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.

Vaccine vials and wastage: introducing pneumococcal vaccines in developing countries

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

Research Papers
Impact of wastage on single and multi-dose vaccine vials: Implications for introducing pneumococcal vaccines in developing countries
Divya Parmar, Elaine M Baruwa, Patrick Zuber and Souleymane Kone

Introduction: Pneumococcal conjugate vaccines are expensive relative to those in the EPI systems of low-income countries. The current single-dose presentation costs more to store in the cold chain relative to multi-dose presentations but also has lower wastage rates. It is, therefore, important to determine the optimal balance of vial size and storage costs after adjusting for wastage.

Objectives: To project the cost implications of wastage when vaccine wastage rates vary across vial sizes using country specific wastage data. Methods: For each potential vial size, we estimated cold chain costs and the cost of wasted vaccine doses using country level wastage data and projections of the price per dose of vaccine and cold chain storage.

Results: Only 19 (26%) of 72 GAVI eligible countries had analyzable wastage data at WHO/HQ. The median wastage rates for single, 2- and 10-dose vials were 5%, 7% and 10% respectively. However wastage varied between 1%-10%, 1%-27% and 4%-44% for single, 2- and 10-dose vials respectively. The increased variance for multi-dose vial wastage implied wastage costs potentially greater than the savings realized from lower storage volumes.

Conclusions: The optimal vial-size for PCV is dependent upon country specific wastage rates but few countries have these data. There may be a role for both single and multi-dose vials that is best determined by local management and storage capacities making local wastage data critical. Without effective wastage monitoring and control there is a risk that wastage costs will possibly exceed the savings from multi-dose vials’ lower storage costs.

Losing the Opportunity to Study Influenza Drugs

JAMA
Vol. 303 No. 9, pp. 813-902, March 3, 2010
http://jama.ama-assn.org/current.dtl

Losing the Opportunity to Study Influenza Drugs
Andrea Meyerhoff; Paul Lietman

[First 150 words per JAMA convention]
Shortly after 2009 influenza A(H1N1) emerged, we advocated for real-time clinical trials to make use of the rare opportunity—and an ethical imperative—to study influenza drugs while the pandemic is ongoing.1 Tran et al2 further emphasized this need for prospective clinical trials during the outbreak. Persistent gaps in knowledge about drugs to treat influenza and the recent decision by the US Food and Drug Administration (FDA) to issue an Emergency Use Authorization for peramivir,3 an unapproved drug, make this need even more acute.

The efficacy of oseltamivir and zanamivir, the main drugs available to treat influenza A(H1N1) in the United States, was based on findings that these drugs shorten the duration of flu symptoms by 1.3 and 1.5 days, respectively. However, a recent meta-analysis of 12 clinical trials of oseltamivir suggested that this drug did not reduce the rate of pneumonia in . . .

Household Transmission of 2009 Influenza A (H1N1)

Journal of Infectious Diseases
1 April 2010  Volume 201, Number 7
http://www.journals.uchicago.edu/toc/jid/current

Major Articles and Brief Reports
Viruses
Household Transmission of 2009 Influenza A (H1N1) Virus after a SchoolBased Outbreak in New York City, April–May 2009
Anne Marie France, Michael Jackson, Stephanie Schrag, Michael Lynch, Christopher Zimmerman, Matthew Biggerstaff, and James Hadler

Abstract
In April 2009, an outbreak due to infection with the 2009 pandemic influenza A (H1N1) virus (pH1N1) was investigated in a New York City high school. We surveyed household contacts of ill students to characterize the extent of transmission within households, identify contact groups at highest risk for illness, and assess the potential for preventing household transmission. Influenza‐like illness (ILI) was reported by 79 of 702 household contacts (11.3% attack rate). Multivariate analysis showed that older age was protective: for each increasing year of age, the risk of ILI was reduced 5%. Additional protective factors included antiviral prophylaxis and having had a household discussion about influenza. Providing care for the index case patient and watching television with the index case patient were risk factors among parents and siblings, respectively. Fifty percent of cases occurred within 3 days of onset of illness in the student. These factors have implications for mitigating the impact of pH1N1 transmission.

7-Valent Pneumococcal Conjugate Vaccine in HIV-Infected Adults

New England Journal of Medicine
Volume 362 — March 4, 2010 — Number 9
http://content.nejm.org/current.shtml

Original Articles
A Trial of a 7-Valent Pneumococcal Conjugate Vaccine in HIV-Infected Adults
N. French and Others

ABSTRACT
Background
Streptococcus pneumoniae is a leading and serious coinfection in adults with human immunodeficiency virus (HIV) infection, particularly in Africa. Prevention of this disease by vaccination with the current 23-valent polysaccharide vaccine is suboptimal. Protein conjugate vaccines offer a further option for protection, but data on their clinical efficacy in adults are needed.

Methods
In this double-blind, randomized, placebo-controlled clinical efficacy trial, we studied the efficacy of a 7-valent conjugate pneumococcal vaccine in predominantly HIV-infected Malawian adolescents and adults who had recovered from documented invasive pneumococcal disease. Two doses of vaccine were given 4 weeks apart. The primary end point was a further episode of pneumococcal infection caused by vaccine serotypes or serotype 6A.

Results
From February 2003 through October 2007, we followed 496 patients (of whom 44% were male and 88% were HIV-seropositive) for 798 person-years of observation. There were 67 episodes of pneumococcal disease in 52 patients, all in the HIV-infected subgroup. In 24 patients, there were 19 episodes that were caused by vaccine serotypes and 5 episodes that were caused by the 6A serotype. Of these episodes, 5 occurred in the vaccine group and 19 in the placebo group, for a vaccine efficacy of 74% (95% confidence interval [CI], 30 to 90). There were 73 deaths from any cause in the vaccine group and 63 in the placebo group (hazard ratio in the vaccine group, 1.18; 95% CI, 0.84 to 1.66). The number of serious adverse events within 14 days after vaccination was significantly lower in the vaccine group than in the placebo group (3 vs. 17, P=0.002), and the number of minor adverse events was significantly higher in the vaccine group (41 vs. 13, P=0.003).

Conclusions
The 7-valent pneumococcal conjugate vaccine protected HIV-infected adults from recurrent pneumococcal infection caused by vaccine serotypes or serotype 6A. (Current Controlled Trials number, ISRCTN54494731

Patient-Held Vaccination Records and Coverage Rates

Pediatrics
March 2010 / VOLUME 125 / ISSUE 3
http://pediatrics.aappublications.org/current.shtml

Articles
Are Patient-Held Vaccination Records Associated With Improved Vaccination Coverage Rates?
James T. McElligott and Paul M. Darden

OBJECTIVE The goal was to determine whether patient-held vaccination records improve vaccination rates.

METHODS The public-use files of the 2004–2006 National Immunization Survey, a national, validated survey of households with children 19 to 35 months of age, were used. The main outcome was up-to-date (UTD) vaccination status (4 diphtheria-tetanus-acellular pertussis/diphtheria-tetanus vaccine, 3 poliovirus vaccine, 1 measles vaccine, 3 Haemophilus influenza type B vaccine, and 3 hepatitis B vaccine doses), and the main predictor was the use of a vaccination record. Control variables were race/ethnicity, maternal education, poverty status, language, number of children in the home, state of residence, and number of health care providers.

RESULTS Overall, 80.8% of children were UTD, and 40.8% of children had vaccination records. Children with vaccination records were more likely to be UTD (83.9% vs 78.6%; P < .0001). The largest effects associated with vaccination records were seen for children with multiple providers, comparing with and without a vaccination record (82.8% vs 71.9%; P < .0001), those with low maternal education, (81.6% vs 72.9%; P < .0001), and those with 4 children in the household, (76% vs 69.6%; P < .004). Logistic regression predicting UTD status and controlling for race/ethnicity, maternal education, poverty level, language, number of children in the home, and number of vaccine providers revealed the vaccination record to be associated with a 62% increase in the odds of UTD status (odds ratio: 1.62 [95% confidence interval: 1.49–1.77]).

CONCLUSIONS Use of patient-held vaccination records is an easily implemented strategy that is associated with increased immunization rates. A greater effect was seen in groups at risk for underimmunization. Methods to incorporate and to ensure effective use of these records should be implemented.

Drivers of Inequality in MDG Progress

PLoS Medicine
(Accessed 7 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

Drivers of Inequality in Millennium Development Goal Progress: A Statistical Analysis David Stuckler, Sanjay Basu, Martin McKee

Abstract
Background
Many low- and middle-income countries are not on track to reach the public health targets set out in the Millennium Development Goals (MDGs). We evaluated whether differential progress towards health MDGs was associated with economic development, public health funding (both overall and as percentage of available domestic funds), or health system infrastructure. We also examined the impact of joint epidemics of HIV/AIDS and noncommunicable diseases (NCDs), which may limit the ability of households to address child mortality and increase risks of infectious diseases.

Methods and Findings
We calculated each country’s distance from its MDG goals for HIV/AIDS, tuberculosis, and infant and child mortality targets for the year 2005 using the United Nations MDG database for 227 countries from 1990 to the present. We studied the association of economic development (gross domestic product [GDP] per capita in purchasing-power-parity), the relative priority placed on health (health spending as a percentage of GDP), real health spending (health system expenditures in purchasing-power-parity), HIV/AIDS burden (prevalence rates among ages 15–49 y), and NCD burden (age-standardised chronic disease mortality rates), with measures of distance from attainment of health MDGs. To avoid spurious correlations that may exist simply because countries with high disease burdens would be expected to have low MDG progress, and to adjust for potential confounding arising from differences in countries’ initial disease burdens, we analysed the variations in rates of change in MDG progress versus expected rates for each country. While economic development, health priority, health spending, and health infrastructure did not explain more than one-fifth of the differences in progress to health MDGs among countries, burdens of HIV and NCDs explained more than half of between-country inequalities in child mortality progress (R2-infant mortality = 0.57, R2-under 5 mortality = 0.54). HIV/AIDS and NCD burdens were also the strongest correlates of unequal progress towards tuberculosis goals (R2 = 0.57), with NCDs having an effect independent of HIV/AIDS, consistent with micro-level studies of the influence of tobacco and diabetes on tuberculosis risks. Even after correcting for health system variables, initial child mortality, and tuberculosis diseases, we found that lower burdens of HIV/AIDS and NCDs were associated with much greater progress towards attainment of child mortality and tuberculosis MDGs than were gains in GDP. An estimated 1% lower HIV prevalence or 10% lower mortality rate from NCDs would have a similar impact on progress towards the tuberculosis MDG as an 80% or greater rise in GDP, corresponding to at least a decade of economic growth in low-income countries.

Conclusions
Unequal progress in health MDGs in low-income countries appears significantly related to burdens of HIV and NCDs in a population, after correcting for potentially confounding socioeconomic, disease burden, political, and health system variables. The common separation between NCDs, child mortality, and infectious syndromes among development programs may obscure interrelationships of illness affecting those living in poor households—whether economic (e.g., as money spent on tobacco is lost from child health expenditures) or biological (e.g., as diabetes or HIV enhance the risk of tuberculosis).

Universal HIV Testing and Treatment

Science
5 March 2010  Vol 327, Issue 5970, Pages 1163-1284
http://www.sciencemag.org/current.dtl

News Focus
17TH CONFERENCE ON RETROVIRUSES AND OPPORTUNISTIC INFECTIONS, 16-19 FEBRUARY, SAN FRANCISCO, CA: Treatment as Prevention
Jon Cohen

An ambitious idea to slow the HIV/AIDS epidemic is gaining traction: Test everyone for the virus and immediately start all HIV-infected people on treatment. But the test-and-treat scheme has epidemic modelers battling it out, with some insisting it’s feasible, both financially and practically, and others denouncing it as a pipe dream and warning that it could increase drug resistance. At the 17th Conference on Retroviruses and Opportunistic Infections, two groups presented some of the firmest data yet to support the concept.

Vaccine adjuvants: A priority for research

Vaccine
Volume 28, Issue 12, Pages 2361-2472 (11 March 2010)
http://www.sciencedirect.com/science/journal/0264410X

Conference Report
Vaccine adjuvants: A priority for vaccine research
Pages 2363-2366
Ali M. Harandi, Donata Medaglini, Robin J. Shattock and Working Group convened by EUROPRISE

Abstract
The workshop on vaccine adjuvants was held in July of 2009 at the European Commission in Brussels, with the goal of identifying key scientific priorities as they pertain to the development of effective vaccines against life-threatening diseases especially those associated with poverty, including HIV/AIDS, malaria and tuberculosis as well as neglected infectious diseases. On the basis of new advances in adjuvant research and related technology as well as potential challenges and roadblocks, six priorities were identified to accelerate development of improved or novel vaccine adjuvants for human use.

Cost-effectiveness of routine infant vaccination/ Prevnar

Vaccine
Volume 28, Issue 12, Pages 2361-2472 (11 March 2010)
http://www.sciencedirect.com/science/journal/0264410X

Short Communication
Huge impact of assumptions on indirect effects on the cost-effectiveness of routine infant vaccination with 7-valent conjugate vaccine (Prevnar)
Pages 2367-2369
Mark H. Rozenbaum, Albert Jan van Hoek, Eelko Hak, Maarten J. Postma

Abstract
Several recently published European cost-effectiveness studies on the 7-valent pneumococcal conjugate vaccine (PCV-7: Prevnar®) have included net-indirect vaccine benefits for non-vaccine protected groups into their studies, which might be too optimistic an approach given recent data. Net-indirect effects result from herd protection minus serotype replacement effects. In this study we analyze the impact of net-indirect effects in non-vaccine protected groups of 5 years of age and older with updated assumptions regarding epidemiologic data and health care unit costs. Without net-indirect benefits for non-vaccine protected groups included the cost-effectiveness ratio is estimated at €72,360 per QALY. In order to obtain cost-effectiveness ratios below the threshold of €50,000 per QALY – which is in the middle of the range that is often referred to in the Netherlands – the net-indirect protective effect should at least be 16% of which has been observed in the USA after the introduction of PCV-7.

Real-time economic evaluation: A/H1N1v vaccine in England

Vaccine
Volume 28, Issue 12, Pages 2361-2472 (11 March 2010)
http://www.sciencedirect.com/science/journal/0264410X

Regular Papers
Vaccination against pandemic influenza A/H1N1v in England: A real-time economic evaluation
Pages 2370-2384
Marc Baguelin, Albert Jan Van Hoek, Mark Jit, Stefan Flasche, Peter J. White, W. John Edmunds

Abstract
Decisions on how to mitigate an evolving pandemic are technically challenging. We present a real-time assessment of the effectiveness and cost-effectiveness of alternative influenza A/H1N1v vaccination strategies. A transmission dynamic model was fitted to the estimated number of cases in real-time, and used to generate plausible autumn scenarios under different vaccination options. The proportion of these cases by age and risk group leading to primary care consultations, National Pandemic Flu Service consultations, emergency attendances, hospitalisations, intensive care and death was then estimated using existing data from the pandemic. The real-time model suggests that the epidemic will peak in early November, with the peak height being similar in magnitude to the summer wave. Vaccination of the high-risk groups is estimated to prevent about 45 deaths (80% credibility interval 26–67), and save around 2900 QALYs (80% credibility interval 1600–4500). Such a programme is very likely to be cost-effective if the cost of vaccine purchase itself is treated as a sunk cost. Extending vaccination to low-risk individuals is expected to result in more modest gains in deaths and QALYs averted. Extending vaccination to school-age children would be the most cost-effective extension. The early availability of vaccines is crucial in determining the impact of such extensions. There have been a considerable number of cases of H1N1v in England, and so the benefits of vaccination to mitigate the ongoing autumn wave are limited. However, certain groups appear to be at significantly higher risk of complications and deaths, and so it appears both effective and cost-effective to vaccinate them. The United Kingdom was the first country to have a major epidemic in Europe. In countries where the epidemic is not so far advanced vaccination of children may be cost-effective. Similar, detailed, real-time modelling and economic studies could help to clarify the situation.

WHO: A(H1N1) “Pandemic Phase” Unchanged

The WHO Director-General issued a statement on 24 February 2010 following the seventh meeting of the Emergency Committee on 23 February 2010 in which the Committee’s views on the determination of the pandemic status were assessed:

“A detailed update was provided to the Committee on the global pandemic situation. After asking additional questions and reviewing the evidence and holding extensive discussion, the Committee was of the view that there was mixed evidence showing declining or low pandemic activity in many countries, but new community level transmission activity in West Africa. Moreover, they expressed concern that the winter months of the Southern Hemisphere had not yet started and there was uncertainty whether additional generalized waves of activity might occur and the need to not undermine preparations.

“The Committee advised that it was premature to conclude that all parts of the world have experienced peak transmission of the H1N1 pandemic influenza and that additional time and information was needed to provide expert advice on the status of the pandemic. The Committee accordingly suggested that the Committee be re-convened in a few weeks to review intervening developments and related epidemiological information.

“Having considered these views, the current epidemiological evidence and other relevant information, the Director-General determined that there had been no change in the pandemic phase, and decided to continue to monitor the situation and developments closely and to convene the Committee again within the next several weeks.

“The WHO Director-General asked the Committee for their views on continuance of the three current temporary IHR recommendations issued for the public health emergency of international concern. The consensus view of the Committee was in favor of continuation but to update the second recommendation by replacing “Intensify” with “Maintain” in recognition of the increased pandemic surveillance already implemented by countries and the need to maintain this activity. Having considered the views of the Emergency Committee, and the ongoing pandemic situation, the Director-General determined to continue the three temporary recommendations, as modified, namely:

– countries should not close borders or restrict international traffic and trade;

– maintain surveillance of unusual flu-like illness & severe pneumonia;

– if ill, it is prudent to delay travel. http://www.who.int/csr/disease/swineflu/7th_meeting_ihr/en/index.html

WHO: Pandemic (H1N1) 2009 – update 89: 26 February 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 89
Weekly update
26 February 2010

As of 21 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 16226 deaths…

Situation update:
In the temperate zone of the northern hemisphere, pandemic influenza virus continues to be detected across many countries, however, overall influenza activity continues to wane in most places. The most active areas of transmission are currently in parts of south and southeast Asia and in limited areas of east and southeastern Europe.

In Southeast Asia, pandemic influenza virus continued to circulate in areas, however, the overall intensity of respiratory diseases activity remained low and unchanged, except in a few countries.

More at: http://www.who.int/csr/don/2010_02_26/en/index.html

FDA approves Prevnar 13

The U.S. Food and Drug Administration approved Prevnar 13, a pneumococcal 13-valent conjugate vaccine for infants and young children ages 6 weeks through 5 years. Prevnar 13 will be the successor to Prevnar, the pneumococcal 7-valent conjugate vaccine licensed by the FDA in 2000 to prevent invasive pneumococcal disease (IPD) and otitis media. The new vaccine extends the protection to six additional types of the disease causing bacteria.  Prevnar 13 is approved for the prevention of invasive disease caused by 13 different serotypes of the bacterium Streptococcus pneumoniae. It also is approved for the prevention of otitis media caused by the seven serotypes shared with Prevnar. The bacterium can cause infections of the blood, middle ear, and the covering of the brain and spinal cord, as well as pneumonia.

Karen Midthun, M.D., acting director of the FDA’s Center for Biologics Evaluation and Research, said, “Although the rates of invasive pneumococcal disease have declined dramatically, there are still children in the United States who are suffering with this serious illness. The availability of Prevnar 13 will help prevent pneumococcal disease caused by the six additional serotypes.”

The FDA said that safety was evaluated in 5,084 infants and young children who received Prevnar 13, compared with 2,760 who received Prevnar, the control vaccine. Common adverse reactions reported after administration of Prevnar 13 were pain, redness and swelling at the injection site, irritability, decreased appetite and fever. These reactions were similar to what has been observed with Prevnar, which has a good safety record in the United States. Post marketing studies will include continued monitoring for reduction in IPD and otitis media, as well as continued evaluation of safety.

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm201758.htm

ACIP votes expanded influenza vax for all aged 6 months and older

CDC’s Advisory Committee on Immunization Practices (ACIP) voted on 24 February to expand the recommendation for annual influenza vaccination to include all people aged 6 months and older. The expanded recommendation is to take effect in the 2010 – 2011 influenza season. The new recommendation “seeks to remove barriers to influenza immunization and signals the importance of preventing influenza across the entire population.” Prior to the action, ACIP recommendations for seasonal influenza vaccination – which focused on vaccination of higher risk persons, children 6 months through 18 years of age and close contacts of higher risk persons – already applied to about 85 percent of the U.S. population.
CDC said that discussion at the ACIP meeting “focused on the value of protecting all people 19 to 49 years of age, who have been hard hit by the 2009 H1N1 pandemic virus, which is likely to continue circulating into next season and beyond. Another reason cited in favor of a universal recommendation for vaccination is that many people in currently recommended “higher risk” groups are unaware of their risk factor or that they are recommended for vaccination. The ACIP discussion also recognized the practicality and value of issuing a simple and clear message regarding the importance of influenza vaccination in the hopes that this would remove impediments to vaccination and expand coverage. Finally, new data collected over the course of the 2009 H1N1 pandemic indicates that some people who do not currently have a specific recommendation for vaccination may also be at higher risk of serious flu-related complications, including those people who are obese, post-partum women and people in certain racial/ethnic groups”

http://www.cdc.gov/media/pressrel/2010/r100224.htm

Comment: Time for fair trade in research data

The Lancet
Feb 27, 2010  Volume 375  Number 9716  Pages 697 – 776
http://www.thelancet.com/journals/lancet/issue/current

Comment
Time for fair trade in research data
Elizabeth Pisani, James Whitworth, Basia Zaba, Carla Abou-Zahr
Preview
Geneticists, astrophysicists, and molecular biologists routinely share research data with colleagues and rivals alike. The reason is that scientists and their funders know we will understand complex issues sooner if people build on one another’s work.1,2 Yet scientists in the complex area of public health have been left behind in the data-sharing revolution.

Editorial: Gates Foundation’s decade of vaccines

The Lancet Infectious Disease
Mar 2010  Volume 10 Number 3  Pages 139 – 212
http://www.thelancet.com/journals/laninf/issue/current

Editorial
Gates Foundation’s decade of vaccines
Original Text
The Lancet Infectious Diseases

The GAVI Alliance celebrated the tenth anniversary of its foundation on Jan 29 this year. During its 10 years GAVI has overseen the delivery of vaccines to around 250 million children in the world’s poorest countries, a programme that has probably averted around 5 million deaths.

To mark GAVI’s birthday, the Bill and Melinda Gates Foundation announced that it will commit US$10 billion over the next 10 years to a so-called decade of vaccines—ie, research and development and delivery of vaccines to the world’s poorest. As an agency whose role is vaccine delivery, rather than research and development, it is not clear how much of the Gates billions will be coming to GAVI. However, GAVI is already the foundation’s largest grantee, having received $1·5 billion in its 10 year history.

Other major GAVI donors are national governments, of which 16 have contributed to the alliance plus the European Commission. Countries that have donated the most to GAVI’s core funding include Canada, the Netherlands, Norway, the UK, and the USA. Although the direct donation made by Gates far outstrip those made by any national government, France and the UK have committed billions of dollars to a funding mechanism called the International Finance Facility for Immunisation and other governments have promised substantial amounts to this scheme.

GAVI currently disburses around $1 billion per year among the 65 countries in which it supports vaccination programmes. The alliance focuses its activities on delivery of a childhood pentavalent vaccine that protects against diphtheria, tetanus, pertussis, hepatitis B, and Haemophilus influenzae type b. However, to roll out this vaccine to all 65 countries by 2015, plus achieve its goal of adding pneumococcal and rotavirus vaccines to the immunisation schedule, will require an additional $3 billion.

A lot more than just wishful thinking has gone into Gates’ decision to donate $10 billion. A model developed at the Johns Hopkins Bloomberg School of Public Health (Baltimore, MD, USA), indicated that 90% vaccine coverage—including the rotavirus and pneumococcal vaccines—would prevent the deaths of 7·6 million children younger than 5 years between now and 2020. Adding the malaria vaccine, which is undergoing clinical trials, from 2014 could save an additional 1·1 million lives. The Gates Foundation will certainly not be funding this expansion in vaccine coverage on its own, but its financial commitment should act as an incentive for donor governments to provide the additional funds to achieve 90% coverage with childhood vaccines in developing countries within the next 10 years.

In addition to the diseases already mentioned, vaccination against measles will likely be targeted for some of the Gates’ billions. Progress in preventing deaths from measles has been remarkable, with around 82% of those eligible worldwide now receiving vaccine and the number of measles-related deaths falling from around 750 000 in 2000 to 164 000 in 2008. GAVI does not currently fund measles vaccination programmes; rather, another international collaboration, the Measles Initiative, provides technical and financial support for national vaccination programmes in developing countries. Other areas that might benefit include the provision of autodisposable syringes that cannot be reused, funding for new vaccines against group A meningococcal meningitis and against tuberculosis, and perhaps even a final push to eliminate polio.

Although the life-saving benefits of vaccination are beyond question, no immunisation programme is without an element of controversy. As pointed out in Newsdesk, GAVI is optimistic about rolling out pneumococcal vaccine on a large scale to developing countries, because it believes the cost of the vaccine can be reduced by 90%; however, little research has been done on the public health effect of widespread pneumococcal vaccine use in the targeted countries—might there, for example, be replacement of the vaccine pneumococcal serotypes with other serotypes, thus making the vaccine only temporarily effective? Given the present influenza pandemic, some of the Gates money could be spent on researching the effect of influenza in developing countries and, if necessary, developing vaccines against influenza that are cheap enough for widespread use in these countries.

These caveats are, of course, minor compared with the beneficial effect on global health that the commitment made by the Gates Foundation is likely to have. The foundation does need to set out a clear plan for how it intends to disburse its money over the decade of vaccines. Nevertheless, many more national governments than are currently backing global vaccine coverage should be inspired to follow the lead taken by the foundation.

Polio eradication within 5 years now a real possibility

The Lancet Infectious Disease
Mar 2010  Volume 10 Number 3  Pages 139 – 212
http://www.thelancet.com/journals/laninf/issue/current

Newsdesk
Polio eradication within 5 years now a real possibility
Kathryn Senior

Last year was a significant one for polio eradication. Real progress was made simultaneously in northern Nigeria, on the Afghanistan–Pakistan border, and in the remaining pockets in Bihar and Uttar Pradesh in India, cutting the number of cases worldwide to 1597 (correct as of Feb 2, 2010). The new bivalent oral polio vaccine (bOPV), which targets type 1 and type 3 polioviruses, was licensed in late 2009 and has been in use since December. Starting in February, March, and April, 2010, multiple mass immunisations are planned in all four remaining countries where polio is endemic, at the start of a 3-year intensive effort to finally halt polio transmission worldwide.