WHO use of advisory bodies in responding to the influenza pandemic
Pandemic (H1N1) 2009 briefing note 19

3 DECEMBER 2009 | GENEVA –
WHO is aware of some concerns, expressed in the media, that ties with the pharmaceutical industry among experts on the Organization’s advisory bodies may influence policy decisions, especially those relating to the influenza pandemic.

WHO has historically collaborated with the pharmaceutical industry for legitimate reasons. Efforts to improve health depend on better access to high-quality and affordable medicines, vaccines, and diagnostics. Medical interventions, including antiviral drugs, vaccines, and diagnostic tests, have long been recognized for their role in mitigating the health impact of an influenza pandemic. Pharmaceutical companies play an essential role in this regard and WHO has engaged with them to pursue its public health objectives.

Conflicts of interest: safeguards in place

Potential conflicts of interest are inherent in any relationship between a normative and health development agency, like WHO, and a profit-driven industry. Similar considerations apply when experts advising the Organization have professional links with pharmaceutical companies. Numerous safeguards are in place to manage possible conflicts of interest or their perception.

External experts who advise WHO are required to provide a declaration of interests that details professional or financial interests that could compromise the impartiality of their advice. Procedures are in place for identifying, investigating and assessing potential conflicts of interest, disclosing them, and taking appropriate action such as excluding an expert from participating in a meeting.

International Health Regulations

The influenza pandemic is providing the first major test of the revised International Health Regulations, which were approved by WHO Member States in 2005 and came into legal force in 2007. The Regulations provide an orderly, rules-based mechanism for coordinating the response to public health emergencies of international concern, such as that caused by the H1N1 pandemic virus.

Apart from protecting public health against the international spread of disease, the Regulations contain provisions for avoiding unnecessary interference with international travel and trade.

Under the provisions of the revised Regulations, an Emergency Committee advises the WHO Director-General on matters such as declaring a public health emergency of international concern, the need to raise the level of pandemic alert following spread of the H1N1 virus, and the need to introduce temporary measures, such as restrictions on travel or trade. Final decisions are made by the Director-General, as guided by the Committee’s advice.

All members of the Emergency Committee sign a confidentiality agreement, provide a declaration of interests, and agree to give their consultative time freely, without compensation. Members of the Committee are drawn from a roster of about 160 experts covering a range of public health areas. The framework for membership is set out in the International Health Regulations. Each State Party to the Regulations is entitled to nominate one member of the roster and additional experts are appointed by the Director-General. Recommendations of the Emergency Committee are immediately made public on the WHO web site together with the relevant decisions of the Director-General.

Strategic Advisory Group of Experts on Immunization

In responding to the pandemic, WHO has also drawn on advice from a standing body of experts, the Strategic Advisory Group of Experts on Immunization (SAGE), which advises WHO on vaccine use. Members of SAGE are likewise required to declare all professional and financial interests, including funding received from pharmaceutical companies or consultancies or other forms of professional engagement with pharmaceutical companies. The names and affiliations of members of SAGE and of SAGE working groups are published on the WHO web site, together with meeting reports and declarations of interest submitted by the experts.

Allegations of undeclared conflicts of interest are taken very seriously by WHO, and are immediately investigated.

Criticisms: understandable but unfounded

Public perceptions about the current H1N1 influenza pandemic, as well as national preparedness plans, were strongly influenced by a five-year close watch over the highly lethal H5N1 avian influenza virus, which was widely regarded as the virus most likely to ignite the next influenza pandemic. A pandemic caused by a virus that kills more than 60% of the people it infects is strikingly, and fortunately, very different from the reality of the current pandemic.

Adjusting public perceptions to suit a far less lethal virus has been problematic. Given the discrepancy between what was expected and what has happened, a search for ulterior motives on the part of WHO and its scientific advisers is understandable, though without justification.

WHO has consistently assessed the impact of the current influenza pandemic as moderate. WHO has consistently reminded the medical community, public, and media that the overwhelming majority of patients experience mild influenza-like illness and recover fully within a week, even without any form of medical treatment. WHO has consistently advised against any restrictions on travel or trade. Although influenza viruses are notoriously unpredictable, it is hoped that this moderate impact will continue throughout the duration of the pandemic. http://www.who.int/csr/disease/swineflu/notes/briefing_20091203/en/index.html

Pandemic (H1N1) 2009 – update 78
Weekly update

11 December 2009 –
As of 6 December 2009, worldwide more than 208 countries and overseas territories or communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including at least 9596 deaths.

As many countries have stopped counting individual cases, particularly of milder illness, the case count is likely to be significantly lower than the actual number of cases that have occurred. WHO is actively monitoring the progress of the pandemic through frequent consultations with the WHO Regional Offices and member states and through monitoring of multiple sources of data.

Situation update:

In the temperate zone* of the northern hemisphere, pandemic influenza activity has passed its peak in North America and in parts of western, northern, and eastern Europe, but activity continues to increase in parts of central and southeastern Europe, as well as in south and east Asia. Influenza transmission remains active in much of western and central Asia and there is evidence of pandemic virus circulation in most regions of Africa.

In United States and Canada, active influenza virus transmission persists but overall ILI** activity continues to decline for the 5th and 3rd consecutive weeks, respectively.    In the US, after 8 weeks of increases, proportional mortality due to pneumonia and influenza (P&I mortality) has begun to decrease but remains elevated above the epidemic threshold; weekly numbers of lab-confirmed hospitalizations and deaths have also recently begun to decline. So far, comparing transmission during the current winter season to transmission during the summer season, there appears to be 2-3 times more hospitalized cases and deaths in the United States and approximately 4-5 times more hospitalized cases and deaths in Canada during the winter season. However, the overall rate of hospitalization and death in the population is similar to that which was observed in temperate countries of the southern hemisphere during their winter. This would indicate that transmission of the virus has been much more widespread and intense during the winter, as predicted, but overall rates of severe illness have not changed compared to southern hemisphere. Similar to seasonal influenza, persons with certain underlying conditions (compared to those without) were at significantly increased risk of hospitalization and death associated with pandemic H1N1 2009 virus infection. During the current winter season in Canada, 52% of hospitalized cases, 60% of cases requiring ICU, and 67% of fatal cases, had a underlying chronic medical illness. Similar to the experience of many countries, the most common underlying conditions among fatal cases in Canada were asthma followed by chronic cardiac disease, immunosuppression, and diabetes.

In Europe, geographically widespread transmission of pandemic influenza virus continued to be observed across the continent. With the exception of France where ILI activity continues to increase, ILI activity has peaked or passed its peak in much of western Europe, including in Belgium, Iceland, Ireland, Netherlands, Spain, Portugal, Italy, and Germany. In northern Europe, intensity remains high, however activity has begun to decline in Norway, Sweden, and Denmark. Increasing activity continues to be observed in parts of central and southeastern Europe, including in Albania, the Czech Republic, Estonia, Greece, Hungary, Latvia, Poland, Romania, Montenegro, Slovenia, and Turkey. Further east, declining rates of ILI or ARI have been observed in Georgia, Bulgaria, and Ukraine. In the Russian Federation, influenza virus circulation remains active, but overall activity may have recently peaked. A high intensity of respiratory diseases activity was reported in Lithuania and Greece, and a moderate impact on the healthcare system was reported in France and in parts of northern and far eastern Europe. 99% of subtyped influenza A viruses in Europe were pandemic H1N1 2009. Of note, detections of RSV in Europe have increased over the past four weeks which may partially account for elevated ILI activity among young children.

In Western and Central Asia, influenza virus transmission remains active. ILI/ARI activity continues to increase in Kazakhstan and Kyrgyzstan, but may have peaked in Afghanistan, Israel, and Oman. Pandemic influenza virus continues to circulate in Iran, Iraq, Jordan, and in much of the surrounding region.

In East Asia, influenza transmission remains variable. Influenza activity continues to increase in Japan and has recently begun to increase in Hong Kong SAR and Chinese Taipei both of which previously experienced a peak of transmission. Elevated but stable ILI activity has been reported in southern China, but declines in activity continue to be observed in northern China and Mongolia. In South Asia, influenza activity has begun to increase in the north-western parts of India and in Sri Lanka. Small number of seasonal influenza viruses continue to be detected in Asia but in decreasing amounts.

In the tropical region of Central and South America and the Caribbean, influenza transmission remains geographically widespread but overall disease activity has been declining in most areas.

In Africa, limited data suggest that pandemic H1N1 2009 virus continues to be detected from all parts of the continent (except South Africa where the winter season has passed). Pandemic H1N1 2009 virus appears to be the predominant influenza virus circulating in northern and eastern Africa.

In the temperate region of the southern hemisphere, sporadic cases of pandemic influenza have been reported in recent weeks but no sustained local transmission has been observed.

The Global Influenza Surveillance Network (GISN) continues monitoring the global circulation of influenza viruses, including pandemic, seasonal and other influenza viruses infecting, or with the potential to infect, humans including seasonal influenza. For more information on virological surveillance and antiviral resistance please see the weekly virology update.

http://www.who.int/csr/don/2009_12_11a/en/index.html

Virological surveillance data: Weekly update (Virological surveillance data)

The CDC released updated estimates for 2009 H1N1 Influenza Cases, Hospitalizations and Deaths in the United States, April – November 14, 2009

– CDC estimates that between 34 million and 67 million cases of 2009 H1N1 occurred between April and November 14, 2009. The mid-level in this range is about 47 million people infected with 2009 H1N1.

– CDC estimates that between about 154,000 and 303,000 2009 H1N1-related hospitalizations occurred between April and November 14, 2009. The mid-level in this range is about 213,000 H1N1-related hospitalizations.

– CDC estimates that between about 7,070 and 13,930 2009 H1N1-related deaths occurred between April and November 14, 2009. The mid-level in this range is about 9,820 2009 H1N1-related deaths.

Note: More than 95% of the increases in the estimated numbers of 2009 H1N1 cases, hospitalizations and deaths between the November 12 and December 10 estimates occurred between October 17 and November 14, 2009. (Less than 5% of increases are the result of delayed reporting in cases, hospitalizations and deaths that occurred prior to October 17, 2009.)

http://www.cdc.gov/h1n1flu/estimates_2009_h1n1.htm

The MMWR for December 11, 2009 / Vol. 58 / No. 48 includes:

Deaths Related to 2009 Pandemic Influenza A (H1N1) Among American Indian/Alaska Natives 12 States, 2009

“In October, health authorities in Arizona and New Mexico noted a disproportionate number of deaths related to H1N1 infection among American Indian/Alaska Natives (AI/ANs). A multidisciplinary workgroup comprised of representatives from 12 state health departments, the Council of State and Territorial Epidemiologists, tribal epidemiology centers, the Indian Health Service, and CDC assessed the burden of H1N1 influenza deaths in the AI/AN population and determined that the mortality rate among AI/ANs was four times higher than that among persons of all other racial/ethnic populations combined.”

The Weekly Epidemiological Record (WER) for 11 December 2009, vol. 84, 50 (pp 517–532) includes Meeting of the Strategic Advisory Group of Experts on immunization, October 2009 – conclusions and recommendations
http://www.who.int/wer/2009/wer8450.pdf

The WHO announced that SAGE made a number of “firm recommendations” on cholera control as a result of the October meeting. The increasing frequency and severity of cholera epidemics during recent years, the availability of a lower-cost cholera vaccine and recent data on the effectiveness, feasibility and cost-effectiveness of oral cholera vaccination were considered, WHO said. Key recommendations were that the two oral cholera vaccines available should be used in areas with endemic cholera and considered for use in areas at risk for cholera outbreaks, in conjunction with other cholera prevention and control strategies. http://www.who.int/immunization/newsroom/news_SAGE_cholera_recommendations/en/index.html

Pfizer said that The European Commission granted European marketing authorization for its pneumococcal conjugate vaccine, Prevenar 13 (Pneumococcal Polysaccharide Conjugate Vaccine [13-valent, adsorbed]). Prevenar 13 is indicated for active immunization for the prevention of invasive disease, pneumonia, and acute otitis media caused by 13 Streptococcus pneumoniae serotypes in infants and children from 6 weeks to 5 years of age. Invasive pneumococcal disease includes sepsis, meningitis, bacteremia, bacteremic pneumonia, and empyema. Emilio Emini, Ph.D., chief scientific officer, Vaccine Research, Pfizer Inc., said, “Although the incidence of pneumococcal disease has been significantly reduced in European countries and elsewhere where Prevenar is routinely used, pneumococcal disease remains a serious threat to children in Europe as strains such as serotypes 19A and 6A are increasing in prevalence and frequently resistant to antibiotics. By providing the broadest serotype coverage of any pneumococcal conjugate vaccine, Prevenar 13 is poised to help reduce the serious public health risk and economic burden associated with pneumococcal disease.” The European Commission’s authorization of Prevenar 13 was based on a clinical trial program of 13 core Phase III studies involving more than 7,000 children. Data from the Phase III trials support the safety and efficacy of Prevenar 13 for the prevention of pneumococcal disease in infants and young children, Pfizer said. Clinical trial data indicate Prevenar 13 has a safety profile similar to that of Prevenar, and can be administered with all routine pediatric vaccines studied.

http://www.businesswire.com/portal/site/home/permalink/?ndmViewId=news_view&newsId=20091211005205&newsLang=en

The International Vaccine Institute (IVI) issued congratulations to the Republic of Korea on becoming the newest member of the Development Assistance Committee (DAC) of the Organization for Economic Cooperation and Development (OECD) in November. Dr. John Clemens, Director-General of the IVI, commented, “By becoming a member of the elite donor nations’ club, Korea has once again demonstrated its commitment to co-prosperity of the international community and world peace. The IVI extends its full support to Korea, which is stepping up its drive to share its development experience and success with the developing world.”

IVI said Korea has been one of the most generous donors to the IVI’s humanitarian efforts to develop and deploy new vaccines for the world’s poor. “The IVI is very privileged to serve as a vehicle for Korea’s contributions to the world. With the continued generosity of Korea and the Korean people, we will make major contributions to our shared vision of a world where all children living in the world’s poorest countries are protected by vaccines against killer infectious diseases.” Dr. Clemens said. http://www.ivi.org/event_news/news_view.asp?enid=106

Journal of Infectious Diseases
1 January 2010  Volume 201, Number 1
http://www.journals.uchicago.edu/toc/jid/current

MAJOR ARTICLE
Sustained Reductions in Invasive Pneumococcal Disease in the Era of Conjugate Vaccine
Tamara Pilishvili, Catherine Lexau, Monica M. Farley, James Hadler, Lee H. Harrison, Nancy M. Bennett, Arthur Reingold, Ann Thomas, William Schaffner, Allen S. Craig, Philip J. Smith, Bernard W. Beall, Cynthia G. Whitney, and Matthew R. Moore, for the Active Bacterial Core Surveillance/Emerging Infections Program Network

Background.Changes in invasive pneumococcal disease (IPD) incidence were evaluated after 7 years of 7-valent pneumococcal conjugate vaccine (PCV7) use in US children.

Methods.Laboratory-confirmed IPD cases were identified during 1998–2007 by 8 active population-based surveillance sites. We compared overall, age group–specific, syndrome-specific, and serotype group–specific IPD incidence in 2007 with that in 1998–1999 (before PCV7) and assessed potential serotype coverage of new conjugate vaccine formulations.

Results.Overall and PCV7-type IPD incidence declined by 45% (from 24.4 to 13.5 cases per 100,000 population) and 94% (from 15.5 to 1.0 cases per 100,000 population), respectively ( for all age groups). The incidence of IPD caused by serotype 19A and other non-PCV7 types increased from 0.8 to 2.7 cases per 100,000 population and from 6.1 to 7.9 cases per 100,000 population, respectively ( for all age groups). The rates of meningitis and invasive pneumonia caused by non-PCV7 types increased for all age groups ( ), whereas the rates of primary bacteremia caused by these serotypes did not change. In 2006–2007, PCV7 types caused 2% of IPD cases, and the 6 additional serotypes included in an investigational 13-valent conjugate vaccine caused 63% of IPD cases among children <5 years-old.

Conclusions.Dramatic reductions in IPD after PCV7 introduction in the United States remain evident 7 years later. IPD rates caused by serotype 19A and other non-PCV7 types have increased but remain low relative to decreases in PCV7-type IPD.

The Lancet
Dec 12, 2009  Volume 374  Number 9706  Pages 1945 – 2026
http://www.thelancet.com/journals/lancet/issue/current

Editorial
Universal health coverage: access to what?
The Lancet
Summary
One of global health’s biggest aims—universal health coverage—received a boost last week at the Commonwealth Heads of Governments’ meeting in Trinidad and Tobago. 54 Commonwealth countries committed themselves to achieve universal coverage of health services free at the point of use. Leaders also agreed on a Commonwealth Health Compact, proposed by UK Prime Minister Gordon Brown, which calls on donor countries to deliver existing commitments for health financing and to identify new ways to increase international resources for health.

The Lancet
Dec 12, 2009  Volume 374  Number 9706  Pages 1945 – 2026
http://www.thelancet.com/journals/lancet/issue/current

Comment
Global access to HPV vaccination: what are we waiting for?
Gary M Clifford

Vaccines have repeatedly proven successful in the fight against infectious diseases, bringing some equity in health care to even the least developed regions of the world. Therefore the hope is that newly licensed human papillomavirus (HPV) vaccines will have an effect on the estimated 0·5 million cases of cervical cancer that arise worldwide every year, including the 80% that occur in developing countries (figure).1,2 From extrapolation of the impressive efficacy against high-grade precancerous lesions in large phase 3 trials,3,4 vaccination of girls before they reach adolescence against HPV types 16 and 18 (HPV 16/18) would be cost effective in the prevention of cervical cancer in even the poorest countries, provided the cost of vaccination falls to US$10.

The Lancet
ec 12, 2009  Volume 374  Number 9706  Pages 1945 – 2026
http://www.thelancet.com/journals/lancet/issue/current

Sustained efficacy and immunogenicity of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine: analysis of a randomised placebo-controlled trial up to 6·4 years
The GlaxoSmithKline Vaccine HPV-007 Study Group

Summary
Background
Prophylactic human papillomavirus (HPV) vaccines have to provide sustained protection. We assessed efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine up to 6·4 years.

Methods
Women aged 15—25 years, with normal cervical cytology, who were HPV-16/18 seronegative and oncogenic HPV DNA-negative (14 types) at screening participated in a double-blind, randomised, placebo-controlled initial study (n=1113; 560 vaccine group vs 553 placebo group) and follow-up study (n=776; 393 vs 383). 27 sites in three countries participated in the follow-up study. Cervical samples were tested every 6 months for HPV DNA. Management of abnormal cytologies was prespecified, and HPV-16/18 antibody titres were assessed. The primary objective was to assess long-term vaccine efficacy in the prevention of incident cervical infection with HPV 16 or HPV 18, or both. We report the analyses up to 6·4 years of this follow-up study and combined with the initial study. For the primary endpoint, the efficacy analysis was done in the according-to-protocol (ATP) cohort; the analysis of cervical intraepithelial neoplasia grade 2 and above (CIN2+) was done in the total vaccinated cohort (TVC). The study is registered with ClinicalTrials.gov, number NCT00120848.

Findings
For the combined analysis of the initial and follow-up studies, the ATP efficacy cohort included 465 women in the vaccine group and 454 in the placebo group; the TVC included 560 women in the vaccine group and 553 in the placebo group. Vaccine efficacy against incident infection with HPV 16/18 was 95·3% (95% CI 87·4—98·7) and against 12-month persistent infection was 100% (81·8—100). Vaccine efficacy against CIN2+ was 100% (51·3—100) for lesions associated with HPV-16/18 and 71·9% (20·6—91·9) for lesions independent of HPV DNA. Antibody concentrations by ELISA remained 12-fold or more higher than after natural infection (both antigens). Safety outcomes were similar between groups: during the follow-up study, 30 (8%) participants reported a serious adverse event in the vaccine group versus 37 (10%) in the placebo group. None was judged related or possibly related to vaccination, and no deaths occurred.

Interpretation
Our findings show excellent long-term efficacy, high and sustained immunogenicity, and favourable safety of the HPV-16/18 AS04-adjuvanted vaccine up to 6·4 years.

Funding
GlaxoSmithKline Biologicals (Belgium).

New England Journal of Medicine
Volume 361 — December 10, 2009 — Number 24
http://content.nejm.org/current.shtml

The Supreme Court, Process Patents, and Medical Innovation
A. S. Kesselheim

[First 100 words per NEJM convention]
On November 9, the U.S. Supreme Court heard oral arguments in Bilski v. Kappos, one of the most closely watched cases in the Court’s current term. The central question involves the legitimacy of a patent on a method for hedging risk in commodities trading, but the outcome will have important implications for health care delivery and research. Although patents covering medicines, devices, and research targets such as DNA sequences have become commonplace, in recent years there has been a surge in new patents on medical processes.1 Patents have been awarded for processes such as making diagnoses, performing surgery, making prescribing…

Science
11 December 2009  Vol 326, Issue 5959, Pages 1445-1576
http://www.sciencemag.org/current.dtl

Editorial
Harmonizing Global Science
Alan I. Leshner1 and Vaughan Turekian2

Summary
Every major problem facing modern society now has a science and technology component—either as a cause or cure—whether it’s energy and the environment, access to water and fertile land, the spread of infectious diseases, or sustaining a viable economy. Although every societal problem has unique regional characteristics that require attention, there are sufficient implications across regions for which only globally coordinated efforts will be successful. The recent assessments of the Intergovernmental Panel on Climate Change and their impacts on public and policy-maker perceptions provide one example of successful cooperation on a near-global scale. The betterment of humankind depends on a deliberate move from being an international community of scientists to being a truly global community.

1 Alan I. Leshner is the chief executive officer of AAAS and executive publisher of Science.
2 Vaughan Turekian is the chief international officer and director of the Center for Science Diplomacy of AAAS.

Vaccine
Volume 27, Issue 52, Pages 7219-7470 (9 December 2009)

Report of the ‘European Expert Meeting on Rotavirus Vaccination’, Tampere, Finland, 19–20 May 2009
Pages 7222-7227
Timo Vesikari, Diane Sutherland, Amy E.M. Jackson
[No abstract published]

Vaccine
Volume 27, Issue 52, Pages 7219-7470 (9 December 2009)

Priorities in research and development of vaccines against Plasmodium vivax malaria
Pages 7228-7235
Graham V. Brown, Vasee S. Moorthy, Zarifah Reed, Kamini Mendis, Myriam Arévalo-Herrera, Pedro Alonso

Abstract
The WHO Initiative for Vaccine Research (IVR) Malaria Vaccine Advisory Committee (MALVAC) provides advice to WHO on priorities in malaria vaccine research and development (R&D). This document summarizes a MALVAC scientific consultation of leading vaccine scientists on priorities in Plasmodium vivax vaccine R&D. The meeting discussed recent advances and key challenges in addressing identified gaps in knowledge. Major areas of discussion included disease burden estimates, clinical disease spectrum definitions, potential target product profiles and immunological and clinical research needed to better inform antigen selection and vaccine design. The need for further development of the human challenge model for P. vivax vaccines and specific considerations for conduct of field trials with P. vivax vaccines was outlined. This report summarizes the discussion and conclusions of the consultation, with recommendations for priority targeted research.

Vaccine
Volume 27, Issue 52, Pages 7219-7470 (9 December 2009)

WHO position on HPV vaccines
Pages 7236-7237
World Health Organization

Abstract
The WHO Position Paper on Vaccines against Human Papillomavirus (HPV): This article presents the WHO recommendations for use of the HPV vaccine excerpted from the recently published WHO Position on HPV Vaccines. These recommendations were formulated in a multiyear collaboration involving internal and external experts in the field, culminating in production of a detailed Background paper summarizing the evidence. After a series of meetings and careful consideration of the evidence for HPV vaccine introduction, WHO’s Strategic Advisory Group of Experts (SAGE) on vaccines and immunization recommended use of HPV vaccine in November 2008. WHO published a complete position paper in April 2009, which presents the WHO Position. Additional evidence including a detailed Background paper summarizing the evidence last presented to SAGE is available at http://www.who.int/immunization/documents/positionpapers/en/index.html

Vaccine
Volume 27, Issue 52, Pages 7219-7470 (9 December 2009)

Regulatory oversight of clinical trials in Africa: Progress over the past 5 years
Pages 7249-7252
Diadié Maïga, Bartholomew Dicky Akanmori, Liliana Chocarro

Abstract
Randomized controlled clinical trials represent the best way to establish the therapeutic or preventive value of medicines. This decade has seen a strong shift in the location of clinical trials from industrialized countries to developing countries, including many in Africa. However, without independent strong regulatory and ethical oversight of clinical trials the safety of research subjects, and scientific integrity of clinical data cannot be verified. This article draws up a portrait of clinical trials regulation in Africa in support of development of priority medicines, highlights challenges and presents the progress made by countries under WHO guidance over the past 5 years.

Vaccine
Volume 27, Issue 52, Pages 7219-7470 (9 December 2009)

Estimating the direct impact of new conjugate vaccines against invasive pneumococcal disease
Pages 7257-7269
W.P. Hausdorff, R. Dagan, F. Beckers, L. Schuerman

Abstract
New pneumococcal conjugate vaccines (PCVs) are now becoming available. These formulations differ from the heptavalent diphtheria toxin variant conjugate vaccine (7vCRM, Prevenar™/Prevnar™) both in the number of serotypes and in serotype-specific immunogenicity. This review proposes an algorithm that attempts to predict the overall impact of these differences in vaccine formulation and immunogenicity on invasive pneumococcal disease (IPD) effectiveness. It builds on the principles underlying WHO licensure criteria for new PCVs, that serotype-specific anti-polysaccharide immunogenicity is potentially predictive of effectiveness. The algorithm used three sources of information: serotype-specific effectiveness data for 7vCRM, serotype-specific head-to-head immunogenicity data with 7vCRM and a recently licensed 10-valent pneumococcal non-typeable H. influenzae protein D-conjugate vaccine (PHiD-CV, Synflorix™), and epidemiological information regarding the serotypes causing IPD in young children. Based on this algorithm, PHiD-CV and 7vCRM are predicted to prevent approximately 60–80% and 45–80%, respectively of IPD in young children worldwide, with significant variability by country and region.

Vaccine
Volume 27, Issue 52, Pages 7219-7470 (9 December 2009)

Safety of human papillomavirus (HPV) vaccines: A review of the international experience so far
Pages 7270-7281
Theodoros Agorastos, Konstantinos Chatzigeorgiou, Julia M.L. Brotherton, Suzanne M. Garland

Abstract
Despite the advent of the Papanicolaou smear test almost 50 years ago, cervical cancer remains the second most common malignant disease in women and the leading cause of cancer death in developing countries. Thus the two prophylactic human papillomavirus (HPV) vaccines currently available have been greeted with enthusiasm internationally, as an emerging primary prevention strategy against cervical cancer. Prior to licensure the vaccines were trialed in over 60,000 women and assessed as safe, within the statistical constraints of the trials to detect very rare events. Post-licensure surveillance is underway as vaccination programs are undertaken. We reviewed published post-licensure surveillance data, as at January 2009, and concur with international advisory bodies that both HPV vaccines are safe, effective and of great importance for women’s health. Ongoing monitoring is required to maintain confidence in the safety of the vaccines.

Vaccine
Volume 28, Issue 1, Pages 1-290 (10 December 2009)

Optimal vaccination choice, vaccination games, and rational exemption: An appraisal
Pages 98-109
Piero Manfredi, Pompeo Della Posta, Alberto d’Onofrio, Ernesto Salinelli, Francesca Centrone, Claudia Meo, Piero Poletti

Abstract
A threat for vaccination policies might be the onset of “rational” exemption, i.e. the family’s decision not to vaccinate children after a seemingly rational comparison between the perceived risk of infection and the perceived risk of vaccine side effects. We study the implications of rational exemption by models of vaccination choice. By a simple model of individual choice we first prove the “elimination impossible” result in presence of informed families, i.e. aware of herd immunity, and suggest that limited information might explain patterns of universal vaccination. Next, we investigate vaccination choice in a game-theoretic framework for communities stratified into two groups, “pro” and “anti” vaccinators, having widely different perceived costs of infection and of vaccine side effects. We show that under informed families neither a Nash nor a Stackelberg behaviour (characterized, respectively, by players acting simultaneously and by an asymmetric situation with a “leader” and a “follower) allow elimination, unless “pro-vaccinators” assign no costs to vaccine side effects. Elimination turns out to be possible when cooperation is encouraged by a social planner, provided, however, he incorporates in the “social loss function” the preferences of anti-vaccinators only. This allows an interpretation of the current Italian vaccination policy.

Vaccine
Volume 28, Issue 2, Pages 291-582 (11 December 2009)

Differential maternal responses to a newly developed vaccine information pamphlet
Pages 323-328
Nicola P. Klein, Jennifer Kissner, Ameth Aguirre, Robert Sparks, Scott Campbell, Kathryn M. Edwards, Cornelia L. Dekker, Irene Shui, Deborah A. Gust

Abstract
We compared the response to a new vaccine information pamphlet with the current CDC Vaccine Information Statements (VIS) among recently delivered mothers who were screened to identify those with concerns about immunization. Eligible mothers (n = 226) were randomly assigned to one of three equal groups; those reviewing only the new pamphlet, those receiving only VIS, or those receiving both. Among those mothers reviewing both, 61% preferred the new pamphlet for its visual appeal (P < 0.0001) and ease of understanding (P = 0.005). Overall, mothers expressed increased confidence and fewer concerns regarding multiple injections after reviewing the pamphlet. However, older, more-highly educated mothers were less likely to report improved vaccine confidence after reviewing either the pamphlet or the VIS. Mothers in all three groups stated a preference for receiving the vaccine information during pregnancy or prior to the actual immunization visit. These data suggest that early provision of tailored immunization material along with the VIS to new mothers may enhance their overall confidence in vaccines and that additional strategies targeted toward certain mothers may be needed.

Vaccine
Volume 28, Issue 2, Pages 291-582 (11 December 2009)

RotaTeq®, a pentavalent rotavirus vaccine: Efficacy and safety among infants in Europe
Pages 345-351
Timo Vesikari, Robbin Itzler, Aino Karvonen, Tiina Korhonen, Pierre Van Damme, Ulrich Behre, Gianni Bona, Leif Gothefors, Penny M. Heaton, Michael Dallas, Michelle G. Goveia

Abstract
A pentavalent human–bovine reassortant oral rotavirus vaccine, RotaTeq®, was evaluated among nearly 70,000 infants in the Rotavirus Efficacy and Safety Trial (REST), of which 30,523 were from Europe. All infants were followed for serious adverse events as well as hospitalizations and emergency department (ED) visits. All adverse events, health care utilization, and RVGE regardless of severity were evaluated in the clinical efficacy cohort (N = 2686) in Finland. RotaTeq® was 98.3% (95% CI, 90.2–100%) and 68.0% (95% CI 60.3–74.4%) efficacious against severe rotavirus gastroenteritis (RVGE) and all RVGE due to any serotype for two rotavirus seasons post-vaccination. The combined rate of hospitalizations and ED visits due to RVGE of any serotype was reduced by 94.5% (95% CI, 91.3–96.8%) for up to 2 years after vaccination. There were no statistically significant differences between RotaTeq® and placebo for any of the safety outcomes. In Europe, RotaTeq® was highly efficacious and well tolerated.

Vaccine
Volume 28, Issue 2, Pages 291-582 (11 December 2009)

Joint reviews and inspections: Strategic forms of collaboration for strengthening the regulatory oversight of vaccine clinical trials in Africa
Pages 571-575
Diadié Maïga, Bartholomew Dicky Akanmori, Liliana Chocarro

Abstract

Vaccine developers are required to submit a clinical trial application to the authorities in each country where a clinical trial will be conducted. The application has to be made both to the relevant Ethics Committees and to the National Regulatory Authorities, and only after appropriate clearance by both can a clinical trial commence.

This paper describes two specific strategies, joint reviews of vaccine clinical trial applications and joint inspections of clinical trial sites by groups of countries, as part of a WHO initiative to strengthen capacity for the regulatory oversight of clinical trials in Africa. Significantly, the joint reviews and inspections contributed to reinforcing the capacities of the regulatory authorities as well as defining an efficient process to maximize the quality of the reviews and minimize undue delays. Finally we will suggest complementary mechanisms to overcome the potential limitations of joint reviews and inspections.

Vaccine
Volume 28, Issue 3, Pages 583-868 (8 January 2010)

Expanding immunization coverage in rural India: A review of evidence for the role of community health workers
Pages 604-613
Amit R. Patel, Mary P. Nowalk

Abstract
Poor routine immunization coverage in India has led to a large burden of vaccine-preventable diseases borne by children under 5 years of age. Despite efforts to strengthen infrastructure and service delivery in the past decade, immunization coverage rates have reached a plateau. To meet the formidable needs of India’s growing population and address the shortcomings of health services for rural populations, the country is now turning toward a new national community health worker (CHW) plan. This article reviews the effectiveness of CHWs in expanding immunization coverage in developing countries and examines the potential contribution of CHWs toward strengthening immunization services in rural India. While the limited number and quality of available studies make it difficult to directly compare CHW interventions to other strategies for improving immunization coverage, it is clear that CHWs make diverse contributions toward strengthening immunization programs. Incorporation of evidence-based strategies for CHW selection, retention, and training is critical for success of India’s immunization program. In addition, there is growing need to develop efficient mechanisms for monitoring children’s vaccination status to generate actionable feedback and identify cost-effective strategies.

Vaccine
Volume 28, Issue 3, Pages 583-868 (8 January 2010)

Reduction in hospitalizations for diarrhea and rotavirus infections in New York state following introduction of rotavirus vaccine
Pages 754-758
Hwa-Gan H. Chang, Perry F. Smith, Bold Tserenpuntsag, Katherine Markey, Umesh Parashar, Dale L. Morse

Abstract
Objectives
To monitor trends and costs of diarrhea and rotavirus-associated hospitalizations in New York before and after rotavirus vaccine implementation in 2006. To examine rotavirus test results from sentinel hospital-associated laboratories.

Methods
Hospital discharge data and laboratory rotavirus testing data were analyzed for children 1 month up to 18 years of age for 10 sentinel and all statewide hospitals from January 1, 2003 through December 31, 2008.

Results
Among children 1–23 months of age, a 40% reduction in diarrhea-associated hospitalizations and 85% decrease in rotavirus-coded hospitalizations at the 10 sentinel hospitals was observed in 2008.

Vaccine
Volume 28, Issue 3, Pages 583-868 (8 January 2010)

Attitudes toward and intention to receive the human papilloma virus (HPV) vaccination and intention to use condoms among female Korean college students
Pages 811-816
Hee Sun Kang, Linda Moneyham

Abstract

This study examined the relationships between attitudes toward and intention to receive the human papilloma virus (HPV) vaccination and intention to use condoms in a sample of female Korean college students. The data were collected in 2008 using a survey administered to a convenience sample of 1359 female Korean college students. Despite the availability of the HPV vaccine in South Korea, many college-age females are not being vaccinated. Attitudes towards the HPV vaccine appear to be an important contributing factor in vaccination, underscoring the need to make information widely available, to promote HPV vaccination, and to help women make informed decisions.

Vaccine
Volume 28, Issue 3, Pages 583-868 (8 January 2010)

Vaccine wastage in Bangladesh
Pages 858-863
Stephane Guichard, Karen Hymbaugh, Brent Burkholder, Serguei Diorditsa, Christine Navarro, Selina Ahmed, Mohd. Mahbubur Rahman

Abstract
The Government of Bangladesh and WHO collaborated in a retrospective vaccine wastage study to estimate overall vaccine wastage rates from January to December 2004 for BCG, measles, DTP and TT. Researchers looked at vaccine distribution and usage patterns in randomly selected districts at both fixed (Upazila) and outreach (Ward) service delivery levels. Wastage was similar at both delivery levels but ranged widely among the sites. Average rates were highest for BCG (84.9%, range 55–93%) and measles (69.7%, range 28–86%) and lower for TT (35.5%, range 10–73%) and DTP (44.4%, range 16–77%). Wastage resulted primarily from opened vials at the ward level but this was reduced at fixed sites where the multi-dose vial policy is followed. A large proportion (30–38%) of records were excluded from the analytic vaccine-specific databases due to data recording errors, mismatches between Ward and Upazila databases, or missing data. The study’s results may provide methodological and programmatic guidance for other countries in addressing vaccine wastage issues.

MMWR Early Release December 4, 2009 / Vol. 58 / Early Release
Safety of Influenza A (H1N1) 2009 Monovalent Vaccines — United States, October 1–November 24, 2009

The Strategic Advisory Group of Experts (SAGE) met on 27–29 October 2009 in Geneva, Switzerland and released its conclusions and recommendations on pandemic influenza A (H1N1) 2009 virus in the Weekly Epidemiological Record on for 4 December 2009.

http://www.who.int/wer/2009/wer8449.pdf

The WHO continues to issue weekly “updates” and briefing notes as below:

Pandemic (H1N1) 2009 – update 77
Weekly update

4 December 2009 –
As of 29 November 2009, worldwide more than 207 countries and overseas territories or communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including at least 8768 deaths.

As many countries have stopped counting individual cases, particularly of milder illness, the case count is likely to be significantly lower than the actual number of cases that have occurred. WHO is actively monitoring the progress of the pandemic through frequent consultations with the WHO Regional Offices and member states and through monitoring of multiple sources of data.

Situation update:

In the temperate zone* of the northern hemisphere, the early arriving winter influenza season continues to intensify across central Europe and in parts of central, eastern, and southern Asia. Disease activity has peaked and is declining in North America and has either recently peaked or is currently peaking in much of western and northern Europe.

In both Canada and the United States, influenza virus circulation remains active and geographically widespread, however, disease activity appears to have peaked in past 3 to 4 weeks. In the United States, deaths due to pneumonia and influenza (P&I mortality) continued to increase past the epidemic threshold for the past 8 weeks and cumulative rates of hospitalizations for the current influenza season have exceeded rates seen in recent seasons among all age groups except those aged ≥ 65.

In Europe, widespread and intense transmission of pandemic influenza virus continued to be observed across most of the continent. In western and northern Europe the peak of disease activity has passed in Belgium, Iceland, Ireland, Netherlands, Norway and parts of the United Kingdom (Northern Ireland, Wales); activity may be peaking or plateauing in Spain, Portugal, Italy, Sweden and Denmark. Influenza activity continues to increase in much of Central Europe in the region between the Baltic and Balkan countries and from Germany to Romania. In Eastern Europe, recent peaks or plateaus in disease activity have also been observed in Ukraine, Belarus, Bulgaria and the Republic of Moldova. In the Russian Federation, influenza activity remains active and intense in some regions, with an overall increasing trend. A moderate impact on the healthcare system has been reported in parts of Northern and Eastern Europe. Over 99% of subtyped influenza A viruses in Europe were pandemic H1N1 2009.

In Western and Central Asia, influenza transmission remains active. Disease activity continues to increase in Kazakhstan, Kyrgyzstan, Uzbekistan, Iran and Iraq, while activity may have peaked in Israel, Jordan, and Afghanistan.

In East Asia, increasing ILI** or respiratory disease activity has been reported in Southern China and Japan. A recent decline in activity has been observed in Northern China. In South and Southeast Asia, influenza activity continues to increase in the north-western parts of India, Nepal, Sri Lanka, and Cambodia, while activity in the rest of region remain low.

In the tropical zone of Central and South America and the Caribbean, influenza transmission remains geographically widespread but overall disease activity has been declining except for focal areas of increasing activity in Jamaica, Venezuela, and Ecuador.

In Africa, pandemic H1N1 2009 virus continues to be isolated from all parts of the continent, and there is evidence of continued co-circulation of pandemic (H1N1) 2009 and seasonal H3N2 viruses.

In the temperate region of the southern hemisphere, little pandemic influenza activity has been reported.

The Global Influenza Surveillance Network (GISN) continues monitoring the global circulation of influenza viruses, including pandemic, seasonal and other influenza viruses infecting, or with the potential to infect, humans including seasonal influenza. For more information on virological surveillance and antiviral resistance please see the weekly virology update (Virological surveillance data, below).

http://www.who.int/csr/don/2009_12_04/en/index.html

Pandemic (H1N1) 2009 briefing note 18
Oseltamivir resistance in immunocompromised hospital patients

2 DECEMBER 2009 | GENEVA — WHO has been informed of two recent clusters of patients infected with oseltamivir-resistant H1N1 viruses. Both clusters, detected in Wales, UK and North Carolina, USA, occurred in a single ward in a hospital, and both involved patients whose immune systems were severely compromised or suppressed. Transmission of resistant virus from one patient to another is suspected in both outbreaks.

The emergence of drug-resistant influenza viruses in severely immunosuppressed or immunocompromised patients undergoing antiviral treatment is not unexpected and has been well documented during seasonal influenza. Virus replication can persist in such patients for prolonged periods of time despite antiviral treatment, creating an environment in which drug-resistant viruses can readily be selected. This phenomenon has also been observed for the pandemic (H1N1) 2009.

Upon receipt of the reports, WHO organized a telephone conference with officials and staff from the hospitals and experts in clinical medicine, epidemiology, and virology to discuss the two outbreaks. Particular attention is being given to the best treatment options for immunocompromised patients who become infected with the pandemic virus.

http://www.who.int/csr/disease/swineflu/notes/briefing_20091202/en/index.html

The Measles Initiative announced that measles deaths worldwide fell by 78% between 2000 and 2008, from an estimated 733 000 in 2000 to 164 000 in 2008. However, global immunization experts warn of a resurgence in measles deaths if vaccination efforts are not sustained. All regions, with the exception of one, have achieved the United Nations goal of reducing measles mortality by 90% from 2000 to 2010, two years ahead of target. Vaccinating nearly 700 million children against measles, through large-scale immunization campaigns and increased routine immunization coverage, has prevented an estimated 4.3 million measles deaths in less than a decade. Dr Margaret Chan, WHO Director-General, said, “So much has been achieved in the past several years thanks to the hard work and commitment of national governments and donors. But with only two years until the target date, there are signs of stalling momentum. This is a highly contagious disease that can quickly take advantage of any lapse in effort.”

http://www.who.int/mediacentre/news/releases/2009/measles_mdg_20091203/en/index.html

http://www.who.int/wer/2009/wer8449.pdf

The Lancet
Dec 05, 2009  Volume 374  Number 9705  Pages 1867 – 1944
http://www.thelancet.com/journals/lancet/issue/current

World Report
Dispute over pneumococcal vaccine initiative
Ann Danaiya Usher

The Global Alliance for Vaccines and Immunisation is at loggerheads with experts critical of the financing mechanism that it administers for pneumococcal vaccines. Ann Danaiya Usher reports.Ann Danaiya Usher covers the AMC for Development Today

New England Journal of Medicine
Volume 361 — December 3, 2009 — Number 23
http://content.nejm.org/current.shtml

The Emergency Use Authorization of Peramivir for Treatment of 2009 H1N1 Influenza
Debra Birnkrant, M.D., and Edward Cox, M.D., M.P.H.

On October 23, 2009, Food and Drug Administration (FDA) Commissioner Margaret Hamburg issued an Emergency Use Authorization (EUA) for peramivir for intravenous injection (BioCryst Pharmaceuticals). Peramivir is an unapproved investigational neuraminidase inhibitor that may be effective in treating certain hospitalized adult and pediatric patients with suspected or confirmed cases of 2009 H1N1 influenza. The EUA allows health care providers to use peramivir, subject to specified conditions. This is the first EUA that has been issued for an unapproved drug.

The legal standard for the authorization of an EUA during a declared public health emergency requires a finding that it is “reasonable to believe” that the product “may be effective,” as well as a finding that its known and potential benefits outweigh its known and potential risks.1 There must also be no other adequate, approved, and available treatment alternatives for the specific indication. This is a lower evidentiary standard than that used for marketing approval, which requires a finding of “substantial evidence” of efficacy for the proposed use based on adequate and well-controlled trials, as well as a robust safety evaluation (see table).

The FDA’s authority to issue an EUA was granted by Congress in the Project Bioshield Act of 2004. An EUA can be issued only after the secretary of health and human services has declared a public health emergency. In the case of the 2009 H1N1 influenza pandemic, such a declaration was made on April 26, 2009. An EUA for a medical product has a term of 1 year, but it can be renewed, depending on the circumstances of the emergency. It is important that product development continue to focus on the goal of approval (there are ongoing clinical trials evaluating the efficacy of intravenous peramivir in treating influenza), because the EUA is only a temporary means for making a product available during an emergency.

The FDA conducted an expedited review of the available data on peramivir, including data in preliminary or summary reports of clinical trials completed to date. Four efficacy trials evaluating the intravenous administration of peramivir have been completed; the details of these trials and information about the use of peramivir are summarized in the “Peramivir Fact Sheet for Health Care Providers” that was issued with the EUA.2 A treatment benefit — alleviation of symptoms approximately 1 day sooner than with placebo — was observed after the administration of single intravenous doses of 300 mg or 600 mg of peramivir in patients with acute, uncomplicated seasonal influenza. This treatment effect is similar to that seen with currently approved oral neuraminidase inhibitors. Two other trials of peramivir were conducted using oral oseltamivir as an active control (with no placebo group). No conclusions about efficacy can be drawn from the results of these trials because they did not demonstrate that peramivir was superior to oseltamivir and a clinically meaningful noninferiority margin for such a comparison has not been established. A fourth small trial revealed no significant differences in efficacy between two different doses of peramivir or between single and multiple doses. There are very limited data available regarding the use of peramivir in seriously ill hospitalized patients. Because the 2009 H1N1 virus is a novel influenza virus, trials of peramivir have not been conducted in patients with this infection. Overall, our determination that intravenous peramivir may be effective in treating hospitalized patients with 2009 H1N1 influenza was based on the drug’s demonstrated activity as a neuraminidase inhibitor and the treatment benefit observed in patients with acute, uncomplicated influenza.

Under the EUA, the usual adult dose for peramivir is 600 mg administered intravenously once daily for 5 to 10 days. This dose was selected on the basis of findings of a treatment benefit at doses of 300 mg or 600 mg in acute, uncomplicated influenza; the expected proportionally greater exposure at 600 mg than at lower doses; and the consideration that patients with more severe disease may need a higher dose. The treatment duration was selected on the basis of the expected need for a longer duration in hospitalized patients and is consistent with the design of ongoing phase 3 trials in hospitalized patients. The available safety data, including data from the limited number of patients who received 600 mg daily for 5 or more days, supported the selection of this dose and duration under the EUA.

Only 1891 clinical trial subjects have received peramivir at any dose, in any formulation (intravenous or intramuscular), or for any duration, including 478 who received a single dose of 600 mg intravenously and 33 who received 600 mg (or more) intravenously once daily for 5 or more days. No pediatric patients have received peramivir in clinical trials. The most commonly reported adverse effects in clinical trials were diarrhea, nausea, vomiting, and neutropenia. A limited number of pediatric and adult patients have also received peramivir under Emergency Investigational New Drug (EIND) procedures.

The FDA determined that despite the limited data on efficacy and safety, the criteria for an EUA for peramivir had been met for the treatment of certain patients hospitalized with known or suspected 2009 H1N1 influenza. Specifically, it is reasonable to believe that peramivir may be effective in patients with the pandemic virus on the basis of the limited results available from trials in patients with seasonal influenza. Furthermore, the serious, and potentially fatal, nature of the disease observed to date in patients who have been hospitalized because of 2009 H1N1 influenza infection and the lack of alternative treatment options (i.e., an intravenous antiviral agent with activity against influenza) for many of these patients led to issuance of the EUA for peramivir.

The Centers for Disease Control and Prevention (CDC) is responsible for managing the drug’s distribution and has established an electronic system through which health care providers can request peramivir under the EUA (www.cdc.gov/h1n1flu/eua/peramivir.htm). Currently, approximately 1200 treatment courses (if all given once daily for 5 days, or 600 treatment courses, if all given once daily for 10 days) of intravenous peramivir are available for distribution; more are expected to become available over time. The CDC will distribute peramivir directly to a hospital after verification of the request from a licensed clinician.

Health care providers and patients considering using peramivir under the EUA must carefully read the “Peramivir Fact Sheet for Health Care Providers” and the “Peramivir Fact Sheet for Patients and Parents/Caregivers” to assess the limited and preliminary nature of the available safety and efficacy data.2,3 Alternatives should be considered in making treatment decisions for individual patients who are hospitalized with 2009 H1N1 influenza.

Prescribing under the EUA is different from prescribing FDA-approved drugs (see table). Health care providers need to recognize that peramivir is an unapproved drug authorized for use only because of and during the 2009 H1N1 public health emergency. Although review by an institutional review board is not required, health care providers who prescribe the drug must fulfill certain requirements. These requirements are detailed in the “Peramivir Fact Sheet for Health Care Providers”2 and include documentation in the medical record that the patient and caregivers have been given the “Peramivir Fact Sheet for Patients and Parents/Caregivers,” informed of alternatives to receiving peramivir, and told that peramivir is an unapproved drug to be used only under the EUA. Providers must also report all medication errors and selected adverse events to the FDA’s MedWatch program (www.fda.gov/medwatch/report.htm), after which the FDA may contact the provider for additional information.

Because of the severity of illness in some patients hospitalized with 2009 H1N1 influenza, it is expected that some patients may not survive, whether or not they are treated with peramivir. Furthermore, it is expected that the evaluation of adverse events will be complicated by patients’ underlying medical conditions, coexisting conditions, and use of concomitant medications. Interpretation of the safety data will be challenging and complex. The FDA will carefully assess all available data on an ongoing basis and will update clinicians and the public as we learn more about this drug’s safety.

Financial and other disclosures provided by the authors are available at NEJM.org.

Source Information

From the Office of New Drugs, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD.
This article (10.1056/NEJMp0910479) was published on November 2, 2009, at NEJM.org.

References

Emergency Use Authorization of medical products: guidance — Emergency Use Authorization of medical products. Silver Spring, MD: Food and Drug Administration, 2009. (Accessed November 2, 2009, at http://www.fda.gov/RegulatoryInformation/Guidances/ucm125127.htm.)

Emergency Use Authorization of peramivir: fact sheet for health care providers. Silver Spring, MD: Food and Drug Administration, 2009. (Accessed November 2, 2009, at http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM187811.pdf.)

Emergency Use Authorization of peramivir: fact sheet for patients and parents/caregivers. Silver Spring, MD: Food and Drug Administration, 2009. (Accessed November 2, 2009, at http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM187799.pdf.)

New England Journal of Medicine
Volume 361 — December 3, 2009 — Number 23
http://content.nejm.org/current.shtml

Original Articles
Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand
S. Rerks-Ngarm and Others

ABSTRACT
Background The development of a safe and effective vaccine against the human immunodeficiency virus type 1 (HIV-1) is critical to pandemic control.

Methods In a community-based, randomized, multicenter, double-blind, placebo-controlled efficacy trial, we evaluated four priming injections of a recombinant canarypox vector vaccine (ALVAC-HIV [vCP1521]) plus two booster injections of a recombinant glycoprotein 120 subunit vaccine (AIDSVAX B/E). The vaccine and placebo injections were administered to 16,402 healthy men and women between the ages of 18 and 30 years in Rayong and Chon Buri provinces in Thailand. The volunteers, primarily at heterosexual risk for HIV infection, were monitored for the coprimary end points: HIV-1 infection and early HIV-1 viremia, at the end of the 6-month vaccination series and every 6 months thereafter for 3 years.

Results In the intention-to-treat analysis involving 16,402 subjects, there was a trend toward the prevention of HIV-1 infection among the vaccine recipients, with a vaccine efficacy of 26.4% (95% confidence interval [CI], –4.0 to 47.9; P=0.08). In the per-protocol analysis involving 12,542 subjects, the vaccine efficacy was 26.2% (95% CI, –13.3 to 51.9; P=0.16). In the modified intention-to-treat analysis involving 16,395 subjects (with the exclusion of 7 subjects who were found to have had HIV-1 infection at baseline), the vaccine efficacy was 31.2% (95% CI, 1.1 to 52.1; P=0.04). Vaccination did not affect the degree of viremia or the CD4+ T-cell count in subjects in whom HIV-1 infection was subsequently diagnosed.

Conclusions This ALVAC-HIV and AIDSVAX B/E vaccine regimen may reduce the risk of HIV infection in a community-based population with largely heterosexual risk. Vaccination did not affect the viral load or CD4+ count in subjects with HIV infection. Although the results show only a modest benefit, they offer insight for future research. (ClinicalTrials.gov number, NCT00223080 [ClinicalTrials.gov] .)

Source Information

From the Department of Disease Control, Ministry of Public Health, Nonthaburi (S.R.-N., R.P., C.N., S.C., C.K., P.T., P.K.); Vaccine Trials Center (P.P.) and Data Management Unit (J.K.), Faculty of Tropical Medicine, Mahidol University, Bangkok; Thai Component (S.N.) and U.S. Army Medical Component (J.C., R.P., M.S., M.B.), Armed Forces Research Institute of Medical Sciences, Bangkok — all in Thailand; the Division of AIDS, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (E.A.); Sanofi Pasteur, Swiftwater, PA (S.G., J.T., J.G.M.); Global Solutions for Infectious Diseases, South San Francisco, CA (D.P.F.); the Emmes Corporation, Rockville, MD (D.S.); the Global AIDS Program, Centers for Disease Control and Prevention, Atlanta (D.L.B.); U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Rockville, MD (M.L.R., N.L.M., J.H.K.); and U.S. Army Medical Materiel Development Activity, Ft. Detrick, MD (J.H.K.).
This article (10.1056/NEJMoa0908492) was published on October 20, 2009, and was last updated on November 19, 2009, at NEJM.org.

Address reprint requests to Dr. Kim at the U.S. Military HIV Research Program, Walter Reed Army Institute of Research, 1600 E. Gude Dr., Rockville, MD 20850, or at jkim@hivresearch.org

.

New England Journal of Medicine
Volume 361 — December 3, 2009 — Number 23
http://content.nejm.org/current.shtml

Editorial
HIV Vaccine Trial Results — An Opening for Further Research
R. Dolin

HIV-AIDS has emerged as an enormous, worldwide public health problem over the past 25 years. An estimated 33 million persons are infected with human immunodeficiency virus type 1 (HIV-1), and more than 7000 new infections occur every day.1 Although major advances have been made in the treatment of HIV-1 infection and in certain behavioral approaches to the prevention of HIV infection, ultimately, control will most likely depend on the development and application of a safe and effective HIV vaccine.

Substantial effort is being expended to develop an HIV vaccine through a variety of approaches.2 However, disappointing results have emerged from the only three large-scale efficacy trials previously carried out in humans.3,4,5 In this issue of the Journal, Rerks-Ngarm et al.6 report the results of a clinical trial of a vaccine regimen (ClinicalTrials.gov number, NCT00223080 [ClinicalTrials.gov] ), describing the first findings of possible prevention of HIV-1 infection in humans. This is of potentially great importance to the field of HIV research. The two analyses specified in the protocol, the intention-to-treat and per-protocol analyses, showed vaccine efficacies of 26.4% (P=0.08) and 26.2% (P=0.16), respectively. A modified intention-to-treat analysis, in which subjects who had HIV-1 infection at the time of randomization were excluded, showed a vaccine efficacy of 31.2% (P=0.04). Although the merits of each type of analysis can be debated, all three yielded a possible, albeit modest, effect of the vaccine in preventing HIV infection, although only the findings from the modified intention-to-treat analysis reached statistical significance at the traditional P<0.05 level. Despite its possible effect on acquisition of HIV-1 infection, the vaccine did not have any effect on the early HIV-1 viral load or CD4+ T-cell counts in vaccinated subjects who eventually became infected. The study was well designed and carefully conducted, and the demographic characteristics and risk factors for acquisition of HIV-1 infection appeared to be well balanced between the vaccine recipients and the placebo recipients. Information on other potential risk factors, such as circumcision status and serologic status for herpes simplex virus type 2, should be sought during follow-up.

The reported findings will be surprising to many investigators in the field because of the disappointing clinical and laboratory data previously reported in similar vaccine candidates. A glycoprotein 120 (gp120) B/B vaccine (AIDSVAX B/B) failed to show efficacy in two previously conducted clinical trials.3,4 The canarypox vector vaccine (ALVAC-HIV, vCP1452), after considerable study, was deemed by the HIV Vaccine Trials Network not to be sufficiently immunogenic to proceed to an efficacy trial.7 That unfavorable view was shared by a number of leading investigators in the field.8 In contrast, a phase 2 study in Thailand of the ALVAC-HIV (vCP1521) vaccine boosted with a gp120 B/E vaccine (AIDSVAX B/E) was believed to show sufficient immunogenicity9 to proceed to the efficacy trial undertaken by Rerks-Ngarm et al.

Despite the large size of the study by Rerks-Ngarm et al. (16,402 subjects and 52,985 person-years of follow-up), it was not designed or powered sufficiently for a number of additional subgroup analyses. Nonetheless, several interesting and potentially important observations are worthy of consideration. First, the population in the current trial was made up largely of persons at low risk (47.5%) or moderate risk (28.4%) for HIV infection, rather than those at high risk, and the means of infection was deemed to be primarily heterosexual sex. In contrast, the previous efficacy trials of a gp120 vaccine were conducted in high-risk populations: men who have sex with men3 and intravenous drug users.4 The recent efficacy trial of an HIV vaccine containing an adenovirus type 5 vector, which failed to show efficacy, was also conducted in high-risk men who have sex with men.7 Perhaps the requirements for protection against transmission in low-risk, heterosexual persons are considerably different or less stringent than those in high-risk subjects, as suggested by the data in Table 2 of the report by Rerks-Ngarm et al. This observation may be important in the design of future clinical trials as well as direction for increased research activity.

Rerks-Ngarm et al. also were not able to determine the duration of the possible vaccine effect. The results are reported after a 3-year follow-up period, but there is a suggestion that more of the effect might have occurred during the first year. The duration of the vaccine’s effect should be addressed by follow-up of the participants in the current study as well as by future trials.

Another important topic raised by the trial is the relative contribution of each of the vaccine components to the observed effects. Does the possible protective effect require the prime–boost combination or just one of the components? What is the relationship between HIV strains represented in the vaccine and the circulating strains that infected the vaccine recipients?

The possible vaccine efficacy observed was modest and indicates that the vaccine regimen studied is unlikely to be a public health control measure for HIV-1 infection, as the authors themselves acknowledge. The most important contribution of the study is most likely the opportunity to investigate possible host-response correlates of protection against infection. The establishment of such correlates is the central question in HIV vaccine development and will have a profound effect on the designs of vaccines and clinical trials to assess their efficacy. Given the lack of detection of conventional immune responses in earlier studies of these vaccine components, as well as the divergence between the vaccine’s effect on the infection and the effect on viral load, the correlates of protection may, indeed, reflect new concepts of host response. This should be the focus of intense research using the most current research techniques. Ultimately, it is the results of such studies that will most likely determine the significance of this clinical trial to the field of HIV vaccine development.

The clinical trial reported here represents an enormous effort by investigators, sponsoring institutions, and participants in the community. The findings raise a number of questions that have important implications for future directions in vaccine research. The answers to these and related questions will require the application of a balanced and coordinated research approach to the complex and difficult problem of the development of an HIV vaccine. This balanced approach includes fundamental laboratory and experimental-model studies, as well as rigorously designed and conducted clinical trials, such as the one reported on here.

No potential conflict of interest relevant to this article was reported.

Source Information
From Beth Israel Deaconess Medical Center, Harvard Medical School, Boston.
This article (10.1056/NEJMe0909972) was published on October 20, 2009, at NEJM.org.

References
Chan M. Towards universal access: scaling up priority HIV/AIDS interventions in the health sector. Geneva: World Health Organization, 2009. (Accessed October 19, 2009, at http://www.who.int/hiv/pub/2008progressreport/en/index.html.)

Barouch DH. Challenges in the development of an HIV-1 vaccine. Nature 2008;455:613-619. [CrossRef][Web of Science][Medline]

Flynn NM, Forthal DN, Harro CD, Judson FN, Mayer KH, Para MF. Placebo-controlled phase 3 trial of a recombinant glycoprotein 120 vaccine to prevent HIV-1 infection. J Infect Dis 2005;191:654-665. [CrossRef][Web of Science][Medline]

Pitisuttithum P, Gilbert P, Gurwith M, et al. Randomized, double-blind, placebo-controlled efficacy trial of a bivalent recombinant glycoprotein 120 HIV-1 vaccine among injection drug users in Bangkok, Thailand. J Infect Dis 2006;194:1661-1671. [CrossRef][Web of Science][Medline]

Buchbinder SP, Mehrotra DV, Duerr A, et al. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet 2008;372:1881-1893. [CrossRef][Web of Science][Medline]

Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, et al. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med 2009;361:2209-2220. [Free Full Text]

Russell ND, Graham BS, Keefer MC, et al. Phase 2 study of an HIV-1 canarypox vaccine (vCP1452) alone and in combination with rgp120: negative results fail to trigger a phase 3 correlates trial. J Acquir Immune Defic Syndr 2007;44:203-212. [CrossRef][Web of Science][Medline]

Burton DR, Desrosiers RC, Doms RW, et al. Public health: a sound rationale needed for phase III HIV-1 vaccine trials. Science 2004;303:316-316. [Free Full Text]

Nitayaphan S, Pitisuttithum P, Karnasuta C, et al. Safety and immunogenicity of an HIV subtype B and E prime-boost vaccine combination in HIV-negative Thai adults. J Infect Dis 2004;190:702-706. [CrossRef][Web of Science][Medline]

The WHO continues to issue weekly “updates” and briefing notes as below:
Pandemic (H1N1) 2009 – update 76
Weekly update
–

As of 22 November 2009, worldwide more than 207 countries and overseas territories or communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including over 7820 deaths.

As many countries have stopped counting individual cases, particularly of milder illness, the case count is likely to be significantly lower than the actual number of cases that have occurred. WHO is actively monitoring the progress of the pandemic through frequent consultations with the WHO Regional Offices and member states and through monitoring of multiple sources of data.

Situation update:
In temperate regions* of the northern hemisphere, the early arriving winter influenza season continues to be intense across parts of North America and much of Europe. In North America, the Caribbean islands and a limited number of European countries there are signs that disease activity peaked.

In the United States and Canada, influenza transmission remains very active and geographically widespread. In the United States, disease activity appears to have peaked in all areas of the country. In Canada, influenza activity remains similar but number of hospitalisations and deaths is increasing. Most countries in the Caribbean have ILI and SARI levels coming down.

In Europe, widespread and increasing transmission of pandemic influenza virus was observed across much of the continent and most countries that were not yet experiencing elevated ILI activity in the last few weeks, have seen a rapid increase in ILI. Very high activity is seen in Sweden, Norway, Moldova and Italy. Over 99% of subtyped influenza A viruses in Europe were pandemic H1N1 2009. Impact on health care services is severe in Albania and Moldova. Some countries seem to have peaked already: Belgium, Bulgaria, Belarus, Ireland, Luxemburg, Norway, Serbia, Ukraine and Iceland.

In East Asia, influenza transmission remains active. Intense influenza activity continues to be observed in Mongolia but has peaked already. In Japan, influenza activity remains stably elevated, but may be decreasing slightly in populated urban areas.

ILI activity in India and Nepal and Sri Lanka has increased.

In the tropical zone of the Americas and Asia, influenza transmission remains variable but low in many countries. In the tropical areas of Central and South America, most countries continue to report declining influenza activity, with the exception of Ecuador and Venezuela.

In the temperate region of the southern hemisphere, little pandemic influenza activity has been reported.

http://www.who.int/csr/don/2009_11_27a/en/index.html

The WHO released an updated child mortality fact sheet available at the link below. Key facts:

– Nearly 9 million children under the age of five die every year, according to 2007 figures.

– Around 70% of these early child deaths are due to conditions that could be prevented or treated with access to simple, affordable interventions.

– Leading causes of death in under-five children are pneumonia, diarrhoea and health problems during the first month of life.

– Over one third of all child deaths are linked to malnutrition.

– Children in developing countries are ten times more likely to die before the age of five than children in developed countries.

“For some of the most deadly childhood diseases, such as measles, polio, diphtheria, tetanus, pertussis, and Haemophilius Influenzae type B, vaccines are available and can protect children from illness and death.”

http://www.who.int/mediacentre/factsheets/fs178/en/index.html

The World Epidemiological Record (WER) for 27 November 2009, vol. 84, 48 (pp 493–504) includes: WHO external quality assessment project for detecting influenza virus subtype A by polymerase chain reaction – summary analysis, 2009; Performance of acute flaccid paralysis (AFP) surveillance and incidence of poliomyelitis, 2009

http://www.who.int/wer/2009/wer8448.pdf

[Editor’s Note: As we have communicated previously, we generally do not cover, and certainly do not endorse, market research or similar studies for sale. We do take note of data promoting such research if it informs general understanding and is linked to ethical and policy issues related to vaccines the Center is following]

Research and Markets: Opportunity Analysis of H1N1 (swine flu) Vaccination Market – The Global H1N1 Influenza Vaccine Market is Estimated to be at 676 Million in 2009

“…The first movers in the vaccines market (for H1N1) are GlaxoSmithKline (GSK), Novartis, CSL, Medimmune, Baxter, Sinovec and Sanofi Pastuer. Medimmune is the only producer of the intranasal vaccine whereas other companies are expected to come out with intramuscular vaccines. The companies have got approvals for their first lots from the governments of the various countries such as U.S., U.K., France, China, Denmark and Australia. The involvement of government bodies, increased awareness about prevention and pandemic situation of the influenza is driving the market for the vaccines.

“…The global H1N1 Influenza vaccine market is estimated to be of 676 million in 2009 with first lot of doses being commercialized on 30th September 2009. The market will see a high CAGR for the next two years i.e. the market is expected to be at $7.03 billion in 2011 with a CAGR of 222.4% from 2009 to 2011. However, the very high CAGR will settle down by 2012 to 30% for the period of 2009 to 2012. The reason for the sudden settle down of the growth is that it is expected that most of the world population will be immunized by the end of 2011.”

http://www.businesswire.com/portal/site/home/permalink/?ndmViewId=news_view&newsId=20091123005448&newsLang=en

The Lancet
Nov 28, 2009  Volume 374  Number 9704  Pages 1793 – 1866
http://www.thelancet.com/journals/lancet/issue/current

Editorial
Can malaria be eliminated?
The Lancet

Preview: At the UK Academy of Medical Sciences’ annual international health lecture last week, Nicholas White asked whether malaria elimination was feasible or futile. By elimination, he means the interruption of malaria transmission, creating zero incidence of locally contracted cases. White reviewed past attempts to control, eliminate, and even eradicate malaria—and their disappointments. But now, he argued, there was a new opportunity to defeat malaria, an opportunity that should be grasped firmly before the fashions of global health divert attention elsewhere.

The Lancet
Nov 28, 2009  Volume 374  Number 9704  Pages 1793 – 1866
http://www.thelancet.com/journals/lancet/issue/current

Correspondence
Scarcity of pneumococcal vaccine where it is needed most
Original Text
Julian Lob-Levyt

In your Sept 12 issue, two studies that estimate the global and country-level burden of childhood disease caused by Streptococcus pneumoniae (pneumococcus)1 and Haemophilus influenzae type b (Hib)2 show concrete evidence of a troubling disparity. A disproportionate toll of these diseases, particularly pneumococcal disease, is levied on African and Asian children. An article from Kenya3 has further shown that African children with sickle-cell disease are particularly vulnerable to bacterial infections such as pneumococcal disease.

Yet, these are precisely the children and the places that lack access to life-saving vaccines. Although Hib vaccine—thanks to a concerted multiyear collaborative effort—has or is planned to arrive in nearly every country in the world by next year, none of the ten countries with the highest pneumococcal disease burden routinely provides the pneumococcal conjugate vaccine.

This chasm between the places where the most children lose their lives to pneumococcal disease and where life-saving vaccines are available can be closed. The GAVI Alliance provides assistance to eligible countries to introduce the pneumococcal vaccine sustainably through innovative donor-led financing mechanisms such as the Advance Market Commitment for as little as US$0·15 per dose. Our hope is to introduce the vaccine in 42 countries by 2015.

Strong evidence is an essential component of successful child health interventions. Armed with robust new studies such as these, now is the time to act by maintaining our commitment to provide financial assistance to resource-poor countries and supporting policy makers to prioritise prevention.

References

1 O’Brien KL, Wolfson LJ, Watt JP, et alfor the Hib and Pneumococcal Global Burden of Disease Study Team. Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates. Lancet 2009; 374: 893-902. Summary | Full Text | PDF(540KB) | CrossRef | PubMed

2 Watt JP, Wolfson LJ, O’Brien KL, et alfor the Hib and Pneumococcal Global Burden of Disease Study Team. Burden of disease caused by Haemophilus influenzae type b in children younger than 5 years: global estimates. Lancet 2009; 374: 903-911. Summary | Full Text | PDF(529KB) | CrossRef | PubMed

3 Williams TN, Uyoga S, Ndila C, et al. Bacteraemia in Kenyan children with sickle-cell anaemia: a retrospective cohort and case—control study. Lancet 2009; 374: 1364-1370. Summary | Full Text | PDF(116KB) | CrossRef | PubMed

Pediatrics
December 2009 / VOLUME 124 / ISSUE 6
http://pediatrics.aappublications.org/current.shtml

Spatial Accessibility to Providers and Vaccination Compliance Among Children With Medicaid
Linda Y. Fu, MD, MSa,b, Nuala Cowan, MAc, Rosie McLaren, MSd, Ryan Engstrom, PhDc and Stephen J. Teach, MD, MPHb
a Goldberg Center for Community Pediatric Health
b Center for Clinical and Community Research, Children’s National Medical Center, Washington, DC
c Department of Geography, George Washington University, Washington, DC
d National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia

OBJECTIVE: We examined the relationship between spatial accessibility to pediatric immunization providers and vaccination compliance in a low-income, urban population of children.

METHODS: In 2007, we accessed the Washington, DC, Immunization Information System (IIS) to collect data on the immunization statuses and residential addresses of children who were aged 19 to 35 months and had Medicaid insurance. In addition, we calculated each child’s spatial accessibility to pediatric vaccination providers by assessing the provider-to-population ratio at each residential address. Spatial accessibility was divided into tertiles (low, medium, and high) of access. The relationship between spatial accessibility to providers and vaccination compliance was examined by using logistic regression analysis adjusting for age, type of vaccination provider, and enrollment in child care status.

RESULTS: Overall for our cohort of 4195 children, 80.5% of the children were up-to-date with vaccinations. Vaccination coverage ranged from 61.6% to 100% (median: 79.2%) among different neighborhoods. Having the highest level of access to pediatric vaccination providers was associated with 36% higher odds of being up-to-date as compared with having the lowest level of access. The middle tertile of access was associated with 25% higher odds of being up-to-date.

CONCLUSIONS: Within our low-income, urban population, children with higher spatial accessibility to pediatric vaccination providers were more likely to be up-to-date with vaccinations. This association may guide future studies and efforts to ensure adequate immunization coverage for children regardless of where they live.

Pediatrics
December 2009 / VOLUME 124 / ISSUE 6
http://pediatrics.aappublications.org/current.shtml

Booster Vaccinations: Can Immunologic Memory Outpace Disease Pathogenesis?
Michael E. Pichichero, MD
Rochester General Research Institute, Rochester General Hospital, Rochester, New York

Almost all current vaccines work by the induction of antibodies in serum or on the mucosa to block adherence of pathogens to epithelial cells or interfere with microbial invasion of the bloodstream. However, antibody levels usually decline after vaccination to undetectable amounts if further vaccination does not occur. Persistence of vaccine-induced antibodies usually goes well beyond the time when they should have decayed to undetectable levels because of ongoing “natural” boosting or other immunologic mechanisms. The production of memory B and T cells is of clear importance, but the likelihood that a memory response will be fast enough in the absence of a protective circulating antibody level likely depends on the pace of pathogenesis of a specific organism. This concept is discussed with regard to Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis; hepatitis A and B; diphtheria, tetanus, and pertussis; polio, measles, mumps, rubella, and varicella; rotavirus; and human papilloma virus. With infectious diseases for which the pace of pathogenesis is less rapid, some individuals will contract infection before the memory response is fully activated and implemented. With infectious diseases for which the pace of pathogenesis is slow, immune memory should be sufficient to prevent disease.

PLoS Medicine
(Accessed 30 November 2009)
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

Editorial
Time for a “Third Wave” of Malaria Activism to Tackle the Drug Stock-out Crisis
PLoS

PLoS Medicine
(Accessed 30 November 2009)
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

The Unequal World of Health Data
Peter Byass

Summary Points
– Health data, poverty, and inequality exist in a complex global co-dependency, therefore making meaningful comparisons of health across widely different settings challenging.
– Less data exist on the health of the poor than of the rich, which in turn raises important questions as to how representative available data are in relation to populations that go uncounted.
– Alternative strategies are needed to fill in inequitable gaps in data.

Poverty either in physical terms or in data does not justify the use of impoverished research methods or ethical standards. Reasonable, realistic, and contextually appropriate approaches to research are needed.

Science
7 November 2009  Vol 326, Issue 5957, Pages 1149-1304
http://www.sciencemag.org/current.dtl

Editorial
On Incentives for Innovation

Bruce Alberts
For science to thrive, it is crucial that the scientific community encourage the bold ambitions and innovative spirit of young researchers. In my own area of science, the United States could do much more to support this important goal. U.S. biomedical science is a large and important research enterprise that currently includes over 100,000 graduate students and postdoctoral fellows. Of these, only a select few will go on to become independent research scientists in academia. Assuming that the system supporting this career path works well, these will be the individuals with the most talent and interest in such an endeavor: young people well positioned to make the scientific breakthroughs that societies need to survive and thrive. But the current system squanders the creativity and energy of these exceptionally gifted young people through a funding process that forces them to avoid risk-taking and innovation.

Bruce Alberts is Editor-in-Chief of Science.

Vaccine
Volume 27, Issue 51, Pages 7139-7218 (27 November 2009)
http://www.sciencedirect.com/science/journal/0264410X

Optimal vaccination choice, vaccination games, and rational exemption: An appraisal
Pages 98-109
Piero Manfredi, Pompeo Della Posta, Alberto d’Onofrio, Ernesto Salinelli, Francesca Centrone, Claudia Meo, Piero Poletti

Abstract
A threat for vaccination policies might be the onset of “rational” exemption, i.e. the family’s decision not to vaccinate children after a seemingly rational comparison between the perceived risk of infection and the perceived risk of vaccine side effects. We study the implications of rational exemption by models of vaccination choice. By a simple model of individual choice we first prove the “elimination impossible” result in presence of informed families, i.e. aware of herd immunity, and suggest that limited information might explain patterns of universal vaccination. Next, we investigate vaccination choice in a game-theoretic framework for communities stratified into two groups, “pro” and “anti” vaccinators, having widely different perceived costs of infection and of vaccine side effects. We show that under informed families neither a Nash nor a Stackelberg behaviour (characterized, respectively, by players acting simultaneously and by an asymmetric situation with a “leader” and a “follower) allow elimination, unless “pro-vaccinators” assign no costs to vaccine side effects. Elimination turns out to be possible when cooperation is encouraged by a social planner, provided, however, he incorporates in the “social loss function” the preferences of anti-vaccinators only. This allows an interpretation of the current Italian vaccination policy.

Vaccine
Volume 27, Issue 51, Pages 7139-7218 (27 November 2009)
http://www.sciencedirect.com/science/journal/0264410X

Which factors are important in adults’ uptake of a (pre)pandemic influenza vaccine?
Pages 207-227
E.A.M. Zijtregtop, J. Wilschut, N. Koelma, J.J.M. Van Delden, R.P. Stolk, J. Van Steenbergen, J. Broer, B. Wolters, M.J. Postma, E. Hak

Abstract
Since 2008, (pre)pandemic vaccines against H5N1 influenza have been available and pandemic vaccines against new influenza H1N1 are currently produced. In The Netherlands, the vaccination call for seasonal influenza among the recommended groups approximates 70%. These statistics raise the question if adults in Western societies are willing to get a (pre)pandemic influenza vaccination, for example, against avian H5N1 or swine-like H1N1 virus. A questionnaire was performed to determine the predictors of a negative intention to be immunized against pandemic influenza among adults. Demographical, behavioural and organisational determinants were studied. Thirty-four and five percent of the respondents were negatively intended to get a pandemic influenza vaccination in a pre-pandemic or pandemic phase, respectively. On the basis of six behavioural determinants negative intention to get a pandemic influenza vaccination can be predicted correctly in almost 80% of the target group. These determinants should be targeted in pandemic preparedness plans.

The WHO continues to issue weekly “updates” and briefing notes as below:
Pandemic (H1N1) 2009 – update 75
Weekly update
20 November 2009 –

As of 15 November 2009, worldwide more than 206 countries and overseas territories or communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including over 6770 deaths.

As many countries have stopped counting individual cases, particularly of milder illness, the case count is likely to be significantly lower than the actual number of cases that have occurred. WHO is actively monitoring the progress of the pandemic through frequent consultations with the WHO Regional Offices and member states and through monitoring of multiple sources of data.

Situation update:

The situation remains similar since the last update. In temperate regions* of the northern hemisphere, the early arriving winter influenza season continues to intensify across parts of North America and much of Europe. However, there are early signs of a peak in disease activity in some areas of the northern hemisphere.

More detail at: http://www.who.int/csr/don/2009_11_20a/en/index.html