Reducing empiricism in malaria vaccine design

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

Personal View
Reducing empiricism in malaria vaccine design
Vasee S Moorthy, Marie Paule Kieny

Preview
Gains in the control of malaria and the promising progress of a malaria vaccine that is partly efficacious do not reduce the need for a high-efficacy vaccine in the longer term. Evidence supports the feasibility of developing a highly efficacious malaria vaccine. However, design of candidate malaria vaccines remains empirical and is necessarily based on many unproven assumptions because much of the knowledge needed to design vaccines and to predict efficacy is not available. Data to inform key questions of vaccine science might allow the design of vaccines to progress to a less empirical stage, for example through availability of assay results associated with vaccine efficacy.

Tuberculosis and air travel: a systematic review and analysis of policy

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

Review
Tuberculosis and air travel: a systematic review and analysis of policy
Abrahim Abubakar

Preview
WHO international guidelines for the control of tuberculosis in relation to air travel require—after a risk assessment—tracing of passengers who sat for longer than 8 h in rows adjacent to people with pulmonary tuberculosis who are smear positive or smear negative. A further recommendation is that all commercial air travel should be prohibited until the person has two consecutive negative sputum smears for drug-susceptible tuberculosis or two consecutive cultures for multidrug-resistant tuberculosis.

VAMPSS (the Vaccines and Medications in Pregnancy Surveillance System)

Science
26 February 2010  Vol 327, Issue 5969, Pages 1043-1162
http://www.sciencemag.org/current.dtl

News of the Week
Drug Safety: New Network to Track Drugs and Vaccines in Pregnancy
Jennifer Couzin-Frankel

Both doctors and patients are jittery about whether to continue or drop potentially risky treatments during pregnancy. A new effort to bring risks into focus is being launched this week with $12.5 million from two U.S. agencies. It will start by examining asthma medications called short-acting beta agonists, as well as flu vaccines and antivirals for influenza. Called VAMPSS (the Vaccines and Medications in Pregnancy Surveillance System), the program will be funded for 5 years by the Agency for Healthcare Research and Quality and for 2 years by the Biomedical Advanced Research and Development Authority and coordinated by the American Academy of Allergy, Asthma, and Immunology. An advisory committee that includes members from pediatric and obstetric groups, and the Centers for Disease Control and Prevention, will guide VAMPSS’s research.

IP: Fixing the Legal Framework for Pharmaceutical Research

Science
26 February 2010  Vol 327, Issue 5969, Pages 1043-1162
http://www.sciencemag.org/current.dtl

Policy Forum
Intellectual Property: Fixing the Legal Framework for Pharmaceutical Research
Sherry M. Knowles

The cost of drug research and development (R&D) has increased from $230 million per drug in the early 1980s to $1.2 billion today, with R&D currently requiring about 10 to 15 years per drug (1–4). This investment of time and money cannot be sustained without a legal system that provides sufficient time to recoup the investment and to secure a reasonable return, as well as the ability to make important business decisions that remain correct over a long period of time. Pharmaceutical companies have historically relied on two kinds of market protection: (i) the exclusive ownership of their own clinical research and (ii) patents. However, the U.S. Hatch-Waxman Act (5), which is designed to strike a balance between innovative pharmaceutical research and access to generic drugs, is flawed. Further, U.S. courts sometimes retroactively change standards for patent protection long after large R&D efforts have been initiated, which increases the risk to defend and rely on patent protection.

Chief Patent Counsel, GlaxoSmithKline, King of Prussia, PA 19406, USA.

Long-term Vaccine Storage: Disaccharide Stabilizers

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

Research Articles
Vaccines
Long-Term Thermostabilization of Live Poxviral and Adenoviral Vaccine Vectors at Supraphysiological Temperatures in Carbohydrate Glass

Robert Alcock, Matthew G. Cottingham, Christine S. Rollier, Julie Furze, Samodh D. De Costa, Marian Hanlon, Alexandra J. Spencer, Jared D. Honeycutt, David H. Wyllie, Sarah C. Gilbert, Migena Bregu, and Adrian V. S. Hill
17 February 2010:19ra12

Abstract [Bolding by Week in Review]
Live recombinant viral vectors based on adenoviruses and poxviruses are among the most promising platforms for development of new vaccines against diseases such as malaria, tuberculosis, and HIV-AIDS. Vaccines based on live viruses must remain infectious to be effective, so therefore need continuous refrigeration to maintain stability and viability, a requirement that can be costly and difficult, especially in developing countries. The sugars sucrose and trehalose are commonly used as stabilizing agents and cryoprotectants for biological products. Here, we have exploited the ability of these sugars to vitrify on desiccation to develop a thermostabilization technique for live viral vaccine vectors. By slowly drying vaccines suspended in solutions of these disaccharide stabilizers onto a filter-like support membrane at ambient temperature, an ultrathin glass is deposited on the fibers of the inert matrix. Immobilization of two recombinant vaccine vectors—E1/E3-deleted human adenovirus type 5 and modified vaccinia virus Ankara—in this glass on the membranes enabled complete recovery of viral titer and immunogenicity after storage at up to 45°C for 6 months and even longer with minimal losses. Furthermore, the membrane carrying the stabilized vaccine can be incorporated into a holder attached to a syringe for almost simultaneous reconstitution and injection at point of use. The technology may potentially be developed for the deployment of viral vector–based biopharmaceuticals in resource-poor settings.

Second Geneva Consensus: Recommendations for novel live TB vaccines

Vaccine
Volume 28, Issue 7, Pages 1661-1892 (17 February 2010)
http://www.sciencedirect.com/science/journal/0264410X

Conference Report
The second Geneva Consensus: Recommendations for novel live TB vaccines
Pages 2259-2270
K.B. Walker, M.J. Brennan, M.M. Ho, J. Eskola, G. Thiry, J. Sadoff, R. Dobbelaer, L. Grode, M.A. Liu, U. Fruth, P.H. Lambert

Abstract
Infection with Mycobacterium tuberculosis continues to be a major public health burden in most developing parts of the world and efforts to develop effective strategies for containing the disease remain a priority. It has long been evident that effective mass vaccination programmes are a cost effective and efficient approach to controlling communicable diseases in a public health setting and tuberculosis (TB) continues to be a major target. One approach with increasing acceptance is based upon on live mycobacterial vaccines, either as recombinant BCG or rationally attenuated M. tuberculosis, thus generating a new live TB vaccine.

The Geneva Consensus published in March 2005 set out the opinion on priorities and requirements for developing live mycobacterial vaccines for Phase I trials. In the intervening period much progress has been made in both preclinical and clinical development of new TB vaccines and has provided the impetus for organising the second Geneva Consensus (held at WHO headquarters, April 2009) to discuss issues, including:

i. Explore the regulatory requirements for live TB vaccines to enter Phase I trials, in particular those based on attenuated M. tuberculosis. Particular attention was paid to the characterisation and safety package likely to be required, including issues of attenuation, the presence of antibiotic resistance markers in live vaccines and the nature of any attenuated vaccine phenotype.
ii. To identify the general criteria for further clinical development from Phase I through to Phase III.
iii. Obtain a perspective of the regulatory landscape of developing countries where Phase II and III trials are to be held.
iv. Review manufacturing considerations for live TB vaccines and relevance of the WHO and European Pharmacopeia guidelines and requirements for BCG vaccine.
v. Consider requirements and associated issues related to the use of these new vaccines within an existing BCG vaccination programme.

Cost-effectiveness of PCV7 in Argentina

Vaccine
Volume 28, Issue 7, Pages 1661-1892 (17 February 2010)
http://www.sciencedirect.com/science/journal/0264410X

Cost-effectiveness of the CRM-based 7-valent pneumococcal conjugated vaccine (PCV7) in Argentina
Pages 2302-2310
Norberto D. Giglio, Alejandro D. Cane, Paula Micone, Angela Gentile

Abstract
Due to the region’s own conditions, universal vaccination with pneumococcal conjugate heptavalent vaccine (PCV-7) in Latin American countries is still controversial.
Objective
To compare projected economic costs and health benefits associated with pneumococcal conjugate heptavalent vaccine as a routine immunization in healthy children in Argentina.

Design
A decision analytic model of Markov simulated lifetime evolution of a birth cohort (n 696,451) was developed and compared costs and health benefits of pneumococcal disease in the presence and absence of vaccination.

Main outcome measures
Cost per life year (LY) gained, reduce in diseases burden and costs of vaccination.

Results
From the society’s perspective, the incremental cost per LY gained was US$ 5599.42 and the purchase of the 4 doses of vaccine for the entire cohort with a cost of US$ 26.5 dose requires an investment of US$ 73,823,806.00.

The model estimated that vaccination reduce the number of death by 159 cases of meningitis, 756 cases of bacteriemias 4594 cases of pneumonias about 84,769 cases of otitis media and 20 meningitis sequelae.

The value of the cost per LY gained was considerably modified by the variation in the cost of the vaccine dose, efficacy/effectiveness of the vaccine for pneumonia the mortality from pneumonia and herd immunity.

Conclusions
Our analysis predicted that routine vaccination of healthy infants <2 years could prevent an important number of pneumococcal infectious and reduce related mortality and morbidity. This strategic could be highly cost-effective in Argentina.

Meningococcal conjugate vaccination: adolescents 13–17: U.S. 2007

Vaccine
Volume 28, Issue 7, Pages 1661-1892 (17 February 2010)
http://www.sciencedirect.com/science/journal/0264410X

Meningococcal conjugate vaccination among adolescents aged 13–17 years, United States, 2007
Pages 2350-2355
Peng-jun Lu, Nidhi Jain, Amanda C. Cohn

Abstract
Background
An estimated 1000–2000 cases of invasive meningococcal diseases occur annually in the United States. In 2005, a new quadrivalent meningococcal conjugate vaccine (MCV4) was approved and, because of supply constraints, was recommended for routine vaccination of some groups of adolescents. In August 2007, vaccination recommendations were expanded for all adolescents 11–18 years.

Methods
We analyzed data from the 2007 National Immunization Survey-Teen (NIS-Teen), a nationally representative random digit dialed telephone survey. Estimates of MCV4 coverage were assessed from provider-reported vaccination histories. A multivariable logistic regression analysis and predictive marginal model were performed to identify factors independently associated with MCV4 vaccination.

Results
Provider-reported vaccination histories were available for 2947 adolescents aged 13–17 years with a response rate of 55.9%. Overall, MCV4 coverage was 32.4% (95% confidence interval (CI) = 30.2–34.7%) in 2007. Vaccination coverage was similar among adolescents aged 13–14 years compared to those aged 15–17 years (32.1% vs. 32.6%, respectively). Coverage was 30.6% for non-Hispanic whites, 35.9% for non-Hispanic blacks, and 36.1% for Hispanics; however, these variations were not statistically significant. Characteristics independently associated with a higher likelihood of MCV4 vaccination included having ≥2 physician contacts in the past year, having a well child visit at age 11–12 years, and ever having a doctor recommendation for meningitis vaccination of the adolescent.

Conclusions
In 2007, MCV4 coverage among 13–17 years old increased 20.7 percentage points from 2006. Achieving high vaccination coverage among adolescents will be challenging. Targeting adolescents with no health insurance and no recent healthcare provider visits may be important to increase coverage.

WHO: Pandemic (H1N1) 2009 – update 88: 19 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 88
Weekly update
19 February 2010

As of 14 February 2010, worldwide more than 212 countries and overseas territories or communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including at least 15921 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 situation is largely unchanged since the previous update. In the temperate zone of the northern hemisphere, active but declining pandemic influenza transmission persists in limited areas of eastern and southern Europe, South Asia, and in East Asia. Several countries in West Africa reported increases in the number of cases but there is as yet insufficient evidence to conclude that widespread community transmission is occurring. An increasing trend in respiratory diseases activity was reported in Thailand and Jamaica, however the cause of the respiratory disease is uncertain at this point.

More at: http://www.who.int/csr/don/2010_02_19/en/index.html

Recommended viruses for influenza vaccines: 2010-2011 season/ northern hemisphere

The WHO released “Recommended viruses for influenza vaccines for use in the 2010-2011 northern hemisphere influenza season, February 2010.” WHO noted that it “convenes technical meetings1 in February and September each year to recommend viruses for inclusion in influenza vaccines for the northern and southern hemispheres, respectively. This recommendation relates to the influenza vaccines for the forthcoming influenza season in the northern hemisphere (2010 – 2011). A recommendation will be made in September 2010 relating to vaccines that will be used for the influenza season in the southern hemisphere (2011). For countries in equatorial regions epidemiological considerations will influence which recommendation (February or September) individual national and regional authorities consider more appropriate.”

“…Based on the analyses 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 B/Victoria/2/87 lineage virus, 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.

# A/Wisconsin/15/2009 is an A/Perth/16/2009 (H3N2)-like virus and is a 2010 southern hemisphere vaccine virus…

http://www.who.int/csr/disease/influenza/201002_Recommendation.pdf

GAVI’s Advance Market Commitment: Letters

The Lancet
Volume 375, Issue 9715, Page 638, 20 February 2010

Correspondence
GAVI’s Advance Market Commitment
Donald W Light

Preview
The World Report on GAVI’s Advance Market Commitment (AMC; Dec 5, p 1879)1 contains irreconcilable claims by GAVI and reveals the inability of the AMC approach to make new vaccines available to low-income countries on a sustainable basis.

GAVI’s Advance Market Commitment
Nina Schwalbe, Ibrahim El-Ziq

Preview
In response to Ann Usher’s World Report,1 it is necessary to clarify how the pilot Advance Market Commitment (AMC) works. The pilot AMC aims to stimulate the manufacture of an adequate supply of affordable pneumococcal vaccines for developing countries. The price of the vaccine is capped at US$3·50 per dose, paid by the GAVI Alliance and countries. Six donors will pay an additional contribution per dose to participating manufacturers in the early years of each contract to offset costs of expanding production.

HPV vaccination: waiting for evidence of effectiveness

The Lancet Infectious Disease
Feb 2010  Volume 10  Number 2  Pages 67 – 138
http://www.thelancet.com/journals/laninf/issue/current

Correspondence

HPV vaccination: waiting for evidence of effectiveness
Eric J Suba, Stephen S Raab, on behalf of the Viet/American Cervical Cancer Prevention Project

Preview
As noted by Gary Clifford (Dec 12, p 1948),1 the greatest source of uncertainty about the potential effectiveness of human papillomavirus (HPV) vaccines remains the duration of the immune response. However, even if the most optimistic scenario of HPV vaccine effectiveness is realised, the introduction of HPV vaccines to populations not yet fully covered by screening services may compete with limited budgets for the build-out of screening services and thereby decelerate global reductions in deaths from cervical cancer by creating populations of women who will not be protected by either screening or vaccination.

Biological, clinical, and ethical advances of placebo effects

The Lancet Infectious Disease
Feb 2010  Volume 10  Number 2  Pages 67 – 138
http://www.thelancet.com/journals/laninf/issue/current

Review
Biological, clinical, and ethical advances of placebo effects
Damien G Finniss, Ted J Kaptchuk, Franklin Miller, Fabrizio Benedetti

Preview
For many years, placebos have been defined by their inert content and their use as controls in clinical trials and treatments in clinical practice. Recent research shows that placebo effects are genuine psychobiological events attributable to the overall therapeutic context, and that these effects can be robust in both laboratory and clinical settings. There is also evidence that placebo effects can exist in clinical practice, even if no placebo is given. Further promotion and integration of laboratory and clinical research will allow advances in the ethical use of placebo mechanisms that are inherent in routine clinical care, and encourage the use of treatments that stimulate placebo effects.

Lancet publishes retraction of Wakefield et al; Offit commentary

Lancet published a retraction of Wakefield AJ, Murch SH, Anthony A, et al. “Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children.” Lancet 1998; 351: 637–41:

“Following the judgment of the UK General Medical Council’s Fitness to Practise Panel on Jan 28, 2010, it has become clear that several elements of the 1998 paper by Wakefield et al are incorrect, contrary to the findings of an earlier investigation.2 In particular, the claims in the original paper that children were “consecutively referred” and that investigations were “approved” by the local ethics committee have been proven to be false. Therefore we fully retract this paper from the published record.”
The Editors of The Lancet
Hodgson H. A statement by The Royal Free and University College Medical School and The Royal Free Hampstead NHS Trust. Lancet 2004; 363: 824.
http://download.thelancet.com/flatcontentassets/pdfs/S0140673610601754.pdf

The Philadelphia Inquirer carries an article by Dr. Paul A. Offit which comments on the retraction and the impact of the original Lancet article.  The MMR vaccine scare: How bad science resulted in suffering and death is available at: http://www.philly.com/inquirer/currents/84326297.html. Dr. Offit is chief of the division of infectious diseases at the Children’s Hospital of Philadelphia and provides oversight for the Center for Vaccine Ethics and Policy, which publishes this weekly update.

WHO: Pandemic (H1N1) 2009 – update 87: 12 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 87
Weekly update
12 February 2010

As of 7 February 2010, worldwide more than 212 countries and overseas territories or communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including at least 15292 deaths. More at: http://www.who.int/csr/don/2010_02_12/en/index.html

Global Health Technologies Coalition (GHTC) launches new website

PATH announced that the Global Health Technologies Coalition (GHTC) launched its new website www.ghtcoalition.org, “detailing health technologies and key issues for advancing global health innovations.” The coalition, housed at PATH and funded by the Bill & Melinda Gates Foundation, includes “more than 30 organizations advocating for research and development of tools to prevent, diagnose, and treat global diseases so health solutions are available when populations need them.” The coalition advocates for new vaccines, microbicides, drugs, devices, and diagnostics that will improve health in developing countries.  PATH said the new site offers numerous resources and can serve as a clearinghouse of information about coalition activities and global health research and development. http://www.path.org/news/an100208-ghtc.php

The MMWR for February 12, 2010: U.S. mumps outbreak

The MMWR for February 12, 2010 / Vol. 59 / No. 5, includes: Update: Mumps Outbreak — New York and New Jersey, June 2009–January 2010

State and local health departments, in collaboration with CDC, continue to investigate a U.S. mumps outbreak that began in June 2009 at a summer camp in New York. As of January 29, 2010, 1,521 cases had been reported, 97% of which have occurred in members of the same tradition-observant religious community. Among patients for whom vaccination status was reported, 88% had received at least 1 dose of mumps-containing vaccine, and 75% had received 2 doses.

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5905a1.htm

Global Maps of the Dominant Anopheles Vectors of Human Malaria

PLoS Medicine
(Accessed 14 February 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

Developing Global Maps of the Dominant Anopheles Vectors of Human Malaria
Simon I. Hay, Marianne E. Sinka, Robi M. Okara, Caroline W. Kabaria, Philip M. Mbithi, Carolynn C. Tago, David Benz, Peter W. Gething, Rosalind E. Howes, Anand P. Patil, William H. Temperley, Michael J. Bangs, Theeraphap Chareonviriyaphap, Iqbal R. F. Elyazar, Ralph E. Harbach, Janet Hemingway, Sylvie Manguin, Charles M. Mbogo, Yasmin Rubio-Palis, H. Charles J Godfray Health in Action, published 09 Feb 2010
doi:10.1371/journal.pmed.1000209

WHO Pandemic (H1N1) 2009 – update 86 Weekly update: 5 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 86
Weekly update: 5 February 2010

As of 31 January 2010, worldwide more than 209 countries and overseas territories or communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including at least 15174 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:

In the temperate zone of the northern hemisphere, overall pandemic influenza activity continues to decline or remain low in most regions since peaking during late October and November 2009. Several areas continue to have evidence of active but declining transmission, particularly in North Africa and in limited areas of Eastern Europe and East Asia… More at: http://www.who.int/csr/don/2010_02_5/en/index.html

Harvard poll: almost half of Americans believe the H1N1 flu outbreak is over (44%)

A new Harvard School of Public Health (HSPH) poll shows that almost half of Americans believe the H1N1 flu outbreak is over (44%), and levels of concern about getting sick with the virus continue to decline. Few (18%) think it is “very likely” there will be another widespread outbreak of the H1N1 virus in the U.S. during the next 12 months, although a larger share of the population (43%) does say such an outbreak is “somewhat likely.” After an initial period of vaccine shortage, 70% of adults said there is now enough vaccine in their community for everyone who wants it. The national poll was conducted January 20-24, 2010.
At this point, the study suggests that more than half of parents (53%) either got the vaccine for their children (40%) or intend to get it before the end of February 2010 (13%). The Centers for Disease Control and Prevention (CDC) had identified children as a priority group for the vaccine.  Among adults, 37% either got the H1N1 vaccine for themselves (21%) or intend to do so before February ends (16%). If perceptions that the outbreak is over spread, those who now say they intend to get the vaccine may ultimately decide not to. The poll also revealed a substantial share of adults who said they have not gotten the vaccine and do not intend to (61%). More at: http://www.hsph.harvard.edu/news/press-releases/2010-releases/poll-half-of-americans-believe-h1n1-outbreak-over.html

FDA- PATH announce vaccine collaboration on pneumococcus

The U.S. Food and Drug Administration (FDA) announced a collaboration with PATH to advance development of a vaccine to protect children against diseases caused by Streptococcus pneumoniae (pneumococcus), especially pneumonia. The project is expected to run for two years and is being conducted under the Cooperative Research and Development Agreement (CRADA) program. The program allows federal laboratories and businesses to form partnerships that help expedite research activities. PATH “will help the FDA obtain materials needed for the agency to develop the conjugate vaccine technology, and will also will provide approximately $480,000 to the FDA for the development of both the conjugation technology and tests to determine if the carrier proteins are properly linked to the polysaccharides.” The stated goal of the CRADA is “to evaluate the application of Center for Biologics Evaluation and Research (CBER) conjugation technology to pneumococcal vaccines. If it holds promise for fulfilling the goal of providing safe, effective, and affordable pneumococcal vaccines, the CRADA permits transfer of the technology to the China National Biotec Group’s Chengdu Institute of Biological Products, and eventually to groups in other developing countries as appropriate.”

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm199479.htm

Fifth joint WHO-UNICEF-GAVI Global Immunization Meeting: Geneva, 1-3 February 2010

The fifth joint WHO-UNICEF-GAVI Global Immunization Meeting was held in Geneva, 1-3 February 2010, “with the purpose of providing a technical update to WHO and UNICEF Regional and country staff as well as immunization partners…to give all involved in immunization a common understanding of the current status and near future plans in the immunization world, particularly after in the current context of the rapid expansion of available vaccines and the financial crisis the world is facing.” The meeting followed the basic structure in Global Immunization Vision and Strategies (GIVS):

– how to the improve routine vaccination and support to the accelerated disease control initiatives;

– introducing new vaccines, including an update on the Hib Initiative and the status of pneumococcal and rotavirus vaccines;

– experiences in integration of EPI with other programmes (including malaria interventions); and

– issues of global interdependence including vaccine supply and the pandemic influenza vaccines.

More at: http://www.who.int/immunization_delivery/gim/en/index.html

Unlicensed pandemic influenza A H1N1 vaccines

The Lancet
Feb 06, 2010  Volume 375  Number 9713  Pages 433 – 524
http://www.thelancet.com/journals/lancet/issue/current

Comment
Unlicensed pandemic influenza A H1N1 vaccines
Arthur L Caplan

Preview
When WHO’s Strategic Advisory Group of Experts (SAGE) on immunisation met on July 7, 2009, they recognised that pandemic influenza A H1N1 vaccines, when they become available, are almost entirely committed under contract to a small number of industrialised countries.1 SAGE commended WHO for trying to improve real-time access in poor countries, but these efforts will not have substantial effects in the short term.

NEJM: Rotavirus and vaccine: four articles

Pediatrics
February 2010 / VOLUME 125 / ISSUE 2
http://pediatrics.aappublications.org/current.shtml

Estimated Burden of Rotavirus-Associated Diarrhea in Ambulatory Settings in the United States
Anthony R. Flores, Peter G. Szilagyi, Peggy Auinger, and Susan G. Fisher

Effectiveness of Pentavalent Rotavirus Vaccine in a Large Urban Population in the United States
Julie A. Boom, Jacqueline E. Tate, Leila C. Sahni, Marcia A. Rench, Jennifer J. Hull, Jon R. Gentsch, Manish M. Patel, Carol J. Baker, and Umesh D. Parashar

Effectiveness of the Pentavalent Rotavirus Vaccine in Preventing Gastroenteritis in the United States
Florence T. Wang, T. Christopher Mast, Roberta J. Glass, Jeanne Loughlin, and John D. Seeger

Sibling Transmission of Vaccine-Derived Rotavirus (RotaTeq) Associated With Rotavirus Gastroenteritis
Daniel C. Payne, Kathryn M. Edwards, Michael D. Bowen, Erin Keckley, Jody Peters, Mathew D. Esona, Elizabeth N. Teel, Diane Kent, Umesh D. Parashar, and Jon R. Gentsch

Adolescents’ intentions to have the HPV vaccine

Vaccine
http://www.sciencedirect.com/science?_ob=PublicationURL&_cdi=5188&_pubType=J&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=06a70dff873c73731f4a31331c8deee2&jchunk=28#28
Volume 28, Issue 7, Pages 1661-1892 (17 February 2010)

Short Communications
Understanding adolescents’ intentions to have the HPV vaccine
Pages 1673-1676
Alice S. Forster, Laura A.V. Marlow, Jane Wardle, Judith Stephenson, Jo Waller

Abstract
From September 2008, older adolescent girls in the UK are eligible to have the HPV vaccine as part of the HPV vaccination ‘catch-up’ programme. Six months before they were due to be offered the vaccine 16–18 year old girls (N = 617) from eight further education/sixth-form colleges reported their intentions to have the HPV vaccine and reasons for this decision. Most intended to have the vaccine (around 70%). Some intentions were influenced by perceptions of risk. Many participants wanted more information and a small minority were scared of needles. Some ‘non-intenders’ were opposed to vaccinations altogether. The HPV vaccine is likely to be popular but non-intenders’ views may be difficult to change.

HPV Vaccine: Mothers’ preferences and willingness to pay

Vaccine
http://www.sciencedirect.com/science?_ob=PublicationURL&_cdi=5188&_pubType=J&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=06a70dff873c73731f4a31331c8deee2&jchunk=28#28
Volume 28, Issue 7, Pages 1661-1892 (17 February 2010)

Regular Papers
Mothers’ preferences and willingness to pay for vaccinating daughters against human papillomavirus
Pages 1702-1708
Derek S. Brown, F. Reed Johnson, Christine Poulos, Mark L. Messonnier

Abstract
A choice-format, conjoint-analysis survey was developed and fielded to estimate how features of human papillomavirus (HPV) vaccines affect mothers’ perceived benefit and stated vaccine uptake for daughters. Data were collected from a national sample of 307 U.S. mothers of girls aged 13–17 years who had not yet received an HPV vaccine. Preferences for four features of HPV vaccines were evaluated: protection against cervical cancer, protection against genital warts, duration of protection, and cost. We estimate that mean maximum willingness-to-pay (WTP)—an economic measure of the total benefits to consumers—for current HPV vaccine technology ranges between $560 and $660. All vaccine features were statistically significant determinants of WTP and uptake. Mothers were willing to pay $238 more for a vaccine that provides 90% protection for genital warts relative to a vaccine that provides no protection against warts. WTP for lifetime protection vs. 10 years protection was $245. Mothers strongly valued greater cervical cancer efficacy, with 100% protection against cervical cancers the most desired feature overall. Adding a second HPV vaccine choice to U.S. consumers’ alternatives is predicted to increase stated uptake by 16%. Several features were significantly associated with stated choices and uptake: age of mother, race/ethnicity, household income, and concern about HPV risks. These findings provide new data on how HPV vaccines are viewed and valued by mothers, and how uptake may change in the context of evolving vaccine technology and as new data are reported on duration and efficacy.

Anti-vaccination misinformation on the Internet

Vaccine
http://www.sciencedirect.com/science?_ob=PublicationURL&_cdi=5188&_pubType=J&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=06a70dff873c73731f4a31331c8deee2&jchunk=28#28
Volume 28, Issue 7, Pages 1661-1892 (17 February 2010)

A postmodern Pandora’s box: Anti-vaccination misinformation on the Internet
Pages 1709-1716
Anna Kata

Abstract
The Internet plays a large role in disseminating anti-vaccination information. This paper builds upon previous research by analyzing the arguments proffered on anti-vaccination websites, determining the extent of misinformation present, and examining discourses used to support vaccine objections. Arguments around the themes of safety and effectiveness, alternative medicine, civil liberties, conspiracy theories, and morality were found on the majority of websites analyzed; misinformation was also prevalent. The most commonly proposed method of combating this misinformation is through better education, although this has proven ineffective. Education does not consider the discourses supporting vaccine rejection, such as those involving alternative explanatory models of health, interpretations of parental responsibility, and distrust of expertise. Anti-vaccination protestors make postmodern arguments that reject biomedical and scientific “facts” in favour of their own interpretations. Pro-vaccination advocates who focus on correcting misinformation reduce the controversy to merely an “educational” problem; rather, these postmodern discourses must be acknowledged in order to begin a dialogue.

HPV vaccine debate on MySpace blogs

Vaccine
Volume 28, Issue 6, Pages 1437-1660 (10 February 2010)
http://www.sciencedirect.com/science?_ob=PublicationURL&_cdi=5188&_pubType=J&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=06a70dff873c73731f4a31331c8deee2&jchunk=28#28

Regular Papers
An analysis of the Human Papilloma Virus vaccine debate on MySpace blogs
Pages 1535-1540
Jennifer Keelan, Vera Pavri, Ravin Balakrishnan, Kumanan Wilson

Abstract
Background
The roll out of HPV immunization programs across the United States was hindered by controversy. We tracked the debate in the United States through MySpace, then the most popular social networking site, in order to better understand the public’s reaction to the vaccine.

Methods
We searched MySpace for all blog discourse related to HPV immunization. We analyzed each blog according to the overall portrayal of HPV immunization, identified the characteristics of the bloggers, and developed a content analysis to categorize the types of supporting arguments made.

Results
303 blogs met our inclusion criteria. 157 (52%) of the blogs were classified as positive, 129 (43%) as negative, and 17 (6%) were ambivalent toward HPV immunization. Positive blogs generally argued that HPV infection was effective and there were no reasonable alternatives to immunizing. Negative blogs focused on the risks of immunizing and relied heavily on vaccine-critical publications to support their viewpoint. Of the blogs where gender could be identified, 75 (25%) were posted by men and 214 (71%) by women. 60% of blogs posted by men were explicitly critical about HPV immunization versus 36% of women’s blogs. Male bloggers also had larger networks of friends.

Conclusions
We describe a novel and promising approach to the surveillance of public opinions and attitudes toward immunization. In our analysis, men were far more likely to hold negative views about HPV immunization than women and disseminate negative messages through larger social networks. Blog analysis is a useful tool for Public health officials to profile vaccine criticism and to design appropriate educational information tailored to respond to alternative media/alternative information actively disseminated via social media tools. Public health officials should examine mechanisms by which to leverage this media to better communicate their message through existing networks and to engage in on-going dialogue with the public.

Bill and Melinda Gates announce $10 billion over 10 years: vaccines for the world’s poorest countries

Bill and Melinda Gates, speaking at the World Economic Forum’s Annual Meeting in Davos, announced that their foundation will commit $10 billion over the next 10 years “to help research, develop and deliver vaccines for the world’s poorest countries, noting that “increased investment in vaccines by governments and the private sector could help developing countries dramatically reduce child mortality by the end of the decade, and they called for others to help fill critical financing gaps in both research funding and childhood immunization programs.”

Bill Gates said, “We must make this the decade of vaccines. Vaccines already save and improve millions of lives in developing countries. Innovation will make it possible to save more children than ever before.” Melinda Gates said, “Vaccines are a miracle—with just a few doses, they can prevent deadly diseases for a lifetime,” said. “We’ve made vaccines our number-one priority at the Gates Foundation because we’ve seen firsthand their incredible impact on children’s lives.”

The Gates Foundation said it used a model developed by a consortium led by the Institute of International Programs at the Johns Hopkins Bloomberg School of Public Health to project the potential impact of vaccines on childhood deaths over the next 10 years.

By significantly scaling up the delivery of life-saving vaccines in developing countries to 90 percent coverage—including new vaccines to prevent severe diarrhea and pneumonia—the model suggests that we could prevent the deaths of some 7.6 million children under 5 from 2010-2019. The foundation also estimates that an additional 1.1 million children could be saved with the rapid introduction of a malaria vaccine beginning in 2014, bringing the total number of potential lives saved to 8.7 million.

If additional vaccines are developed and introduced in this decade—such as for tuberculosis—even more lives could be saved. The new funding announced today is in addition to the $4.5 billion that the Gates Foundation has already committed to vaccine research, development and delivery to date across its entire disease portfolio since its inception.

The announcement noted that “many of the recent advances in vaccine development and delivery have been driven by public-private partnerships such as the GAVI Alliance and the Rotavirus Vaccine Program at PATH, which coordinate the resources and expertise of vaccine companies, donors, UNICEF, WHO, the World Bank, and developing countries.” Mr. Gates said these partnerships are “transforming the business of vaccines.”

Commenting on the announcement, WHO Director-General Margaret Chan said, “The Gates Foundation’s commitment to vaccines is unprecedented, but just a small part of what is needed. It’s absolutely crucial that both governments and the private sector step up efforts to provide life-saving vaccines to children who need them most.”

http://www.gatesfoundation.org/press-releases/Pages/decade-of-vaccines-wec-announcement-100129.aspx

PATH and GAVI discuss rotavirus vaccine studies in Mexico and Africa

PATH and GAVI, in a joint media release, discuss studies in Mexico and Africa which, “for the first time ever, demonstrate a reduction in diarrheal disease deaths following rotavirus vaccine introduction in Mexico and vaccine efficacy among impoverished populations in Malawi and South Africa.” The research is published in the New England Journal of Medicine [see Journal Watch below for citation and free full text access] Both studies “underscore the importance of vaccination in achieving significant reduction of severe rotavirus infections among children in the developing world, where disease impact is greatest.”

In an editorial accompanying the studies’ results, Mathuram Santosham, Professor of International Health and Pediatrics at Johns Hopkins University, Baltimore, welcomed these studies for supporting the use of rotavirus vaccines in the poorest countries of the world: “We now have another powerful weapon to add to our armamentarium to combat diarrheal deaths – rotavirus vaccines…Rotavirus vaccine should be introduced immediately in high mortality areas and it should be used as a trigger to energize diarrhea control programs and improve coverage for all the proven interventions for diarrhea.”

Tachi Yamada, president of the Global Health Program at the Bill & Melinda Gates Foundation, commented, “Diarrhea is rarely a life-threatening problem in rich countries, but in the developing world it is a leading cause of death in children. The world now has an effective vaccine against rotavirus, with the potential to save hundreds of thousands of lives every year. The next challenge is to ensure that rotavirus vaccines reach all those in need.”

The GAVI Alliance said it has launched efforts to support the introduction of rotavirus vaccines in at least 44 low-income countries by 2015. Global health organizations have issued a call to action on diarrheal disease to advocate for adequate funding for rotavirus vaccines to prevent and treat this major cause of severe diarrheal disease. The vaccine is an important part of a coordinated approach that combines proven strategies for prevention and treatment of diarrhea, such as oral rehydration therapy, exclusive breastfeeding, zinc supplementation, and improved sanitation to achieve the greatest impact on diarrheal disease morbidity and mortality.

http://www.path.org/news/an100129-davos.php

WHO: Pandemic (H1N1) 2009 – update 85

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 85
Weekly update
29 January 2010

As of 24 January 2010, worldwide more than 209 countries and overseas territories or communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including at least 14711 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:
Although much of the temperate northern hemisphere passed a peak of fall and wintertime pandemic influenza activity between late October and late November 2009, virus transmission remain active in several later affected areas, particularly in North Africa, limited areas of eastern and southeastern Europe, and in parts of South and East Asia… More at: http://www.who.int/csr/don/2010_01_29/en/index.html

WHO responds to “allegations” around management of the H1N1 pandemic

[Editor’s Note: As the title of its statement just below describes, WHO continues to respond to various “allegations” around management of the H1N1 pandemic]

22 January 2010
WHO Statement of the World Health Organization on allegations of conflict of interest and ‘fake’ pandemic

Providing independent advice to Member States is a very important function of the World Health Organization (WHO). We take this work seriously and guard against the influence of any improper interests. The WHO influenza pandemic policies and response have not been improperly influenced by the pharmaceutical industry.

WHO recognizes that global cooperation with a range of partners, including the private sector, is essential to pursue public health objectives today and in the future. Numerous safeguards are in place to manage conflicts of interest or perceived conflicts of interest among members of WHO advisory groups and expert committees. Expert advisers provide a signed declaration of interests to WHO detailing any professional or financial interest that could affect the impartiality of their advice. WHO takes allegations of conflict of interest seriously and is confident of its decision-making independence regarding the pandemic influenza.

Additional allegations that WHO created a ‘fake’ pandemic to bring economic benefit to industry are scientifically wrong and historically incorrect.

Lab analyses showed that this influenza virus was genetically and antigenically very different from other influenza viruses circulating among people

Epidemiological information provided by Mexico, the US and Canada demonstrated person-to-person transmission.

Clinical information, especially from Mexico, indicated this virus also could cause severe disease and death. At the time, those reports did not indicate a pandemic situation, but taken together sent a very strong warning to WHO and other public health authorities to be ready for one.

As the pandemic evolved, clinicians identified a very severe form of primary viral pneumonia, which was rapidly progressive and frequently fatal, that is not part of the disease pattern seen during seasonal influenza. While these cases were relatively rare, they imposed a heavy burden on intensive care units.

Geographical spread was exceptionally rapid.

On 29 April 2009, WHO reported lab confirmed cases in 9 countries.

About 6 weeks later, on 11 June, WHO reported cases in 74 countries and territories in more than two WHO regions. It is this global spread which led WHO to call for increasing phases and finally, to announce that a pandemic was underway.

By 1 July, infections had been confirmed in 120 countries and territories.

The world is going through a real pandemic. The description of it as a fake is wrong and irresponsible. We welcome any legitimate review process that can improve our work.

An explanation of how WHO uses advisory bodies in responding to the influenza pandemic was made publicly available on the WHO web site on 3 December 2009

http://www.who.int/mediacentre/news/statements/2010/h1n1_pandemic_20100122/en/index.html

26 January 2010
Statement by Dr Keiji Fukuda on behalf of WHO at the Council of Europe hearing on pandemic (H1N1) 2009
[Initial paragraph and closing paragraphs. Full text available at the link below]

WHO is pleased to take part in this hearing, and thanks the Council of Europe for taking this initiative. The H1N1 influenza pandemic has created immensely complicated challenges for countries as well as the global community. At the same time, rising to this challenge has created an unprecedented level of global cooperation and coordination among countries in confronting a fast-moving threat in this increasingly linked and globalized world. There is much to learn about how the world can improve its handling of such events and a need to separate fact from rhetoric. Again, we welcome this opportunity….

…Pharmaceutical industry
“Recently, accusations have been made that policies and recommendations of WHO were influenced by the pharmaceutical industry. Providing independent advice to Member States is a very important function of the WHO that is taken seriously. WHO guards against the influence of any improper interests.

Let me state clearly for the record. The influenza pandemic policies and responses recommended and taken by WHO were not improperly influenced by the pharmaceutical industry.

WHO recognizes that global cooperation with a range of partners, including the private sector, is essential for optimally addressing the public health challenges of today and tomorrow. Numerous safeguards are in place to manage conflicts of interest or perceived conflicts of interest among members of WHO advisory groups and expert committees. Expert advisers provide a signed declaration of interests to WHO detailing any professional or financial matters that could affect the impartiality of their advice.     WHO takes allegations of conflicts of interest seriously and is confident of the integrity and scientific validity of its decision-making during this influenza pandemic. An explanation of how WHO uses advisory bodies in responding to the influenza pandemic was made publicly available on the WHO web site on 3 December 2009.

Closing remarks
In closing, I would like to reiterate the most basic point. This current influenza pandemic is a scientifically well-documented event in which the emergence and spread of a new influenza virus has caused an unusual epidemiological pattern of disease throughout the world. This is not an arbitrary matter of word-smithing, definitions or polemics. The labelling of the pandemic as “fake” is to ignore recent history and science and to trivialize the deaths of over 14 000 people and the many additional serious illnesses experienced by others.

As we go forward, the world will continue to face many difficult health challenges. The resources to face them are limited, especially among developing countries, and finding ways to do this better is the shared responsibility of Member States and organizations, such as the Parliamentary Assembly of the Council of Europe, as well as WHO. Thank you.

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

Weekly Epidemiological Record (WER) for 29 January 2009

The Weekly Epidemiological Record (WER) for 29 January 2009, vol. 85, 5 (pp 29–36) includes Yellow fever fact sheet (revised in December 2009), and Global Advisory Committee on Vaccine Safety (GACVS) , 3–4 December 2009:

“GACVS held its twenty-first meeting in Geneva, Switzerland, during 3–4 December 2009.2 The committee reviewed the safety of pandemic A (H1N1) influenza vaccines and the safety profile of a meningococcus A conjugate vaccine that will soon be deployed in sub-Saharan Africa. The committee also discussed the use of bacille Calmette–Guérin (BCG) vaccine in areas with a high prevalence of infection with human immunodeficiency virus (HIV) and reviewed progress with global monitoring of adverse events following immunization (AEFI)…”

http://www.who.int/wer/2010/wer8505.pdf

Health system financing to achieve MDG goals in low-income countries

The Lancet
Jan 30, 2010 Volume 375  Number 9712  Pages 347 – 432
http://www.thelancet.com/journals/lancet/issue/current

Health Policy
Financing of health systems to achieve the health Millennium Development Goals in low-income countries
Robert Fryatt, Anne Mills, Anders Nordstrom

Preview
Concern that underfunded and weak health systems are impeding the achievement of the health Millennium Development Goals in low-income countries led to the creation of a High Level Taskforce on Innovative International Financing for Health Systems in September, 2008. This report summarises the key challenges faced by the Taskforce and its Working Groups. Working Group 1 examined the constraints to scaling up and costs. Challenges included: difficulty in generalisation because of scarce and context-specific health-systems knowledge; no consensus for optimum service-delivery approaches, leading to wide cost differences; no consensus for health benefits; difficulty in quantification of likely efficiency gains; and challenges in quantification of the financing gap owing to uncertainties about financial commitments for health.

Serogroup B meningococcal vaccines—an unfinished story

The Lancet Infectious Disease
Feb 2010  Volume 10  Number 2  Pages 67 – 138
http://www.thelancet.com/journals/laninf/issue/current

Review
Serogroup B meningococcal vaccines—an unfinished story
Manish Sadarangani, Andrew J Pollard

Summary
Most invasive meningococcal disease in developed countries is caused by Neisseria meningitidis with a serogroup B capsule. However, despite availability of vaccines for other serogroups since the 1960s, no serogroup B vaccine exists. In this Review we look at the development of serogroup B vaccines over the past 40 years. Outer membrane vesicle vaccines have been successfully used to control geographically isolated epidemics, but most have not been highly immunogenic in young children or provided broad cross-protection from infections with other strains. Vaccines based on subcapsular antigens have recently produced promising results in early clinical trials, and the disease burden might be substantially reduced over the next few years.

The elusive malaria vaccine: miracle or mirage?

The Lancet Infectious Disease
Feb 2010  Volume 10  Number 2  Pages 67 – 138
http://www.thelancet.com/journals/laninf/issue/current

Book Review
The elusive malaria vaccine: miracle or mirage?
Vasee S Moorthy

The author of The Elusive Malaria Vaccine: Miracle or Mirage? has spent several decades engaged in malaria research. Given the start in May, 2009, of the Phase 3 trial of RTS,S/AS01, the first malaria vaccine that might be registered and that could potentially be available for use in sub-Saharan Africa, this book is timely and provides a very good overview of the prehistory and history of microbiology, parasitology, and vaccinology. Its strengths include illuminating details into the life of figures such as Robert Koch and Louis Pasteur, the seminal malaria work of some of the doyens of the 1960s, 1970s, and 1980s, and outlining preclinical research on the blood stages of non-human plasmodia.

Adherence to cervical screening in the era of HPV vaccination

The Lancet Infectious Disease
Feb 2010  Volume 10  Number 2  Pages 67 – 138
http://www.thelancet.com/journals/laninf/issue/current

Personal View
Adherence to cervical screening in the era of human papillomavirus vaccination: how low is too low?
Chris T Bauch, Meng Li, Gretchen Chapman, Alison P Galvani

Human papillomavirus vaccine prevents infection by two major oncogenic types of the virus. Continued screening is needed in vaccinated women to prevent cancers caused by high-risk types not included in the vaccine. An exaggerated sense of protection from the vaccine could lead to a decline in the rate of screening among vaccinated women, which in principle could lead to an increase in the incidence of cervical cancer. We present a simple mathematical model of vaccination, screening, and disease incidence, including an analysis of the effect of data uncertainties.

GSK opens its database of potential malaria drugs

Nature
Volume 463 Number 7280 pp401-578  28 January 2010
http://www.nature.com/nature/journal/v463/n7280/

Editorial
Learning to share

Abstract [initial paragraphs]
By opening up its database of potential malaria drugs, GlaxoSmithKline has blazed a path that other pharmaceutical companies should follow.

It was heartening to learn last week that British pharmaceutical company GlaxoSmithKline (GSK) is to make publicly available a database containing the structures and pharmacological data for 13,500 possible drugs against malaria. The database, obtained by screening two million compounds in GSK’s library, promises to be a windfall for malaria drug development.

More broadly, the move highlights ongoing efforts by GSK and many other drug companies to re-engage with the ‘neglected’ diseases that predominantly affect poor countries, reversing decades of indifference. Some firms are already making their libraries available to public–private partnerships such as the Medicines for Malaria Venture (MMV) and the Global Alliance for TB Drug Development. This month’s announcement, however, marks the first time that any drug-maker has made public domain a substantial database of possible drug leads.

The move advances the pharmaceutical industry’s slow but steady shift towards more open sharing of data. At least for early-stage, precompetitive research, drug companies are finding it useful to lower the firewalls around their intellectual property and pool their resources. Making data public brings fresh eyes and minds to the problem, and has the potential to accelerate the discovery process….

http://www.nature.com/nature/journal/v463/n7280/full/463401a.html

NEJM: special focus on rotavirus vaccine trials in Mexico and Africa

New England Journal of Medicine
Volume 362 — January 28, 2010 — Number 4
http://content.nejm.org/current.shtml

[Editor’s Note: Please see the joint GAVI/PATH media release on this material above. NEJM is providing the first three articles below as free full text]

Editorial
Rotavirus Vaccine — A Powerful Tool to Combat Deaths from Diarrhea
M. Santosham

Original Articles
Effect of Human Rotavirus Vaccine on Severe Diarrhea in African Infants
S. A. Madhi and Others

Effect of Rotavirus Vaccination on Death from Childhood Diarrhea in Mexico
V. Richardson and Others

Brief Report: Vaccine-Acquired Rotavirus in Infants with Severe Combined Immunodeficiency
N. C. Patel and Others

A Call for Action on Health Data from Eight Global Health Agencies

PLoS Medicine
(Accessed 24 January 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

Meeting the Demand for Results and Accountability: A Call for Action on Health Data from Eight Global Health Agencies
Margaret Chan, Michel Kazatchkine, Julian Lob-Levyt, Thoraya Obaid, Julian Schweizer, Michel Sidibe, Ann Veneman, Tadataka Yamada Essay, published 26 Jan 2010
doi:10.1371/journal.pmed.1000223

[Initial paragraph and selected text]
“Recent substantial increases in international attention to health have been accompanied by demands for statistics that accurately track health progress and performance, evaluate the impact of health programs and policies, and increase accountability at country and global levels. The use of results-based financing mechanisms by major global donors has created further demand for timely and reliable data for decision-making. In addition, there is increasing country demand for data in the context of health sector strategic plans, including in countries that have established International Health Partnership (IHP+) compacts. In spite of recognized efforts by programs and countries, the ability to respond to this demand is constrained by limited data availability, quality, and use. Many developing countries have limitations that hamper the production of data of sufficient quality and timeliness to permit regular tracking of progress made in scaling up and strengthening health systems. Data gaps span across the range of input, output, outcome, and impact indicators. New ways of working and a more systematic approach by all partners are needed to better monitor and evaluate progress and performance. We believe that this global public good is a necessary foundation to improve health investments and programs and accelerate progress towards the Millennium Development Goals (MDGs) and other major international health goals…”

Eight agencies working in global health – Bill & Melinda Gates Foundation; GAVI; Global Fund to Fight AIDS, Tuberculosis & Malaria; UNAIDS; UNFPA; UNICEF; World Bank, and the World Health Organization – “…agree that it is critical to strengthen the five key data sources and capacity for analysis, synthesis, validation, and use of health data in countries. This should enable countries to better monitor and evaluate their own progress and performance and, secondarily, allow them to respond to the increased emphasis on results and accountability. The eight agencies propose four global actions to support these country goals:”

– Increase Levels and Efficiency of Investments in Health Information
– Develop a Common Data Architecture
– Strengthen Performance Monitoring and Evaluation
– Increase Data Access and Use

WHO: Pandemic (H1N1) 2009 – update 84 Weekly 22 January 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 84
Weekly update
22 January 2010

As of 17 January 2010, worldwide more than 209 countries and overseas territories or communities have reported laboratory confirmed cases of pandemic influenza H1N1 2009, including at least 14142 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 overall situation in largely unchanged since last week. The most intense transmission of pandemic influenza virus continues to occur in North Africa, South Asia, and in limited areas of Eastern Europe. Overall pandemic influenza activity in the temperate northern hemisphere peaked between late October and late November 2009 and has continued to decline since…

More at: http://www.who.int/csr/don/2010_01_22/en/index.html

WHO Director-General Report: Progress in public health during the previous decade, major challenges ahead

WHO published the report by the Director-General to the Executive Board at its 126th session in Geneva, Switzerland on 18 January 2010. We excerpt a portion of the speech which addresses immunization issues and the H1Ni pandemic below. Dr. Chan’s full speech text is available at the link below and is titled:

Progress in public health during the previous decade and major challenges ahead

“…We are at the start of the second decade of the 21st century. And we are just five years away from 2015. A report on progress towards the health-related Millennium Development Goals is on your agenda.

Several other reports describe activities that are contributing to achievement of the Goals or point to specific challenges that need to be addressed. As these reports show, progress in individual countries tends to be greatest in the better-off populations. We are still not doing enough to improve life for the most vulnerable and the poorest of the poor.

At the international level, the picture is mixed, and the African region must continue to be a focus of particular concern. But there are many bright and motivating examples of success everywhere.

Some of these examples come from big-picture trends. Towards the end of last year, WHO and other agencies issued substantial reports on trends for HIV/AIDS, tuberculosis, malaria, vaccines and immunization, and the health of children.

You will be familiar with the positive trends in all these areas. The progress is sometimes fragile, threatened by factors ranging from drug resistance to uncertain funding for the future. But the trends are definitely positive. While optimism about the malaria situation must be cautious, this is the first time, in decades, that we are getting some good news. This, too, is progress.

We can all be proud that the drive to reach international health commitments has never faltered, even at a time of multiple global crises on multiple fronts.

Apart from these big-picture trends, reports prepared for this session cover many specific indicators of progress. Vitamin A supplementation has been implemented as a life-saving measure in 66 of 68 countries with a high burden of child deaths. Since 2000, measles deaths have dropped by 78%. As the report on this item concludes, measles eradication is achievable. If we want to do this, we can.

By 2007, 98% of reported tuberculosis cases were being diagnosed and treated in DOTS programmes. WHO Child Growth Standards have been adopted by more than 100 countries. This, in turn, has led to increased investment in programmes to reduce undernutrition, but also to tackle the growing problem of childhood obesity. As I have said on many occasions, what gets measured gets done.

Ten years into this new century, we are seeing signs that aid for health development can bring solid results. Equally important, in the drive to reach a limited number of time-bound health goals, fundamental problems are being uncovered, and solutions are being found that benefit public health across the board.

We are making progress, as the reports before you show. We need to keep on setting our sights higher, aiming to do more, for more and more people.

Ladies and gentlemen,

For me, the best health news of the previous decade is the fact that the long overdue influenza pandemic has been so moderate in its impact. Had the pandemic taken another course, the agenda for this session would have looked very different. Had the virus mutated to a more virulent form, we would not be talking about forging ahead. We would be standing still or dealing with serious setbacks.

We have been fortunate since the very emergence of the new H1N1 virus, and have remained fortunate up to now. The virus initially spread in countries with good surveillance systems. The honesty and speed of early reporting set the standard for the international response.

The virus did not mutate to a more virulent form. Resistance to oseltamivir did not become widespread. The vaccine proved safe and a close match with circulating virus. Things could have gone wrong in any of these areas.

We were fortunate in other ways. This is the first pandemic to occur since the revolution in communications and information technologies. For the first time in history, the international community could watch a pandemic unfold, and chart its evolution, in real time.

The amount of data that have been collected since April of last year, and the number of research reports and studies that have been published, have been remarkable. This quick collection of information has allowed WHO to issue treatment guidelines, track the epidemiology, and keep a close watch for mutations, including those that confer resistance to antiviral drugs.

When the history of this pandemic is written, I believe that the speed of actions taken by governments to protect their populations will earn the highest marks. Though the burden on emergency rooms and intensive care units has been heavy, nearly all health systems have coped well. Let me pay tribute to all the health care workers who have worked tirelessly to care for patients.

The early standard of rapid and transparent reporting was upheld, and the sharing of information, diagnostic support, test kits, and viruses has been commendably generous. To date, well over 23,000 viruses and other specimens have been submitted to WHO network laboratories for analysis.

During any public health emergency, health officials must make urgent, often far-reaching decisions in an atmosphere of considerable scientific uncertainty. Given our duty to safeguard public health, the tendency of officials facing such a situation is nearly always to err on the side of caution. I believe we would all rather see a moderate pandemic with ample supplies of vaccine than a severe pandemic with inadequate supplies of vaccine.

In some countries in the northern hemisphere with good surveillance systems, the pandemic appears to be easing. The worst may be over. But it would be unwise for anyone to reach firm conclusions before April, when the normal influenza season usually ends. There is still quite a lot of winter left.

In addition, we cannot predict what will happen between now and later in the year, when the southern hemisphere enters its influenza season and the virus becomes more transmissible.

Data for most parts of Africa are sparse. We are concerned that some countries in the western part of the continent remain susceptible to intense waves of transmission. We do not know for sure, but we are keeping a careful watch.

Population susceptibility to infection by a new virus drives the dynamics of an influenza pandemic. This is the critical question. Are there enough susceptible people left to sustain further waves of community-wide transmission? At present, we simply do not have enough data to answer this question with certainty. Studies are, however, under way.

We can estimate how much immunity has been conferred through vaccination. But knowing how much natural immunity has been acquired through infection is more difficult, especially given the very mild nature of illness in the vast majority of patients. Some infections produced no symptoms, and quick surveys of influenza-like illness will not capture these infections.

In short: I believe that what most countries are doing, that is, urging their populations to get vaccinated, is the prudent public health approach. Each country has to assess its own epidemiological situation and the needs and concerns of its citizens. For developing countries concerned about their lack of access to pandemic vaccines, WHO is ramping up its donation programme.

This pandemic has also been the first major test of the revised International Health Regulations. They have given the world an orderly, rules-based way to respond, and this has been an asset. With few exceptions, social and economic disruptions have been far less significant than feared. Another strength of the International Health Regulations is its system of checks and balances. They ensure that no one, myself included, has unfettered power.

Although the virus has not yet delivered any devastating surprises, we have seen some surprises on other fronts. We anticipated problems in producing enough vaccine fast enough, and this did indeed happen. But we did not anticipate that people would decide not to be vaccinated.

I mentioned the revolution in communications and information technologies. In today’s world, people can draw on a vast range of information sources. People make their own decisions about what information to trust, and base their actions on those decisions.

The days when health officials could issue advice, based on the very best medical and scientific data, and expect populations to comply, may be fading. It may no longer be sufficient to say that a vaccine is safe, or testing complied with all regulatory standards, or a risk is real.

In my view, this is a new communications challenge that we may need to address. As the items on your agenda show, persuading people to adopt healthy behaviours is one of the biggest challenges in public health.

In terms of managing public perceptions, part of the problem arises from the big difference between what was expected, after watching the highly lethal H5N1 virus for so long, and what fortunately happened. An event similar to the 1918 pandemic was feared, when what actually happened is probably closer to the 1957 or 1968 pandemics.

Let me introduce a word of caution. Reliable estimates of the number of deaths and the mortality rate during the current pandemic will not be possible until one to two years after the pandemic has ended.

Let me reassure you on a final point. This has been the most closely watched and carefully scrutinized pandemic in history. We will have a wealth of new knowledge as a result. It is natural that every decision or action that shaped the response will likewise be closely and carefully scrutinized.

WHO can withstand this scrutiny…”

http://www.who.int/dg/speeches/2010/executive_board_126_20100118/en/index.html

PATH welcomes GSK announcements on RTS,S malaria vaccine candidate

PATH said it welcomed announcements made by GlaxoSmithKline (GSK) CEO Andrew Witty concerning sustainable pricing and vaccine donations for RTS,S malaria vaccine candidate, currently in a large, late-stage clinical trial that is supported by the PATH Malaria Vaccine Initiative (MVI). Christian Loucq, director of MVI, said, “The announcements…are positive steps in the long pathway from discovery to delivery of RTS,S. These commitments help to illustrate the potential of product development partnerships—like the one between MVI and GSK Biologicals—for meeting the health needs of people in developing countries.”

In a speech at the Council on Foreign Relations, Mr. Witty “committed to setting a price for RTS,S that would cover GSK’s costs and generate a small return that would be re-invested in research and development for next-generation malaria vaccines and vaccines against other neglected diseases. GSK also committed to donating at least 12.5 million doses of RTS,S (if approved for use) to PATH.”

PATH said that GSK Biologicals, the vaccine division of GSK, and PATH signed a collaboration agreement in 2001 to pursue the pediatric clinical development of RTS,S in Africa. To advance the development program, African research centers in five countries, and collaborating institutions, joined the partnership. Centers in two additional African countries have joined for the Phase 3 trial. Together, these partners comprise the Clinical Trials Partnership Committee and lead the clinical development of RTS,S, PATH said.

Christopher J. Elias, president and CEO of PATH, commented, “Like other PATH programs, MVI’s mission goes beyond development of a health intervention to ensuring that it is available at the lowest price possible and readily accessible to all who need it. In light of the commitments made today and as we get closer to the day that the RTS,S vaccine candidate—if all goes well—could be available for use, we look forward to working with GSK, as well as other global partners, to ensure that malaria vaccines are available to the children that need them most.”

20 January 2010. http://www.path.org/news/an100120-MVI.php

IVI announces the licensure of oral cholera vaccine

IVI announced the licensure of Shanchol, an oral cholera vaccine, in India in 2009, noting that “efforts to accelerate the global use of new generation cholera vaccines gained significant momentum with the licensure. IVI said its scientists developed this vaccine, with funding from the Bill & Melinda Gates Foundation, “by significantly modifying a vaccine used and produced only in Vietnam so that it meets international Good Manufacturing Practice (GMP) standards and WHO production guidelines.”

http://www.ivi.org/popup/files/ocv_article.pdf

Weekly Epidemiological Record (WER) for 22 January 2009

The Weekly Epidemiological Record (WER) for 22 January 2009, vol. 85, 4 (pp 21–28) includes: Preliminary review of D222G amino acid substitution in the haemagglutinin of pandemic influenza A (H1N1) 2009 viruses; African Programme for Onchocerciasis Control – report of the sixth meeting of national task forces, October 2009

http://www.who.int/wer/2010/wer8504.pdf