WHO: Pandemic (H1N1) 2009 – update 93: 26 March 2010

The WHO continues to issue weekly “updates” and briefing notes on the H1N1 pandemic at: http://www.who.int/csr/disease/swineflu/en/index.html

Pandemic (H1N1) 2009 – update 93
Weekly update
26 March 2010

As of 21 March 2010, worldwide more than 213 countries and overseas territories or communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including over 16,931 deaths.

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 information.

Situation update:
The most active areas of pandemic influenza virus transmission currently are in parts of Southeast Asia, West Africa, and in the tropical zone of the Americas…

More at: http://www.who.int/csr/don/2010_03_26/en/index.html

GAVI: GSK, Pfizer commit pneumococcal vaccine under AMC

The GAVI Alliance announced that GlaxoSmithKline (GSK) and Pfizer became “the first two companies to make long-term commitments to supply new vaccines against pneumococcal disease” under the Advance Market Commitment (AMC) for pneumococcal disease. The AMC has been supported by the governments of Italy, the United Kingdom, Canada, Russia, Norway and the Bill & Melinda Gates Foundation. GAVI CEO Julian Lob-Levyt said, “Today’s landmark announcement promises to make new vaccines available affordably, where they are urgently needed, and faster than ever before. Through this AMC, and thanks to the political will demonstrated by donors and least developed nations and the participation of the pharmaceutical companies, prevention against the world’s biggest childhood killer is now within reach.” GAVI estimates that the introduction of suitable and affordable vaccines against the disease could save approximately 900,000 lives by 2015 and up to seven million lives by 2030.

Pfizer and GSK “have committed to supply 30 million doses each per year, for a 10 year period…(to be) made available at US$ 3.50 per dose to be paid by GAVI and the developing country governments that introduce the vaccines.” GAVI said that, for approximately 20% of the doses, companies will also receive an additional payment of US$3.50 for each dose they provide, which is paid with donor commitments (AMC funds). In total, this is a fraction of the current cost of pneumococcal vaccines in many industrialised countries, GAVI noted.

http://www.gavialliance.org/media_centre/press_releases/2010_03_23_amc_commitment.php

FDA, WHO, Global Advisory Committee Statements on porcine circovirus 1 (PCV1) in Rotarix

The FDA recommended that “healthcare practitioners temporarily suspend use of the Rotarix vaccine for rotavirus immunization in the United States while the agency learns more about components of an extraneous virus detected in the vaccine, noting that there is no evidence at this time that this finding poses a safety risk. Full text of the announcement follows:

“The agency recently became aware that an independent U.S. academic research team, using a novel technique, has found DNA from porcine circovirus 1 (PCV1) in Rotarix, which is manufactured by GlaxoSmithKline.  PCV1 is not known to cause illness in humans or other animals.  In addition, Rotarix has been studied extensively, before and after approval, and found to have an excellent safety record.

“Follow-up tests by GlaxoSmithKline and FDA scientists confirmed the academic team’s findings and confirmed that viral components have been present since the early stages of the vaccine’s development, including during clinical studies.  Preliminary testing by both the academic researchers and FDA scientists of another licensed vaccine against rotavirus infection, RotaTeq, has not detected components of PCV1.

“”We are making clinicians aware of information recently received by FDA about the Rotarix vaccine,” said Dr. Margaret A. Hamburg, Commissioner for Food and Drugs. “There is no evidence at this time that there is a safety concern.  FDA is recommending that clinicians temporarily suspend use of Rotarix until we can learn more about the situation.  We will keep the public and the clinical community updated on our findings…”

“…In many countries, rotavirus causes so much severe illness and death that the known benefits of continued use of Rotarix far outweigh any theoretical risk of harm from the vaccine,” said Dr. Thomas Frieden, Director of the Centers for Disease Control and Prevention.  “We anticipate that many countries will decide to continue vaccinating with Rotarix while more information becomes known.”

“FDA will continue to gather more information about the PCV1 components in Rotarix, including whether intact virus, as opposed to DNA fragments, is present.  The agency is assessing current vaccine testing methods.  In four to six weeks, FDA will convene an expert advisory committee and make additional recommendations on the use of rotavirus vaccines.

“FDA will provide updates to patients, providers, and the general public as more information becomes available.  The agency will also continue to communicate with the World Health Organization and counterpart regulatory agencies in other countries.

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm205625.htm

WHO: Rotavirus vaccination – WHO does not recommend any change to use of Rotarix vaccine 22 March 2010

Following announcements today by the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) regarding use of the rotavirus vaccine, Rotarix, the World Health Organization (WHO) encourages all countries using the vaccine to carefully consider the significant benefits of continued use of the vaccine in any decisions about further use.

The FDA and EMA statements follow the recent report to the vaccine manufacturer that DNA sequences originating from porcine circovirus 1 (PCV1) had been detected in two batches of the vaccine during a study undertaken in the United States of America (USA).

WHO concurs with the views of the FDA and EMA that the findings do not present a threat to public health. Moreover, rotaviruses are the most common cause of severe diarrhoeal disease in young children throughout the world, with an estimated 527 000 deaths among children under five years old, most of whom live in low-income countries. Therefore, WHO does not recommend any change to use of the vaccine. The vaccine is prequalified by WHO, and the prequalification status remains unchanged.

WHO will continue to work closely with the FDA , EMA and other regulatory agencies to evaluate further information that the manufacturer will be providing as a matter of urgency.

http://www.who.int/immunization/newsroom/news_rotavirus_vaccine_use/en/index.html

Statement of the Global Advisory Committee on Vaccine Safety on Rotarix

On 25 March 2010, WHO’s Global Advisory Committee on Vaccine Safety (GACVS) met by teleconference to review new data on Rotarix, an oral vaccine for prevention of rotavirus gastroenteritis. Academic investigators recently reported to the vaccine manufacturer, GlaxoSmithKline, that the vaccine contains DNA from porcine circovirus type 1 (PCV1). PCV1 is not known to cause disease in animals or humans. Further analysis of the master cell bank and master viral seed used for vaccine production have demonstrated the presence of PCV1 DNA, which in retrospect has been in the vaccine throughout its clinical development, including the prelicensure clinical trials. There are studies underway both by the manufacturer and others that will provide additional information to help more fully assess this new finding.

The safety of Rotarix is supported by both large clinical trials prelicensure and an extensive (>60 million doses) postlicensure safety experience. GACVS reviewed the safety data from both clinical trials and spontaneous reports, both of which supported the continued safety of Rotarix. Rotavirus gastroenteritis is the most common cause of severe diarrheal disease in young children throughout the world, with an estimated 527 000 deaths annually among children under five years old. Given the extensive clinical data supporting the safety of Rotarix and the benefits of rotavirus vaccination for children, GACVS considers that the benefits of vaccination far outweigh any currently known risk associated with use of Rotarix. GACVS will continue to review data as it becomes available and will update this statement as we learn more.

http://www.who.int/vaccine_safety/topics/rotavirus/rotarix_statement_march_2010/en/index.html

Partnership: PATH and International Enteric Vaccine Consortium (EntVac)

PATH and the International Enteric Vaccine Consortium (EntVac) announced a new partnership for early-stage research into a vaccine concept against enterotoxigenic E. coli (ETEC), described as one of the leading bacterial causes of diarrheal disease. PATH will fund EntVac, a consortium of universities anchored by the University of Maryland School of Medicine, to pursue preclinical proof of concept of a stable toxin (ST) toxoid vaccine. PATH said such a vaccine “offers the prospect of broad protection against ETEC, but requires additional research and evaluation.” PATH will provide funding of US$1.1 million over 2.5 years for the research effort. ETEC is responsible for up to 840 million infections and approximately 400,000 deaths worldwide each year, mostly in children in developing countries. The research will be conducted at the University of Maryland School of Medicine’s Center for Vaccine Development, the University of Bergen, the University of South Dakota, and Tulane University. The Research Council of Norway is also funding the EntVac consortium for this research project.

http://www.path.org/news/pr100326-entvac.php

CSIS releases Smart Global Health Policy report

The Center for Strategic and International Studies (CSIS) Commission on Smart Global Health Policy launched its final report – A Healthier, Safer and More Prosperous World – “promoting a long-term, strategic US approach to global health.” The report advises U.S. policymakers in five major issue areas which “chart a course for US global health investment through 2025”:

– Maintaining commitments to HIV/AIDS, tuberculosis, and malaria

– Narrowing health gaps for women and children

– Strengthening prevention and preparedness capabilities

– Improving coordination and increasing capacity between implementers and policymakers

– Making smart investments in multilateral institutions.

Dr. Christopher Elias, president and CEO of PATH and a member of the CSIS commission, said, “The report from the CSIS Commission on Smart Global Health Policy highlights how crucial research and innovation for new global health products are to overall US global health efforts. It also illustrates how innovative financing mechanisms play vital roles in spurring the development of new vaccines, drugs, and other tools that save lives worldwide. US policymakers should implement these recommendations to maximize the country’s efforts to improve health around the world.”

The report and additional information available at: http://smartglobalhealth.org/content/report

http://www.path.org/news/an100324-csis.php

MMWR Weekly for March 26, 2010

The MMWR Weekly for March 26, 2010 / Vol. 59 / No. 11 includes:
2009 Pandemic Influenza A (H1N1) in Pregnant Women Requiring Intensive Care — New York City, 2009

To characterize the severity of 2009 H1N1 virus infection in pregnant women, the New York City Department of Health and Mental Hygiene conducted surveillance for cases in pregnant women requiring intensive care. The findings indicated that, during 2009, 16 pregnant women and one who was postpartum were admitted to intensive-care units. Two women died. Of the 17 women, 12 had no risk factors for severe influenza complications other than pregnancy, and only one woman received antiviral treatment within 2 days of symptom onset.

PPD forms Vaccines & Biologics Center of Excellence

PPD, Inc. announced the launch of PPD Vaccines & Biologics Center of Excellence, described as “a first-in-kind comprehensive network of integrated, world-class laboratory services focused specifically on vaccine and biologic drug development.” PPD said the Center significantly expands vaccine testing services PPD acquired from Merck in 2009. “With the industry’s largest collection of commercial vaccine assays and strong immunochemistry, cell culture and cGMP lab operations, PPD is the first CRO to offer the type of laboratory support that has the potential to bring significant efficiencies to the development of vaccines and biologics,” the company said.

Christine Dingivan, M.D., chief medical officer, PPD, commented, “With the industry’s largest collection of commercial vaccine assays and strong immunochemistry, cell culture and cGMP lab operations, PPD is the first CRO to offer the type of laboratory support that has the potential to bring significant efficiencies to the development of vaccines and biologics. The Vaccines & Biologics Center of Excellence provides the high quality scientific support our clients are seeking in a way that allows them to bypass costly capital and resource investments necessary to develop and maintain these capabilities internally.”

http://www.businesswire.com/portal/site/home/permalink/?ndmViewId=news_view&newsId=20100323007191&newsLang=en

H1N1 infection in England: cross-sectional serological study

The Lancet
Mar 27, 2010  Volume 375  Number 9720  Pages 1053 – 1134
http://www.thelancet.com/journals/lancet/issue/current

Incidence of 2009 pandemic influenza A H1N1 infection in England: a cross-sectional serological study
Elizabeth Miller, Katja Hoschler, Pia Hardelid, Elaine Stanford, Nick Andrews, Maria Zambon

Summary
Background
Knowledge of the age-specific prevalence of immunity from, and incidence of infection with, 2009 pandemic influenza A H1N1 virus is essential for modelling the future burden of disease and the effectiveness of interventions such as vaccination.

Methods
In this cross-sectional serological survey, we obtained 1403 serum samples taken in 2008 (before the first wave of H1N1 infection) and 1954 serum samples taken in August and September, 2009 (after the first wave of infection) as part of the annual collection for the Health Protection Agency seroepidemiology programme from patients accessing health care in England. Antibody titres were measured by use of haemagglutination inhibition and microneutralisation assays. We calculated the proportion of samples with antibodies to pandemic H1N1 virus in 2008 by age group and compared the proportion of samples with haemagglutination inhibition titre 1:32 or more (deemed a protective response) before the first wave of infection with the proportion after the first wave.

Findings
In the baseline serum samples from 2008, haemagglutination inhibition and microneutralisation antibody titres increased significantly with age (F test p<0·0001). The proportion of samples with haemagglutination inhibition titre 1:32 or more ranged from 1·8% (three of 171; 95% CI 0·6—5·0) in children aged 0—4 years to 31·3% (52 of 166; 24·8—38·7) in adults aged 80 years or older. In London and the West Midlands, the difference in the proportion of samples with haemagglutination inhibition titre equal to or above 1:32 between baseline and September, 2009, was 21·3% (95% CI 8·8—40·3) for children younger than 5 years of age, 42·0% (26·3—58·2) for 5—14-year-olds, and 20·6% (1·6—42·4) for 15—24-year-olds, with no difference between baseline and September in older age groups. In other regions, only children younger than 15 years showed a significant increase from baseline (6·3%, 1·8—12·9).

Interpretation
Around one child in every three was infected with 2009 pandemic H1N1 in the first wave of infection in regions with a high incidence, ten times more than estimated from clinical surveillance. Pre-existing antibody in older age groups protects against infection. Children have an important role in transmission of influenza and would be a key target group for vaccination both for their protection and for the protection of others through herd immunity.

Funding
National Institute for Health Research Health Technology Assessment Programme.

Global Climate Change and Infectious Diseases

New England Journal of Medicine
Volume 362 — March 25, 2010 — Number 12
http://content.nejm.org/current.shtml

Perspective
Global Climate Change and Infectious Diseases
E. K. Shuman

[Initial article language per NEJM convention]
The 2009 United Nations Climate Change Conference in Copenhagen ended on December 18 without passage of a binding resolution for tackling global climate change. With the debate over U.S. health care reform raging, this event went largely unnoticed by the U.S. health care community. However, climate change will have enormous implications for human health, especially for the burden of vectorborne and waterborne infectious diseases…

Universal Mass Rotavirus Vaccination: Austria

The Pediatric Infectious Disease Journal
April 2010 – Volume 29 – Issue 4
http://journals.lww.com/pidj/pages/currenttoc.aspx

Original Studies
Universal Mass Vaccination Against Rotavirus Gastroenteritis: Impact on Hospitalization Rates in Austrian Children

Paulke-Korinek, Maria; Rendi-Wagner, Pamela; Kundi, Michael; Kronik, Renate; Kollaritsch, Herwig

Abstract
Background: Since July 2007, rotavirus vaccinations have been subsidized in Austria for all children from the seventh week up to the sixth month of life. Vaccination coverage over the whole period was 72% with an increase to 87% in 2008.

Methods: In a sentinel network including 11 pediatric hospital wards in Austria, data of children up to 15 years of age and hospitalized due to rotavirus gastroenteritis between January 2001 and December 2008 have been collected.

Results: The hospitalization rates of children up to 12 months of age with rotavirus gastroenteritis were 2066 x 10-5 between 2001 and 2006 and decreased to 631 x 10-5 in 2008. For children between 12 and 24 months of age the hospitalization rate decreased from 1822 x 10-5 (2001-2006) to 1456 x 10-5 in 2008. In children aged 2 to less than 5 years, incidence rates were 436 x10-5 (2001-2006) and 461 x 10-5 in 2008. In older children, the hospitalization rates remained unchanged. In the target population for the RV-vaccine, a decrease of hospitalization rates due to rotavirus gastroenteritis of 74% was observed compared to the era before the introduction of the vaccine. The field effectiveness of the vaccine was estimated between 61% and 98%, depending on assumptions about the vaccination status.

Conclusions: Within 18 months, the universal mass vaccination program against rotavirus led to a substantial decrease in the hospitalization rates of the target cohort of the immunization program in Austria.

(C) 2010 Lippincott Williams & Wilkins, Inc.

News: 1918 Virus Matches 2009 H1N1 Strain

Science
26 March 2010  Vol 327, Issue 5973, Pages 1543-1678
http://www.sciencemag.org/current.dtl

News of the Week
Swine Flu Pandemic: What’s Old Is New: 1918 Virus Matches 2009 H1N1 Strain
Jon Cohen

The “novel” H1N1 swine influenza virus that last year caused the first human pandemic in 4 decades has one feature that is hardly novel: Its surface protein, hemagglutinin (HA)—which spikes cells and starts an infection—closely matches the HA in the H1N1 virus responsible for the 1918 pandemic. Separated by 91 years, the two strains of the highly mutable virus ought to be vastly different. This newfound similarity answers many mysteries about the 2009 pandemic, including why it largely spared the elderly. The new findings, reported online this week in Science and Science Translational Medicine, also suggest intriguing explanations for how the 1918 influenza virus has evolved since it swept across the globe in several waves, killing more than 50 million people by the winter of 1919. And the investigators are proposing provocative—some say far-fetched—vaccination strategies to preempt future pandemics. Science Express Index

Published Online March 25, 2010
Reports

Structural Basis of Preexisting Immunity to the 2009 H1N1 Pandemic Influenza Virus
Rui Xu,1, Damian C. Ekiert, Jens C. Krause, Rong Hai, James E. Crowe, Jr., Ian A. Wilson

The 2009 H1N1 swine flu is the first influenza pandemic in decades. The crystal structure of the hemagglutinin from the A/California/04/2009 H1N1 virus shows that its antigenic structure, particularly within the Sa antigenic site, is extremely similar to human H1N1 viruses circulating early in the 20th century. The co-crystal structure of the 1918 HA with 2D1, an antibody from a survivor of the 1918 Spanish flu that neutralizes both 1918 and 2009 H1N1 viruses, reveals an epitope that is conserved in both pandemic viruses. Thus, antigenic similarity between the 2009 and 1918-like viruses provides an explanation for the age-related immunity to the current influenza pandemic.

1918 and 2009 Influenza Viruses: Common Features

Science Translational Medicine
24 March 2010 vol 2, issue 24
http://stm.sciencemag.org/content/2/19/19cm7.abstract

Research Articles
Influenza
Cross-Neutralization of 1918 and 2009 Influenza Viruses: Role of Glycans in Viral Evolution and Vaccine Design
Chih-Jen Wei, Jeffrey C. Boyington, Kaifan Dai, Katherine V. Houser, Melissa B. Pearce, Wing-Pui Kong, Zhi-yong Yang, Terrence M. Tumpey, and Gary J. Nabel

Editor’s Abstract
New strains of H1N1 influenza virus have emerged episodically over the last century to cause human pandemics, notably in 1918 and recently in 2009. Pandemic viruses typically evolve into seasonal forms that develop resistance to antibody neutralization, and cross-protection between strains separated by more than 3 years is uncommon. Here, we define the structural basis for cross-neutralization between two temporally distant pandemic influenza viruses—from 1918 and 2009. Vaccination of mice with the 1918 strain protected against subsequent lethal infection by 2009 virus. Both were resistant to antibodies directed against a seasonal influenza, A/New Caledonia/20/1999 (1999 NC), which was insensitive to antisera to the pandemic strains. Pandemic strain–neutralizing antibodies were directed against a subregion of the hemagglutinin (HA) receptor binding domain that is highly conserved between the 1918 and the 2009 viruses. In seasonal strains, this region undergoes amino acid diversification but is shielded from antibody neutralization by two highly conserved glycosylation sites absent in the pandemic strains. Pandemic HA trimers modified by glycosylation at these positions were resistant to neutralizing antibodies to wild-type HA. Yet, antisera generated against the glycosylated HA mutant neutralized it, suggesting that the focus of the immune response can be selectively changed with this modification. Collectively, these findings define critical determinants of H1N1 viral evolution and have implications for vaccine design. Immunization directed to conserved receptor binding domain subregions of pandemic viruses could potentially protect against similar future pandemic viruses, and vaccination with glycosylated 2009 pandemic virus may limit its further spread and transformation into a seasonal influenza.

Rotavirus seasonality and vaccination: England and Wales

<strong>Vaccine</strong>
<strong><a href=”http://www.sciencedirect.com/science/journal/0264410X”>http://www.sciencedirect.com/science/journal/0264410X</a></strong&gt;
<strong>Volume 28, Issue 18, Pages 3071-3264 (19 April 2010)</strong>

<strong><em>Regular Papers</em></strong>
<strong>Modelling the seasonality of rotavirus disease and the impact of vaccination in England and Wales</strong>
Pages 3118-3126
Christina Atchison, Ben Lopman, William John Edmunds

<em>Abstract</em>
Two rotavirus vaccines are currently recommended for inclusion in routine childhood immunization programmes. We developed a deterministic age-structured model of rotavirus transmission and disease to investigate the population-level effects of vaccination in England and Wales. The model explicitly captures the natural history of infection and uses realistic population mixing patterns. The model accurately reproduces the strong seasonal pattern and age distribution of rotavirus disease observed in England and Wales. We predict vaccination will provide both direct and indirect protection within the population. If coverage levels comparable to other childhood vaccines are achieved, we predict that vaccination will reduce rotavirus disease incidence by 61% resulting in a potential fall in burden on health-care services.

Criteria for inclusion of vaccinations in public programmes

<strong>Vaccine</strong>
<strong>Volume 28, Issue 17, Pages 2917-3070 (9 April 2010)</strong>
<strong><a href=”http://www.sciencedirect.com/science/journal/0264410X”>http://www.sciencedirect.com/science/journal/0264410X</a></strong&gt;

<strong><em>Regular Papers</em></strong>
<strong>Criteria for inclusion of vaccinations in public programmes</strong>
Pages 2924-2931
Hans Houweling, Marcel Verweij, E. Joost Ruitenberg and on behalf of the National Immunisation Programme Review Committee of the Health Council of the Netherlands

<em>Abstract</em>
As more and more new vaccines are developed and brought to the market, governments have to make decisions about which vaccinations to include in public programmes. This paper describes the experience in the Netherlands in developing a framework for assessing whether a vaccination should be included in the National Immunization Programme (NIP). Bearing in mind the public nature, the factors that determine a vaccine’s suitability for inclusion in a communal vaccination programme have been translated into seven selection criteria, grouped under five thematic headings: seriousness and extent of the disease burden, effectiveness and safety of the vaccination, acceptability of the vaccination, efficiency of the vaccination, and priority of the vaccination. The seven criteria and the explanation of them provide a framework for the systematic examination of arguments for and against the inclusion and prioritisation of particular vaccinations. As an illustration, the vaccinations currently provided in the Netherlands through public programmes as well as 23 ‘candidate’ vaccinations are assessed against the seven criteria. The proposed assessment framework including the selection criteria can take full account of the values and specificities as they may differ between situations and countries; the transparency of the approach may help to clarify which elements of the assessment are pivotal in specific situations. Using the criteria furthers a trustworthy, transparent and accountable process of decision-making about inclusion of new vaccinations in public vaccination programmes and may help to retain public confidence.

Anit-vaccination campaigns: common features

<strong>Vaccine</strong>
<strong>Volume 28, Issue 17, Pages 2917-3070 (9 April 2010)</strong>
http://www.sciencedirect.com/science/journal/0264410X

<strong>“All manner of ills”: The features of serious diseases attributed to vaccination</strong>
Pages 3066-3070
Julie Leask, Simon Chapman, Spring Chenoa Cooper Robbins

<em>Abstract</em>
Anti-vaccination writings have linked vaccines with a wide range of negative outcomes. The majority of evidence negates such connections raising the question of what makes these attributions attractive. This research identified diseases and conditions which are claimed to have been caused by vaccines and identified their shared societal features. They shared an idiopathic origin; apparent rise in incidence; face-value biological plausibility of a link to vaccines; dreaded outcomes; and their onset having close proximity to immunisation. Any attempt to re-frame erroneous claims about vaccination first requires an identification of the deeper anxieties in which they are located.

TPPs: helping vaccines overcome post-approval obstacles

<strong>Vaccine
Volume 28, Issue 16, Pages 2799-2916 (1 April 2010)</strong>
http://www.sciencedirect.com/science/journal/0264410X

<strong><em>Short Communication</em></strong>
<strong>Constructing target product profiles (TPPs) to help vaccines overcome post-approval obstacles</strong>
Pages 2806-2809
Bruce Y. Lee, Donald S. Burke

<em>Abstract</em>
As history has demonstrated, post-approval obstacles can impede a vaccine’s use and potentially lead to its withdrawal. Addressing these potential obstacles when changes in a vaccine’s technology can still be easily made may improve a vaccine’s chances of success. Augmented vaccine target product profiles (TPPs) can help vaccine scientists better understand and anticipate these obstacles and galvanize conversations among various vaccine stakeholders (e.g., scientists, marketers, business development managers, policy makers, public health officials, health care workers, third party payors, etc.) earlier in a vaccine’s development.

Economics in vaccine expert reviews

<strong>Vaccine</strong>
<strong>Volume 28, Issue 16, Pages 2799-2916 (1 April 2010)</strong>
http://www.sciencedirect.com/science/journal/0264410X

<strong>Regular Papers</strong>
<strong>A comparison of the use of economics in vaccine expert reviews</strong>
Pages 2841-2845
Philip Jacobs, Arto Ohinmaa

<em>Abstract</em>
We reviewed how health economics has been included in the vaccine expert review processes in a sample of countries. We identified two kinds of review processes – those in which vaccines and drugs are assessed using a common process, and those in which vaccines are assessed within the infectious disease framework. In either process, the countries recommend that their national pharmaco-economic (i.e., guidelines developed for drugs) guidelines be used to conduct the studies, although the guidelines themselves differ between countries. As a result of these factors, the decision process and the study outcomes can differ between countries, but because the vaccine adoption process includes other criteria as well, economic factors will not necessarily alter the outcome.

WHO: Pandemic (H1N1) 2009 – update 92: Weekly update 19 March 2010

The WHO continues to issue weekly “updates” and briefing notes on the H1N1 pandemic at: http://www.who.int/csr/disease/swineflu/en/index.html
Pandemic (H1N1) 2009 – update 92
Weekly update
19 March 2010

As of 14 March 2010, worldwide more than 213 countries and overseas territories or communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including at least 16813 deaths.
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 information.
Situation update:
The most active areas of pandemic influenza transmission continue to be in Southeast Asia and West Africa. Limited data suggests that pandemic influenza activity may be increasing across parts of Central America and the Caribbean. Low levels of pandemic influenza virus continue to circulate across southern and south-eastern Europe and in East, West, and South Asia. Although pandemic influenza virus continues to be the predominant influenza virus circulating worldwide, seasonal influenza B viruses are predominate in East Asia, and have been detected at low levels across southeast Asia and eastern Africa….

More at: http://www.who.int/csr/don/2010_03_19/en/index.html

U.K. doubles pledge of support to GAVI

GAVI Alliance CEO Julian Lob-Levyt welcomed the United Kingdom’s pledge of GBP 150 million noting that it “represents a ringing endorsement of our public-private partnership’s mission to save children’s lives and protect people’s health by increasing access to immunisation in the poorest countries.” GAVI said it will use the UK funding, which more than doubles DFID’s previous direct contributions to the Alliance, to help developing countries access vaccines with the greatest potential to achieve progress on the MDGs. http://www.gavialliance.org/media_centre/statements/2010_03_16_dfid_10_year_donation.php

PATH: First Report: Malaria Funding and Resource Utilization

PATH said that 18 March 2010 “marks a crucial stage in the fight against malaria as key stakeholders convene in London and Paris for the launch of Malaria Funding and Resource Utilization, the first report in the Roll Back Malaria (RBM) Progress & Impact Series. The series—recently launched by the RBM Partnership—benchmarks progress and highlights what is needed to ensure sustained, long-term commitment and success toward ultimately ridding the world of malaria.” The first report in the series, co-authored by MACEPA (Malaria Control and Evaluation Partnership in Africa) at PATH, addresses malaria control funding in sub-Saharan Africa. The Progress & Impact Series is a collection of comprehensive reports that will be developed through September 2011. The series aims “to inform advocacy efforts to resolve implementation bottlenecks in a strategic effort to secure high levels of commitment for malaria control from donor countries, international health organizations, and governments of endemic and epidemic countries.”

http://www.path.org/news/an100318-rbm-report.php

PDVI (Pediatric Dengue Vaccine Initiative) announces website

PDVI (Pediatric Dengue Vaccine Initiative) announced the launch of www.denguewatch.org: a news hub for tracking dengue fever epidemics worldwide which includes “breaking news articles from reliable sources are displayed on a world map according to the location of dengue outbreaks.” PDVI is a program of the International Vaccine Institute (IVI) funded by the Bill & Melinda Gates Foundation. Dr. John Clemens, IVI Director General, and PDVI Acting Director, said, “Denguewatch.org is an important public health tool providing instant access to news regarding dengue fever epidemics and their impact on global health. We believe that news reports about dengue hot spots and other important developments can help public health officials track the spread and understand the growing importance of this disease.” http://www.ivi.org/event_news/news_view.asp?enid=107

WHO: Multidrug and Extensively Drug-Resistant Tuberculosis: 2010 Global Report

WHO released Multidrug and Extensively Drug-Resistant Tuberculosis: 2010 Global Report on Surveillance and Response, which includes estimates that 440,000 people had MDR-TB worldwide in 2008 and that a third of them died. The report notes that, “in sheer numbers, Asia bears the brunt of the epidemic. Almost 50% of MDR-TB cases worldwide are estimated to occur in China and India. In Africa, estimates show 69 000 cases emerged, the vast majority of which went undiagnosed.” WHO is engaged in a five year project to strengthen TB laboratories with rapid tests in nearly 30 countries. This will ensure more people benefit early from life-saving treatments. It is also working closely with the Global Fund to Fight AIDS, Tuberculosis and Malaria and the international community on increasing access to treatment….

http://www.who.int/mediacentre/news/releases/2010/drug_resistant_tb_20100318/en/index.html

The study is available at: http://whqlibdoc.who.int/publications/2010/9789241599191_eng.pdf

The MMWR Weekly for March 19, 2010

The MMWR Weekly for March 19, 2010 / Vol. 59 / No. RR–2 includes:
Use of a Reduced (4-Dose) Vaccine Schedule for Postexposure Prophylaxis to Prevent Human Rabies — Recommendations of the Advisory Committee on Immunization Practices
This report summarizes new recommendation and updates previous recommendations of the Advisory Committee on Immunization Practices (ACIP) for postexposure prophylaxis (PEP) to prevent human rabies. Previously, ACIP recommended a 5-dose rabies vaccination regimen with human diploid cell vaccine (HDCV) or purified chick embryo cell vaccine (PCECV). These new recommendations reduce the number of vaccine doses to four. ACIP recommendations for the use of rabies immune globulin (RIG) remain unchanged. For persons who previously received a complete vaccination series (pre- or postexposure prophylaxis) with a cell-culture vaccine or who previously had a documented adequate rabies virus-neutralizing antibody titer following vaccination with noncell-culture vaccine, the recommendation for a 2-dose PEP vaccination series has not changed. Similarly, the number of doses recommended for persons with altered immunocompetence has not changed; for such persons, PEP should continue to comprise a 5-dose vaccination regimen with 1 dose of RIG. Recommendations for preexposure prophylaxis also remain unchanged, with 3 doses of vaccine administered on days 0, 7, and 21 or 28. Prompt rabies PEP combining wound care, infiltration of RIG into and around the wound, and multiple doses of rabies cell culture vaccine continue to be highly effective in preventing human rabies.

Preparing for Epidemic and Pandemic Respiratory Illness in the Shadow of H1N1 Influenza

Clinical Infectious Diseases
15 April 2010  Volume 50, Number 8
http://www.journals.uchicago.edu/toc/cid/current

Invited Articles
Healthcare Epidemiology: Planning for the Inevitable: Preparing for Epidemic and Pandemic Respiratory Illness in the Shadow of H1N1 Influenza
Elizabeth Lee Daugherty, Abigail L. Carlson, and Trish M. Perl

Abstract
The recent outbreak of novel H1N1 influenza has underscored the importance of hospital preparedness in responding to epidemic and pandemic respiratory illness. Comprehensive planning for the emergence of novel respiratory pathogens should be based on an all‐hazards approach, with the input of key stakeholders. A staged, scalable model allows for a flexible response, and the addition of a medical control chief and a situational assessment chief to the incident command system provides the clinical and epidemiologic expertise essential for effective implementation. Strategies for coordinated and efficient communication both within and outside the institution should be clearly outlined. Furthermore, the outbreak of novel H1N1 influenza demonstrated the necessity of (1) additional support roles within the hospital, (2) development of employee databases, and (3) incorporation of disease severity into staged planning. Careful consideration of these issues will allow institutions to better meet the challenges of treating epidemic and pandemic respiratory illness, both now and in the future.

Japanese Encephalitis: New Options for Active Immunization

Clinical Infectious Diseases
15 April 2010  Volume 50, Number 8
http://www.journals.uchicago.edu/toc/cid/current

Invited Articles

Vaccines: Japanese Encephalitis: New Options for Active Immunization
Scott B. Halstead and Stephen J. Thomas

Abstract
Japanese encephalitis (JE) is a mosquito‐borne flavivirus infection responsible for significant morbidity and mortality across Asia. Indigenous populations and those who undertake short- and long-term travel to endemic regions are at risk of infection and development of neuroinvasive disease. Effective mouse brain–derived vaccines have been available in select countries, including the United States, for decades. Limited access in Asia and safety concerns with regard to mouse brain products prompted the Chinese to develop a live, attenuated virus vaccine (SA14-14-2; Chengdu Institute of Biological Products), which has proven to be safe and efficacious following administration of >300 million doses. Recently, the portfolio of JE vaccines increased again with licensure in the United States, Europe, and Australia of a purified, inactivated virus JE vaccine (IC51; Intercell AG) and filing for licensure in Thailand and Australia of a Yellow fever–JE chimeric vaccine (ChimeriVax-JE; Sanofi Pasteur). JE is a vaccine‐preventable disease with numerous options now available for active immunization. Aggressive and responsible vaccination programs should greatly diminish the burden of disease.

Comment: Gardasil: from bench, to bedside, to blunder

The Lancet
Mar 20, 2010  Volume 375  Number 9719  Pages 955 – 1052
http://www.thelancet.com/journals/lancet/issue/current

Comment
Gardasil: from bench, to bedside, to blunder
Peter B Bach

Preview
The 2006 approval of Merck’s human papillomavirus (HPV) vaccine (Gardasil) by the US Food and Drug Administration (FDA) exemplified the potential of bench-to-bedside research. This vaccine against the virus that causes cervical cancer received immediate recommendation by the Advisory Committee on Immunization Practices at the US Centers for Disease Control and Prevention (CDC)1 for routine use in girls aged 11 and 12 years, along with catch-up vaccination for girls and women aged 13–26 years. The vaccine was incorporated into the CDC’s Vaccines for Children Program at the same time…

News Analysis: Cash crisis looms for vaccine drive (GAVI)

Nature
Volume 464 Number 7287 pp325-456 18 March 2010
http://www.nature.com/nature/current_issue.html

News
Cash crisis looms for vaccine drive
Rising demand for immunization programmes in developing countries could outstrip funding.
Declan Butler

[Full text]
Up to 4.2 million people, mostly young children, will die needlessly over the next 6 years unless donors fill a looming multibillion-dollar shortfall in the budget of the GAVI Alliance.

The warning from GAVI, which focuses on getting vaccines into low-income countries, is contained in advocacy documents it sent to its donors last weekend, in the run up to an extraordinary meeting due to be held on 25–26 March in The Hague, the Netherlands. It is the first time that the global-health partnership, based in Geneva, Switzerland, has brought together all of its major donors — countries and philanthropic organizations — at a single fund-raising event. It is also a sign of the current woes at the organization, which since its creation in 2000 has taken vaccination rates in low-income countries to record highs. “The funding crisis at GAVI is acute,” says Daniel Berman, deputy director of the Access to Essential Medicines Campaign at the medical charity Médecins Sans Frontières.

According to the World Health Organization, GAVI has immunized more than 250 million children and prevented some 5.4 million premature deaths over the past decade. But it now risks becoming a victim of its own success, with demand for its immunization efforts outstripping donor contributions just as the financial crisis has begun to bite.

The GAVI documents show that its projected spending for 2010–15 is US$7 billion, which, given existing and promised donations, leaves a $4.3-billion shortfall. If existing donors maintain their funding at current levels, the shortfall would shrink by $1.7 billion, leaving enough money to maintain existing programmes. But GAVI’s future initiatives would stall. It had hoped to roll out two additional vaccines between now and 2015, spending $2.4 billion on a campaign against pneumococcal disease and $750 million to tackle rotavirus. Together, these would reduce pneumonia and diarrhoea, which are the top two vaccine-preventable causes of child deaths and account for around 40% of deaths in children under five — a key target in achieving the United Nations’ Millennium Development Goals on global health.

The fund-raising meeting will focus on soli­citing new donors to broaden GAVI’s funding base. Around 80% of GAVI cash comes from a handful of country donors which has left the alliance highly vulnerable during the global economic downturn to funding reductions by only a few nations.

GAVI is hoping that one of its key financial innovations, the International Finance Facility for Immunisation, will prove particularly recession-proof. The facility does not require countries to put money on the table immediately, but rather to make 10–20-year legally binding commitments, which the facility then borrows against on capital markets. New long-term pledges by countries or foundations could help the alliance to free up cash in the short term, says Joelle Tanguy, a GAVI spokeswoman.

The billion-dollar question is how much cash might be forthcoming from the Bill & Melinda Gates Foundation, a founder of GAVI that has pledged $1.55 billion to the alliance up to 2014. In January, the foundation promised $10 billion to support a ten-year effort to research, develop and deliver vaccines, but declined to comment on how much of that will go to GAVI. It will be difficult for donors at the Hague meeting to come to decisions without a firmer idea of any extra contribution by the foundation, says Berman.

GAVI’s activities are widely applauded, but even supporters say that it could be doing more to make its funds go further. Vaccines amount to 80% of its costs, and Médecins Sans Frontières, for example, has criticized as “too lucrative for the drug industry” an ‘advance market commitment’ deal that GAVI and its partners signed in June 2009 to secure lower prices for pneumococcal vaccines. GAVI promised to guarantee a $1.5-billion market as an initial incentive to roll out the vaccines; in exchange, drug companies including GlaxoSmithKline agreed to charge $7 per dose for the first batches of vaccine and $3.50 in the longer term, compared with the $70 per dose charged in rich countries.

But GAVI should have got a better deal, says Berman. “The crisis is a good opportunity to make some reforms of how GAVI works,” he says. He suggests that it needs to pursue more aggressive policies to promote greater competition between vaccine makers to further reduce prices. For example, the Meningitis Vaccine Project, funded by the Gates Foundation, is developing a meningitis vaccine that will be manufactured by the Serum Institute of India in Pune, and will cost just $0.40 per dose. Tanguy says that GAVI’s $7-billion projected spending up to 2015 already takes into account its goal of saving $1 billion on vaccines, and that cutting vaccine prices is “one of our critical strategies”.

The US government should also help, according to Bill Gates, who testified at a US Senate committee hearing last week on President Barack Obama’s global health plans. Although getting more US government money for global health would be an “uphill battle”, he said, funding for GAVI should get high priority.

The Obama administration intends to spend $9.7 billion on global health in its 2011 budget, 80% of which would go towards fighting AIDS (through the President’s Emergency Plan for AIDS Relief) and malaria. The budget includes a modest increase in GAVI funding, from $78 million to $90 million.

“An investment in GAVI will give American taxpayers the best bang for their buck,” said Gates, “and the committee should consider increasing the level of funding beyond the administration’s request

Accelerating Policy Decisions to Adopt Hib Vaccine

PLoS Medicine
(Accessed 21 March 2010)
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

Accelerating Policy Decisions to Adopt Haemophilus influenzae Type b Vaccine: A Global, Multivariable Analysis
Jessica C. Shearer, Meghan L. Stack, Marcie R. Richmond, Allyson P. Bear, Rana A. Hajjeh, David M. Bishai Research Article, published 16 Mar 2010
doi:10.1371/journal.pmed.1000249

Abstract
Background
Adoption of new and underutilized vaccines by national immunization programs is an essential step towards reducing child mortality. Policy decisions to adopt new vaccines in high mortality countries often lag behind decisions in high-income countries. Using the case of Haemophilus influenzae type b (Hib) vaccine, this paper endeavors to explain these delays through the analysis of country-level economic, epidemiological, programmatic and policy-related factors, as well as the role of the Global Alliance for Vaccines and Immunisation (GAVI Alliance).

Methods and Findings
Data for 147 countries from 1990 to 2007 were analyzed in accelerated failure time models to identify factors that are associated with the time to decision to adopt Hib vaccine. In multivariable models that control for Gross National Income, region, and burden of Hib disease, the receipt of GAVI support speeded the time to decision by a factor of 0.37 (95% CI 0.18–0.76), or 63%. The presence of two or more neighboring country adopters accelerated decisions to adopt by a factor of 0.50 (95% CI 0.33–0.75). For each 1% increase in vaccine price, decisions to adopt are delayed by a factor of 1.02 (95% CI 1.00–1.04). Global recommendations and local studies were not associated with time to decision.

Conclusions
This study substantiates previous findings related to vaccine price and presents new evidence to suggest that GAVI eligibility is associated with accelerated decisions to adopt Hib vaccine. The influence of neighboring country decisions was also highly significant, suggesting that approaches to support the adoption of new vaccines should consider supply- and demand-side factors.

Pandemic (H1N1) 2009 – update 91: 12 March 2010

The WHO continues to issue weekly “updates” and briefing notes on the H1N1 pandemic at: http://www.who.int/csr/disease/swineflu/en/index.html

Pandemic (H1N1) 2009 – update 91
Weekly update
12 March 2010

As of 7 March 2010, worldwide more than 213 countries and overseas territories or communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including at least 16713 deaths.

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 information.

Situation update:
The most active areas of pandemic influenza transmission are currently in Southeast Asia, however, lower levels of pandemic virus circulation persist in other parts of Asia and in Eastern and South-eastern Europe. In West Africa, limited data suggests that pandemic influenza virus transmission may be increasing in region. Of note, seasonal influenza B viruses have been increasingly detected in Asia and appear to be spreading westward….

…Although pandemic influenza virus continues to be the predominant circulating influenza virus worldwide, circulation of seasonal influenza B viruses continue to increase and spread across Asia, parts of Eastern Europe, and Eastern Africa, but most notably in China, Mongolia, Iran and the Russian Federation…”

More at: http://www.who.int/csr/don/2010_03_12/en/index.html

CDC updates estimates of 2009 H1N1 influenza cases, hospitalizations and deaths

CDC updated estimates of 2009 H1N1 influenza cases, hospitalizations and deaths in the United States from April 2009 – February 13, 2010:

– CDC estimates that between 42 million and 86 million cases of 2009 H1N1 occurred between April 2009 and February 13, 2010. The mid-level in this range is about 59 million people infected with 2009 H1N1.

– CDC estimates that between about 188,000 and 389,000 H1N1-related hospitalizations occurred between April 2009 and February 13, 2010. The mid-level in this range is about 265,000 2009 H1N1-related hospitalizations.

– CDC estimates that between about 8,520 and 17,620 2009 H1N1-related deaths occurred between April 2009 and February 13, 2010. The mid-level in this range is about 12,000 2009 H1N1-related deaths.

Note: Less than 5% of increases in the estimates from one reporting date to the next are the result of delayed reporting in cases, hospitalizations and deaths.

The release also noted that “…The latest estimates through February 13, 2010 show a relatively small increase in the total number of 2009 H1N1 cases, hospitalizations and deaths since the previous estimates posted on February 12, 2010. The additional four weeks of flu activity data added to derive these updated estimates correlate with a four week period of ongoing but generally low flu activity in the United States….

“…As of February 13, 2010, approximately 86 million people had received 97 million doses of 2009 H1N1 vaccine. When the numbers of people vaccinated against 2009 H1N1 is combined with the number of people previously infected with 2009 H1N1, a significant number of people in the United States likely have immunity to the 2009 H1N1 virus. However, with a population of more than 300 million in this country, a substantial number of people likely remain susceptible to 2009 H1N1, which continues to circulate at this time…”

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

WHO: Universal testing/new guidelines for malaria treatment

WHO released new guidelines for the treatment of malaria, and “the first ever guidance on procuring safe and efficacious anti-malarial medicines.” The Guidelines for the Treatment of Malaria (second edition) provide “evidence-based and current recommendations for countries on malaria diagnosis and treatment.” The main changes from the first edition of the guidelines (published in 2006) are the emphasis on testing before treating and the addition of a new ACT to the list of recommended treatments.

Dr Robert Newman, Director of the WHO Global Malaria Programme (GMP), commented

“The world now has the means to rapidly diagnose malaria and treat it effectively. WHO now recommends diagnostic testing in all cases of suspected malaria. Treatment based on clinical symptoms alone should be reserved for settings where diagnostic tests are not available.”

WHO said the move towards universal diagnostic testing of malaria “is a critical step forward in the fight against malaria as it will allow for the targeted use of ACTs for those who actually have malaria. The aim is to reduce the emergence and spread of drug resistance and to help identify patients who have fever, but do not have malaria, so that alternative diagnoses can be made and appropriate treatment provided. Therefore, better management of malaria has a positive impact on management of other childhood illness and overall child survival.”

WHO estimates that 80 countries have adopted ACTs for first-line treatment of uncomplicated P. falciparum malaria. In the guidelines, WHO emphasizes the importance of treating this deadliest form of the disease with artemisinin-based combination therapies. WHO has now added a fifth ACT – dihydroartemisinin plus piperaquine – to the previous list of recommended medicines. http://www.who.int/mediacentre/news/releases/2010/malaria_20100308/en/index.html

Weekly Epidemiological Record (WER) for 12 March 2010

The Weekly Epidemiological Record (WER) for 12 March 2010, vol. 85, 11 (pp 93–108) includes Progress towards eradicating poliomyelitis in Afghanistan and Pakistan, 2009; Antigenic and genetic characteristics of influenza A(H5N1) and influenza A(H9N2) viruses and candidate vaccine viruses developed for potential use in human vaccines – February 2010

http://www.who.int/wer/2010/wer8511.pdf

MMWR Weekly for 12 March 2010

The MMWR Weekly for March 12, 2010 / Vol. 59 / No. 9 includes:

Invasive Pneumococcal Disease in Young Children Before Licensure of 13-Valent Pneumococcal Conjugate Vaccine — United States, 2007
In February 2010, the Advisory Committee on Immunization Practices (ACIP) issued recommendations for use of a newly licensed 13-valent pneumococcal conjugate vaccine (PCV13). To characterize the potential effect of the new vaccine on invasive pneumococcal disease among children aged <5 years in the United States, CDC and investigators analyzed data from Active Bacterial Core surveillance. This report summarizes the results of that analysis.

Japanese Encephalitis Vaccines — Recommendations of the Advisory Committee on Immunization Practices (ACIP)
Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, is the most common vaccine-preventable cause of encephalitis in Asia. Japanese encephalitis (JE) occurs throughout most of Asia and parts of the western Pacific. This report updates the 1993 recommendations by CDC’s Advisory Committee on Immunization Practices (ACIP) regarding the prevention of JE among travelers. This report summarizes the epidemiology of JE, describes the two JE vaccines that are licensed in the United States, and provides recommendations for their use among travelers and laboratory workers.

http://www.cdc.gov/mmwr/

Influenza Vaccination of Children in Hutterite Communities

JAMA
Vol. 303 No. 10, pp. 913-1000, March 10, 2010
http://jama.ama-assn.org/current.dtl

Original Contribution
Effect of Influenza Vaccination of Children on Infection Rates in Hutterite Communities: A Randomized Trial
Mark Loeb; Margaret L. Russell; Lorraine Moss; Kevin Fonseca; Julie Fox; David J. D. Earn; Fred Aoki; Gregory Horsman; Paul Van Caeseele; Khami Chokani; Mark Vooght; Lorne Babiuk; Richard Webby; Stephen D. Walter
JAMA. 2010;303(10):943-950.

Abstract
Context
Children and adolescents appear to play an important role in the transmission of influenza. Selectively vaccinating youngsters against influenza may interrupt virus transmission and protect those not immunized.

Objective
To assess whether vaccinating children and adolescents with inactivated influenza vaccine could prevent influenza in other community members.

Design, Setting, and Participants
A cluster randomized trial involving 947 Canadian children and adolescents aged 36 months to 15 years who received study vaccine and 2326 community members who did not receive the study vaccine in 49 Hutterite colonies in Alberta, Saskatchewan, and Manitoba. Follow-up began December 28, 2008, and ended June 23, 2009.

Intervention
Children were randomly assigned according to community and in a blinded manner to receive standard dosing of either inactivated trivalent influenza vaccine or hepatitis A vaccine, which was used as a control.

Main Outcome Measures
Confirmed influenza A and B infection using a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay and by measuring serum hemagglutination inhibition titers.

Results
The mean rate of study vaccine coverage among eligible participants was 83% (range, 53%-100%) for the influenza vaccine colonies and 79% (range, 50%-100%) for the hepatitis A vaccine colonies. Among nonrecipients, 39 of 1271 (3.1%) in the influenza vaccine colonies and 80 of 1055 (7.6%) in the hepatitis A vaccine colonies had influenza illness confirmed by RT-PCR, for a protective effectiveness of 61% (95% confidence interval [CI], 8%-83%; P = .03). Among all study participants (those who were and those who were not vaccinated), 80 of 1773 (4.5%) in the influenza vaccine colonies and 159 of 1500 (10.6%) in the hepatitis A vaccine colonies had influenza illness confirmed by RT-PCR for an overall protective effectiveness of 59% (95% CI, 5%-82%; P = .04). No serious vaccine adverse events were observed.

Conclusion
Immunizing children and adolescents with inactivated influenza vaccine significantly protected unimmunized residents of rural communities against influenza.

Trial Registration  clinicaltrials.gov Identifier: NCT00877396

Editorial: The Global Fund: replenishment and redefinition in 2010

The Lancet
Mar 13, 2010  Volume 375  Number 9718  Pages 865 – 954
http://www.thelancet.com/journals/lancet/issue/current

Editorial
The Global Fund: replenishment and redefinition in 2010
The Lancet

Preview
On March 8, the Global Fund to Fight AIDS, Tuberculosis and Malaria launched its report, The Global Fund 2010: Innovation and Impact, presenting results so far and outlining challenges and new strategies. Since its inception in 2002, the Fund has grown into an impressive force in the landscape of global health initiatives. By its own estimation, the Fund has supported programmes that have saved around 4·9 million lives. It has allocated US$19·2 billion and disbursed $10 billion to 144 countries.

Nature Cover Issue: The Elusive Aids Vaccine

Nature
Volume 464 Number 7286 pp141-316  11 March 2010
http://www.nature.com/nature/current_issue.html

[This week’s issue features a cover with the lead title “The Elusive Aids Vaccine”]

Opinion
Accelerating HIV vaccine development
Wayne C. Koff

Translational-research programmes supported by flexible, long-term, large-scale grants are needed to turn advances in basic science into successful vaccines to halt the AIDS epidemic,

Perspectives
Immunology and the elusive AIDS vaccine
Herbert W. Virgin (1) & Bruce D. Walker (2)

[Nature Editor’s Summary]
Several lines of evidence suggest that simply generating an immune response similar to that seen in natural infections is unlikely to protect against HIV/AIDS. With this in mind, Herbert Virgin and Bruce Walker argue that our fundamental approach to HIV vaccination needs to be re-examined. Their review outlines the immunological questions still to be answered if an effective vaccine is to be produced.

[Author’s First Paragraph per Nature convention]
Developing a human immunodeficiency virus (HIV) vaccine is critical to end the global acquired immunodeficiency syndrome (AIDS) epidemic, but many question whether this goal is achievable. Natural immunity is not protective, and despite immunogenicity of HIV vaccine candidates, human trials have exclusively yielded disappointing results. Nevertheless, there is an indication that success may be possible, but this will be dependent on understanding the antiviral immune response in unprecedented depth to identify and engineer the types of immunity required. Here we outline fundamental immunological questions that need to be answered to develop a protective HIV vaccine, and the immediate need to harness a much broader scientific community to achieve this goal.

(1)Washington University School of Medicine and Midwest Regional Center of Excellence for Biodefense and Emerging Infectious Disease Research, Campus Box 8118, 660 South Euclid Avenue, Saint Louis, Missouri 63110, USA

(2) Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Howard Hughes Medical Institute, 149 13th Street, Charlestown, Massachusetts 02129, USA

Editorial: Peace Through Vaccine Diplomacy

Science
12 March 2010  Vol 327, Issue 5971, Pages 1285-1414
http://www.sciencemag.org/current.dtl

Editorial
Peace Through Vaccine Diplomacy
Peter J. Hotez

Preview
Can vaccinations help to resolve conflicts and nurture diplomacy? Later this month, Indonesia, the world’s most populous Islamic country, will host U.S. President Obama, a visit that could establish important scientific ties between the United States and Indonesia and implement a potentially powerful piece of vaccine diplomacy.

Peter J. Hotez is Distinguished Research Professor at the George Washington University and president of the Sabin Vaccine Institute in Washington, D
C.

Impacts of school-based influenza vaccine delivery: Ontario, Canada

Vaccine
Volume 28, Issue 15, Pages 2687-2798 (24 March 2010)
http://www.sciencedirect.com/science/journal/0264410X

School-based influenza vaccine delivery, vaccination rates, and healthcare use in the context of a universal influenza immunization program: An ecological study
Pages 2722-2729
Jeffrey C. Kwong, Hong Ge, Laura C. Rosella, Jun Guan, Sarah Maaten, Kathy Moran, Helen Johansen, Astrid Guttmann

Abstract
Influenza vaccines are universally funded in Ontario, Canada. Some public health units (PHUs) vaccinate children in schools. We examined the impact of school-based delivery on vaccination rates and healthcare use of the entire population over seven influenza seasons (2000–2007) using population-based survey and health administrative data. School-based vaccination was associated with higher vaccination rates in school-age children only. Doctors’ office visits were lower for PHUs with school-based vaccination for children aged 12–19 but not for other age groups. Emergency department use and hospitalizations were similar between the two groups. In the context of universal influenza vaccination, school-based delivery is associated with higher vaccination rates and modest reductions in healthcare use in school-age children.

WHO: deployment update on pledged A(H1N1) pandemic vaccine “stockpile”

WHO issued an update on its deployment of pledged A(H1N1) pandemic vaccine in its “stockpile,” noting that it has received pledges of approximately 200 million doses of vaccine, 74 million syringes (about 130 million short of goal) and US$48 million for operations (about US$14.5 million short of goal). WHO and partners are assisting the 95 countries to receive and use vaccines, with an immediate focus on a first group of 35 countries which must complete three steps: 1) make a request to receive donated vaccines, 2) sign an agreement accepting the terms and conditions of support and 3) develop a national vaccine deployment plan. The report notes that:
– 92 of the 95 countries have requested vaccine donations.
– 59 countries have signed agreements with WHO.
– 37 countries have finalized a National Deployment Plan.

To date, through the first two months of deployment activity, about 2.2 million doses, or about 1% of the pledged stockpile of pandemic vaccine, had been delivered to seven countries. Planned deliveries during March will deploy an additional 15.2 million doses.

The report notes that in the required national deployment plans countries must submit, “…The first target group is health-care workers, as they are a vulnerable group because of their exposure to disease, and vital in keeping a country’s health system functioning.”

http://www.who.int/csr/disease/swineflu/vaccines/h1n1_vaccine_deployment_update20100301.pdf

WHO: Pandemic (H1N1) 2009 – update 90: 5 March 2010

The WHO continues to issue weekly “updates” and briefing notes on the H1N1 pandemic at: http://www.who.int/csr/disease/swineflu/en/index.html

Pandemic (H1N1) 2009 – update 90
Weekly update
5 March 2010

As of 28 February 2010, worldwide more than 213 countries and overseas territories or communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including at least 16455 deaths…

Situation update:
Summary: In the temperate zone of the northern hemisphere, transmission of virus persists in some areas of Europe and Asia but influenza activity is declining and at low level in the most areas. The most active areas of transmission are currently observed in parts of Southeast Asia and East and South-eastern Europe. Recently, influenza type B is increasingly reported in Asia.

More at: http://www.who.int/csr/don/2010_03_05/en/index.html

WER: Recommended viruses for influenza vaccines: 2010–2011 northern hemisphere

The Weekly Epidemiological Record (WER) for 5 March 2010, vol. 85, 10 (pp 81–92) includes: Recommended viruses for influenza vaccines for use in the 2010–2011 northern hemisphere influenza season. The discussion notes “…it is expected that A(H1N1) pandemic 2009, A(H3N2) and B viruses will co-circulate in the northern hemisphere 2010-2011 with the likelihood that the pandemic A(H1N1) 2009 viruses will predominate. Based on recent epidemiological evidence it is anticipated that seasonal A(H1N1) viruses are unlikely to circulate at significant levels during the 2010–2011

northern hemisphere season; hence it has not been recommended for inclusion in the 2010–2011 vaccine. A virus of B/Victoria/2/87 lineage, the predominant lineage of type B viruses circulating since September 2009, has been recommended…

It is recommended that the following viruses be used for influenza vaccines in the 2010-2011 influenza season (northern hemisphere):

– an A/California/7/2009 (H1N1)-like virus;

– an A/Perth/16/2009 (H3N2)-like virus;

– a B/Brisbane/60/2008-like virus.

http://www.who.int/wer/2010/wer8510.pdf

MMWR: Malaria Acquired in Haiti — 2010

The MMWR Weekly for March 5, 2010 / Vol. 59 / No. 8 includes: Malaria Acquired in Haiti — 2010

Malaria caused by Plasmodium falciparum infection is endemic in Haiti. The principal mosquito vector is Anopheles albimanus. In the aftermath of the January 12 earthquake, displaced persons living outdoors or in temporary shelters and thousands of emergency responders in Haiti are at substantial risk for malaria. During January 12–February 25, CDC received reports of 11 laboratory-confirmed cases of P. falciparum malaria acquired in Haiti. This report summarizes the cases.

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5908a1.htm

Surgical Masks, HCWs and A (H1N1)–2009

Clinical Infectious Diseases
1 April 2010   Volume 50, Number 7
http://www.journals.uchicago.edu/toc/cid/current

Brief Report
Surgical Masks for Protection of Health Care Personnel against Pandemic Novel SwineOrigin Influenza A (H1N1)–2009: Results from an Observational Study

There is ongoing debate about the efficacy of surgical masks versus N95 respirators for protection against pandemic novel swine-origin influenza A (H1N1)–2009. Our hospital, which is designated to manage outbreaks of emerging infection, has robust surveillance systems to detect infection in staff. The incidence of pandemic H1N1-2009 remained low in staff with use of surgical masks.

Effects of Mumps Outbreak in Hospital, Chicago

Emerging Infectious Diseases
Volume 16, Number 3–March 2010
http://www.cdc.gov/ncidod/EID/index.htm

Research
Effects of Mumps Outbreak in Hospital, Chicago, Illinois, USA, USA
A.L. Bonebrake et al.

Abstract
In 2006, nearly 6,000 mumps cases were reported in the United States, 795 of which occurred in Illinois. In Chicago, 1 healthcare institution experienced ongoing transmission for 4 weeks. This study examines the outbreak epidemiology and quantifies the financial affect on this organization. This retrospective cohort study was conducted through case and exposure identification, interviews, medical record reviews, and immunologic testing of blood specimens. Nine mumps cases resulted in 339 exposures, 325 (98%) among employees. During initial investigation, 186 (57%) of the exposed employees had evidence of mumps immunity. Physicians made up the largest group of noncompliers (55%) with mumps immunity testing. The cost to the institution was $262,788 or $29,199 per mumps case. The outbreak resulted in substantial staffing and financial challenges for the institution that may have been minimized with readily accessible electronic employee vaccination records and adherence to infection control recommendations.

School Closure and Pandemic (H1N1) 2009 Mitigation: Hong Kong

Emerging Infectious Diseases
Volume 16, Number 3–March 2010
http://www.cdc.gov/ncidod/EID/index.htm

Dispatches
School Closure and Mitigation of Pandemic (H1N1) 2009, Hong Kong
J.T. Wu et al.

Abstract
In Hong Kong, kindergartens and primary schools were closed when local transmission of pandemic (H1N1) 2009 was identified. Secondary schools closed for summer vacation shortly afterwards. By fitting a model of reporting and transmission to case data, we estimated that transmission was reduced ≈25% when secondary schools closed.

Editorial: Stabilization of vaccines: Lessons learned

Human Vaccines
Volume 6, Issue 3  March 2010
http://www.landesbioscience.com/journals/vaccines/toc/volume/6/issue/3/

Editorial
Stabilization of vaccines: Lessons learned
Debra Kristensen and Dexiang Chen

Exposure to extreme heat or cold can ruin desperately needed vaccines, especially in developing countries where intermittent electricity and a lack of resources make it challenging to maintain appropriate storage temperatures. PATH reflects on nearly eight years of work to optimize the heat stability of seven types of vaccines with 33 collaborators. We also explore the key logistical, regulatory, procurement, and policy issues associated with the development and use of temperature-stabilized vaccines.

In the editorial, we suggest seven recommendations for developing and commercializing vaccines with enhanced temperature stability:
– Stabilization efforts should be integrated into early vaccine development.
– There are circumstances where it makes sense to stabilize existing vaccines.
– Freeze stabilization is possible for vaccines containing aluminum adjuvant.
– Heat stabilization requires a customized approach, and results will be variable.
– The full benefits of heat-stable vaccines will only be realized after programmatic and policy changes are made to storage guidelines.
– Improvements in vaccine heat stability are inextricably tied to product format, and careful consideration should be given to the end-product attributes and priorities during vaccine development. Some heat-stability improvements result in inferior product formats while others enable new, beneficial formats.
– Products with enhanced stability can benefit both vaccine producers and purchasers.