where the disease is endemic — they should be on board
as equals and not, as is too often the case, afterthoughts.
New England Journal of Medicine
Volume 359 — November 6, 2008 — Number 19
http://content.nejm.org/current.shtml
Perspective
Drug Development for Neglected Diseases — The Trouble with FDA Review Vouchers
Aaron S. Kesselheim, M.D., J.D., M.P.H.
[Full text]
September 2008 marked the beginning of a new federal program intended to promote the development of
pharmaceutical products for so-called neglected diseases — infectious diseases that disproportionately affect poor
populations in developing countries. Implemented by the Food and Drug Administration (FDA) Amendments Act of
2007, this program will give the sponsor of a drug for a tropical disease a "voucher" entitling the company to
expedited FDA review of a new drug application for any other product it makes.1
The need to encourage additional research in this field is clear. Diseases such as tuberculosis, malaria, leishmaniasis,
and trypanosomiasis affect millions of people each year, but these people live primarily in resource-poor settings with
underdeveloped health care systems. As a result, the for-profit pharmaceutical industry has invested little in
treatments for these conditions. One study found that of the 1393 new chemical entities marketed between 1975
and 1999, only 16 were for such diseases.2
The new program links the development of drugs targeting tropical diseases to accelerated approval of a company's
other, more profitable drugs for conditions prevalent in wealthier countries. A voucher obtained after the approval of
a drug for a tropical disease can be used to require accelerated regulatory review (in 6 months or less) of a
cholesterol-lowering drug or an antidepressant, for example, that the sponsor might sell in the United States for
thousands of dollars per year of treatment. According to the arrangement's proponents, vouchers could speed up
FDA evaluation time by an average of 12 months, providing domestic patients with more rapid access to the latter
types of drugs.3 A voucher could be worth more than $300 million, thanks to the earlier period of market exclusivity
afforded by decreasing the time a drug spends in FDA review.
As enacted, however, priority-review vouchers represent an inefficient and potentially dangerous way of encouraging
research into tropical diseases. It is inefficient because the program does not directly connect the incentive with the
innovation. Large pharmaceutical companies traditionally have not conducted effective research programs on
tropical diseases. These manufacturers will be unlikely to start such a program merely because of the prospect of
earning a voucher some years in the future, since the voucher's value depends on the success of potential
"blockbuster" drugs that are currently in their pipelines, which is far from assured. In fact, tropical-disease research is
predominantly conducted by small pharmaceutical companies with limited drug portfolios. Such companies will often
be unable to use their vouchers, although the law permits voucher rights to be sold to a large manufacturer. Relying
on these sorts of transactions to spur innovation is speculative as well, and the deals between small and large
pharmaceutical companies affecting agents of great importance to global health will lack transparency. Such deals
may include other payments or exchanges of intellectual property that raise the cost or restrict the future availability
of the products.
Another source of inefficiency is that a voucher's value will bear no relation to the usefulness of the drug whose
development it is intended to reward. For example, the law stipulates that no voucher will be earned for a product
whose "active ingredient" was previously approved. As a result, an effective novel antimalarial drug that degrades in
the heat and must be taken six times a day would earn its sponsor a voucher, but no voucher would be granted for
a follow-on formulation that might be more useful in resource-poor settings. Even more problematically, a sponsor
rewarded with a voucher for FDA approval of a product for a neglected disease will have no incentive to follow
through with implementation of the therapy. After an innovative product is approved in the United States, there can
be significant delays before it reaches patients in developing countries, and drug-company ownership of its intellectual
property may make it unaffordable. The human papillomavirus vaccine, for example, could be useful in combating
cervical cancer in developing countries, but while it remains under patent protection, intellectual property rights and
logistic problems have hindered its dissemination in resource-poor settings.4
In addition, too-speedy FDA review may lead to bad regulatory decision making. The "priority review" designation
was meant to shorten the review time of products that represent major advances in treatment or that treat
conditions for which no adequate therapy exists, such as certain types of cancer and infection with the human
immunodeficiency virus (HIV). In such circumstances, accelerating the review process is reasonable, given the serious
problems faced by patients. But the voucher program will allow drugs for which there is little or no clinical urgency to
be subject to accelerated deadlines and may lead to approval of products without adequate consideration by the
FDA.
The program reflects a growing trend in health policy toward reliance on substantial financial incentives to achieve a
socially desirable outcome. Such initiatives may achieve short-term gains, but they do not consistently lead to
sustained improvement and may have important unintended consequences. It is especially problematic to rely on
pharmaceutical companies' profit motive as the key to developing drugs for resource-poor settings. Effectively
conducting research into treatments for neglected diseases involves a more sustained commitment than can be
achieved simply by rationalizing the revenue that arises from it. If any changes in the drug-development
marketplace, such as initiation of federal drug-reimbursement guidelines in the United States, diminish the perceived
value of these vouchers, then any research started solely in anticipation of voucher revenue will again cease, to the
detriment of public health.
Though Congress should reconsider the usefulness of the voucher program, there are more direct ways to
encourage drug development for medical conditions for which current incentives have proven inadequate. For
example, wealthier countries could, in concert with international public health groups, set up independent funds that
award reasonable compensation for the development of a safe and useful drug or vaccine and then continue to
compensate companies for the appropriate implementation of treatment programs. The level of payment could be
adjusted according to the degree of success in controlling the disease in question.5
Another alternative would be for governments to work with nonprofit foundations to develop treatments for
neglected diseases. The drugs could then be licensed to for-profit pharmaceutical manufacturers for dissemination.
Incentives for the manufacturers to become involved could take the form of advance-purchasing promises or grants
of extended periods of market exclusivity for such drugs, with accompanying price restrictions to ensure affordability
and modest but predictable profits. Precedents exist for such partnerships, including the combined efforts by
GlaxoSmithKline and the Bill and Melinda Gates Foundation to create a malaria vaccine and the work of Institute for
OneWorld Health, a nonprofit drug-development firm that has produced a treatment for visceral leishmaniasis and
implemented a program to distribute it.
Over the past few decades, the patent system has provided the primary incentive structure for drug development,
with the result that needed drugs have not been developed for certain diseases affecting people in resource-poor
settings. At the same time, many patients in these environments continue to have inadequate access to important
products for more widely prevalent conditions, such as routine immunizations and drugs for cardiovascular disease,
cancer, and HIV. It is encouraging to see Congress addressing neglected diseases and taking an interest in an area in
which the market has been unable to provide sufficient results. But as the patent system's limitations have shown us,
incentives in this field must be narrowly tailored to the desired result and tied to implementation to avoid misuse and
to have the greatest effect on global health.
No potential conflict of interest relevant to this article was reported. Source Information
Dr. Kesselheim is a patent attorney and an instructor in medicine in the Division of Pharmacoepidemiology and
Pharmacoeconomics at Brigham and Women's Hospital, Harvard Medical School, Boston.
References
Food and Drug Administration Amendments Act of 2007, 1102 (codified at 21 U.S.C. 524) (2007).
Trouiller P, Olliaro P, Torreele E, Orbinski J, Laing R, Ford N. Drug development for neglected diseases: a deficient
market and a public-health policy failure. Lancet 2002;359:2188-2194.
Ridley DB, Grabowski HG, Moe JL. Developing drugs for developing countries. Health Aff (Millwood) 2006;25:313-
324. [Free Full Text]
Outterson K, Kesselheim AS. Market-based licensing for HPV vaccines in developing countries. Health Aff (Millwood)
2008;27:130-139. [Free Full Text]
Love J, Hubbard T. The big idea: prizes to stimulate R&D for new medicines. Chic-Kent Rev 2007;82:1519-54.
PLoS Medicine
[Accessed 10 November 2008)
http://medicine.plosjournals.org/perlserv/?request=browse&issn=1549-
1676&method=pubdate&search_fulltext=1&order=online_date&row_start=1&limit=10&document_count=1533&ct
=1&SESSID=aac96924d41874935d8e1c2a2501181c#results
[No new content]
Science
7 November 2008 Vol 322, Issue 5903, Pages 805-1008
http://www.sciencemag.org/current.dtl
[No relevant content]
Vaccine
Volume 26, Issue 49, Pages 6173-6292 (18 November 2008)
http://www.sciencedirect.com/science/journal/0264410X
[This issue celebrates 25 years of publication and leads with a series of editorials on that milestone. Vaccine requires
an individual or institutional subscription for access]
“Vaccine”; 25 years on
Pages 6173-6176
Ray Spier
The end of the beginning: Vaccines for the next 25 years
Pages 6179-6182
J.S. Oxford
New vaccine approaches for seasonal and pandemic influenza
Pages 6232-6236
Bram Palache
Abstract
“Inactivated influenza vaccines have been available since the late 1940s for the prevention of influenza disease. Based
on the available scientific evidence, many public health authorities, including the World Health Organization,
recommend annual use of these vaccines for specific populations, including the elderly. Despite these
recommendations, actual vaccination uptake rates are very limited in many countries. Influenza vaccine research is
confounded by the variable nature of the influenza viruses and annual influenza epidemics and by non-specific clinical
diagnostic criteria. These confounding factors complicate evaluation not only of overall vaccine effectiveness, but also
of the relative efficacy and effectiveness of different vaccine formulations. This paper summarizes recent advances in
the development of seasonal and (pre-)pandemic vaccines, discusses the methodologic constraints on influenza
vaccine research, and proposes measures to reduce the level of potential bias and confounding in influenza vaccine
research.”
Cost-effectiveness of HPV vaccination compared with Pap smear screening on a national scale: A literature review
Pages 6258-6265
Win Techakehakij, Roger D. Feldman
Abstract
“Recommendations for worldwide use of human papillomavirus (HPV) vaccine are increasing. This study conducted a
systematic review of articles related to cost-effectiveness analysis of wide-range HPV vaccination programs compared
with Pap smear screening published before August 2007. Eight articles were identified using predefined inclusion and
exclusion criteria. After excluding two outliers, the range of incremental cost-effectiveness ratios (ICERs) from six
articles is between $16,600 and $27,231 per quality-adjusted life year (QALY) gained. The World Health Organization’
s guideline that compares incremental cost-effectiveness ratios (ICERs) with per capita Gross Domestic Product
(GDP) was used to determine whether nation-wide application of HPV vaccine would be cost-effective. The HPV
vaccination program is cost-effective in only 46 countries where per capita GDP is high. Further cost-effectiveness
studies in developing and third-world countries are needed for making policy decisions.
______________________________________________________________________________________________________
4 November 2008
The GAVI Alliance announced that former President of Ireland and High Commissioner for Human
Rights Mary Robinson will lead its new executive board “to strengthen the organisation’s ability to meet global
health challenges.” President Robinson commented, “I feel humbled and honored to be elected. Over these past few
years, I have witnessed GAVI achieve extraordinary success through its unique public and private approach to
improving the health of the world’s poor, especially children. The new board structure embodies this approach and
will enable us to meet the challenges ahead...As the global economy enters into a period of recession, it will be our
challenge to stay focused on reaching the Millennium Development Goals through increasing the positive impact that
immunisation provides on people’s lives.”
The 28-member board has representatives from developing countries, donor governments, UNICEF, WHO and the
World Bank, private institutions like the Gates Foundation, civil society, and the vaccine industry, plus independent
experts. A 10-member executive committee and five committees for programme and policy, audit and finance,
governance, investment, and fundraising will provide support. WHO Assistant Director-General Denis Aitken was
elected as the board’s Vice Chairman. Graça Machel, former first lady of Mozambique and a GAVI founding member,
will retain a board seat. The new body replaces a two board structure that was created when the alliance was
launched and will help support the establishment of the alliance as an international institution in Switzerland.
http://www.gavialliance.org/media_centre/statements/2008_10_30_Board_MaryRobinson.php
The Washington Post of 30 October 2008 carried the followed opinion piece, carried in turn on the GAVI Alliance site
[link below]:
Our Vote to End Cervical Cancer
By Lance Armstrong and John Seffrin
Preventing, treating and defeating cancer are among the greatest scientific challenges and personal triumphs of our
time. And right now, we have the power to save our mothers, sisters and daughters from a type of cancer that
claims a life every two minutes globally.
Cervical cancer progresses over decades, attacking women who might never know they are sick until it is too late. It
often hits women in their prime, when they're raising children, working hard and fully engaged in family, community
and economic life, making these unnecessary deaths especially tragic.
Cervical cancer is unique among cancers because we know one of the main causes for it: certain strains of the
human papilloma virus (HPV). We also know how to prevent it. There are now vaccines available that, when given to
girls before they become sexually active, will later protect them from the potentially deadly strains of HPV.
In the United States and other wealthy countries, HPV vaccines, along with screening and early detection
technologies, have become the standard. Yet cervical cancer remains the number one cause of cancer death among
women in the developing world, because they do not have access to these technologies.
It's hard to stop all HPV strains from spreading, but we can stop certain ones from killing.
Today in Geneva, the Board of the Global Alliance for Vaccines and Immunization (GAVI), which includes a U.S.
representative, will decide whether to commit to making HPV vaccines available to girls in the 72 poorest countries.
GAVI is an international alliance of governments, international agencies and nongovernmental organizations that helps
bring needed vaccines to countries that can't otherwise afford them. Once GAVI commits to a vaccine, it works with
leaders in the public and private sectors to deliver its promise. But without a GAVI commitment, this lifesaving vaccine
will remain the privilege of the few, rather than being deployed on the front lines of this terrible disease.
We have the data to prove that providing HPV vaccines to the poorest regions of the world is feasible, affordable and
necessary. GAVI calculates that the cost of HPV vaccine at $10 per dose is possible, and in all likelihood, far less. The
purchase price for GAVI-eligible countries will be $.30 per dose, which even the poorest of countries can pay. The
difference will be covered through international financing and dramatic discounts from the pharmaceutical companies
that make the vaccine. This combination of need, and a simple, affordable solution, makes the path forward clear.
To be sure, no new innovation or technology is without some controversy, and the HPV vaccine is no exception.
Some concerns have been raised over the impact the vaccine may have on sexual behavior; however, there is no
evidence that the introduction of this or any other effective vaccine leads to changes in human behavior, including
sexual activity.
At the same time, we recognize that HPV vaccine alone is not enough to eradicate cervical cancer in the coming
decades. We need to bring simple new screening technologies to women for whom the vaccine is not appropriate.
Vaccines are most effective when they are given to girls before they become sexually active and contract the virus.
For all other women, screening tools, as well as treatments for both precancerous cervical abnormalities and cancer
itself, must be made more widely available. In places where screening and treatment may always be out of reach,
vaccination is paramount.
Indeed, it is one of the miracles of our young century that cervical cancer prevention now comes in a vial. The HPV
vaccine is built on Nobel-recognized science. It is effective. It is safe. It is affordable. And it is needed most in the
places where it is hardest to get it.
The United States has another opportunity to show our belief and leadership in the powers of innovation and
technology, by this commitment to improve lives of families, communities and nations. We urge our delegation to
GAVI to vote "yes" on the commitment today in Geneva.
Lance Armstrong is a champion cyclist, cancer survivor and chairman of the Lance Armstrong Foundation . John
Seffrin is chief executive officer of the American Cancer Society.
http://www.gavialliance.org/media_centre/news/WashPost___HPV.php
WHO’s Global Immunization News for 30 0ctober 2008 includes reports on endorsement of a new regional
strategy in the Americas to “prevent cervical cancer using new technologies.” The endorsement came as
part of recent 48th Directing Council of the Pan-American Health Organization held 29 Sep – 3 Oct 2008. The action
“will give priority to cervical cancer prevention and control treatment and palliative care, and evidence-based policy
decisions on whether and how to introduce HPV vaccines...” The issue also notes that PATH launched a new Vaccine
Resource Library (VRL) which “seeks to gather the leading immunization resources in a single, easy-to-use website”
available at www.path.org/vaccineresources/
http://www.who.int/immunization/GIN_October2008.pdf
Journal Watch
[Editor’s Note]
Vaccines: The Week in Review continues a new feature, scanning key journals to identify and cite articles, comment
and editorials, books reviews and other content supporting our focus on vaccine ethics and policy. Journal Watch is
not intended to be exhaustive, but indicative of themes and issues the center is actively tracking. We selectively
provide full text of some editorial and comment articles that are specifically relevant to our work. Successful access to
some of the links provided may require subscription or other access arrangement unique to the publisher. Our initial
scan list includes the journals below. If you would like to suggest other titles, please write to David Curry at david.r.
curry@centerforvaccineethicsandpolicy.org
JAMA
Vol. 300 No. 16, pp. 1845-1962, October 22/29, 2008
http://jama.ama-assn.org/current.dtl
Research Letters
Upper Income Limit for SCHIP and Forgone Care Among Uninsured US Children
Laura P. Shone; Jonathan D. Klein; Aaron K. Blumkin; Peter G. Szilagyi
JAMA. 2008;300(16):1882-1884.
Journal of Infectious Disease
15 November 2008 Volume 198, Number 10
http://www.journals.uchicago.edu/toc/jid/current
p 1427
Cross-Protection between Successive Waves of the 1918–1919 Influenza Pandemic: Epidemiological
Evidence from US Army Camps and from Britain
John M. Barry, Cécile Viboud, and Lone Simonsen
“…Conclusion. Exposure to influenza in the spring and summer of 1918 provided mortality and morbidity protection
during the fall pandemic wave. The intensity of the first wave may have differed across US cities and countries and
may partly explain geographical variation in pandemic mortality rates in the fall. Pandemic preparedness plans should
consider that immune protection could be naturally acquired during a first wave of mild influenza illnesses.”
The Lancet
Nov 01, 2008 Volume 372 Number 9649 Pages 1519 - 1606
http://www.thelancet.com/journals/lancet
The Lancet, Volume 372, Issue 9649, Pages 1563 - 1569, 1 November 2008
WHO's budgetary allocations and burden of disease: a comparative analysis
David Stuckler MPH, Lawrence King PhD, Helen Robinson MPhil, Prof Martin McKee MD
Summary
Background
Ministers of health, donor agencies, philanthropists, and international agencies will meet at Bamako, Mali, in November,
2008, to review global priorities for health research. These individuals and organisations previously set health priorities
for WHO, either through its regular budget or extra-budgetary funds. We asked what insights can be gained as to
their priorities from previous decisions within the context of WHO.
Methods
We compared the WHO biennial budgetary allocations with the burden of disease from 1994—95 to 2008—09. We
obtained data from publicly available WHO sources and examined whether WHO allocations varied with the burden of
disease (defined by death and disability-adjusted life years) by comparing two WHO regions—Western Pacific and
Africa—that are at differing stages of epidemiological transition. We further assessed whether the allocations differed
on the basis of the source of funds (assessed and voluntary contributions) and the mechanism for deciding how
funds were spent.
Findings
We noted that WHO budget allocations were heavily skewed toward infectious diseases. In 2006—07, WHO allocated
87% of its total budget to infectious diseases, 12% to non-communicable diseases, and less than 1% to injuries and
violence. We recorded a similar distribution of funding in Africa, where nearly three-quarters of mortality is from
infectious disease, and in Western Pacific, where three-quarters of mortality is from non-communicable disease. In
both regions, injuries received only 1% of total resources. The skew towards infectious diseases was substantially
greater for the WHO extra-budget, which is allocated by donors and has risen greatly in recent years, than for the
WHO regular budget, which is decided on by member states through democratic mechanisms and has been held at
zero nominal growth.
Interpretation
Decision makers at Bamako should consider the implications of the present misalignment of global health priorities and
disease burden for health research worldwide. Funds allocated by external donors substantially differ from those
allocated by WHO member states. The meeting at Bamako provides an opportunity to consider how this disparity
might be addressed.”
Nature
Volume 455 Number 7217 pp1149-1278 (30 October 2008)
http://www.nature.com/nature/journal/v455/n7214/
[No relevant content]
New England Journal of Medicine
Volume 359 — October 30, 2008 — Number 18
http://content.nejm.org/current.shtml
[No relevant content]
PLoS Medicine
[Accessed 4 November 2008)
http://medicine.plosjournals.org/perlserv/?request=browse&issn=1549-
1676&method=pubdate&search_fulltext=1&order=online_date&row_start=1&limit=10&ct=1
The Effects of Influenza Vaccination of Health Care Workers in Nursing Homes: Insights from a
Mathematical Model
Carline van den Dool, Marc J. M. Bonten, Eelko Hak, Janneke C. M. Heijne, Jacco Wallinga
“Annual influenza vaccination of institutional health care workers (HCWs) is advised in most Western countries, but
adherence to this recommendation is generally low. Although protective effects of this intervention for nursing home
patients have been demonstrated in some clinical trials, the exact relationship between increased vaccine uptake
among HCWs and protection of patients remains unknown owing to variations between study designs, settings,
intensity of influenza seasons, and failure to control all effect modifiers. Therefore, we use a mathematical model to
estimate the effects of HCW vaccination in different scenarios and to identify a herd immunity threshold in a nursing
home department.
Methods and Findings
We use a stochastic individual-based model with discrete time intervals to simulate influenza virus transmission in a 30-
bed long-term care nursing home department. We simulate different levels of HCW vaccine uptake and study the
effect on influenza virus attack rates among patients for different institutional and seasonal scenarios. Our model
reveals a robust linear relationship between the number of HCWs vaccinated and the expected number of influenza
virus infections among patients. In a realistic scenario, approximately 60% of influenza virus infections among
patients can be prevented when the HCW vaccination rate increases from 0 to 1. A threshold for herd immunity is
not detected. Due to stochastic variations, the differences in patient attack rates between departments are high and
large outbreaks can occur for every level of HCW vaccine uptake.
Conclusions
The absence of herd immunity in nursing homes implies that vaccination of every additional HCW protects an
additional fraction of patients. Because of large stochastic variations, results of small-sized clinical trials on the effects
of HCW vaccination should be interpreted with great care. Moreover, the large variations in attack rates should be
taken into account when designing future studies.”
Science
31 October 2008 Vol 322, Issue 5902, Pages 633-804
http://www.sciencemag.org/current.dtl
[No relevant content]
Vaccine
Volume 26, Issue 46, Pages 5775-5896 (29 October 2008)
http://www.sciencedirect.com/science/journal/0264410X\
[Reviewed last week]
________________________________________________________________________________________
27 October 2008
The WHO released “The global burden of disease: 2004 update,” describing it as “a comprehensive
assessment of the health of the world's population. It provides detailed global and regional estimates of premature
mortality, disability and loss of health for 135 causes by age and sex, drawing on extensive WHO databases and on
information provided by Member States.” The update is available at: http://www.who.
int/healthinfo/global_burden_disease/2004_report_update/en/index.html
THE REPORT IN SECTIONS
Part 1: Introduction [pdf 577kb]
Part 2: Causes of death [pdf 635kb]
Part 3: Disease incidence, prevalence and disability [pdf 247kb]
Part 4: Burden of disease: DALYs [pdf 395kb]
Annex A: Deaths and DALYs 2004 Annex tables [pdf 581kb]
Annex B: Data sources and methods [pdf 300kb]
Annex C: Analysis categories and mortality data sources [pdf 224kb]
References [pdf 144kb]
STATISTICS FROM THE REPORT
Regional estimates of YLL, YLD, and DALYs, deaths, incidence and prevalence for 2004
Regional projections of deaths and DALYs for 2008, 2015, and 2030
The Bill & Melinda Gates Foundation announced 104 grants “to explore bold and largely unproven ways
to improve global health.” The grants of US$100,000 each will be made to scientists from 22 countries and five
continents, and mark the first round of funding from Grand Challenges Explorations, an initiative to help lower the
barriers for testing innovative ideas in global health. Gates said the initial set of grants will “inject fresh perspective into
research for preventing or curing infectious diseases such as HIV/AIDS and TB, and limiting the emergence of drug
resistance. Successful applicants showed how their project falls outside current scientific paradigms and could lead to
significant advances if successful—in just two pages.” Dr. Tachi Yamada, president of global health at the Gates
Foundation, who announced the grants at the fourth annual meeting of the Grand Challenges in Global Health
initiative in Bangkok, said, “We were hoping this program would level the playing field so anyone with a
transformational idea could more quickly assess its potential for the benefit of global health. The quality of the
applications exceeded all of our expectations. It was so hard for reviewers to champion just one great idea that we
selected almost twice as many projects for funding as we had initially planned.” The 104 grants were selected from
nearly 4,000 proposals, “with the geographic distribution of applicants largely matching the geographic distribution of
awards.” A complete list of the funded projects is available at the Grand Challenges Explorations web site.
(Gates Foundation Media Release, 22 October 2008)
http://www.gatesfoundation.org/press-releases/Pages/grand-challenges-explorations-recipients-081022.aspx
The WHO issued a request for comments on a new draft document: Guidance on Pandemic Influenza
Preparedness and Response. The request “…invites Member States, technical institutions, sub-regional, regional
and international organizations, whether governmental or nongovernmental, and all experts concerned with
pandemic influenza preparedness to participate in a web-based review of draft WHO guidance on Pandemic Influenza
Preparedness and Response (2008). Comments will be accepted online from 15 October through 3 November.”
WHO Guidance on Pandemic Influenza Preparedness and Response- Explanation of the revision process
Contact
WHO Global Influenza Programme
avenue Appia 20
CH-1211 Geneva 27
Switzerland
E-mail: WHOInfluenza@who.int
http://www.who.int/csr/disease/influenza/EN_guidancereview/en/index.html
The Weekly Epidemiological Record (WER) 24 October 2008, vol. 83, 43 (pp 385–392) includes:
- Evaluating clinical trial data and guiding future research for rotavirus vaccines
- Worldwide progress in introducing pneumococcal conjugate vaccine, 2000–2008
http://www.who.int/wer/2008/wer8343.pdf
Journal Watch
[Editor’s Note]
Vaccines: The Week in Review continues a new feature, scanning key journals to identify and cite articles, comment
and editorials, books reviews and other content supporting our focus on vaccine ethics and policy. Journal Watch is
not intended to be exhaustive, but indicative of themes and issues the center is actively tracking. We selectively
provide full text of some editorial and comment articles that are specifically relevant to our work. Successful access to
some of the links provided may require subscription or other access arrangement unique to the publisher. Our initial
scan list includes the journals below. If you would like to suggest other titles, please write to David Curry at david.r.
curry@centerforvaccineethicsandpolicy.org
JAMA
Vol. 300 No. 16, pp. 1845-1962, October 22/29, 2008
http://jama.ama-assn.org/current.dtl
[No relevant content]
Journal of Infectious Disease
1 November 2008 Volume 198, Number 9
http://www.journals.uchicago.edu/toc/jid/current
[Reviewed last week]
The Lancet
Volume 372, Number 9648, 25 October 2008
The Lancet 2008; 372:1438
DOI:10.1016/S0140-6736(08)61603-7
Editorial [full text]
Raising the profile of pneumococcal disease
Pneumococcal disease has never received the high-level, international attention that it deserves. Developments such
as the formation of the Global Fund to Fight AIDS, Malaria, and Tuberculosis and the advent of Integrated
Management of Childhood Illnesses, which moved attention away from programmes for acute respiratory infections,
have inadvertently contributed to this situation. But now efforts are being made to shine a spotlight on this neglected
disease. The latest is a report by the All-Party Parliamentarian Group on Pneumococcal Disease Prevention in the
Developing World—a group formed in January, 2007, to raise awareness about the disease.
The report, compiled from expert evidence, makes a welcome series of recommendations, including a request to the
UK Government to give equal standing and prominence to pneumococcal disease in its statements and policies as to
HIV/AIDS, tuberculosis, and malaria. There is also a call for developing countries to increase their commitments to
treating and preventing pneumonia and meningitis—the two most common manifestations of serious pneumococcal
disease.
Launched at the House of Lords in London, the report's recommendations are likely to be taken seriously by the UK
Government. Douglas Alexander, the UK Secretary of State for International Development, has written the report's
foreword, and the UK already contributes financially to the Advanced Market Commitment—an innovative financing
mechanism to improve access to effective vaccines against pneumococcal disease in developing countries. The
report might also influence some Members of the European Parliament. But whether its impact will be felt any further
than Brussels is uncertain.
The Global Action Plan for the Prevention and Control of Pneumonia, launched by WHO and UNICEF in 2007, also
seems to have fizzled out. Perhaps what is needed to kick-start a campaign against the disease is for all interested
parties—parliamentarians, UN agencies, and those outside the UN system—to form a powerful advocacy group,
similar to the Roll Back Malaria partnership. Such a development would form a united front and would be more
effective than individual attempts to push this major killer higher up the global-health agenda.
The Lancet
Nature
Volume 455 Number 7216 pp1007-1148 (23 October 2008)
http://www.nature.com/nature/journal/v455/n7214/
[No relevant content]
New England Journal of Medicine
Volume 359 — October 23, 2008 — Number 17
http://content.nejm.org/current.shtml
[No relevant content]
PLoS Medicine
[Accessed 27 October 2008]
http://medicine.plosjournals.org/perlserv/?request=browse&issn=1549-
1676&method=pubdate&search_fulltext=1&order=online_date&row_start=1&limit=10&ct=1
[No relevant content]
Science
24 October 2008 Vol 322, Issue 5901, Pages 501-608
http://www.sciencemag.org/current.dtl
ETHICS: Clinical Trials Guidelines at Odds With U.S. Policy
Dennis Normile
Science 24 October 2008: 516
Summary: The World Medical Association last week reaffirmed its opposition to the use of placebos in clinical trials and
urged trial sponsors to provide care for participants after studies are done.
Vaccine
Volume 26, Issue 46, Pages 5775-5896 (29 October 2008)
http://www.sciencedirect.com/science/journal/0264410X\
[Reviewed last week]
____________________________________________________________________________________________________
20 October 2008
BIO Ventures for Global Health (BVGH) announced that the Bill & Melinda Gates Foundation expanded
its support of the organization with a US$7 million grant, “so it can further engage biotechnology industry
innovation to create new medicines for infectious diseases of the developing world.” The new support “will help BVGH
build the market case for biotechnology industry investment through market-based incentives and to create new
opportunities for R&D collaborations.” Christopher D. Earl, PhD, President and CEO of BVGH, commented, "We are
thrilled by the Bill & Melinda Gates Foundation's support for expanding the BVGH mission. Biotechnology industry
resources are integral to the discovery of new solutions for the millions of patients suffering from diseases such as
malaria, tuberculosis and African sleeping sickness." Tachi Yamada, MD, President of the Gates Foundation's Global
Health Program, said "The biotech industry has an exceptional opportunity to apply its innovative skills to create new
global health solutions. BVGH designs economic incentives and partnerships that help make this industry commitment
possible."
(BVGH Media Release, 14 October 2008)
The GAVI Alliance said it welcomes a new report released in the United Kingdom by the All Party Group
on Pneumococcal Disease Prevention (APPG) “which highlights the devastating global health burden
caused by Streptococcus pneumoniae, a group of bacteria that kills up to one million children every
year.” The APPG report – Improving Global Health by Preventing Pneumococcal Disease – “provides strong
evidence from governments, multilateral agencies, NGOs, pharmaceutical companies and funding organizations about
the human and economic burden of pneumococcal disease. It points to the interventions available to prevent and
treat pneumonia and meningitis, and calls for them to be made a top health priority along with HIV, malaria and TB.”
According to the World Health Organisation, at least one child dies of pneumococcal disease every minute, making it
the leading cause of childhood pneumonia deaths in the developing world and the number one vaccine-preventable
cause of death in children worldwide.
The new report endorses the Advance Market Commitment (AMC) pilot mechanism to accelerate
pneumococcal vaccines launched by the Governments of Italy, the United Kingdom, Canada, Russia, and Norway
and the Bill & Melinda Gates Foundation. Julian Lob Levyt, Executive Director, GAVI Alliance, commented, “The GAVI
Alliance applauds the work of the APPG in highlighting pneumococcal as an unrecognized global health tragedy. The
report is a wakeup call to the international community that increased attention and commitment are vital. Innovative
initiatives such as the AMC and the strengthening of health systems are vital to bolster efforts to prevent this disease
and save more children’s lives, faster.”
(GAVI Media Release, 16 October 2008)
A new internal World Bank study assessing the potential impacts of an avian flu pandemic is reported on
by Bloomberg News. The study suggests that severe pandemic could kill 71 million people worldwide and push the
global economy into a “major global recession” cost the world economy up to US$3 trillion.
http://www.bloomberg.com/apps/news?pid=newsarchive&sid=ashmCPWATNwU# and
Separately, Lloyd’s Bank Emerging Risks Team released a new report: "Pandemic: Potential Insurance
Impact"
http://www.lloyds.com/NR/rdonlyres/08B1357D-AD59-4C48-8064-
599AF6F4F340/0/ER_Pandemic_InsuranceImpacts.pdf
The International Vaccine Institute (IVI) announced that Madame Kim Yoon-ok, First Lady of the
Republic of Korea, was inaugurated as the Honorary President of the Korea Support Committee (KSC)
for IVI on October 6. IVI describes itself as “a Seoul-based international organization exclusively devoted to the
accelerated development and introduction of new vaccines for children, and the only international organization
headquartered in Korea.” The KSC for the IVI is “a non-profit organization committed to improving the welfare of
humanity and to enhancing science and technology by supporting IVI´s humanitarian research. The Committee has
70 members, including prominent figures such as former prime ministers.” Madame Kim was appointed as the KSC’s
third Honorary President during a ceremony marking the IVI’s 11th Anniversary held at the IVI’s headquarters. In her
acceptance remarks, Madame Kim said, “Despite advances in medicine, 7 million children are dying from infectious
diseases. I will make my utmost efforts to ensure that children will no longer die needlessly from preventable diseases
because vaccines are unavailable to them.” She also urged more countries of the world to join in these global
humanitarian efforts by becoming signatories to the IVI’s charter.
(IVI Media Release, 6 October 2008)
The Weekly Epidemiological Record (WER) 7 October 2008, vol. 83, 42 (pp 373–384) includes: “23-valent
pneumococcal polysaccharide vaccine: WHO position paper.”
http://www.who.int/wer/2008/wer8342.pdf
Journal Watch
[Editor’s Note]
Vaccines: The Week in Review continues a new feature, scanning key journals to identify and cite articles, comment
and editorials, books reviews and other content supporting our focus on vaccine ethics and policy. Journal Watch is
not intended to be exhaustive, but indicative of themes and issues the center is actively tracking. We selectively
provide full text of some editorial and comment articles that are specifically relevant to our work. Successful access to
some of the links provided may require subscription or other access arrangement unique to the publisher. Our initial
scan list includes the journals below. If you would like to suggest other titles, please write to David Curry at david.r.
curry@centerforvaccineethicsandpolicy.org
JAMA
Vol. 300 No. 15, pp. 1729-1836, October 15, 2008
http://jama.ama-assn.org/current.dtl
[No relevant content]
Journal of Infectious Disease
1 November 2008 Volume 198, Number 9
http://www.journals.uchicago.edu/toc/jid/current
EDITORIAL COMMENTARY
Human Genetics and Malaria: Relevance for the Design of Clinical Trials
Sunil Parikh and Philip J. Rosenthal
Department of Medicine, San Francisco General Hospital, University of California, San Francisco
Received 1 July 2008; accepted 7 July 2008; electronically published 27 August 2008.
MAJOR ARTICLE
Sickle Cell Trait Is Associated with a Delayed Onset of Malaria: Implications for Time-to-Event Analysis in
Clinical Studies of Malaria
Peter D. Crompton,1; Boubacar Traore,5; Kassoum Kayentao,5; Safiatou Doumbo,5; Aissata Ongoiba,5; Seidina A.
S. Diakite,5; Michael A. Krause,3; Didier Doumtabe,5
Younoussou Kone,5; Greta Weiss,1; Chiung-Yu Huang,2; Seydou Doumbia,5; Aldiouma Guindo,5; Rick M. Fairhurst,
3; Louis H. Miller,4; Susan K. Pierce,1 and
Ogobara K. Doumbo5
1Laboratory of Immunogenetics, 2Biostatistics Research Branch, 3Laboratory of Malaria and Vector Research, and
4Malaria Vaccine Development Branch, National Institute of Allergy and Infectious Diseases, National Institutes of
Health, Bethesda, Maryland; 5Malaria Research and Training Centre, Department of Epidemiology of Parasitic
Diseases, Faculty of Medicine, Pharmacy, and Odonto-Stomatology, University of Bamako, Mali
“Background. The World Health Organization (WHO) recently recommended that the time to first malaria episode
serve as the primary end point in phase III malaria vaccine trials—the first of which will be held in Africa. Although
common red blood cell (RBC) polymorphisms such as sickle hemoglobin (HbS) are known to protect against malaria
in Africa, their impact on this end point has not been investigated.
Methods. A longitudinal study of 225 individuals aged 2–25 years was conducted in Mali. The association between
common RBC polymorphisms and the time to first malaria episode was evaluated.
Results. Among children aged 2–10 years, sickle cell trait (HbAS) was associated with a 34-day delay in the median
time to first malaria episode ( ). Cox regression analysis showed that greater age (hazard ratio [HR], 0.87 [95% CI,
0.80–0.94]; ), HbAS (HR, 0.48 [95% CI, 0.26–0.91]; ), and asymptomatic parasitemia at enrollment (HR, 0.35
[95% CI, 0.14–0.85]; ) were associated with decreased malaria risk.
Conclusion. Given the delay in the time to first malaria episode associated with HbAS, it would be advisable for clinical
trials and observational studies that use this end point to include Hb typing in the design of studies conducted in
areas where HbAS is prevalent.”
The Lancet
Volume 372, Number 9647, 18 October 2008
http://www.thelancet.com/journals/lancet
World Report
HIV discoverers awarded Nobel Prize for medicine
Stephen Pincock, page 1373
Virologist wins Nobel for cervical cancer discovery
Stephen Pincock, page 1374
Nature
Volume 455 Number 7215 pp835-1006 (16 October 2008)
http://www.nature.com/nature/journal/v455/n7214/
[No relevant content]
New England Journal of Medicine
Volume 359 — October 16, 2008 — Number 16
http://content.nejm.org/current.shtml
Monovalent Oral Poliovirus Vaccines — A Good Tool but Not a Total Solution
Ellie Ehrenfeld, Ph.D., and Konstantin Chumakov, Ph.D.
Partial text as available via online access
“The polio eradication campaign initiated in 1988 by the World Health Organization (WHO) led to an impressive
decline in cases of paralytic poliomyelitis around the world. The eradication strategy involved highly organized mass
immunization campaigns, relying solely on the trivalent oral polio vaccine developed by Albert Sabin and licensed in
the United States in 1963. Monovalent versions of oral polio vaccine had been licensed earlier but were abandoned in
favor of the trivalent combination oral polio vaccine to simplify immunization schedules. Efficacy was not considered
to be a significant issue, and differences between monovalent and trivalent vaccines were never formally…”
Monovalent Type 1 Oral Poliovirus Vaccine in Newborns
Nasr El-Sayed, M.D., M.P.H., Yehia El-Gamal, M.D., Ph.D., Ahmed-Amr Abbassy, M.D., Ph.D., Iman Seoud, M.D., Ph.
D., Maha Salama, M.D., Amr Kandeel, M.D., M.P.H., Elham Hossny, M.D., Ph.D., Ahmed Shawky, M.D., Heba Abou
Hussein, M.D., Ph.D., Mark A. Pallansch, Ph.D., Harrie G.A.M. van der Avoort, Ph.D., Anthony H. Burton, B.S.,
Meghana Sreevatsava, M.P.H., Pradeep Malankar, M.D., Mohamed H. Wahdan, M.D., Ph.D., and Roland W. Sutter, M.
D., M.P.H.T.M.
ABSTRACT
“Background: In 1988, the World Health Assembly resolved to eradicate poliomyelitis. Although substantial progress
toward this goal has been made, eradication remains elusive. In 2004, the World Health Organization called for the
development of a potentially more immunogenic monovalent type 1 oral poliovirus vaccine.
Methods: We conducted a trial in Egypt to compare the immunogenicity of a newly licensed monovalent type 1 oral
poliovirus vaccine with that of a trivalent oral poliovirus vaccine. Subjects were randomly assigned to receive one
dose of monovalent type 1 oral poliovirus vaccine or trivalent oral poliovirus vaccine at birth. Thirty days after birth,
a single challenge dose of monovalent type 1 oral poliovirus vaccine was administered in all subjects. Shedding of
serotype 1 poliovirus was assessed through day 60.
Results: A total of 530 subjects were enrolled, and 421 fulfilled the study requirements. Thirty days after the study
vaccines were administered, the rate of seroconversion to type 1 poliovirus was 55.4% in the monovalent-vaccine
group, as compared with 32.1% in the trivalent-vaccine group (P<0.001). Among those with a high reciprocal titer
of maternally derived antibodies against type 1 poliovirus (>64), 46.0% of the subjects in the monovalent-vaccine
group underwent seroconversion, as compared with 21.3% in the trivalent-vaccine group (P<0.001). Seven days
after administration of the challenge dose of monovalent type 1 vaccine, a significantly lower proportion of subjects
in the monovalent-vaccine group than in the trivalent-vaccine group excreted type 1 poliovirus (25.9% vs. 41.5%,
P=0.001). None of the serious adverse events reported were attributed to the trial interventions.
Conclusions: When given at birth, monovalent type 1 oral poliovirus vaccine is superior to trivalent oral poliovirus
vaccine in inducing humoral antibodies against type 1 poliovirus, overcoming high preexisting levels of maternally
derived antibodies, and increasing the resistance to excretion of type 1 poliovirus after administration of a challenge
dose. (Current Controlled Trials number, ISRCTN76316509)”
Effectiveness of Immunization against Paralytic Poliomyelitis in Nigeria
Helen E. Jenkins, M.Sc., R. Bruce Aylward, M.D., Alex Gasasira, M.B., Ch.B., Christl A. Donnelly, Sc.D., Emmanuel A.
Abanida, M.P.H., Titi Koleosho-Adelekan, Ph.D., and Nicholas C. Grassly, D.Phil.
ABSTRACT
“Background: The number of cases of paralytic poliomyelitis has declined in Nigeria since the introduction of newly
licensed monovalent oral poliovirus vaccines and new techniques of vaccine delivery. Understanding the relative
contribution of these vaccines and the improved coverage to the decline in incident cases is essential for future
planning.
Methods: We estimated the field efficacies of monovalent type 1 oral poliovirus vaccine and trivalent oral poliovirus
vaccine, using the reported number of doses received by people with poliomyelitis and by matched controls as
identified in Nigeria's national surveillance database, in which 27,379 cases of acute flaccid paralysis were recorded
between 2001 and 2007. Our estimates of vaccine coverage and vaccine-induced immunity were based on the
number of doses received by children listed in the database who had paralysis that was not caused by poliovirus.
Results: The estimated efficacies per dose of monovalent type 1 oral poliovirus vaccine and trivalent oral poliovirus
vaccine against type 1 paralytic poliomyelitis were 67% (95% confidence interval [CI], 39 to 82) and 16% (95% CI,
10 to 21), respectively, and the estimated efficacy per dose of trivalent oral poliovirus vaccine against type 3
paralytic poliomyelitis was 18% (95% CI, 9 to 26). In the northwestern region of Nigeria, which reported the majority
of cases during the study period, coverage with at least one dose of vaccine increased from 59 to 78%. Between
2005 and 2007, vaccine-induced immunity levels among children under the age of 5 years more than doubled, to
56%.
Conclusions: The higher efficacy of monovalent type 1 oral poliovirus vaccine (four times as effective as trivalent oral
poliovirus vaccine) and the moderate gains in coverage dramatically increased vaccine-induced immunity against
serotype 1 in northern Nigeria. Further increases in coverage in Nigerian states with infected populations are required
to achieve the levels of vaccine-induced immunity associated with the sustained elimination achieved in other parts of
the country.”
PLoS Medicine
[Accessed 20 October 2008]
http://medicine.plosjournals.org/perlserv/?request=browse&issn=1549-
1676&method=pubdate&search_fulltext=1&order=online_date&row_start=1&limit=10&ct=1
[No relevant content]
Science
17 October 2008 Vol 322, Issue 5900, Pages 329-488
http://www.sciencemag.org/current.dtl
[No relevant content]
Vaccine
Volume 26, Issue 46, Pages 5775-5896 (29 October 2008)
http://www.sciencedirect.com/science/journal/0264410X\
Air travel as a risk factor for introduction of measles in a highly vaccinated population
Pages 5775-5777
Robert S. van Binnendijk, Susan Hahné, Aura Timen, Gijs van Kempen, Robert H.G. Kohl, Hein J. Boot, Katja C.
Wolthers, José C.F.M. Wetsteijn, Anne de Vries, Krista Westert, Kevin E. Brown, Rik L. de Swart
Abstract
“Epidemiological and molecular investigation of two small measles clusters in The Netherlands in July/August 2007
revealed an association with travel by air of the index cases and nosocomial spread in the first cluster. Although these
importations did not result in an outbreak among unvaccinated subjects, the observations illustrate the challenges
for measles control in a country with high measles vaccination coverage (>95%) but with pockets of low coverage.”
Internationally adopted children: What vaccines should they receive?
Pages 5784-5790
M.J. Cilleruelo, F. de Ory, J. Ruiz-Contreras, R. González-González, M.J. Mellado, M. García-Hortelano, J. Villota, M.
García-Ascaso, R. Piñeiro, P. Martín-Fontelos, R. Herruzo
Abstract
“It is of paramount importance to know the vaccination status in internationally adopted children, so that they can
be correctly immunized. This study ascertains the seroprotection rate for vaccine-preventable diseases and the
validity of the immunization cards in 637 adopted children. The absence of the immunization card (13% of children)
correlated with a poor global vaccine protection. Children with immunization records (87%) had a better global
seroprotection but the information obtained from the card did not accurately predict seroprotection for each
particular antigen. The best variable to predict the status of seroprotection was the country of origin. The highest
rate of protection was found in children from Eastern Europe and, in descending order, India, Latin America, China
and Africa. General recommendations for immunization of internationally adopted children are difficult to establish.
Actions for vaccination have to be mainly implemented on the basis of the existence of the immunization card and of
the country of origin.”
_____________________________________________________________________________________________________
13 October 2008
The MMWR for October 10, 2008 / 57(40);1100-1103 includes: Vaccination Coverage Among Adolescents
Aged 13--17 Years --- United States, 2007. The media release notes that “The nation’s immunization coverage
rates for preteens and teens are increasing for routinely recommended vaccines, but most still do not have all of the
recommended immunizations. Dr. Lance Rodewald, director of the Division of Immunization Services at the CDC′s
National Center for Immunization and Respiratory Diseases, commented, “The overall trends are good news. We are
seeing more preteens and teenagers being protected against serious, sometimes deadly diseases. But we remain
short of our goals—for almost all of these vaccines we want at least 90 percent of adolescents to be fully immunized.
As such, we have much work to do to get many more adolescents protected.”
The survey provides estimates for three vaccines recommended at 11 or 12 years of age: the tetanus-diphtheria-
acellular pertussis (Tdap) vaccine, the meningococcal conjugate vaccine (MCV4), and the human papillomavirus
(HPV4) vaccine for girls and young women. It also includes estimates of the percentage of 13- through 17-year-old
teens who should have received the recommended immunizations for measles, mumps and rubella vaccine (MMR),
hepatitis B (HepB) vaccine, and varicella vaccine (VAR) earlier in life.
Specific findings included:
- Vaccination coverage levels for three or more doses of hepatitis B (HepB) and two or more doses of measles,
mumps and rubella vaccine (MMR) were over 80 percent;
- Coverage with one dose of varicella vaccine (VAR) was high at 75.7 percent but coverage with two doses was low
at 18.8 percent among preteens and teens without a previous history of disease;
- 32.4 percent of preteens and teens surveyed had received MCV4 vaccination, up from 11.7 percent in 2006 (a
20.7 percentage point increase);
- 30.4 percent had received Tdap vaccination, up from 10.8 percent in 2006 (a 19.6 percentage point increase);
- 25.1 percent of adolescent females had received at least one dose of HPV vaccine
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5740a2.htm
The Association for Professionals in Infection Control and Epidemiology (APIC) announced its support
for requiring flu immunization for healthcare workers who have direct patient contact as well as ancillary
staff. APIC further recommended that healthcare facilities “obtain informed statements acknowledging the risk to
patients from employees who decline the vaccine for reasons other than medical.” APIC states that healthcare
facilities should implement a comprehensive strategy incorporating all of the guidelines for influenza vaccination of
healthcare personnel from the Centers for Disease Control and Prevention’s (CDC) Healthcare Infection Control
Practices Advisory Committee (HICPAC) and the Advisory Committee on Immunization Practices (ACIP). Linda R.
Greene, RN, MPS, CIC, lead author of APIC’s position paper, noted, “We must do a better job of immunizing
healthcare workers every year to ensure patient safety and protect those individuals at high risk of developing
complications of influenza. Despite longstanding recommendations by government agencies and national healthcare
organizations, only 42 percent of healthcare workers receive yearly flu vaccines. Voluntary efforts are clearly not
effective – it’s time for hospitals and other healthcare facilities to require influenza immunization.”
http://www.apic.org/AM/Template.cfm?Section=Featured_News_and_Events&TEMPLATE=/CM/ContentDisplay.
cfm&CONTENTID=11963
Merck announced that ROTATEQ (rotavirus vaccine, live, oral, pentavalent) was awarded pre-
qualification status by the WHO, which “allows for expanded access to ROTATEQ and provides a
greater opportunity to help protect millions of babies from rotavirus gastroenteritis.” This pre-
qualification means that the vaccine is now eligible for procurement by the Pan American Health Organization (PAHO),
UNICEF and other United Nations agencies for use in national vaccination programs. Merck noted that rotavirus
infects nearly all children worldwide by age 5 and causes approximately 1.9 million hospitalizations each year in
developing countries, and that ROTATEQ is the only ready-to-use oral liquid rotavirus vaccine to receive WHO pre-
qualification. Mark Feinberg, M.D., Ph.D., vice president, Medical Affairs and Policy, Merck Vaccines and Infectious
Diseases, said “WHO pre-qualification of ROTATEQ is an important milestone in expanding the global availability of
ROTATEQ, and importantly, for facilitating efforts to accelerate the introduction of the vaccine in the world's poorest
countries. Merck's pledge to provide ROTATEQ to GAVI-eligible countries at prices at which we do not profit is
another step to make this vaccine accessible to all who need it in every part of the world.”
(BUSINESS WIRE, 9 October 2008)
Journal Watch
[Editor’s Note]
Vaccines: The Week in Review continues a new feature, scanning key journals to identify and cite articles, comment
and editorials, books reviews and other content supporting our focus on vaccine ethics and policy. Journal Watch is
not intended to be exhaustive, but indicative of themes and issues the center is actively tracking. We selectively
provide full text of some editorial and comment articles that are specifically relevant to our work. Successful access to
some of the links provided may require subscription or other access arrangement unique to the publisher. Our initial
scan list includes the journals below. If you would like to suggest other titles, please write to David Curry at david.r.
curry@centerforvaccineethicsandpolicy.org
JAMA
Vol. 300 No. 14, pp. 1621-1718, October 8, 2008
http://jama.ama-assn.org/current.dtl
[No relevant content]
Journal of Infectious Disease
15 October 2008 Volume 198, Number 8
http://www.journals.uchicago.edu/toc/jid/current
[Reviewed last week (no relevant content)]
The Lancet
Volume 372, Number 9646, 11 October 2008
http://www.thelancet.com/journals/lancet
The Lancet 2008; 372:1287-1290
DOI:10.1016/S0140-6736(08)61534-2
Special Report
Nigeria struggles to contain poliomyelitis
Margaret Harris Cheng
“Nigeria has had several setbacks in its bid to control poliomyelitis, including false rumours about vaccine safety. Now
public anger over the failure of the ailing health system to deliver for its people threatens to derail the country's
eradication campaign. Margaret Harris Cheng reports.”
Nature
Volume 455 Number 7214 pp707-834 (9 October 2008)
http://www.nature.com/nature/journal/v455/n7214/
Editorial
Malaria's watershed
Nature 455, 707 (9 October 2008) | doi:10.1038/455707a; Published online 8 October 2008
Abstract [Full text]
Malaria's moment has come, but success in control, let alone eradication, demands a renewed commitment to basic
research.
A Global Malaria Action Plan, announced at the UN Millennium Development Goals Malaria Summit in New York on 25
September, has the ambitious goals of both reducing the malaria burden and eradicating the disease entirely.
Eradication any time soon might seem hopelessly optimistic, given the failure so far to make a serious dent in the
number of malaria deaths. But much of the 274-page plan makes good sense. It calls for scaling up the use of
existing tools, such as bednets, drugs and spraying, to near universal coverage, and then sustaining this effort for
decades. True, this won't come cheaply. Funds for control have already grown from US$250 million annually in 2004
to an estimated US$1.1 billion this year; the plan calls for increasing that to $5 billion annually until at least 2020.
Likewise, total spending on malaria-related research has risen from $265 million in 2003 to $422 million in 2007; the
plan would see that figure double to between $750 million and $900 million annually until 2018. Whether donors will
rise to the challenge is a big question, given current economic woes. Still, it is heartening that at the summit, donors
from governments, industry and philanthropic organizations pledged US$3 billion.
Striking the right balance between basic and applied research is also critical. For example, the sequencing in 2002 of
the genome of Plasmodium falciparum, the main parasite that causes malaria, has stimulated the hunt for new drug
and vaccine candidates. This week's issue of Nature sees the addition of two more parasite sequences: P. vivax,
which is less deadly than P. falciparum, and P. knowlesi, which mainly infects monkeys (pages 751, 757 and 799).
These new sequences show how much more there is to learn: more than half of P. falciparum's encoding genes still
have no known function.
Basic research is also needed to stay ahead of drug resistance in the parasite and insecticide resistance in mosquitoes,
and to get a better understanding of natural infection in humans. One surprise from P. falciparum's genome is
evidence that it evades the human immune system mainly by genomic and gene-expression diversity. Plasmodium
seems to have different metabolic and physiological states, and can reprogram its gene expression. These findings
could alter the way researchers think about both drug and vaccine development.
The malaria drug and vaccine pipelines are healthier now than they have been for decades, but they are in urgent
need of new candidates and approaches. So it was welcome news when the Bill & Melinda Gates Foundation, already
the largest donor in malaria research, announced at the UN summit that it would spend US$168 million to develop
next-generation malaria vaccines. Moreover, this initiative will include early-stage laboratory research — most of the
Gates Foundation's funding has so far focused on translational and clinical research.
Many scientists would like to see the foundation fund even more basic research, but this cannot be the foundation's
responsibility alone. Its support of translational work has rejuvenated the field over the past decade, and has helped
get tools into the field. In the process, the malaria research community has become excessively and undesirably
dependent on this one entity. Other research organizations would do well to step up to the plate and match the
Gates Foundation's spending with their own basic-research funds. That would also go some way to addressing what
scientists say is an unfortunate consequence of the emphasis on translational research: that scientists entering
malaria research are less likely to choose basic science.
Any massive increase in research funding means that the malaria community must think about how to coordinate
research across funding agencies. It is encouraging that the main research funders and scientists are to sit down as a
group — called MalERA — over the next year to thrash out a research agenda for eradication. One lesson of the
malaria and human genome projects is that consortia are a key route to delivery, focusing resources wisely, and
avoiding duplication and excessive bureaucracy. It is also essential that international research recognizes the maturity
of the malaria research community in the poorer countries where the disease is endemic — they should be on board
as equals and not, as is too often the case, afterthoughts.”
Article
Comparative genomics of the neglected human malaria parasite Plasmodium vivax
Nature 455, 757-763 (9 October 2008) | doi:10.1038/nature07327; Received 18 January 2008; Accepted 8 August
2008
Jane M. Carlton et al
[First paragraph full text] “The human malaria parasite Plasmodium vivax is responsible for 25–40% of the 515
million annual cases of malaria worldwide. Although seldom fatal, the parasite elicits severe and incapacitating clinical
symptoms and often causes relapses months after a primary infection has cleared. Despite its importance as a major
human pathogen, P. vivax is little studied because it cannot be propagated continuously in the laboratory except in
non-human primates. We sequenced the genome of P. vivax to shed light on its distinctive biological features, and as
a means to drive development of new drugs and vaccines. Here we describe the synteny and isochore structure of
P. vivax chromosomes, and show that the parasite resembles other malaria parasites in gene content and metabolic
potential, but possesses novel gene families and potential alternative invasion pathways not recognized previously.
Completion of the P. vivax genome provides the scientific community with a valuable resource that can be used to
advance investigation into this neglected species….”
New England Journal of Medicine
Volume 359 — October 9, 2008 — Number 15
http://content.nejm.org/current.shtml
[No relevant content]
PLoS Medicine
[Accessed 13 October 2008]
[No relevant content]
Science
10 October 2008 Vol 322, Issue 5899, Pages 161-290
http://www.sciencemag.org/current.dtl
Special Issue on Clinical Trials
Science 10 October 2008:
Vol. 322. no. 5899, p. 209
DOI: 10.1126/science.322.5899.209
[Full text]
Introduction to special issue:
Lemons, Oranges, and Complexity
Eliot Marshall
“Faced with an epidemic of scurvy, British surgeon James Lind decided to test some cures in 1747. In a legendary
trial, he put 12 sickly sailors on a fixed diet and divided the group into twos. Each pair received a different
supplement--cider, seawater, dilute acid, and so on. The result: After 6 days, the two who ate lemons and oranges
improved so much that they were sent back on duty. The navy was slow to recognize the significance of Lind's work
but eventually decreed that citrus (a source of vitamin C that prevents scurvy) must be in all sailors' rations.
By modern standards, Lind's test was weak. It had no control group. No placebo. No blinding of data. But it worked.
By controlling the environment and varying treatments, it made possible an accurate reading of the human body's
response. This idea, with many refinements, drives the modern clinical trial. But now the clinical trial itself is facing an
epidemic--of rising costs and blurred objectives.
On page 210, David Malakoff reports on the view, as one U.S. researcher puts it, that the "system isn't working."
Malakoff describes factors that are driving inflation. Among them are complex rules for reporting, the proliferation of
required tests, the difficulty of recruiting and keeping volunteers, and waste in the design and management of trials.
But there is an encouraging note, too: Public and private organizations are aware of these problems and are pushing
for reform.
One counterpoint to problems in the West is a boom in the East. Dennis Normile describes the expansion of clinical
studies in Asia on page 214. A desire to cut costs is only part of this trend; China and India see clinical trials as a
means of growing their economies and developing skills.
Jocelyn Kaiser reports on page 217 about ongoing efforts to make Western trial data more accessible. A mandate
requiring disclosure of results from all trials of drugs approved by the U.S. Food and Drug Administration takes effect
this fall, for example.
On page 219, Constance Holden gives an update on efforts to ensure that U.S. government-sponsored trials are
balanced by gender. And Jennifer Couzin dissects an important series of interventions designed to prevent heart
disease by controlling cholesterol (p. 220). The results raise fundamental questions about how cholesterol functions in
the body--and about the usefulness of certain biomarkers as surrogates for health outcomes.
A video report by Robert Frederick on progress in testing drugs for children, "Pediatric Medicines: Prescribing Off-
Label," appears online at www.sciencemag.org/clinicaltrials.
The subtlety and cost of these modern clinical trials would amaze James Lind.”
Vaccine
Volume 26, Issue 45, Pages 5669-5774 (23 October 2008)
http://www.sciencedirect.com/science/journal/0264410X\
[Reviewed last week]
_____________________________________________________________________________________________________
6 October 2008
Wyeth Pharmaceuticals announced the initiation of the Community Acquired Pneumonia Immunization
Trial in Adults, described as a major study in adults of an investigational 13-valent conjugate vaccine
designed to help prevent pneumococcal pneumonia, the leading cause of bacterial pneumonia in adults.
Wyeth noted that in Europe and the United States, pneumococcal pneumonia is the most common community-
acquired bacterial pneumonia, for which the adult mortality rate averages between 10 to 20 percent, and that rate
may exceed 50 percent in high-risk groups worldwide. The Community Acquired Pneumonia Immunization Trial in
Adults is a double-blind, placebo-controlled study expected to enroll approximately 85,000 participants 65 years of
age and older. The study is being conducted by the Julius Center for Health Sciences and Primary Care at the
University Medical Center Utrecht in the Netherlands. Participants in the trial will receive either Wyeth's investigational
13-valent pneumococcal conjugate vaccine or placebo.
(PRNewswire, 26 September 2008)
HHS Secretary Mike Leavitt announced two new actions in the department’s “ongoing activities to
bolster the nation’s preparedness for a potential outdoor anthrax attack.” The first action “focuses on
United States Postal Service letter carriers who volunteer to deliver medicines directly to residences in their
communities during an emergency.” Homeland Security Secretary Michael Chertoff and HHS Secretary Leavitt “have
invoked their authority under section 564 of the Federal Food, Drug, and Cosmetic Act to make the determination
and declaration of emergency required by law in order for HHS’ Food and Drug Administration (FDA) to consider
issuing an Emergency Use Authorization (EUA) allowing eligible letter carriers to receive kits containing small quantities
of antibiotics for future use by them and other members of their households during an anthrax emergency.” These
antibiotics “would help protect volunteers against contracting anthrax if, following an outdoor anthrax attack, the
Postal Service was called upon to deliver the same life-saving antibiotics directly to homes across their community
where people may have been exposed to the bacterium that causes anthrax. Although no imminent threat
currently exists, these legal actions would enable FDA to issue a EUA.”
Secretary Leavitt commented, “In an anthrax attack, time is of the essence in preventing illness and death by getting
antibiotics to those who may have been exposed. By providing advance protection to letter carriers who volunteer
to deliver antibiotics in an affected community, we can gain the benefits of the unique capabilities of the Postal
Service to get much needed medicines to those who need it quickly. This is one part of our strategy to encourage
preparedness at all levels of government to enable our nation to respond effectively in the event of an anthrax
emergency.”
HHS said that over the past several years, under the Cities Readiness Initiative (CRI), HHS and the Postal Service
“have successfully developed and tested in three U.S. cities -- Seattle, Philadelphia and Boston --the ability of letter
carriers to quickly deliver door-to-door quantities of antibiotics from the Strategic National Stockpile to residential
addresses. This quick-strike capability is intended to buy time for local and State public health authorities to set up
points of dispensing for further provision of antibiotics across the community.”
“The letter carrier has long been a reliable presence in America's neighborhoods. This important and potentially life
saving undertaking is a natural extension of what the carriers see as a service to their community,” Postmaster
General John E. Potter said.
Begun in 2004, CRI is a federally funded effort to prepare 72 major U.S. cities and metropolitan areas to effectively
respond to a large scale bioterrorist event by dispensing antibiotics to their entire identified population within 48 hours
of the decision to do so. With today’s actions, CRI cities will now have another distribution tool at their disposal when
crafting their plans to protect their populations. Such innovations have been encouraged by the National Academy
of Sciences’ Institute of Medicine, which earlier this year conducted an evaluation of medical countermeasure
distribution capabilities.
In a related action, HHS said Secretary Leavitt issued a declaration under the Public Readiness and Emergency
Preparedness Act (PREP Act) that “provides liability protection for activities related to developing, manufacturing,
distributing, prescribing, dispensing, administering and using anthrax countermeasures in preparation for, and in
response to, a potential anthrax attack. This includes entities, such as large “big-box” retail stores, retail pharmacies,
and other private sector businesses, that help to deliver and distribute medicines.” Secretary Leavitt said,
“Preparedness is a shared responsibility that must involve all sectors of society, including the private sector,
community groups, families and individuals. We are using the authorities available to us to do all we can to support
preparedness at all levels.”
The DHS Determination of an Emergency (under Section 564(b) of the Federal Food, Drug and Cosmetic Act) is
available at http://www.dhs.gov/xlibrary/assets/ofsec_signed_determination092308.pdf; the HHS Declaration of an
Emergency (under Section 564(b) of the Federal Food, Drug and Cosmetic Act) is available at http://www.hhs.
gov/disasters/emergency/manmadedisasters/bioterorism/564anthrax-declaration.html; and the HHS PREP Act
Declaration available at http://www.hhs.gov/disasters/emergency/manmadedisasters/bioterorism/prepact-081001.
html.
(HHS Media Release, 1 October 2008)
Emergent BioSolutions announced it signed a new, multi-year, firm fixed price contract to supply an
additional 14.5 million doses of BioThrax (Anthrax Vaccine Adsorbed), its FDA licensed anthrax vaccine,
from the U.S. Department of Health and Human Services (HHS)for inclusion in the Strategic National Stockpile (SNS).
The total value of this follow-on contract is between US$364 million and US$404 million, with the higher amount tied
to the delivery of product having four-year expiry dating. Fuad El-Hibri, chairman and CEO of Emergent BioSolutions,
commented, “This follow-on contract with HHS is continuing evidence of the government’s steadfast commitment to
procure critical countermeasures to protect against the threat of bioterrorism in our country,”
(BUSINESS WIRE, 1 October 2008)
GenVec said the National Institutes of Health (NIH) executed its second option period (year three)
under a previously announced, five-year contract with GenVec valued at up to US$52 million for the
production of HIV vaccines. GenVec will receive up to $3.8 million for the third year of activities, and said the
funds will continue to support the development of new HIV vaccine candidates based on its proprietary adenovirus
vector and production cell line technologies. Dr. Rick King, GenVec’s Senior Vice President of Research and
Development, said, “We appreciate NIAID’s decision to execute its renewal option under our contract. This renewal
will help fund the development of new HIV vaccine candidates, which are based on multiple serotypes of adenovirus.
GenVec’s adenovector technology platform now includes six distinct serotypes that can be used singly or in
combination.”
(BUSINESS WIRE, 2 October 2008)
VGX Pharmaceuticals announced that the National Institute of Allergy and Infectious Diseases (NIAID)
awarded the company a contract to develop a preventive HIV DNA vaccine candidate in conjunction
with VGX’s constant current electroporation technology for intradermal delivery of DNA vaccines. The
contract is part of the NIAID’s HIV Vaccine Design and Development Teams program, and brings together HIV
vaccine experts from the University of Pennsylvania School of Medicine and VGX. The contract, titled “Development
of Improved DNA Vaccines and Electroporation Delivery Devices for Prophylactic HIV Vaccines”, provides US$23.5
million of funding over seven years, including a base period and follow-on option years. VGX’s vaccine candidate,
PENNVAX-G (targeting HIV clades A, C, and D), was developed in the laboratory of Professor David B. Weiner at the
University of Pennsylvania School of Medicine and licensed to VGX. The DNA-based vaccine will be delivered using VGX’
s intradermal electroporation (ID-EP) technology.
(BUSINESS WIRE, 1 October 2008)
Novavax announced that it was recognized at the annual meeting of the Clinton Global Initiative
("CGI") “for developing affordable methods of producing an H5N1 avian influenza vaccine and a
seasonal influenza vaccine using the company's proprietary recombinant virus-like particles ("VLPs").”
Novavax said it is working “to create novel vaccines and manufacturing solutions for producing avian and seasonal
influenza vaccines with portable equipment that can be deployed worldwide,” and that it believes its vaccine initiatives
“have the potential to impact millions of people affected by infectious diseases each year by creating novel vaccines
that can be produced in a cost effective and timely manner within the same scalable manufacturing platform
worldwide.”
(PRNewswire-FirstCall, 29 September 2008)
Journal Watch
[Editor’s Note]
Vaccines: The Week in Review continues a new feature, scanning key journals to identify and cite articles, comment
and editorials, books reviews and other content supporting our focus on vaccine ethics and policy. Journal Watch is
not intended to be exhaustive, but indicative of themes and issues the center is actively tracking. We selectively
provide full text of some editorial and comment articles that are specifically relevant to our work. Successful access to
some of the links provided may require subscription or other access arrangement unique to the publisher. Our initial
scan list includes the journals below. If you would like to suggest other titles, please write to David Curry at david.r.
curry@centerforvaccineethicsandpolicy.org
JAMA
Vol. 300 No. 13, pp. 1489-1610, October 1, 2008
http://jama.ama-assn.org/current.dtl
[No relevant content]
Journal of Infectious Disease
15 October 2008 Volume 198, Number 8
http://www.journals.uchicago.edu/toc/jid/current
[No relevant content]
The Lancet
Volume 372, Number 9645, 4 October 2008
http://www.thelancet.com/journals/lancet
The Lancet 2008; 372:1193
DOI:10.1016/S0140-6736(08)61494-4
Editorial
Rolling back malaria—the next 10 years
The Roll Back Malaria (RBM) partnership is 10 years old this month. What started out in 1998 as an alliance of four UN
agencies, to facilitate and coordinate implementation of malaria control, has grown exponentially to become a
coalition of more than 500 partners. In the early years, RBM faced several problems: uncertainty around its role, four
leadership changes in 5 years, and a catalogue of missed opportunities and failures to make any substantial headway
to tackle malaria. But last week, the partnership launched their Global Malaria Action Plan to a huge fanfare at the high-
level UN Millennium Development Goal meeting in New York. The promise of US$3 billion, new technologies, increased
awareness, and political will to fight this ancient scourge signals a new era of confidence and support for the
previously beleaguered partnership.
The plan lays out three goals to reduce malaria: in the short-term, to reduce mortality and morbidity by half from
2000 levels by scaling up the available methods of prevention and treatment for all those in need by 2010; in the
medium term, to reduce the number of malaria deaths to near zero by 2015 through sustained coverage of these
tools; and in the long-term, to maintain near zero deaths worldwide, while eliminating malaria transmission in feasible
countries and moving towards eradication of malaria with new tools and approaches.
The plan is far more comprehensive than previous versions. It provides an evidence-informed approach to deliver
effective prevention and treatment to those at risk. It also estimates the annual funding needed to achieve the goals
of the partnership, with at least US$62 billion being required by 2020. Having been sent for wide consultation to
countries, experts, and institutions, it is perhaps the closest the malaria community has got to a consensus-based
plan. RBM estimates that if the plan is successfully implemented, 4.2 million lives could be saved by 2015 in the 20
highest-burden African countries alone. What makes the plan ambitious is the focus on elimination and ultimately
eradication. These terms are attractive and hold much political weight, but one only has to look at the poliomyelitis
eradication programme to know in reality that such ambition can turn out to be a great deal more complex. There
are dangers in setting the bar too high.
To date the actual burden of malaria has been difficult to be sure of. The second WHO Malaria Report 2008
(containing data up to 2006) estimates a substantial decrease in the number of cases and deaths compared with
previous years. But these numbers are disputed by experts. Without proper baseline assessments of what the
current burden was in 2000, it is unclear how exactly the partnership will know when it has reached its 50% target.
Furthermore, changes in malaria epidemiology and transmission make it vital that success is measured properly in
terms of health outcomes, infection rates, and intervention coverage. Monitoring, evaluation, and surveillance must
be prioritised, funded properly, and put in place at the country level. Progress in achieving these goals should be
reviewed regularly and independently.
A major challenge in countries with high malaria mortality is the lack of human capacity and health systems to deliver
interventions. It is encouraging to see capacity building and health system strengthening being included in the plan,
but these commitments, so often given before, need to translate into practice. Too frequently, donors tend to be
commodity-driven and would rather invest in bednets and medicines. The returns on health-system strengthening
are enormous and provide the opportunity of integration with broader global-health initiatives.
One threat to progress is the commitment to long-term funding. Just to reach the 2010 coverage targets will require
four times the funds currently available. Along-side continued donor contributions, increased funding by malaria-
endemic countries, monitoring financial commitments against actual needs, and a formal external evaluation of
impact and progress of the plan over time are imperative. Partners, donors, and country leaders should all be held to
account; here an independent and transparent scientific evaluation would be most useful.
RBM has raised the profile of malaria, taking the disease from being grossly under funded and largely neglected to
being widely recognised as an exemplary investment opportunity in the development agenda. It has achieved this
through stronger leadership, better cooperation between its partners, and responding to country needs by
improved coordination around their national strategic and implementation plans. During the next decade, RBM has
huge challenges. But for the first time, we sense these challenges might be met. The decisions taken in New York last
week have created an unprecedented opportunity, one that must be grasped firmly by all parties.
The Lancet
The Lancet 2008; 372:1203-1205
DOI:10.1016/S0140-6736(08)61499-3
Comment
Blocking humanitarian assistance: a crime against humanity?
John D Kraemer, Dhrubajyoti Bhattacharya and Lawrence O Gostin
In May, Cyclone Nargis left nearly 140,000 people dead or missing in Burma, while the Government severely
restricted international assistance.1 More recently, Zimbabwean President Robert Mugabe cut off international
assistance, apparently to manipulate an election but leaving millions without food aid or medical care.2 The global
community has a long and sad history of exalting human rights in the abstract but failing to protect them in practice.
When political leaders willfully block vital humanitarian aid to their people, they violate international human rights and
potentially commit a crime against humanity. Such violations give the international community a legal right of
intervention, with force if necessary. While intervention is best pursuant to authorisation from the UN Security
Council, without such authorisation regional organisations or individual nations should prioritise the survival of large
populations over the sovereignty claims of despotic leaders.
Can a right to health overcome barriers of national sovereignty? Human rights prevent states from claiming that
systematic maltreatment of their nationals is exclusively a domestic concern. International law holds the state
accountable for safeguarding the human rights of its people, and legitimises the actions of the international
community to monitor and redress violations. This view was affirmed in the UN Charter, which proclaimed the UN's
mission as solving international humanitarian concerns through international cooperation.3
The International Covenant on Civil and Political Rights guarantees the right to life, and the International Covenant on
Economic, Social, and Cultural Rights codifies the right to health. Neither has been signed by Burma, although
Zimbabwe has signed both but respected neither. Nonetheless, the rights to life and health are so widely accepted
that they are part of international customary law. WHO's Constitution also requires nations to seek to attain the
highest possible level of health for all peoples.4 But it stops short of mandating countries to accept international aid
during crises.
The right to health requires states to respect, protect, and fulfill basic health needs. This demands, at the least, the
bare minimums to ensure survival, including medical aid and supplies, potable water, and food for the most
vulnerable populations.5 During crises, countries have limited capacity to secure these public goods, but international
law requires cooperation with the international community to meet these obligations. Additionally, the right to life is a
non-derogable right, and even the most hardened isolationist regimes must respect it.
Even governments as repressive as Burma and Zimbabwe have ratified the Convention on the Rights of the Child
(CRC), which recognises the rights to health and life, and demands international cooperation. The CRC requires
states to ensure to the maximum extent possible children's survival and development, including access to basic
determinants of health. Moreover, signatories must “promote and encourage international cooperation with a view to
achieving progressively the full realization of the right”.6 Consequently, they cannot invoke sovereignty to belie
obligations to secure the health and wellbeing of their children. Humanity knows no borders and, though imperfect,
human-rights laws should be applied vigorously to secure health and life during intentionally exacerbated public-
health emergencies.
International crimes—which include genocide, war crimes, and crimes against humanity—are breaches of international
norms that result in individual liability. The primary purpose of international criminal law is to bring the perpetrators of
international crimes to justice. But when officials commit atrocities, the international community should not remain
idle. If leaders act, or fail to act, in ways that will lead to widespread death—and then block those who seek to
prevent it—they commit a crime against humanity and intervention is appropriate.
Assessing a county's response to crises under a lens of preventing potential crimes against humanity proffers a useful
and pragmatic standard. Generally, crimes against humanity are particularly serious attacks on human dignity. A
finding of such crimes rests solely on the widespread or systematic practice of atrocities. Unlike war crimes, crimes
against humanity may be committed during times of peace. And unlike genocide, crimes against humanity do not
require a special intent to kill on account of group status. Perpetrators need only act with the wilful intent to inflict
widespread or systematic harm on their victims—a bar that is readily met when officials block assistance to large
populations with vital need.
Crimes against humanity require the infliction of “great suffering, or serious injury to body or to mental or physical
health”—or extermination.7 Both acts that directly inflict injury and refusals to act can constitute a crime. In 2003,
the International Criminal Tribunal for the Former Yugoslavia found a physician guilty of extermination for the
treatment of prisoners during the 1990s' Bosnian–Serb conflict, including for “conditions imposed on a [prisoner]
whose health was fragile, [which] alone would inevitably cause his death”.8 The Court held that it was not only the
resultant deaths but also the creation of conditions leading to a large number of deaths that justified a conviction.
Accordingly, where governments block food, medical supplies, and health care to meet basic survival needs,
preventing atrocities is consonant with securing the right to health.
Does international law permit humanitarian intervention? During humanitarian crises, the desire for assistance by the
affected country almost invariably exceeds its available resources. Thus the normal crisis model is to request
assistance from donor countries. However, when official conduct constitutes a crime against humanity, either by
refusing aid to those in need (as in Burma) or actively creating a humanitarian emergency (Zimbabwe), ameliorating
the emergency may require foreign intervention without host-country consent.
The UN Charter prohibits countries from intervening “in matters which are essentially within the domestic jurisdiction”
of another state.3 However, under modern conceptions, sovereignty inheres in the people, not the government, so
a government's sovereign authority is conditional on refraining from grievous violations of human dignity.9 Thus
sovereignty yields to human rights when a government has wilfully taken steps to cause death or widespread
suffering.
Non-consensual intervention to relieve grave humanitarian need would likely require military force or its threat if relief
efforts were resisted or endangered. This point subjects humanitarian intervention to the body of use-of-force law
that prohibits the use or threat of force “against the territorial integrity or political independence of any state, or in
any other manner inconsistent with the purposes of the United Nations.”3
Intervention sanctioned by the UN Security Council to ameliorate a crime against humanity would be legal. The
Charter permits the Council to authorise intervention if a crisis poses a “threat to the peace, breach of the peace, or
act of aggression”.3 Threats to the peace extend beyond armed attack and include widespread suffering and crimes
against humanity. This was the basis of the Council's determination in 1992 that the “human tragedy” of famine in
Somalia, exacerbated by deteriorations in that country's stability, posed a “threat to international peace and
security” even though the effects of the crisis were not significantly felt outside of Somalia.10 Upon a subsequent
finding that non-forcible measures were unlikely to succeed, the Council authorised an American-led contingent to
ensure delivery of humanitarian aid to starving Somalis.10
A 2005 resolution of the UN General Assembly reiterated the Council's power to act when governments “manifestly
fail to protect their populations from…crimes against humanity” if peaceful means cannot avert the crisis.11 This
authority would permit limited interventions, such as airdrops, but, if necessary, would permit broader Somalia-style
“boots on the ground” interventions.
Unfortunately, the Council is often paralysed by its five permanent members' ability to veto initiatives, necessitating
examination of the legality of unilateral or coalition interventions. Notably, the Charter prohibits force only where
“inconsistent” with UN purposes and when used against the “territorial integrity or political independence of any
state”. “Territorial integrity” refers to shifting international borders, and “political independence” to states gaining
control of other's political machinations. Intervention solely to stop a crime against humanity infringes on neither of
these, so it does not fall within the Charter's force prohibition. Furthermore, humanitarian intervention is within the
principles of the UN, because the Charter's dual purposes are preserving peace and promoting human rights.12
Additionally, international law requires the existence of grave violations of human rights, an exhaustion of non-forcible
responses, and the unavailability of UN-sanctioned action. The response must be proportionate—no more than
necessary to achieve humanitarian ends—and it must not interfere unnecessarily with a country's self-determination.
Finally, the interveners must disengage upon securing fundamental rights and report their actions to the Security
Council.13
Nations should be justifiably cautious about using or threatening intervention to stop crimes against humanity. Policy
makers must carefully consider risks to relief workers, civilians, and troops, as well as the danger of complicating
future health-promotion activities. Forced intervention is a complex policy question, but blanket rejection may
condemn innocent civilians and prevent deterrence of crimes against humanity. Where leaders engage in intentional
acts of cruelty toward their populations, wealthy nations should be prepared to intervene beyond their borders to
safeguard health and human rights.
We declare that we have no conflict of interest.
References
1. Ohmar K. Burma aid efforts press on despite blocks. UPI Asia Online. June 26, 2008:
http://www.upiasiaonline.com/Politics/2008/06/26/burma_...
(accessed July 3, 2008)..
2. Rotberg RI. Who will have the courage to save Zimbabwe?. Boston Globe June 25 2008; A15.
3. UN. Charter of the United Nations. June 26, 1945:
http://www.un.org/aboutun/charter
4. WHO. Constitution of the World Health Organization. October, 2006:
http://www.who.int/governance/eb/who_constitution_en.pd...
(accessed July 3, 2008)..
5. UN Economic and Social Council. The right to the highest attainable standard of health. Aug 11, 2000:
http://www.unhchr.ch/tbs/doc.nsf/(symbol)/E.C.12.2000.4...
(accessed July 3, 2008)..
6. Office of the United Nations High Commissioner for Human Rights. Convention on the rights of the child, article 24
(4). Sept 2, 1990
http://www2.ohchr.org/english/law/crc.htm
(accessed July 8, 2008)..
7. International Criminal Court. Rome Statute of the International Criminal Court, article 7(1). July 1, 2002
http://untreaty.un.org/cod/icc/statute/romefra.htm
(accessed July 3, 2008)..
8. Prosecutor v, Milomir Stakić, Case No. IT-97-24-T, International Criminal Tribunal for the Former Yugoslavia. July
31, 2003
http://www.un.org/icty/stakic/trialc/judgement/index.ht...
(accessed July 8, 2008)..
9. Saechao TR. Natural disasters and the responsibility to protect: from chaos to clarity. Brookland J Int Law 2007;
32: 663-707.
10. Hutchinson MR. Restoring hope: UN Security Council resolutions for Somalia and an expanded doctrine of
humanitarian intervention. Harvard Int Law J 1993; 34: 624-640.
11. UN General Assembly. 2005 World Summit outcome. Oct 24, 2005:
http://unpan1.un.org/intradoc/groups/public/documents/U...
(accessed July 8, 2008)..
12. Mertus J. The imprint of Kosovo on the law of humanitarian intervention. ILSA J Int Comparative Law 2000; 6:
527-540.
13. Terry JP. Rethinking humanitarian intervention after Kosovo: legal reality and political pragmatism. Army Lawyer
2004; 8: 36-46.
Nature
Volume 455 Number 7213 pp565-706 (2 October 2008)
http://www.nature.com/nature/journal/v455/n7212/
[No relevant content]
New England Journal of Medicine
Volume 359 — October 2, 2008 — Number 14
http://content.nejm.org/current.shtml
[No relevant content]
PLoS Medicine
Week of 30 September 2008
Informed Consent in the Genomics Era
Deborah Mascalzoni, Andrew Hicks, Peter Pramstaller, Matthias Wjst
Since the Nuremberg trials, informed consent (IC) has been recognized as a basic ethical requirement for research
involving human participants. Such consent encompasses two distinct elements: (1) researchers communicate
detailed information about study procedures, outcomes, risks, and benefits for the participating individual or
community, and (2) after understanding and careful consideration, the participants consent to take part under these
conditions. However, the suitability of IC for genomic studies has been recently challenged. Because the research
protocol for such studies may evolve over time, the condition in IC of providing detailed information for a well-defined
protocol is not easily satisfied.
Large amounts of data stored as electronic records allow multiple post-hoc analyses, which in many cases were not
foreseen at the beginning of a study. The potential for analysis is constantly growing and recently has increased
dramatically with the development of high-throughput sequencing and genotyping technologies. More than one
million genetic variants of an individual may be determined within hours—and even the full genetic sequence within
weeks. Such technical advances expose participants to a new class of risk different from the physical harm usually
considered in ethical reviews. Release of genetic information could lead to uninsurability, unemployability,
discrimination, and the breakdown of family relationships by unintentionally demonstrating missing or unknown
relatedness. Moreover, participants usually do not get any direct benefit from the research. All of these concerns raise
the question: are IC procedures still in accordance with the currently accepted ethical standards of autonomy,
beneficence, and non-maleficence?
Summary Points
- Genetic cohort studies storing biological materials hold great promise for medical research, but also present new
problems that are profoundly different from the classical clinical trial for which informed consent was developed.
- The classical risk/benefit analysis of physical harm doesn't take into account new threats to the individual such as
uninsurability, unemployability, genetic discrimination, or disruption of family relationships.
- Traditional informed consent may therefore no longer be appropriate when dealing with long-term studies using
biological materials.
- Informed consent should be seen as an ongoing process between researcher and participant, and not just as a
once-and-for-all decision.
- Research following the initial storage of samples needs to be likewise explained and may be announced using new
communication methods.
There is pressure to harmonize different views, since a shared ethical and legal framework is still missing and
approaches vary greatly. A wide spectrum of opinions exists: Some researchers believe that available sample
collections do not need any further consent, even for large-scale genotyping, while some institutional review boards
recommend the destruction of samples immediately after testing (MW, personal observation).
Citation: Mascalzoni D, Hicks A, Pramstaller P, Wjst M (2008) Informed Consent in the Genomics Era. PLoS Med 5(9):
e192 doi:10.1371/journal.pmed.0050192
Published: September 16, 2008
Deborah Mascalzoni, Andrew Hicks, Peter Pramstaller, and Matthias Wjst are at the Institute of Genetic Medicine,
EURAC Research, Bozen, Italy. Matthias Wjst is also at the Helmholtz Zentrum München, German Research Center
for Environmental Health, Neuherberg, Germany.
Science
3 October 2008 Vol 322, Issue 5898, Pages 1-148
http://www.sciencemag.org/current.dtl
Science 3 October 2008:
Vol. 322. no. 5898, pp. 26 - 27
DOI: 10.1126/science.322.5898.26
News of the Week
INFECTIOUS DISEASE:
New Malaria Plan Called Ambitious By Some, Unrealistic by Others
Leslie Roberts
It was standing room only last week at U.N. headquarters in New York City when a star-studded cast, including
philanthropist Bill Gates, U2 rocker Bono, and British Prime Minister Gordon Brown, kicked off the latest in a string of
grand plans to conquer malaria, the mosquito-transmitted scourge that kills some 1 million people a year, mostly
African children.
The goals of the Global Malaria Action Plan (GMAP) are stunningly ambitious: Reduce malaria deaths to near zero by
2015, then progressively eliminate the disease from countries and regions until it is eradicated from the planet. That
will take mosquito- and parasite-foiling technologies that have yet to be invented, along with billions of new dollars a
year that the plan's architects hope generous donors will provide. GMAP, assembled over the past year with input
from more than 250 experts, is the creation of the Roll Back Malaria (RBM) partnership, a coalition of international
agencies, public and private donors, and malaria-affected countries.
Regina Rabinovich, head of infectious diseases at the Bill and Melinda Gates Foundation and one of the key forces
behind the plan, calls the goals "ambitious but achievable." But many malaria experts say it's unlikely that GMAP will
meet its targets--even with abundant funding--although they applaud the renewed commitment. Several also
caution that donors and agencies should be careful in what they promise, given the humbling outcomes of previous
grand plans (see table, above).
Scientists and the World Health Organization (WHO) also exuded confidence in the 1950s when they vowed to
eradicate malaria, for instance. After that initiative's spectacular demise in the 1960s, malaria cases surged worldwide,
and support for malaria control and research essentially dried up.
After a long hiatus, international health and development agencies reentered the fight against malaria in the late
1990s, setting a series of increasingly ambitious targets. They culminated in Bill and Melinda Gates' unexpected call
last year to again attempt to eradicate the disease, a word that hadn't been uttered in the context of malaria for
some 40 years (Science, 7 December 2007, p. 1544).
"We set year after year new goals and never meet any of them," says Christian Lengeler, a malaria researcher at the
Swiss Tropical Institute. Lengeler, who has worked extensively in Tanzania, calls GMAP's 2015 target of zero deaths
"totally unrealistic." "Silly," says another scientist. As for the eventual eradication of malaria, "maybe, but not in my
lifetime," seems to be the general consensus.
This time it is different, insist Rabinovich and Awa Marie Coll-Seck, executive director of RBM. For one, coffers are
flush. Thanks to contributions from the Gates Foundation, the Global Fund to Fight AIDS, Tuberculosis and Malaria,
the World Bank, the President's Malaria Initiative, and others, international funding for malaria control jumped from
$51 million in 2003 to an estimated $1.1 billion in 2008. Last week, the Global Fund announced that it will award
$1.62 billion over the next 2 years to help poor countries fight malaria, and the World Bank pledged $1.1 billion to
expand its Malaria Booster Program. These and other smaller contributions unveiled last week still fall significantly
short of the $5 billion or $6 billion a year GMAP says is needed.
Also in the past few years, malaria interventions, such as long-lasting insecticide-treated bed nets and a new class of
drugs known as artemisinin-based combination therapies (ACTs), have proved their mettle (Science, 26 October
2007, p. 556). A half-dozen African countries with committed leadership and a lot of outside support have scaled up
these interventions rapidly--Ethiopia, for instance, distributed 20 million bed nets in just 18 months. A few of these
countries or areas, those with small populations and high access to prevention and treatment, have seen roughly a
50% decline in malaria cases and deaths since 2000, WHO notes in its 2008 World Malaria Report. Ensuring universal
access to these and other tools such as indoor insecticide spraying and preventive treatments in pregnant women
can halve deaths by 2010, says GMAP, and then reduce them to near zero 5 years out.
But none of the countries has reached the target of 80% coverage with existing interventions, set just a few years
ago, much less the 90% called for by GMAP. Across the continent, just 23% of children slept under a bed net in
2006, and only 3% of patients were treated with ACTs, according to WHO estimates.
The challenges facing big countries like the Democratic Republic of the Congo (DRC) and Nigeria are especially
daunting. They account for about 20% to 25% of malaria deaths, although hard data are scarce, and are plagued
by civil unrest and weak health systems. "That it can be done in Zambia, with a population of 10 million and a
dynamic minister of health, does not say a thing about what to do in DRC," agrees Rabinovich.
To develop the radical types of new vaccines, drugs, and insecticides needed for the toughest areas--as well as for
eradication many decades from now--GMAP calls for pumping $750 million to $900 million a year into research. A
working group is already hammering out a detailed research and development plan, which Rabinovich says should be
ready in 15 months.
To prime the pump, Gates announced $168 million for research on the next generation of malaria vaccines. The
award is going to the Bethesda, Maryland-based PATH Malaria Vaccine Initiative, which will try to build off the
experience gained from vaccine candidates already in the pipeline, says MVI Director Christian Loucq.
GlaxoSmithKline's RTS,S, which targets the malaria parasite form that infects the liver, for instance, is about to enter
phase III trials--the first malaria vaccine candidate to get that far. MVI is investigating additional antigens that target
different stages in the parasite's life cycle that could be used in combination, as well as novel adjuvants to boost
vaccine power. Although expected to be significantly more efficacious, such second-generation vaccines won't be
available until well after 2015 and, like RTS,S, will still be only partially protective.
Another intriguing possibility is a transmission- blocking vaccine that would be administered to humans but that
would target the parasite after it is taken up by the mosquito in her blood meal. Loucq calls the approach "elegant,"
the equivalent of an "immunological bed net," but cautions that it is early days.
Whether the exact targets are met is beside the point, says RBM leader Coll-Seck. "I am a glass-half-full person," she
says. If GMAP leads to a significant reduction in malaria cases and deaths--even if the plan promised much more--who
would call that a failure, she asks.
Vaccine
Volume 26, Issue 45, Pages 5669-5774 (23 October 2008)
http://www.sciencedirect.com/science/journal/0264410X\
Community perspectives on the ethical issues surrounding adolescent HIV vaccine trials in South Africa
Pages 5679-5683
Heather B. Jaspan, Nosiphiwo F. Soka, Ann E. Strode, Catherine Mathews, Daniella Mark, Alan J. Flisher, Robin Wood,
Linda-Gail Bekker
Abstract
“Adolescents globally are at high risk for HIV acquisition and are the targets of HIV prevention interventions such as
HIV vaccines. In order to understand stakeholders’ attitudes towards the ethical issues of adolescent involvement in
HIV vaccine trials, we conducted focus group discussions with key members of a semi-urban, informal Cape Town
community with high HIV prevalence in which HIV vaccine trials are taking place. Themes were identified from focus
group transcripts by four researchers, and included necessity of guardian consent, age of independent consent, and
confidentiality of in-trial medical results. In general, ethical adolescent HIV vaccine trials will be feasible in this
community.”
Epidemiology of poliomyelitis—Options and update
Pages 5767-5773
Anil Dutta
Abstract
“Poliomyelitis is a disease of major public health importance. Since the launch of the Global Poliomyelitis Eradication
Initiative in 1988, considerable progress has been achieved globally. At present, the causative agent for the disease –
poliovirus – remains endemic in only four countries (Afghanistan, India, Nigeria and Pakistan). The poliovirus
eradication plan, as outlined in the WHO strategic plan for 2004–2008, incorporates priority activities for each phase
of the plan: (i) polio eradication certification for regions, (ii) oral poliovirus vaccine (OPV) cessation phase, and (iii) post-
OPV phase. The ultimate goal to eventually stop all vaccination is, however, jeopardized by the emergence of
vaccine-derived polioviruses and the risk of bioterrorism. In the post-eradication era, individual countries will be
presented with guidelines on OPV cessation and inactivated poliovirus vaccine (IPV) usage. This paper, presented
during the Asian Pacific Pediatric Association (APPA) meeting in Pattaya, Thailand from 20 to 22 July 2006, provides
an update on the current global situation, focusing on the progress and challenges faced by different countries in
their quest for
____________________________________________________________________________________________________
29 September 2008
The Bill & Melinda Gates Foundation announced that it will provide US$168.7 million to PATH for its
Malaria Vaccine Initiative. The PATH Malaria Vaccine Initiative (MVI) is “working with GlaxoSmithKline Biologicals to
develop a first-generation vaccine candidate, known as RTS,S, which could become the first-ever approved malaria
vaccine. With the new grant announced today, MVI will support the development of next-generation vaccines that
could provide even greater and longer-lasting protection.” Bill Gates, co-chair of the Gates Foundation, commented,
"I'm very hopeful that the malaria vaccine currently in advanced testing will be proven effective, but that will just be
the first step. Now it's time to develop a new generation of vaccines that are even more effective, and could
someday help eradicate malaria altogether." Mr. Gates announced the new funding at the UN Millennium
Development Goals Malaria Summit. The event included launch of the Global Malaria Action Plan by the Roll Back
Malaria Partnership.
The Gates Foundation grant will “support MVI's efforts to expand its vaccine R&D pipeline with projects ranging from
early-stage laboratory research to advanced clinical testing. MVI will work with partners to discover new antigens and
adjuvants that could lead to more effective vaccines, and develop new tools to select the most promising candidates
for further development. MVI will also work to foster a more competitive vaccine marketplace and help ensure that
future vaccines will be affordable and accessible in developing countries. They will conduct market assessments,
demand forecasting, and modeling studies to guide policymakers and vaccine manufacturers, and partner with
vaccine makers in developing countries to keep costs low,: the media release noted.
Dr. Christian Loucq, Director of MVI, said, "These new funds are recognition that we have a solid research and
development strategy, and the team to deliver on it. This commitment should signal to potential research partners
that the time is ripe to work with us to help defeat this horrible disease. Already, we have added to our roster of
partners and entered into collaborative agreements on vaccine components, ways to boost their potency, and
methods for testing their biological activity." Dr. Christopher J. Elias, president and CEO of PATH, commented, "Our
strategy for developing a malaria vaccine follows the PATH approach to neglected diseases, which has shown that
investment in core areas of research and development, particularly vaccine technology, does yield important
advances. The PATH Malaria Vaccine Initiative is now ready to accelerate further the development of what the world
urgently needs: safe, effective, and affordable vaccines that reduce the suffering caused by malaria."
(Gates Foundation Media Release, 25 September 2008)
http://www.gatesfoundation.org/GlobalHealth/Pri_Diseases/Malaria/Announcements/Announce-080925.htm
The Centers for Disease Control and Prevention (CDC) said it awarded US$24 million to fund 55
projects in 29 state and local public health departments “that could serve as innovative approaches for
influenza pandemic preparedness.” Richard Besser, MD, Director of CDC′s Coordinating Office for Terrorism
Preparedness and Emergency Response, commented, “What is learned from these projects can benefit everyone
because it could improve national, regional and local public health detection and response to a pandemic involving
influenza.” A total of 184 funding applications were submitted by state and local health departments in a competitive
application process. Eligible applicants for the awards were limited to the 62 state, local and territorial public health
departments that currently receive federal funding through CDC′s Public Health Emergency Preparedness (PHEP)
Cooperative Agreement.
The projects focus on seven key areas and include:
- Use of public engagement as part of the public health decision-making process
- Electronic laboratory data exchange to support influenza pandemic monitoring
- Integration of state-based immunization information systems to track distribution of influenza pandemic
countermeasures.
- Development of statewide electronic death reporting systems compliant with Public Health Information Network
(PHIN) requirements
- Collaborative planning among healthcare providers to ensure the delivery of essential services during an influenza
pandemic
- Development of interventions that promote preparedness for pandemic disease among identified vulnerable
populations
- Distribution and dispensing of antiviral drugs to self-isolated or self-quarantined persons in an influenza pandemic
event
A list of the 29 award recipients and their projects can be found at: http://emergency.cdc.
gov/cotper/coopagreement/07/funding-schedule-pan-flu.asp.
Media Release: http://www.cdc.gov/media/pressrel/2008/r080924.htm
UNICEF Executive Director Ann M. Veneman, speaking on a panel on the opening day of the United
Nations General Assembly session, said “there is a long way to go” to reach the Millennium
Development Goals by their 2015 target date. And the challenges are greatest in countries dealing with conflict
and post-conflict situations, as well as those most affected by HIV/AIDS. Ms. Veneman highlighted the progress that
UNICEF and its partners have made towards achieving the MDG target on rates of mortality for children under the
age of five. According to data released last week, she noted, the number of children under five who died in 2007
dropped to 9.2 million, compared to 12.7 million in 1990. Since 1960, the global under-five mortality rate has
declined more than 60 per cent, and the new data show that downward trend continuing, Ms. Veneman added.
The panelists agreed that one intervention – immunisation – “has proven highly successful and cost-effective in
saving children’s lives throughout the developing world. Childhood immunisation coverage for the six major vaccine-
preventable diseases – diphtheria, measles, pertussis, polio, tetanus and tuberculosis – rose from less than 5 per cent
in 1974 to more that 75 per cent in 2006.” As the world’s largest purchaser of vaccines for developing countries,
UNICEF is a key partner in global immunisation efforts. In the last decade, immunisation is the only public health
intervention that has consistently reached over 70 per cent of children under five. And there is the potential for an
even greater impact. The panel called for an increased level of access to life-saving resources – including vaccines, as
well as anti-retroviral drugs for HIV infection, bed nets to prevent malaria, and more health information – for millions
of people in developing countries. Of particular concern, they said, are children and families who are the hardest to
reach, the most impoverished and the most marginalized. To make achievement of the MDGs possible, Ms. Veneman
concluded, humanitarian and development partners must focus on integrated approaches using solid data and good
mechanisms for evaluation of their work.
GAVI Media release, 23 September 2008)
The Weekly Epidemiological Record (WER) 26 September 2008, vol. 83, 39 (pp 349–356) includes:
- Outbreak news: Cholera, Iraq
- Melamine-contaminated powdered infant formula, China
- Progress towards eliminating measles in Japan, 2008
- WHO web sites on infectious diseases
http://www.who.int/wer/2008/wer8339.pdf
Journal Watch
[Editor’s Note]
Vaccines: The Week in Review continues a new feature, scanning key journals to identify and cite articles, comment
and editorials, books reviews and other content supporting our focus on vaccine ethics and policy. This scan is not
intended o be exhaustive, but indicative of themes and issues the center is actively tracking. Successful access to
some of the links provided may require subscription or other access arrangement unique to the publisher. Our initial
scan list includes the journals below. If you would like to suggest other titles, please write to David Curry at david.r.
curry@centerforvaccineethicsandpolicy.org
JAMA
Vol. 300 No. 12, pp. 1383-1480, September 24, 2008
http://jama.ama-assn.org/current.dtl
[No relevant content]
Journal of Infectious Disease
15 October 2008 Volume 198, Number 8
http://www.journals.uchicago.edu/toc/jid/current
[No relevant content]
The Lancet
Volume 372, Number 9644, 27 September 2008
http://www.thelancet.com/journals/lancet
The Lancet 2008; 372:1135-1136
DOI:10.1016/S0140-6736(08)61462-2
World Report
The global fight against rabies
Talha Burki
[Editor’s Summary] This report is occasioned by World Rabies Day (28 September), spearheaded by the Alliance for
Rabies Control. The author notes that rabies kills at least 55,000 people every year worldwide (under-reporting and
misdiagnosis may mean that the actual figure is higher). In Asia, the death toll numbers around 30,000. But reliable
information for many geographic areas is scant. WHO has endorsed several vaccines and issued directives for
treating potentially dangerous animal bites. If followed correctly, these post-exposure prophylaxis (PEP) guidelines
are virtually 100% effective—PEP is thought to prevent around 280,000 deaths per year. The author notes that
human rabies vaccines need multiple applications, so it is not usually practical for developing populations to vaccinate
the entire population. Hence it is crucial that canine-rabies is controlled—dog bites account for over 99% of human
rabies. For this to happen, 75% of dogs must be vaccinated. Malaysia is an excellent example, says Wilde, of a
country that eliminated rabies by concerted culling, neutering, and vaccination of the dog population. The report
focuses on some of the unique challenges in addressing this disease in India and Pakistan, and other perspectives on
strategies employed in China and other selected geographies.
The Lancet 2008; 372:1150
DOI:10.1016/S0140-6736(08)61480-4
Correspondence
The right to health and accountability
Peter Hall
[Editor’s Summary] The author speaks to the right to the highest attainable standard of health and state
accountability embodied in the International Covenant on Economic, Social and Cultural Right, ratified by more than
80% of the world's countries. A new publication (3 below) from the office of the Special Rapporteur on the right to
the highest attainable standard of health emphasises the importance of accountability. Five broad types of
accountability mechanism are discussed in the publication: (1) judicial—e.g., judicial review of executive acts and
omissions, constitutional redress, statutory interpretation, and public interest litigation; (2) quasijudicial—e.g., national
human rights institutions, and regional and international human rights treaty bodies; (3) administrative—e.g., human
rights impact assessment; (4) political—e.g., parliamentary committee review of budgetary allocations and the use of
public funds, and democratically elected health councils and health-care commissions; and (5) social—e.g., the
involvement of civil society (independently or in collaboration with government) in budget monitoring, health-centre
monitoring, public hearings, and social audits.
The author notes that “the right to the highest attainable standard of health is the entitlement to an optimum health
outcome that takes into account a patient's pre-existing health status and national resources.” General Comment 14,
(4 below) in defining governments' responsibilities for health in a structured way within a human rights framework,
“has galvanised and empowered human rights activists and health professionals alike to use health rights as a vehicle
with which to promote health,” the author argues.
References
1. Horton R. What does a National Health Service mean in the 21st century?. Lancet 2008; 371: 2213-2218.
http://www.thelancet.com/journals/lancet/article/PIIS0140673608609563/fulltext
2. Office of the High Commissioner for Human Rights. International covenant on economic, social and cultural rights.
Geneva: Office of the High Commissioner for Human Rights, 1966:
http://www.unhchr.ch/html/menu3/b/a_cescr.htm
(accessed Aug 13, 2008)..
3. Potts H. Accountability and the right to the highest attainable standard of health. Colchester: University of Essex,
2008:
http://www2.essex.ac.uk/human_rights_centre/rth/project...
(accessed Aug 13, 2008)..
4. Office of the High Commissioner for Human Rights. Substantive issues arising in the implementation of the
International Covenant on Economic, Social and Cultural Rights. General comment no. 14: the right to the highest
attainable standard of health (article 12 of the International Covenant on Economic, Social and Cultural Rights).
Geneva: Office of the High Commissioner for Human Rights, 2000:
http://www.unhchr.ch/tbs/doc.nsf/(symbol)/E.C.12.2000.4...
(accessed Aug 13, 2008)..
Nature
Volume 455 Number 7212 pp431-564 (25 September 2008)
http://www.nature.com/nature/journal/v455/n7212/
[No relevant content]
New England Journal of Medicine
Volume 359 — September 25, 2008 — Number 13
http://content.nejm.org/current.shtml
[No relevant content]
Science
26 September 2008 Vol 321, Issue 5897, Pages 1737-1860
http://www.sciencemag.org/current.dtl
[No relevant content]
Vaccine
Volume 26, Issue 44, Pages 5547-5668 (16 October 2008)
http://www.sciencedirect.com/science/journal/0264410X\
The ethics of mandatory vaccination against influenza for health care workers
Pages 5562-5566
J.J.M. van Delden, R. Ashcroft, A. Dawson, G. Marckmann, R. Upshur, M.F. Verweij
Abstract
“Vaccination of health care workers (HCW) in long-term care results in indirect protection of patients who are at high-
risk for influenza. The voluntary uptake of influenza vaccination among HCW is generally low. We argue that
institutions caring for frail elderly have the responsibility to implement voluntary programmes for vaccination against
influenza of HCW. When uptake falls short a mandatory programme may be justified. The main justification stems
from the duty of care givers not to harm one's patient when one knows there is a significant risk of harm and the
intervention to reduce this chance has a favourable balance of benefit over burdens and risks.”
Decline in influenza-associated mortality among Dutch elderly following the introduction of a nationwide
vaccination program
Pages 5567-5574
Angelique G.S.C. Jansen, Elisabeth A.M. Sanders, Kristin L. Nichol, Anton M. van Loon, Arno W. Hoes, Eelko Hak
Abstract
“With a retrospective nationwide cohort study in the Netherlands over 1992–2003, using mortality and viral
surveillance data, the aim was to assess by means of rate difference methods the influenza-associated mortality in the
elderly before and after the introduction of a nationwide influenza vaccination program in 1996 (vaccination
coverage raised from below 50 to 80%). The average annual influenza-associated mortality declined in the years
before and after the introduction from 131 to 105 per 100,000 persons (relative risk 0.80). The decline was largest in
the age group 65–69 years (relative risk 0.54) and less in those aged 75 years and older. Validation by Serfling-type
regression analysis revealed similar results. In conclusion, routine influenza vaccination among Dutch elderly was
associated with a significant decrease in influenza-associated mortality, notably in those aged 65–69 years.”
Cost-effectiveness of human papillomavirus vaccine in reducing the risk of cervical cancer in Ireland due
to HPV types 16 and 18 using a transmission dynamic model
Pages 5654-5661
Cara Usher, Lesley Tilson, Jens Olsen, Martin Jepsen, Cathal Walsh, Michael Barry
Abstract
“We evaluated the cost-effectiveness of combining a cervical cancer screening programme with a national HPV
vaccination programme compared to a screening programme alone to prevent cervical dysplasia and cervical cancer
related to HPV types 16 and 18 in the Irish healthcare setting. The incremental cost effectiveness of vaccination
strategies for 12-year-old females (base-case) and 12–26-year-old catch-up vaccination strategies were examined.
The base-case incremental cost-effectiveness ratio was €17,383/LYG. Using a probabilistic sensitivity analysis about
the base-case, the 95% CI for cost per LYG was (€3400 to €38,400). This suggests that vaccination against HPV
types 16 and 18 would be cost-effective from the perspective of the Irish healthcare payer.”
_____________________________________________________________________________________________________
22 September 2008
The American Academy of Pediatrics announced formation of a new coalition – The Immunization
Alliance – involving “the nation’s leading medical and advocacy groups…to raise the public’s confidence
in vaccines…(calling) on policymakers, public health agencies, physicians, and the public to work together to
preserve the health of the nation’s children through immunization.” Renee Jenkins, MD, FAAP, president of the
American Academy of Pediatrics, said, “We do not want to become a nation of people who are vulnerable to diseases
that are deadly or that can have serious complications, especially if those diseases can be prevented. The groups in
this Alliance have made a commitment to pool our resources and expertise, and to ask the government to help avert
what could become a national emergency. We want to impress upon the public the possible consequences—safety,
medical, personal, and economic issues—of having a population that is not adequately protected against measles,
whooping cough, meningitis, and many other diseases.”
The Alliance stated its commitment to “ensure adequate levels of immunization in the United States,” and jointly
endorsed a Call to Action to enlist health professionals, the public, the media and the government in supporting
immunizations and their importance to the public’s health. Included are “requests for a public information campaign
by the government; a commitment to ongoing research to ensure the continued safety, efficacy and development
of vaccines; balanced reporting by the media; continued efforts from doctors in working with parents; and
confidence from parents themselves.” The group noted that although the Centers for Disease Control and
Prevention (CDC) announced that 2007 immunization rates were adequate, recent data show that approximately
one-fourth of toddlers are not properly immunized, and that recent outbreaks of measles in several cities, the worst
in a decade, are just one example of how the decision not to vaccinate can affect individual children and the public’s
health. Most cases have been among the unvaccinated.
The Alliance also said that adolescents and adults should receive immunizations and vaccine boosters according to
recommendations from the CDC, the American Academy of Family Physicians, the American Academy of Pediatrics,
the American College of Physicians, the American Medical Association, and the American College of Obstetricians and
Gynecologists “in order to protect themselves and to do their part to keep infectious diseases at bay in their
communities.”
The Immunization Alliance, which comprises the groups listed below, sets forth the following
Call to Action for public health organizations, government, health care professionals, the media and the
public:
What the Alliance commits to:
We commit to continued partnerships with policy makers to ensure that:
- children receive recommended immunizations on time (according to the schedule of the Centers for Disease Control
and Prevention/Advisory Committee on Immunization Practices, the American Academy of Family Physicians and the
American Academy of Pediatrics) to protect them against vaccine-preventable diseases and to protect the public’s
health;
- vaccines are as safe as possible and vaccine safety research is adequately funded;
- the vaccine supply is sufficient and equitably distributed;
- parents and caregivers have the knowledge and information they need to make fully-informed decisions in the best
interests of their child.
What the Alliance asks:
- We ask the U.S. Department of Health and Human Services to undertake a public information campaign reinforcing
the value and importance of immunization to empower parents to make informed decisions about vaccinating their
children.
- We ask physicians and other health care professionals to work closely with parents and patients to foster an
understanding of the need for, and timing of, recommended vaccines, and to assess what is needed to earn or
regain the trust of some parents. The goal is to work as a team to fully protect infants and children against diseases
that can result in death or life-long disability.
- We ask medical professional organizations and public health agencies to provide support and guidance to physicians
in counseling parents about the importance and safety of vaccines. The goal is to facilitate informed decision-making
by parents and caregivers.
- We encourage parents to ask questions at the doctor’s office, and to expect answers based on the best scientific
information available. We ask them to rely on credible sources for their information about vaccine safety and
effectiveness, and to take the time to understand the evidence on which immunization recommendations are based
in order to make fully informed decisions about their children’s health.
- We ask the federal government to dedicate funding for continued research into vaccine safety and effectiveness.
- We ask the media to take the time to understand vaccine science and the evidence on which immunization
recommendations are based. We also ask the media to keep the public interest foremost in their treatment of this
subject, and to consider the potential consequences of lending credence to various publicity efforts and
spokespersons without a complete and critical review of the scientific merit of these sources.
- We ask that, given the importance of communicating scientifically based and trustworthy information, all editors of
Internet content, publications and blogs should ensure that appropriate efforts are made to comply with the high
standards associated with responsible journalism.
List of Participating Organizations
American Academy of Family Physicians
American Academy of Pediatrics
American Academy of Physician Assistants
American College of Preventive Medicine
American College of Obstetricians and Gynecologists
American College of Osteopathic Pediatricians
American Medical Association
American Public Health Association
America’s Health Insurance Plans
Association of State and Territorial Health Officials
California Immunization Coalition
Every Child By Two
Immunization Action Coalition
Infectious Diseases Society of America
March of Dimes
National Foundation for Infectious Diseases
Parents of Kids with Infectious Diseases
Pediatric Infectious Diseases Society
Sabin Vaccine Institute
UnitedHealth Group
Vaccine Education Center at The Children's Hospital of Philadelphia
Voices for Vaccines
(Sept. 18, 2008)
http://www.aap.org/advocacy/releases/sept08Immunizationalliance.htm
The WHO reported that progress is being made in malaria control, but the overall disease burden is still
enormous, and that new methods estimate that the number of malaria cases in 2006 was 247 million,
substantially lower than previous estimates. Access to malaria control interventions, especially bednets in Africa,
increased sharply between 2004 and 2006, says the WHO report [link below]. WHO Director-General Dr Margaret
Chan said, "With dramatic increases in funding and intense momentum towards reducing the malaria burden in
recent years, we have a greater need for reliable information and analysis. This report begins to answer that need.
Progress in malaria control has accelerated dramatically since 2006, especially in the wake of the UN Secretary-
General’s call for universal malaria control coverage by the end of 2010. We expect these expanded efforts to be
reflected in future reports."
Overall, the report finds that recent increases in malaria funding were beginning to translate into coverage of key
malaria interventions, especially bednets, by 2006. The percentage of children protected by insecticide-treated nets
increased almost eightfold, from 3% in 2001 to 23% in the 18 African countries where surveys were held in 2006.
Procurement of antimalarial medicines also increased sharply between 2001 and 2006. About 100 million people,
including 22 million in Africa, were protected by indoor spraying of insecticide, the report notes. In Africa, only 125
million people were protected by bednets in 2007, while 650 million are at risk.
(18 September 2008)
http://www.who.int/mediacentre/news/releases/2008/pr32/en/index.html
Report: http://www.who.int/malaria/wmr2008/
The Weekly Epidemiological Record (WER) for 12 September 2008, vol. 83, 37 (pp 333 348) includes:
- Global programme to eliminate lymphatic filariasis;
- Conclusions of the meeting of the Technical Advisory Group on the Global Elimination of Lymphatic Filariasis,
November 2007;
- WHO web sites on infectious diseases
http://www.who.int/wer/2008/wer8337.pdf
Journal Watch
[Editor’s Note]
Vaccines: The Week in Review continues a new feature, scanning key journals to identify and cite articles, comment
and editorials, books reviews and other content supporting our focus on vaccine ethics and policy. This scan is not
intended o be exhaustive, but indicative of themes and issues the center is actively tracking. Successful access to
some of the links provided may require subscription or other access arrangement unique to the publisher. Our initial
scan list includes the journals below. If you would like to suggest other titles, please write to David Curry at david.r.
curry@centerforvaccineethicsandpolicy.org
JAMA
Vol. 300 No. 11, pp. 1273-1374, September 17, 200808
http://jama.ama-assn.org/current.dtl
[No relevant content]
Journal of Infectious Disease
1 October 2008 Volume 198, Number 7
http://www.journals.uchicago.edu/toc/jid/current
[reviewed earlier]
The Lancet
Volume 372, Number 9643, 20 September 2008
http://www.thelancet.com/journals/lancet
The Lancet 2008; 372:1025-1026
DOI:10.1016/S0140-6736(08)61425-7
[Editor’s Note: We present this report in full text due to its importance and as a courtesy to our project team]
World Report
Predicting the next pandemic
Eliza Barclay
“Even as HIV/AIDS and avian influenza remain unresolved threats to human health, increasingly attention is shifting
to the next pandemic, and how to predict and prevent the disastrous consequences of wide-spread transmission of
a new disease. That undiscovered viruses and pathogens are evolving with the potential to infect the human
population is not under dispute. According to an analysis published in Nature in February, 2008, 335 emerging
infectious disease events occurred between 1940 and 2004. Of those, 60·3% were zoonoses, and most originated in
wildlife, including the virus that causes severe acute respiratory syndrome (SARS) and the Ebola virus. Vectorborne
diseases made up 22·8% of the total. The analysis also found that the threat of emerging infectious diseases to
global health has been increasing over time. As international travel and trade have proliferated, disease-causing
agents now have the ability to move around the globe at faster rates. Human beings and animals are also finding
themselves in increasingly closer contact with each other from deforestation and higher demand for animal products
in local and international markets.
Google.org—the philanthropic arm of the technology giant—has surfaced as one of the champions of intercepting
emerging diseases before they become pandemics with its Predict and Prevent initiative. “Zoonoses have only come
to our attention when people start dying in the USA”, said Frank Rijsberman, Google.org’s director of water and
climate adaptation initiatives. “We want to move surveillance to the places of origin and the current hotspots to find
out when people get sick.” At the moment “there are few systematic ways to do that”.
Predict and Prevent has a special interest in two regional hot spots: southeast Asia—where animals and human
beings coexist more intimately than anywhere else in the world—and sub-Saharan Africa—which has the greatest
burden of infectious diseases and worst public-health infrastructure in the world. Poverty makes both regions
exceptionally vulnerable to new diseases. Until recently scientists' understanding of the process of disease emergence
was poor. But with viral genetics, researchers can now follow the evolution of a virus at a molecular level and estimate
its ability to infect large numbers of human beings.
Many infectious-disease experts believe widespread transmission of HIV/AIDS could have been prevented if the
proper surveillance systems had been in place in the 1970s and 80s as the disease emerged. Nathan Wolfe, professor
of epidemiology at the University of California, Los Angeles and the founder and director of the Global Viral
Forecasting Initiative, says the failure of the “wait-and-respond” approach to HIV/AIDS and the lack of an early
warning system cost millions of lives. Wolfe's work on prediction of zoonosis emergence has shown that the global
emergence of a zoonotic pathogen such as SARS or HIV/AIDS depends on three steps. First, the pathogen must be
successfully transmitted between a wild reservoir and human beings or their domestic animals. Second, the pathogen
must be directly transmitted between humans. Finally, the pathogen must move from a local epidemic into the global
population. “We work with bushmeat hunters and other people who [often come into contact with] wild animals
because these people are highly exposed to viral agents that could be emerging diseases”, said Wolfe. “We also look
at animal die-offs as important indicators of an emerging disease.”
According to Wolfe, samples from human beings in close contact with animals can reveal patterns of viral chatter,
where viruses bubbling up in animal populations are constantly crossing into human populations. “These viruses are
pinging humans, or chattering. In the same way we monitor cellphone conversations for key words, we are
monitoring viral chatter, and looking for viruses that are transmissible and cause disease”, said Wolfe. “Not all of the
chatter will be real; we'll have to understand patterns of chatter to improve our ability to predict a pandemic.” As
scientists like Wolfe gather samples from human beings on potentially threatening new viruses, other scientists
interested in emerging infectious diseases are trying to cull data gathered by wildlife biologists and veterinarians on
zoonoses.
The Wild Bird Global Avian Influenza Network for Surveillance (GAINS) is a mapping and data sharing initiative of the
Wildlife Conservation Society with partners in 34 countries. The project was launched during the avian influenza scare
in 2006 and currently has over 100 million birds with their Global Positioning System [GPS] locations logged into the
system, along with other relevant data. “We can't begin to predict and prevent until we have information on what's
going on and where”, said William Karesh, vice president for global-health programmes at the Wildlife Conservation
Society. “The information has to be readily available so that people can look in the right place.” Although data are
currently available only for wild birds, GAINS has the technological capacity to make data for other animal species
available in the future. GAINS also counts on an unusual relationship with scientists—that they will share their data
before they are published in a journal in hopes that they will be useful to other researchers interested in or working
on similar issues.
With systems like GAINS and other resources, the world took one step closer to anticipating the potential of avian flu
to become a pandemic. “Avian influenza helped a lot of people get mobilised but so far it is a relatively isolated event”,
said Rijsberman. “We would like to use some of the tools developed for avian flu for other emerging infectious
diseases.” What Rijsberman foresees is a broad, international community of people bringing data together to build
early warning systems covering various diseases. Thus far, most of the scientific and surveillance effort has focused
on developed countries from where the next emerging infectious disease is least likely to originate.
Several web-based tracking initiatives are attempting to broaden the scope of available information on outbreaks and
emerging diseases by culling information from news reports around the world. The best developed of these initiatives
are HealthMap, ProMED-mail, and the Public Health Agency of Canada's Global Public Health Intelligence Network
(GPHIN). GPHIN helped establish the credibility and need for online tracking systems when it helped to capture and
disseminate initial reports of SARS in China.
HealthMap is a free, web-based program that searches news and other non-traditional or informal web information
sources to assist and publicise early outbreaks using Google Maps. John Brownstein, co-creator of HealthMap and an
assistant professor of paediatrics at Harvard Medical School, says HealthMap is one of the few systems tracking
outbreaks in real time with respect to when news gets posted, whereas official government sites usually confirm
outbreaks before posting them online. One of the challenges for HealthMap is filling in the gaps between what is
happening on the ground in disease hot spots and what information is making it into the news. HealthMap says it is
on the cusp of integrating text messages into its system as cellphone usage is increasing at a more dramatic pace
than is internet use. “As we roll out the system eventually we want to build in ways to allow anyone to input
information”, said Brownstein. Clark Freifeld, co-creator of HealthMap, says HealthMap is also looking at ways to build
in data from scientists like Wolfe and those who are contributing to GAINS. “We are building up a database of
infectious disease reports, which we will catalogue in a way to look at different pathogens” he said.
ProMED-mail is one key source of relevant news reports for HealthMap and another web-based surveillance system
that is helping to monitor disease emergence. The service is daily report, monitored and edited by public health
experts affiliated with the International Society for Infectious Diseases.
Although HealthMap and ProMED-mail are the free, multilingual programs accessible to anyone, GPHIN is available by
subscription only and is limited to officials and institutions that are involved in public-health surveillance.
As existing systems for disease surveillance develop and integrate, Google.org is looking at creating new ways to
share information globally using the internet. “We would love to see something like an eBay or a virtual marketplace
for samples where demand, supply, and knowledge would come together, where people doing research on diseases
in Africa collaborate with sites in Asia”, said Rijsberman. “The current systems are very far behind the power of the
internet, and Google has the ability to build new platforms for researchers. In a couple of years we could see real
concrete outputs that allow us to predict and prevent in new ways.”
Nature
Volume 455 Number 7211 pp263-430 (18 September 2008)
http://www.nature.com/nature/journal/v455/n7209/
[No relevant content]
New England Journal of Medicine
Volume 359 — September 18, 2008 — Number 12
http://content.nejm.org/current.shtml
[No relevant content]
Science
19 September 2008 Vol 321, Issue 5896, Pages 1589-1724
http://www.sciencemag.org/current.dtl
[No relevant content]
Vaccine
Volume 26, Issue 42, Pages 5331-5434 (3 October 2008)
http://www.sciencedirect.com/science/journal/0264410X\
(reviewed last week)
______________________________________________________________________________________________________
15 September 2008
GAVI said that some 2,2 million people were successfully vaccinated in Abidjan, Cote d'Ivoire following
an urban yellow fever outbreak. The national Ministry of Health, WHO, UNICEF, NGOs and others in the Yellow
Fever Partnership combined their forces to vaccinate people in the Ivorian capital in a campaign which lasted 14 days
and finished on Friday 5 September, GAVI said. Vaccine financed by the GAVI Alliance was distributed to points across
the capital, and administered by trained health teams. GAVI said that “by ensuring that over 2.2 million non-
vaccinated people out of a total population of approximately 5 million in the capital received their Yellow Fever (YF)
vaccination, YF vaccination coverage rates were brought up to levels in the city where the entire population can be
expected to be protected against epidemics.” It is estimated that at least 60-80% of a given population has to be
vaccinated for epidemics to be obviated in the entire population. Prior to this vaccination campaign, the last YF
vaccination campaign in Abidjan had taken place in 2001, achieving a coverage rate above 90%. But vaccination
coverage rates were estimated to have slipped down to 60% in the intervening years, due to population movements
and births.
GAVI noted that this emergency campaign comes as the Yellow Fever Initiative, with $58 million worth of support
from GAVI, is continuing its mass vaccination programmes across West Africa aimed at drastically reducing the
numbers at risk from Yellow Fever. So far, three countries - Mali, Senegal and Togo - have undertaken national
preventive vaccination campaigns as part of the Initiative, with other countries due to follow suit as soon as sufficient
vaccine is available. The ministries of Health of these 12 countries are being supported financially and technically by a
Yellow Fever partnership which was launched in February 2006 and now includes WHO, UNICEF, GAVI, Médecins
Sans Frontières, IFRC, the Association pour la Médecine Préventive (AMP), the Programme for Appropriate
Technology (PATH), the European Union Humanitarian Aid Office (ECHO), the United States Centers for Disease
Control and Prevention (CDC), the Global Outbreak Alert and Response Network (GOARN) and the Institut Pasteur.
The partnership continues to take on new members.
http://www.gavialliance.org/media_centre/press_releases/2008_09_09_WHO_pr_Abidjan_yellow_fever.php
The International Federation of Pharmaceutical Manufacturers & Associations (IFPMA) said it created a
special Pediatric Task Force “to enhance the contribution of industry expertise to the important task of
improving the availability of medicines and vaccines for children.” The IFPMA Pediatric Task Force “will work
with relevant intergovernmental organizations, non-governmental organizations and other key stakeholders to
identify and address opportunities for the systematic expansion of medicine development for younger age groups.”
IFPMA Director General Alicia Greenidge said, “The IFPMA Pediatric Task Force will enable more focused work between
the industry and other stakeholders, to address effectively and concretely the various obstacles to developing more
medicines adapted for children, especially for the developing world. This new task force will serve as a catalyst for that
process, inspired by regulatory, World Health Organization and other initiatives -- principally, the critical needs of the
world's children.”
IFPMA said the Task Force “will build on the industry’s existing range of pediatric medicine and vaccine development
and access activities, and work to address specific concerns highlighted by the WHO(1) and other organizations.
These include identifying appropriate dosage forms and strengths of medicines for children (starting with HIV/AIDS,
tuberculosis, malaria and chronic diseases), encouraging R&D of appropriate medicines for diseases that specifically
affect children, and ensuring high quality and ethical standards in clinical trials involving children, including informed
consent.”
The new body will also serve as an industry discussion forum, “to ensure pediatric medicine R&D and related topics
have a prominent position in the industry’s agenda.” It will also provide a global complement to existing regional and
national industry association pediatric medicine groups, such as those set up by the European Federation of
Pharmaceutical Industries and Associations (EFPIA) in the European Union, the Japan Pharmaceutical Manufacturers
Association (JPMA) in Japan and the Pharmaceutical Research and Manufacturers of America (PhRMA) in the USA.
( IFPMA Media Release, 15 September 2008)
The Fogarty International Center of the National Institutes of Health, said it will award $4.6 million over
three years “to expand its network of global health education programs to include 12 additional
campuses in the United States, China and Mexico” through its Framework Programs for Global Health.
The initiative aims “to raise awareness of global health within the academic community and support development of
new curricula and degree programs that cut across departments and schools to create a pipeline for the next
generation of global health researchers.” NIH Director Elias A. Zerhouni, M.D., said,
"As the world becomes increasingly interconnected, there is a compelling need for novel, multidimensional
approaches to global health research. By removing the existing academic silos and working across disciplines, we can
better leverage our knowledge and skills to tackle difficult global health challenges and save lives around the world."
Each site will receive approximately $400,000 over three years “…to develop a structure and activities that best suit
its existing strengths and research capabilities.” NIH said the new awardees will join the existing network of 19 sites
that have received Framework grants since the program’s inception in 2005. Within these institutions, faculty from
more than 17 different disciplines have participated including those from schools of medicine, public health,
anthropology, law, engineering, environmental sciences, journalism, business and others, NIH said
2008 Framework Awards:
Brown University, Providence, R.I.
Duke University, Durham, N.C.
Fudan University, Shanghai, China
Harvard University, Cambridge, Mass.
National Institute of Public Health, Cuernavaca, Mexico
Northwestern University, Evanston, Ill.
Ohio State University, Columbus, Ohio
Oregon Health and Science University, Portland, Ore.
Tulane University, New Orleans
University of California, San Francisco
University of Pittsburgh
University of Texas Medical Branch at Galveston, Texas
(NIH Media Release, 10 September 2008)
http://www.nih.gov/news/health/sep2008/fic-10.htm
The Heinz Foundation honored five Americans with 14th Annual Human Achievement Prize. The
$250,000 awards recognize significant accomplishments in five distinct categories – the arts and humanities; the
environment; human condition; public policy; and technology, the economy and employment. Each area was of
particular interest to John Heinz, the late U.S. Senator for whom the awards are named. The recipient in the
Technology, the Economy and Employment category is Joseph DeRisi, Ph.D., 38, a molecular biologist,
researcher and inventor, from San Francisco.
The award media release noted:
“An innovative, selfless and generous researcher whose breakthrough creation of a viral detection platform for
malaria and other infectious diseases has helped advance biomedicine’s ability to detect both existing and new
viruses, Dr. Joseph DeRisi stands at the intersection of the disciplines driving the life sciences – genomics,
bioinformatics, virology, materials science and computer engineering. His pioneering invention – the ViroChip, a band-
aid-sized glass wafer that contains a microarray of 22,000 DNA sequences from more than 1,300 viral families –
provides “diagnostics on a chip,” enabling scientists to not only quickly and accurately identify existing viruses, but
also to detect new viruses that could emerge as pandemic threats. In 2003, the ViroChip identified the SARS virus
within 24 hours.
“Notwithstanding his work in virus detection, Dr. DeRisi’s primary focus has been on finding a cure for malaria, a
disease that infects up to 500 million people annually, killing between 700,000 and 2.7 million, mostly children. Dr.
DeRisi, together with his longtime collaborator, Dr. Don Ganem, and his team at the University of California, San
Francisco developed a malaria-specific DNA chip, similar to the ViroChip, that enabled them to characterize the
parasite’s distinctive 48-hour life cycle, a breakthrough that could pave the way for potential drug and vaccine
therapy. He also has taken on a number of other challenges, from investigating a cure for the common cold to an
analysis of the disappearance of a half-million honeybee colonies in the United States. Driven by scientific discovery
alone, Dr. DeRisi has distinguished himself within the highly competitive world of biomedicine by giving most of his
research and knowledge away for free.”
(Business Wire, 9 September 2008)
The U.S. Food and Drug Administration approved “expanded uses” of Gardasil vaccine for the
prevention of vaginal and vulvar cancer caused by Human Papillomavirus (HPV) types 16 and 18 in girls
and women ages 9 to 26. These two HPV types cause 70 percent of cervical cancers, and are known to also
cause some vulvar and vaginal cancers, but the percentages are not well defined. Jesse L. Goodman, M.D., M.P.H.,
director of the FDA’s Center for Biologics Evaluation and Research, commented, “There is now strong evidence
showing that this vaccine can help prevent vulvar and vaginal cancers due to the same viruses for which it also helps
protect against cervical cancer. While vulvar and vaginal cancers are rare, the opportunity to help prevent them is
potentially an important additional benefit from immunization against HPV.” The FDA originally approved Gardasil in
2006 for girls and women ages 9 to 26 for the prevention of cervical cancer caused by HPV types 16 and 18,
precancerous genital lesions caused by HPV types 6, 11, 16, and 18 and genital warts caused by HPV types 6 and
11. HPV includes more than 100 related viruses and more than 30 types can be transmitted via sexual contact.
According to the U.S. Centers for Disease Control and Prevention, HPV is the most common sexually transmitted
infection in the United States with 6.2 million Americans becoming infected with genital HPV each year.
(FDA Media Release, 12 September 2008)
http://www.fda.gov/bbs/topics/NEWS/2008/NEW01885.html
WHO: Avian influenza – situation in Indonesia – update 44
10 September 2008 -- The Ministry of Health of Indonesia has retrospectively announced two confirmed cases of
human infection with the H5N1 avian influenza virus. The first case, a 38 year old male from Tangerang Municipality,
Banten Province developed symptoms on 4 July 2008, was hospitalized on 9 July and died on 10 July. There were
free roaming poultry throughout his neighbourhood, including a commercial poultry pen owned by a neighbour. The
second case, a 20 year old male from Tangerang District, Banten Province developed symptoms on 20 July, was
hospitalized on 29 July, and died on 31 July. Reports indicate that chickens from the case's household had died in
the week preceding the onset of his symptoms and that he had slaughtered and consumed some of his stock during
this period. Of the 137 cases confirmed to date in Indonesia, 112 have been fatal.
The Weekly Epidemiological Record (WER) 12 September 2008, vol. 83, 37 (pp 333–348) includes:
- Global programme to eliminate lymphatic filariasi
- Conclusions of the meeting of the Technical Advisory Group on the Global Elimination of Lymphatic Filariasis,
November 2007
- WHO web sites on infectious diseases
http://www.who.int/wer/en/
Journal Watch
[Editor’s Note]
Vaccines: The Week in Review continues a new feature, scanning key journals to identify and cite articles, comment
and editorials, books reviews and other content supporting our focus on vaccine ethics and policy. This scan is not
intended o be exhaustive, but indicative of themes and issues the center is actively tracking. Successful access to
some of the links provided may require subscription or other access arrangement unique to the publisher. Our initial
scan list includes the journals below. If you would like to suggest other titles, please write to David Curry at david.r.
curry@centerforvaccineethicsandpolicy.org
JAMA
Vol. 300 No. 10, pp. 1115-1262, September 10, 2008
http://jama.ama-assn.org/current.dtl
[No relevant content]
Journal of Infectious Disease
1 October 2008 Volume 198, Number 7
http://www.journals.uchicago.edu/toc/jid/current
[reviewed last week]
The Lancet
Volume 372, Number 9642, 13 September 2008
http://www.thelancet.com/journals/lancet
[This issue of The Lancet focuses on the state of global primary health care. The Editorial on this theme is presented
in full text below as a courtesy to our working group.]
Editorial
“30 years ago, in the midst of the Cold War, health experts and policy makers from 134 WHO member states
convened in the former USSR to attend a conference on international primary health care. On Sept 12, 1978, the
Alma-Ata Declaration was signed, with the ambitious target of achieving “Health for All by 2000”.
“In 1978, 2000 million people were estimated to have no access to adequate health care. There were vast inequalities
between rich and poor countries, and between rich and poor populations within countries. The Alma-Ata Declaration
revolutionised the world's interpretation of health. Its message was that inadequate and unequal health care was
unacceptable: economically, socially, and politically. Unfortunately, the goal of “health for all”, while a rallying call to
action, was not met. Theories for this failure abound: the vision for primary health care was politically unacceptable to
some nations and so was marginalised; emerging health threats took precedence (no one imagined the global disease
burden that HIV/AIDS would bring); and health priorities shifted (to the Millennium Development Goals [MDGs]).
“30 years on, what is the relevance of the Alma-Ata Declaration in 2008? In short, primary health care is now offering
global health a lifeline. Progress towards the MDGs has stalled. Weak health systems have restricted the success of
efforts to improve maternal, newborn, and child health, and to reduce the disease burden from malaria and
tuberculosis. New epidemics of chronic disease threaten to reverse what small gains have been achieved. To get back
on track, and to meet the MDGs by 2015, countries need to strengthen their health systems through the
implementation of effective primary health care.
“Now is the right moment to proclaim the urgent need for a renaissance in primary health care. The continuing
relevance of this 30-year-old Declaration is remarkable. Many of the challenges faced in 1978 remain, such as
infectious diseases (e.g., the ongoing threat of H5N1 avian influenza and HIV/AIDS), political instability and conflict
(most recently seen in Iraq and Zimbabwe), and worsening poverty (the World Bank last month estimated that 1•4
billion people now live in poverty).
“In recognition of this timely reawakening of interest in primary health care, this week's Lancet revisits, updates, and
relaunches the key messages from Alma-Ata. A series of eight papers begins with an analysis of modern primary
health care, and issues such as implementing cost-effective interventions in low-resource settings and tackling the
growing burden of chronic diseases. We publish an analysis of individual country progress since 1978, with possible
lessons for those who have shown the least advance. Involvement of communities in planning and implementation of
health care (one of the main tenets of the Alma-Ata Declaration) is explored in the context of maternal, newborn,
and child health, as are the roles of national policies and effective service integration, all foundations of a successful
primary health care service. The final paper in the series looks to the future and provides a series of action points to
revitalise primary health care, both nationally and globally.
“WHO's vision for health—complete physical, mental, and social wellbeing—is the key to achieving Alma-Ata's prime
goal of “health for all”. This week's research articles also focus on these three principles. Stephen Tollman and
colleagues discuss the challenges in managing chronic diseases in primary health care and the importance of
providing adequate services to ensure physical wellbeing. Atif Rahman and co-workers tackle mental health in
Bangladesh, with a psychological intervention that can be delivered within communities to treat mothers with
perinatal depression. And the importance of social development is shown by Luis Huicho and authors who present
data from four countries highlighting the importance of health workers with shorter durations of training in providing
vital care to people in low-resource settings.
“Importantly, WHO, under Margaret Chan's effective leadership and together with her regional directors, has
reaffirmed its commitment to primary health care. This revisioning of the principles of Alma-Ata is welcome and
illustrates a new unity of purpose across global health institutions. Political progress is also encouraging. Following the
G8 meeting earlier this year, Japan has announced its own commitment to lead international initiatives to strengthen
health systems. Such renewed global interest in primary health care is promising. The need remains great and there
are no shortcuts to success. But with refined international relationships, new and emerging technologies, and 30
years of experience, “health for all” need not be a dream buried in the past. The right to the highest attainable
standard of health can be a reality within our grasp.”
Nature
Volume 455 Number 7210 pp137-262 (11 September 2008)
http://www.nature.com/nature/journal/v455/n7209/
[No relevant content]
New England Journal of Medicine
Volume 359 — September 11, 2008 — Number 11
http://content.nejm.org/current.shtml
[No relevant content]
Science
12 September 2008 Vol 321, Issue 5895, Pages 1401-1588
http://www.sciencemag.org/current.dtl
[No relevant content]
Vaccine
Volume 26, Issue 42, Pages 5331-5434 (3 October 2008)
http://www.sciencedirect.com/science/journal/0264410X\
The role of economic information in decision-making by the Advisory Committee on Immunization
Practices
Pages 5389-5392
Amanda F. Dempsey, Anne E. Cowan, Shannon Stokley, Mark Messonnier, Sarah J. Clark, Matthew M. Davis
Abstract
“With cost of vaccines steadily increasing, recommendations of the Advisory Committee on Immunization Practices
(ACIP) have growing economic implications for the public. We used semi-structured telephone interviews to assess
the knowledge, attitudes, and practices of the 15 voting members of the 2006–2007 ACIP regarding the use of
economic information by the committee in their deliberations about new vaccine recommendations. These interviews
demonstrated the importance of economic information in ACIP deliberations, but also revealed that many members
felt economic information should not be outweighed by the more important issues of vaccine efficacy, disease
burden, and safety. In addition, though members had variable levels of expertise in analyzing economic data, there
was a general concern that assumptions inherent in the development of cost-effectiveness models made
interpretation of the data resulting from these models difficult. To counteract this concern, several ACIP members
suggested standardizing the process of how economic data are presented to the committee so that a more uniform
consideration of consequential information might be undertaken by the ACIP in their deliberations.”
H5N1 VLP vaccine induced protection in ferrets against lethal challenge with highly pathogenic H5N1
influenza viruses
Pages 5393-5399
Kutubuddin Mahmood, Rick A. Bright, Nutan Mytle, Donald M. Carter, Corey J. Crevar, Jenna E. Achenbach, Penny
M. Heaton, Terrence M. Tumpey, Ted M. Ross
Abstract
“In this study, recombinant virus-like particles (VLPs) were evaluated as a candidate vaccine against emerging
influenza viruses with pandemic potential. The VLPs are composed of the hemagglutinin (HA), neuraminidase (NA),
and matrix 1 (M1) proteins of the H5N1 A/Indonesia/05/2005 (clade 2.1; [Indo/05]) virus, which were expressed
using baculovirus in Spodoptera frugiperda (Sf9) cells. Ferrets received either 2 injections of the VLP vaccine at
escalating doses (based on HA content), recombinant HA, or were mock vaccinated. Vaccinated ferrets were then
challenged with either H5N1 Indo/05 or H5N1 A/Viet Nam 1203/2004 (VN/04) wild-type viruses. All ferrets that
received the VLP vaccine survived regardless of the VLP dose or challenge strain, whereas seven of eight mock
vaccinated ferrets died. The VLP vaccine induced HAI antibodies against the homologous H5N1 clade 2.1 strain, as
well as heterologous strains from H5N1 clades 1, 2.2, and 2.3. The magnitude of the HAI titers correlated with VLP
dose. Neutralizing antibody responses against the Indo/05 and VN/04 strains showed a similar pattern. Affinity of the
anti-HA antibodies raised by the H5N1 Indo/05 VLPs had a higher association rate to the homologous clade 2.1 HA
than to the clade 1 (VN/04) HA; however, once bound, antibodies had similar slow disassociation rates. These results
provide support for continued development of the H5N1 VLPs as a candidate vaccine against pandemic influenza.
Exploration of immunologic correlates of protection for H5N1 vaccines beyond HAI and neutralizing antibody
responses is warranted.”
______________________________________________________________________________________________________
8 September 2008
A new UN report – “Delivering on the Global Partnerships for Achieving the Millennium Development
Goals” – highlights “the existence of large gaps in the availability of medicines in both the public and
private sectors, as well as a wide variation in prices which render essential medicines unaffordable to
poor people.” Launched on September 4th by the UN Secretary-General, the report describes progress towards
achieving MDG 8 (Develop a global partnership for development) and its related targets in the areas of essential
medicines, official development assistance, trade, external debt and technology.
[MDG 8, Target 8.E: In cooperation with pharmaceutical companies, provide access to affordable essential
medicines in developing countries was measured using nine indicators for measuring access to
medicines using data collected by WHO and its partners.]
The report found that “in the public sector, generic medicines are only available in 34.9% of facilities, and on average
cost 250% more than the international reference price. In the private sector, those same medicines are available in
63.2% of facilities, but cost on average about 650% more than the international reference price. While policies that
promote access such as generic substitution are in place in many countries, additional national and international
efforts are required to improve the availability and affordability of medicines.”
http://www.who.int/medicines/mdg/en/index.html
The WHO reported that health ministers from countries of the African meningitis belt have “committed
themselves to introduce a highly promising candidate meningitis vaccine,” designed to prevent periodic
epidemics. The ministers were meeting at the 58th session of the WHO Regional Committee for Africa, held in
Yaoundé from 1 to 5 September, and the ministers adopted the Yaoundé Declaration, committing themselves to ”
…prepare comprehensive meningitis control plans, including the introduction of the new vaccine once available; to
implement meningitis control strategies; to undertake joint action vis-à-vis the threat; to improve information
exchange for epidemic response; and to contribute financially to epidemic control activities.”
Professor Avocksouma Djona, Minister of Public Health, Chad, said, "Several hundred million people are at risk of
meningitis in 25 African countries. Many generations have suffered. On behalf of all affected countries in Africa, today
we are collectively committing ourselves to put an end to devastating outbreaks of this disease. We will ensure that
this effective new vaccine is made available to populations throughout the Meningitis belt." WHO Director-General, Dr
Margaret Chan noted that WHO will provide technical support for introduction of the vaccine. The meningitis
prevention and control strategy was reviewed and endorsed by WHO's Strategic Advisory Group of Experts on
Immunization in April 2008 and by the GAVI Alliance Board in June 2008.
The new product, conjugate meningococcal A vaccine ("MenAfriVac"), was developed through the Meningitis Vaccine
Project, a product development partnership between WHO and the Program for Appropriate Technology in Health
(PATH), a non-governmental organization. The project was set up in 2001 with core funding from the Bill & Melinda
Gates Foundation. The new vaccine is expected to be introduced starting 2009-10 in Burkina Faso and will be phased
into an additional 24 countries between 2010 and 2015, with GAVI support. GAVI funding will also go towards
ensuring sufficient stocks of the current vaccines are available for epidemic response during the introduction of
MenAfriVac.
http://www.who.int/mediacentre/news/releases/2008/pr31/en/index.html
GAVI Alliance Executive Secretary Julian Lob-Levyt GAVI, speaking at the opening plenary of the Third
High-Level Forum on Aid Effectiveness in Accra, Ghana, “highlighted the experience of GAVI and other
global partnerships, saying that the strong focus on country ownership to achieve results had proved
effective.” He observed, “Country ownership has to be the starting point of aid effectiveness. The challenge is
genuinely to put the country in charge, to listen, adjust priorities, and measure results…” The conference involved
some 1,300 delegates, including more than 100 government ministers and heads of development agencies, donor
organisations and civil society organisations (CSOs) “committed to making aid more transparent, accountable and
results-oriented.” Julian Lob-Levyt also underlined GAVI’s commitment to the principles of aid effectiveness by
endorsing the International Aid Transparency Initiative, http://www.dfid.gov.uk/news/files/pressreleases/aid-
transparency-intiative.asp which is being launched in Accra. The initiative commits donors and agencies to improve
public access to information on aid flows.
http://www.gavialliance.org/media_centre/statements/2008_09_03_Accra_statement.php
The Bill & Melinda Gates Foundation said it is now accepting grant proposals for Round 2 of Grand
Challenges Explorations, described as a five-year US$100 million initiative “to encourage bold and
unconventional research on new global health solutions.” Proposals for six topics will be accepted online
through November 2, 2008 and “…follows on the heels of the initiative's first funding round, which closed in May of
this year, and generated nearly 4,000 applications from scientists in more than 100 countries.” The Gates Foundation
noted that one of the primary objectives of Grand Challenges Explorations is “to involve scientists around the world
who do not typically work in global health. This includes those with innovative ideas in Africa, Asia, and other parts of
the developing world; people working in the private sector; and young investigators.” Gates said the topic areas for
which proposals will be accepted in Round 2 are:
- Create new vaccines for diarrhea, HIV, malaria, pneumonia, and TB.
- Create new tools to accelerate the eradication of malaria.
- Create new ways to protect against infectious diseases, including alternatives to traditional vaccination.
- Create new drugs and delivery systems to limit the emergence of resistance in the disease-causing agent.
- Create new ways to prevent or cure HIV infection that fall outside current research on vaccines and other
biomedical and behavior-change strategies.
- Explore the basis for latency in TB, with the goal of discovering new ways to identify and eliminate latent infection.
The foundation and an independent group of reviewers will select the most innovative proposals, and grants will be
awarded within approximately three months from the proposal submission deadline. Initial grants will be $100,000
each. Projects showing success will have the opportunity to receive additional funding of $1 million or more. Round 1
grants are expected to be announced in October, the foundation said.
(Gates Media Release, 3 September 2008)
http://www.gatesfoundation.org/GlobalHealth/Announcements/Announce-080903.htm?version=print
Murdoch Children’s Research Institute (MCRI) and PATH announced a new partnership to support the
further development of the MCRI rotavirus vaccine candidate, RV3. PATH will provide up to US$350,000 to
assist MCRI in the production of clinical trial lots of RV3 under Good Manufacturing Practices (GMP) at Meridian Life
Science in Memphis, Tennessee, in preparation for Phase 1 and 2 clinical trials to be conducted by MCRI. Dr. Georges
Thiry, director of PATH’s Advancing Rotavirus Vaccine Development project, said, ”PATH is pleased to collaborate
with MCRI on the further development of the RV3 vaccine. RV3 represents a promising approach in the fight against
rotavirus, and MCRI’s clinical trials will provide critical evidence to advance the development of this potential tool.” The
organizations said the RV3 vaccine candidate was developed from a strain of rotavirus that was discovered in babies
at a newborn nursery in Melbourne, Australia. Babies who were naturally infected with the RV3 strain had no
symptoms and were protected from contracting rotavirus disease in the first three years of life. Professor Julie Bines
of the University of Melbourne and MCRI, commented, “This vaccine candidate was created from a strain of the
natural infection found in healthy babies, but provides protection from disease due to rotavirus infection later in life,
making it an ideal vaccine candidate to provide protection from birth. Our vaccine could offer a major boost for
global efforts to reduce death and suffering due to rotavirus gastroenteritis in children worldwide.”
Murdoch Childrens Research Institute describes itself as “Australia’s largest and most prestigious child health institute.
Its staff work side by side with the doctors and nurses at Melbourne’s Royal Children’s Hospital and have a unique
opportunity to make discoveries and translate them into real benefits for children. The team of 1,100 passionate
researchers conduct innovative, world class research into a wide range of conditions affecting children, including
asthma, premature birth, cancer, depression, genetic conditions, obesity, and infectious diseases.”
(PATH Media release, 2 September 2008)
http://www.path.org/news/pr080901-mcri.php
MMWR News Synopsis for September 4, 2008
National, State, and Local Area Vaccination Coverage Among Children Aged 19–35 Months – United
States, 2007
According to the CDC′s 2007 National Immunization Survey (NIS), childhood immunization rates remain at or near
record levels with at least 90 percent coverage for all but one of the vaccines in the recommended series for young
children. More than 77 percent of children were fully vaccinated for the complete series of recommended vaccines,
and there were no differences in coverage among any racial or ethnic group for the complete series. Importantly,
less than one percent of children had received no vaccines by age 19 to 35 months. The NIS coverage data includes
children born between January 2004 and July 2006. There were no statistically significant decreases in individual
vaccine coverage from 2006 to 2007. For the first time in 2007, there was 90% coverage for varicella vaccine and
for the third dose of PCV. One dose of varicella vaccine increased in 2007 to 90 percent compared to the 2006
coverage rate of 89.2 percent. There were also significant increases for pneumococcal conjugate vaccine. Coverage
of three or more doses of increased from 86.9 percent in 2006 to 90.0 percent in 2007, and coverage four or more
doses rose from 68.4 percent in 2006 to 75.3 percent in 2007. Varicella vaccine and pneumococcal conjugate
vaccine coverage among American Indian and Alaska Native children increased significantly. Varicella coverage
increased from 85.4 percent in 2006 to 94.9 percent in 2007 and coverage with the fourth dose of PCV7 increased
from 64.8 percent to 80.4 percent.
http://www.cdc.gov/media/mmwrnews/2008/n080904.htm
The Weekly Epidemiological Record (WER), 5 September 2008, vol. 83, 36 (pp 321–332), includes:
- 321 Laboratory surveillance for wild and vaccine-derived polioviruses, January 2007–June 2008
- 328 Performance of acute flaccid paralysis (AFP) surveillance and incidence of poliomyelitis, 2008
http://www.who.int/wer/2008/wer8336/en/index.html
Journal Watch
[Editor’s Note]
Vaccines: The Week in Review continues a new feature, scanning key journals to identify and cite articles, comment
and editorials, books reviews and other content supporting our focus on vaccine ethics and policy. This scan is not
intended o be exhaustive, but indicative of themes and issues the center is actively tracking. Successful access to
some of the links provided may require subscription or other access arrangement unique to the publisher. Our initial
scan list includes the journals below. If you would like to suggest other titles, please write to David Curry at david.r.
curry@centerforvaccineethicsandpolicy.org
JAMA
Vol. 300 No. 9, pp. 995-1104, September 3, 2008
http://jama.ama-assn.org/current.dtl
[No relevant content]
Journal of Infectious Disease
1 October 2008 Volume 198, Number 7
http://www.journals.uchicago.edu/toc/jid/current
Editorial Commentary
Planning for an Influenza Pandemic: Thinking beyond the Virus
Jonathan A. McCullers
[Excerpt; citation indicators removed]
“…A shift in focus is required. Pandemic planning must take into account the possibility that secondary bacterial
pneumonia will be a frequent complication of pandemic influenza. Basic research into the interactions between
influenza viruses and bacteria is needed. Modeling studies extrapolating the breadth of potential risk should be
undertaken. Planning for prevention of disease must include pneumococcal vaccines as well as influenza vaccines. A
comprehensive survey of the sources, supply, and surge capacity of important antibiotics should be undertaken.
This should include analysis of distribution patterns, as has been done for influenza vaccines; it is likely that many of
the countries in the developing world, where complications of pandemic influenza are likely to be worst, will have little
to no access to appropriate antimicrobials in this scenario. Planners should consider strengthening and diversifying
these pipelines—in the United States alone in the last 3 years, there have been shortages of more than a dozen
antibiotics. Included among these is vancomycin, an important drug used in the treatment of antibiotic-resistant
infections due to Streptococcus pneumoniae and Staphylococcus aureus, the 2 most common secondary
pathogens in the infections that follow influenza. If these shortages are occurring in times of constant demand, it
seems likely that worse will occur when there is a surge in demand.
Since the 1997 H5N1 outbreak in Hong Kong, a tremendous amount of work has been done to understand influenza
viruses and prepare for the next pandemic. As Morens et al. have reminded us, however, the virus is only half of the
story, and the bacterial superinfections may be the more deadly half [3]. Harry S. Truman may have summed it up
best, “The only thing new in the world is the history you don't know” [13]. This timely reminder of our past should
act as an impetus to help prevent the history of the 1918 pandemic from repeating itself.”
Predominant Role of Bacterial Pneumonia as a Cause of Death in Pandemic Influenza: Implications for
Pandemic Influenza Preparedness
David M. Morens, Jeffery K. Taubenberger, and Anthony S. Fauci
[Excerpt from Abstract at http://www.journals.uchicago.edu/doi/abs/10.1086/591708]
“Conclusions. The majority of deaths in the 1918–1919 influenza pandemic likely resulted directly from secondary
bacterial pneumonia caused by common upper respiratory–tract bacteria. Less substantial data from the subsequent
1957 and 1968 pandemics are consistent with these findings. If severe pandemic influenza is largely a problem of viral-
bacterial copathogenesis, pandemic planning needs to go beyond addressing the viral cause alone (e.g., influenza
vaccines and antiviral drugs). Prevention, diagnosis, prophylaxis, and treatment of secondary bacterial pneumonia,
as well as stockpiling of antibiotics and bacterial vaccines, should also be high priorities for pandemic planning.”
Persistence of Genital Human Papillomavirus Infection in a Long-Term Follow-Up Study of Female
University Students
Laura K. Sycuro, Long Fu Xi, James P. Hughes, Qinghua Feng, Rachel L. Winer, Shu-Kuang Lee, Sandra O'Reilly,
Nancy B. Kiviat, and Laura A. Koutsky
http://www.journals.uchicago.edu/doi/abs/10.1086/591625
The Lancet
Volume 372, Number 9641, 6 September 2008
http://www.thelancet.com/journals/lancet
Childhood pneumonia deaths: a new role for health workers?
Igor Rudan, Harry Campbell
pages 781-782
[Excerpt; citation indicators removed]
“Pneumonia is the leading cause of child death worldwide, causing the deaths of more than 2 million children every
year. Deaths from pneumonia, more than any other major childhood disease, affect mainly underprivileged and poor
children who have limited or no access to health systems. Most of these deaths are potentially avoidable through
application of existing interventions. However, highly cost-effective interventions are neither being adequately
implemented in local settings, nor being implemented at a scale that reaches all children nationwide….In today's
Lancet, Enayet Chowdhury and colleagues show the importance of implementation research. The investigators
found that many sick children who were referred for hospital care by health workers in first-level facilities in
Bangladesh never actually received treatment. They proposed a modification to WHO's Integrated Management of
Childhood Illness (IMCI) guidelines in response to this problem. Chowdhury evaluated an extension of the role of
health workers from simple triage and hospital referral of very sick children to include treatment of children with
severe pneumonia (IMCI classification) with oral amoxicillin at home. Allowing health workers to give antibiotic
treatment was both safe and effective in this study setting, and the investigators recommended adoption of the
modified guideline by IMCI national programmes…”
Care at first-level facilities for children with severe pneumonia in Bangladesh: a cohort study
Enayet K Chowdhury, Shams El Arifeen, Muntasirur Rahman, DM Emdadul Hoque, M Altaf Hossain, Khadija Begum,
Ashraf Siddik, Nazma Begum, Qazi Sadeq-ur Rahman, Tasnima Akter, Twaha M Haque, ZA Motin Al-Helal, Abdullah H
Baqui, Jennifer Bryce, Robert E Black
pages 822-830
Nature
Volume 455 Number 7209 pp1-136
http://www.nature.com/nature/journal/v455/n7209/
[No relevant content]
New England Journal of Medicine
Volume 359 — September 4, 2008 — Number 10
http://content.nejm.org/current.shtml
[No relevant content]
Science
5 September 2008 Vol 321, Issue 5894, Pages 1268-1374
http://www.sciencemag.org/current.dtl
[No relevant content]
Vaccine
Volume 26, Issue 41, Pages 5239-5338 (26 September 2008)
http://www.sciencedirect.com/science/journal/0264410X\
Seroepidemiology as basis for design of a human papillomavirus vaccination program
Pages 5263-5268
J. Ryding, K.M. French, P. Naucler, R.V. Barnabas, G.P. Garnett, J. Dillner
Preview:
“We have performed a serological survey of HPV type 16-antibody prevalence by age and sex in Sweden and used it
as a basis for modelling the optimal vaccination strategies in this population. Samples of 3317 subjects were tested
for HPV16-specific antibodies. The observed age-specific seroprevalences along with sexual behaviour data were used
to infer parameter values for a mathematical model representing Sweden and the preventive effect of possible
strategies estimated. By the year 2055, vaccination of females starting at age 12 in 2008 was most efficient,
estimated to prevent 5.8 million cumulative HPV16 infections. Catch-up programs had a strong additional preventive
effect. Vaccination also targeting males increased protective effect by about 4%, but had lower preventive effect per
vaccination given. Addition of an HPV serosurvey to existing models and data has enabled us to estimate effect of
different vaccination strategies, optimized to the HPV epidemiology in our population.”
The GAVI Financing Task Force: One model of partner collaboration
Pages 5296-5302
Julie B. Milstien, Lidija Kamara, Patrick Lydon, Violaine Mitchell, Steve Landry
Abstract
Preview:
“The Global Alliance for Vaccines and Immunization, now called the GAVI Alliance, was launched in 2000 as a coalition
of partners, including countries, international organizations, bilateral donors, the vaccine production industry, and
nongovernmental organizations; most activities were to be implemented through these partner organizations. Four
task forces were established at the outset to define issues relevant to GAVI Alliance goals and to recommend actions.
This paper describes the innovations and outputs of the Financing Task Force (FTF), which worked in three areas:
country support to sustainably finance vaccines and immunization programs in the context of introducing new
vaccines; vaccine supply and demand issues as they impact vaccine choice, production costs and price/dose;
innovative financing mechanisms for vaccines and immunization programs through, for example, capital markets.
This analysis particularly focuses on the FTF's work on financial sustainability. Through its partnership, the FTF was
able to leverage organizational change in its participating organizations, in the countries supported by the GAVI
Alliance, and in the policies of GAVI itself. These achievements, along with areas where the desired outcome was not
achieved, are summarized with lessons that may be useful to other multi-partner health alliances.”
_________________________________________________________________
1 September 2008
The World Health Organization's Commission on the Social Determinants of Health presented its
findings to WHO Director-General Dr Margaret Chan. These "social determinants of health" have been the
focus of a three-year investigation by the Commission, “an eminent group of policy makers, academics, former
heads of state and former ministers of health.” The report – Closing the Gap in a Generation: Health Equity through
Action on the Social Determinants of Health – states ”(The) toxic combination of bad policies, economics, and politics
is, in large measure responsible for the fact that a majority of people in the world do not enjoy the good health that
is biologically possible. Social injustice is killing people on a grand scale."
Sir Michael Marmot, Commission Chair said, “Central to the Commission’s recommendations is creating the conditions
for people to be empowered, to have freedom to lead flourishing lives. Nowhere is lack of empowerment more
obvious than in the plight of women in many parts of the world. Health suffers as a result. Following our
recommendations would dramatically improve the health and life chances of billions of people.” Health inequities,
defined as “unfair, unjust and avoidable causes of ill health,” have long been measured between countries but the
Commission documents "health gradients" within countries as well. The Commission found evidence that
“demonstrates in general the poor are worse off than those less deprived, but they also found that the less deprived
are in turn worse than those with average incomes, and so on. This slope linking income and health is the social
gradient, and is seen everywhere – not just in developing countries, but all countries, including the richest. The slope
may be more or less steep in different countries, but the phenomenon is universal.”
The Commission makes three overarching recommendations to tackle the "corrosive effects of inequality of life
chances”:
- Improve daily living conditions, including the circumstances in which people are born, grow, live, work and age.
- Tackle the inequitable distribution of power, money and resources – the structural drivers of those conditions –
globally, nationally and locally.
- Measure and understand the problem and assess the impact of action.
The report also highlights how “over 100 million people are impoverished due to paying for health care – a key
contributor to health inequity.” The Commission thus calls for health systems to be “based on principles of equity,
disease prevention and health promotion with universal coverage, based on primary health care.” WHO will now
make the report available to Member States which will determine how the health agency is to respond.
http://www.who.int/mediacentre/news/releases/2008/pr29/en/index.html
(WHO Media Release, 28 August 2008)
[Editor’s Note: The Commission Report Executive Summary is available at http://whqlibdoc.who.
int/hq/2008/WHO_IER_CSDH_08.1_eng.pdf. The document does not address vaccines or immunization to any
substantial degree.]
The University of Pittsburgh’s Graduate School of Public Health said it received a $10 million grant from
the Gates Foundation for the Vaccine Modeling Initiative, which will create computer simulations of epidemics,
showing worst- and best-case outbreak scenarios, and be used to evaluate new vaccine technologies and modes of
vaccine delivery.” The Vaccine Modeling Initiative is a research partnership among infectious disease modeling teams
at the University of Pittsburgh, The Pennsylvania State University and Imperial College London, and is headquartered
at Pitt’s Graduate School of Public Health. The project also involves collaborations with leading infectious disease
experts, computational modelers and public health officials at Johns Hopkins University, the Pittsburgh
Supercomputing Center, Médecins Sans Frontières Epicentre, University of Georgia, Resources for the Future, and
the World Health Organization. The models they develop “will be designed to fit the prevalence, incidence and
geographic spread patterns of past epidemics in developing countries worldwide, and will help prevent future
infectious disease epidemics by optimizing vaccine strategies for particular diseases and regions.” Initially, the project
will focus on evaluation of new vaccine technologies for influenza, measles and dengue. Later, the project will develop
vaccine models of epidemic pertussis, rotavirus, polio, pneumococcus, malaria and tuberculosis.
Donald S. Burke, MD, principal investigator of the grant and dean of GSPH, said, “Infectious diseases create an
enormous burden on the world’s population, from both a human suffering and an economic development
perspective. One of the major challenges we face in stopping infectious disease outbreaks is predicting how control
strategies, such as vaccines, will work. By using computer models to conduct ‘epidemiology in silicon,’ we will be able
to test the impact of new candidate vaccine technologies and select the most effective strategies.”
http://www.publichealth.pitt.edu/news.php?id=45
(UP Media Release, 20 August 2008)
CDC’s National Center for Immunization and Respiratory Diseases launched a public service
announcement (PSA)campaign to “encourage parents to protect their 11-and 12-year-olds from
meningitis, whooping cough, and the virus that causes cervical cancer." The three pre-teen vaccines
involved in the campaign include MCV4, which protects against meningitis and its complications, Tdap, a booster
against tetanus, diphtheria, and pertussis or “whooping cough,” and for girls, HPV vaccine. The PSAs, available in
both English and Spanish and at lengths of 60, 30 and 15 seconds, are available for download and broadcast at www.
countingonyoupsas.com.
The MMWR August 29, 2008 / Vol. 57 / No. 34 includes:
Progress Toward Poliomyelitis Eradication --- Nigeria, January 2007--August 12, 2008
“Nigeria is one of only four countries that have never interrupted poliovirus transmission (the others are Afghanistan,
India, and Pakistan). A resurgence in wild poliovirus (WPV) transmission occurred in Nigeria during 2003--2004 after a
loss of public confidence in oral poliovirus vaccine (OPV) and suspension of supplementary immunization activities
(SIAs) in several northern states. Subsequently, WPV spread within Nigeria and ultimately into 20 previously polio-free
countries during 2003--2006. Even after national SIAs resumed, limited acceptance and ongoing operational
problems resulted in low polio vaccination coverage and continued WPV transmission. Beginning in 2006, health
authorities in Nigeria introduced new initiatives to control the spread of WPV, including a focus on interrupting type 1
WPV (WPV1) transmission and use of monovalent type 1 OPV (mOPV1) for most of the SIAs to increase vaccine
effectiveness.
Nigeria also instituted changes in SIA implementation to increase community acceptance of vaccination.
Subsequently, 285 polio cases were reported in Nigeria in 2007, the lowest number since sensitive surveillance has
been in place. As of August 12, 2008, confirmed polio cases reported in Nigeria totaled 556 (including 511 WPV1
cases), compared with 176 cases (53 WPV1) reported during the same period in 2007. This report updates overall
progress toward polio eradication in Nigeria during 2007--2008. Given the increase in WPV transmission thus far in
2008, urgent measures are needed to reach all children during SIAs to bring WPV under control in Nigeria.
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5734a4.htm
EndoBiologics and PATH said they formed a new research partnership “to investigate novel conjugate
vaccine candidates against enteric bacteria that cause dysentery and severe diarrhea.” PATH will fund
EndoBiologics to complete preclinical research into process development, mucosal immunization, and evaluation of
novel antigens for potential protection in animal models. EndoBiologics will focus on vaccines against Shigella bacteria
that cause more than 165 million episodes of severe dysentery and diarrhea and kill more than 600,000 children
each year. Since many forms of Shigella mediate disease, “the challenge is to produce a vaccine that provides broad-
spectrum protection.” EndoBiologics said it believes that the unique composition of its new conjugate vaccine
candidates “holds special promise in meeting this challenge.” The Shigella vaccines are part of a pipeline of subunit
vaccines that EndoBiologics said it is developing to provide broad protection against diarrhea, fever, and septic
symptoms caused by enteric bacteria.
(BUSINESS WIRE, 19 August 2008)
Novavax announced “favorable results” from the second stage of the Phase I/IIa human clinical trial of
its pandemic influenza virus-like particle (VLP) vaccine candidate. The vaccine, which does not contain an
adjuvant, “induced robust neutralizing antibody responses” and is directed against the H5N1 A/Indonesia/05/2005
avian influenza strain. VLPs “are recombinant structures mimicking the size and shape of the virus but lack genetic
material and are therefore incapable of replication. Because they resemble actual infectious particles presenting
proteins in the same conformation as on the wild-type virus, they are able to induce a potent immune response,”
Novavax said. Dr. Rahul Singhvi, president and CEO of Novavax. Commented, "These data are exciting because
they demonstrate that recombinant VLPs are a valid and potent vaccine approach against influenza. Combined with
our innovative manufacturing approach, our VLP vaccine candidate has the potential to address an unmet need in
pandemic influenza preparedness efforts being planned by health authorities around the world."
(PRNewswire-FirstCall, 26 August 2008)
Journal Watch
[Editor’s Note]
Vaccines: The Week in Review continues a new feature, scanning key journals to identify and cite articles, comment
and editorials, books reviews and other content supporting our focus on vaccine ethics and policy. This scan is not
intended o be exhaustive, but indicative of themes and issues the center is actively tracking. Successful access to
some of the links provided may require subscription or other access arrangement unique to the publisher. Our initial
scan list includes the journals below. If you would like to suggest other titles, please write to David Curry at david.r.
curry@centerforvaccineethicsandpolicy.org
JAMA
Vol. 300 No. 8, pp. 875-986, August 27, 2008
http://jama.ama-assn.org/current.dtl
Special Communication
Opt-Out Testing for Human Immunodeficiency Virus in the United States
Progress and Challenges
John G. Bartlett, MD; Bernard M. Branson, MD; Kevin Fenton, MD, PhD; Benjamin C. Hauschild, MPH; Veronica Miller,
PhD; Kenneth H. Mayer, MD
JAMA. 2008;300(8):945-951.
“The Centers for Disease Control and Prevention (CDC) has recommended human immunodeficiency virus (HIV)
testing for all persons aged 13 to 64 years in all health care settings. Signed consent would not be required and
counseling with referral would be managed as it is for other serious conditions. The goal of the recommendations is to
promote earlier entry into care to reduce unnecessary mortality and facilitate prevention by behavioral changes that
accompany knowledge of serostatus. Concerns about the change include laws in some states that mandate signed
consent and counseling, a perception that counseling is an effective prevention strategy, variability in payment
coverage for the test, concerns about the stigma and discrimination that may accompany the HIV diagnosis, and the
possibility that other testing policies would be more effective. Eleven of 16 states have changed legislation to reduce
barriers to testing, 35 of 74 national professional societies have endorsed the new recommendations, and multiple
demonstration projects have shown feasibility. Metrics to evaluate the health outcomes of the CDC's
recommendations for HIV testing have been defined, but the data necessary to determine the effects on early entry
into care, the actual reduction in disease incidence, and the unanticipated consequences are not yet available.”
Book Review
Biomedical Ethics: A Multidisciplinary Approach to Moral Issues in Medicine and Biology
Edited by David Steinberg
346 pp, $40
Lebanon, NH, University Press of New England, 2007
ISBN-13: 978-1-5846-5643-2
“Biomedical Ethics contains more than 100 essays previously published in the journal Medical Ethics, many with
commentaries and responses. Overall, the book is a satisfying read that presents many different complex ethical
problems in an engaging manner. Many of the dilemmas highlight just how complicated bioethics and medical science
have become in the 21st century…”
Stephen Workman, MD, MSc, Reviewer
Queen Elizabeth II Health Sciences Center
Halifax, Nova Scotia, Canada
Journal of Infectious Disease
Volume 198, Number 6, 15 September 2008 http://www.journals.uchicago.edu/toc/jid/current
[This issue reviewed last week]
The Lancet
Volume 372, Number 9640, 30 August 2008
http://www.thelancet.com/journals/lancet
[No relevant content]
Nature
Volume 454 Number 7208 pp1029-1150, 28 August 2008
http://www.nature.com/nature/journal/v454/n7205/
[No relevant content]
New England Journal of Medicine
Volume 359 — August 28, 2008 — Number 9
http://content.nejm.org/current.shtml
Perspective
An HIV Vaccine — Challenges and Prospects
Margaret I. Johnston, Ph.D., and Anthony S. Fauci, M.D.
The authors conclude:
”… We may not be able to develop an HIV vaccine that is highly effective in the classic sense of successful viral
vaccines. If we do, it will be in the face of enormous scientific challenges. To tackle these challenges we must turn to
fundamental research to a degree that has not been required in the development of vaccines for other viral diseases.
We remain cautiously optimistic that a substantial increase in our understanding of HIV infection and disease will lead
to creative ideas about how to design an effective HIV vaccine.
Selected Obstacles to HIV-Vaccine Development and Their Implications
Obstacles
- The window of opportunity for the immune system to clear the initial infection is narrow, since HIV integrates and
establishes latent infection within days or weeks.
- Destruction of CD4+ T cells begins early after infection.
- Enormous genetic diversity and mutations that occur with replication enable HIV to avoid immune surveillance.
- Conserved antibody targets on the outer envelope protein are "hidden" from immune recognition.
Implications
- Rational, empirical approaches to vaccine development have not been successful to date.
- Fundamental questions regarding HIV disease and the host response to the virus need to be answered.”
Fresh new ideas beyond the scope of classic vaccinology are urgently needed.”
http://content.nejm.org/cgi/content/full/359/9/888
Book Review
The Oxford Textbook of Clinical Research Ethics
Edited by Ezekiel J. Emanuel, Christine Grady, Robert A. Crouch, Reidar K. Lie, Franklin G. Miller, and David Wendler.
827 pp., illustrated. New York, Oxford University Press, 2008. $150. ISBN 978-0-19-516865-5.
“The Oxford Textbook of Clinical Research Ethics is a resource suitable for a course in research ethics and would also
be helpful for those starting a career in clinical research. It is an accessible synthesis and discussion of the many facets
of research ethics — a massive undertaking, as its size indicates. Scholars and students will find the book valuable, but
it is also an important resource for those already conducting clinical research as investigators (or those contemplating
becoming investigators), as well as for research team members, reviewers, sponsors, research advocacy groups, and
regulators…” http://content.nejm.org/cgi/content/extract/359/9/982
Science
29 August 2008 Vol 321, Issue 5893, Pages 1129-1232
http://www.sciencemag.org/current.dtl
[No relevant content]
Vaccine
Volume 26, Issue 38, Pages 4877-4974 (8 September 2008)
http://www.sciencedirect.com/science/journal/0264410X\
Impact of the introduction of pneumococcal conjugate vaccine on rates of community acquired
pneumonia in children and adults
Pages 4947-4954
Jennifer C. Nelson, Michael Jackson, Onchee Yu, Cynthia G. Whitney, Lora Bounds, Rachel Bittner, Ann Zavitkovsky,
Lisa A. Jackson
Abstract
“Pneumococcal conjugate vaccine use among young children has led to significant declines in invasive
pneumococcal disease in the United States, but the impact on community-acquired pneumonia is unknown. We
conducted population-based pneumonia surveillance among 794,282 Group Health members before and after infant
vaccine introduction in 2000. We presumptively identified pneumonia episodes using diagnosis codes assigned to
medical encounters and confirmed 17,513 outpatient and 6318 hospitalized events by reviewing chest radiograph
reports or hospitalization records. There was evidence for a decline in rates of both outpatient and hospitalized
pneumonia in children less than 1 year of age following vaccine introduction but there were no consistent reductions
in pneumonia rates among older children and adults.”
