New England Journal of Medicine
June 21, 2012  Vol. 366 No. 25
http://content.nejm.org/current.shtml

Perspective
200th Anniversary Article: The Burden of Disease and the Changing Task of Medicine
D.S. Jones, S.H. Podolsky, and J.A. Greene

Extract
At first glance, the inaugural 1812 issue of the New England Journal of Medicine and Surgery, and the Collateral Branches of Science seems reassuringly familiar: a review of angina pectoris, articles on infant diarrhea and burns. The apparent similarity to today’s Journal, however, obscures a fundamental discontinuity (1812a, b, c; see Historical Journal Articles Cited). Disease has changed since 1812. People have different diseases, doctors hold different ideas about those diseases, and diseases carry different meanings in society. To understand the material and conceptual transformations of disease over the past 200 years, one must explore the incontrovertibly social nature of disease.

Disease is always generated, experienced, defined, and ameliorated within a social world. Patients need notions of disease that explicate their suffering. Doctors need theories of etiology and pathophysiology that account for the burden of disease and inform therapeutic practice. Policymakers need realistic understandings of determinants of disease and medicine’s impact in order to design systems that foster health. The history of disease offers crucial insights into the intersections of these interests and the ways they can inform medical practice and health policy…

PLoS Medicine
(Accessed 23 June 2012)
http://www.plosmedicine.org/article/browse.action?field=date

Comparative Performance of Private and Public Healthcare Systems in Low- and Middle-Income Countries: A Systematic Review
Sanjay Basu, Jason Andrews, Sandeep Kishore, Rajesh Panjabi, David Stuckler
Research Article, published 19 Jun 2012
doi:10.1371/journal.pmed.1001244

Abstract 
Introduction
Private sector healthcare delivery in low- and middle-income countries is sometimes argued to be more efficient, accountable, and sustainable than public sector delivery. Conversely, the public sector is often regarded as providing more equitable and evidence-based care. We performed a systematic review of research studies investigating the performance of private and public sector delivery in low- and middle-income countries.

Methods and Findings
Peer-reviewed studies including case studies, meta-analyses, reviews, and case-control analyses, as well as reports published by non-governmental organizations and international agencies, were systematically collected through large database searches, filtered through methodological inclusion criteria, and organized into six World Health Organization health system themes: accessibility and responsiveness; quality; outcomes; accountability, transparency, and regulation; fairness and equity; and efficiency. Of 1,178 potentially relevant unique citations, data were obtained from 102 articles describing studies conducted in low- and middle-income countries. Comparative cohort and cross-sectional studies suggested that providers in the private sector more frequently violated medical standards of practice and had poorer patient outcomes, but had greater reported timeliness and hospitality to patients. Reported efficiency tended to be lower in the private than in the public sector, resulting in part from perverse incentives for unnecessary testing and treatment. Public sector services experienced more limited availability of equipment, medications, and trained healthcare workers. When the definition of “private sector” included unlicensed and uncertified providers such as drug shop owners, most patients appeared to access care in the private sector; however, when unlicensed healthcare providers were excluded from the analysis, the majority of people accessed public sector care. “Competitive dynamics” for funding appeared between the two sectors, such that public funds and personnel were redirected to private sector development, followed by reductions in public sector service budgets and staff.

Conclusions
Studies evaluated in this systematic review do not support the claim that the private sector is usually more efficient, accountable, or medically effective than the public sector; however, the public sector appears frequently to lack timeliness and hospitality towards patients.

Science        
22 June 2012 vol 336, issue 6088, pages 1473-1608
http://www.sciencemag.org/current.dtl

Special Issue: H5N1
Introduction to Special Issue
Bruce Alberts, Editor-in-Chief of Science
Science 22 June 2012: 152

The publication in this issue of the research paper Airborne Transmission of Influenza A/H5N1 Virus Between Ferrets, plus its newer companion The Potential for Respiratory Droplet–Transmissible A/H5N1 Influenza Virus to Evolve in a Mammalian Host, marks the end of more than 8 months of widely reported controversy over whether some of the data now freely accessible should be withheld in the public interest (see http://scim.ag/H5N1_Flu for a compilation of News and Commentary recently published in Science). As a result, people worldwide are now much more aware of the potential threat that this virus, commonly known as “bird flu,” poses to humanity. And the open publication of new data concerning the potential of H5N1 to convert directly to a form that can be transferred through the air between ferrets will motivate many more policy-makers and scientists to work to reduce the likelihood that this virus will evolve to cause a pandemic. Breakthroughs in science often occur when a scientist with a unique perspective combines prior knowledge in novel ways to create new knowledge, and the publication of the two research Reports in this issue will hopefully help to stimulate the innovation needed, perhaps from unsuspected sources, to make the world safer.

As described in News and Commentary pieces in this special section, the prolonged controversy has also provided a “stress test” of the systems that had been established to enable the biological sciences to deal with “dual-use research of concern” (DURC): biological research with legitimate scientific purposes that may be misused to pose a biologic threat to public health and/or national security. One centerpiece of this system is the U.S. National Science Advisory Board for Biosecurity (NSABB). Science strongly supports the NSABB mechanism, which clearly needs to be supplemented and further strengthened to deal with the inevitable future cases of publication of dual-use research, both before and after their submission to journals. Still missing is a comprehensive international system for assessing and handling DURC—one that provides access, for those with a need to know, to any information deemed not to be freely publishable.

If fields subject to DURC are to attract the outstanding young scientists required to address problems such as those posed by H5N1, the appropriate experts may need to define in advance the most promising research strategies and, acting in concert with security experts, agree on responsible ways to address them. It is our hope that the thoughtful Commentaries, News, and research Reports in this special issue will help to jump-start intensive efforts along these lines  Podcast Interview

Policy Forum
Benefits and Risks of Influenza Research: Lessons Learned
Anthony S. Fauci and Francis S. Collins
Science 22 June 2012: 1522-1523.
Abstract

Implementing the New U.S. Dual-Use Policy
Carrie D. Wolinetz
Science 22 June 2012: 1525-1527.
Abstract

Evolution, Safety, and Highly Pathogenic Influenza Viruses
Marc Lipsitch, Joshua B. Plotkin, Lone Simonsen, and Barry Bloom
Science 22 June 2012: 1529-1531.
Abstract

Influenza: Options to Improve Pandemic Preparation
Rino Rappuoli and Philip R. Dormitzer
Science 22 June 2012: 1531-1533.
Abstract

Perspectives
Regulating the Boundaries of Dual-Use Research
Mark S. Frankel
Science 22 June 2012: 1523-1525.
Abstract

Securing Medical Research: A Cybersecurity Point of View
Bruce Schneier
Science 22 June 2012: 1527-1529.
Abstract

Reports
Airborne Transmission of Influenza A/H5N1 Virus Between Ferrets
Sander Herfst, Eefje J. A. Schrauwen, Martin Linster, Salin Chutinimitkul, Emmie de Wit, Vincent J. Munster, Erin M. Sorrell, Theo M. Bestebroer, David F. Burke, Derek J. Smith, Guus F. Rimmelzwaan, Albert D. M. E. Osterhaus, and Ron A. M. Fouchier
Science 22 June 2012: 1534-1541.

Avian flu can acquire the capacity for airborne transmission between mammals without recombination in an intermediate host.
Abstract

The Potential for Respiratory Droplet–Transmissible A/H5N1 Influenza Virus to Evolve in a Mammalian Host
Colin A. Russell, Judith M. Fonville, André E. X. Brown, David F. Burke, David L. Smith, Sarah L. James, Sander Herfst, Sander van Boheemen, Martin Linster, Eefje J. Schrauwen, Leah Katzelnick, Ana Mosterín, Thijs Kuiken, Eileen Maher, Gabriele Neumann, Albert D. M. E. Osterhaus, Yoshihiro Kawaoka, Ron A. M. Fouchier, and Derek J. Smith
Science 22 June 2012: 1541-1547.

Some natural influenza viruses need only three amino acid substitutions to acquire airborne transmissibility between mammals.
Abstract

Tropical Medicine & International Health
July 2012  Volume 17, Issue 7  Pages 795–933
http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1365-3156/currentissue

NTDs
Nationwide integrated mapping of three neglected tropical diseases in Togo: countrywide implementation of a novel approach (pages 896–903)
A. M. Dorkenoo, R. N. Bronzan, K. D. Ayena, G. Anthony, Y. M. Agbo, K. S. E. Sognikin, K. S. Dogbe, A. Amza, Y. Sodahlon and E. Mathieu
Article first published online: 18 MAY 2012 | DOI: 10.1111/j.1365-3156.2012.03004.x

Abstract
Objective  To conduct a nationwide integrated neglected tropical disease (NTD) prevalence survey to define the need for public health interventions using an innovative mapping protocol.

Methods  Two villages were selected in every peripheral health unit in endemic districts: 29 districts for schistosomiasis and STH, 15 of them for trachoma. In each village, 15 children aged 6–9 years at a randomly selected school were tested. An additional convenience sample of 35 children aged 1–5 years underwent an eye examination for trachoma. This integrated mapping was followed by a 20-cluster trachoma survey in each district that surpassed the WHO-defined threshold of 10% prevalence of trachomatous inflammation-follicular (TF).

Results  A total of 1096 villages were surveyed in <6 weeks. The district prevalence of schistosomiasis ranged from 2 to 49% and of STH from 5 to 70%, with prevalence at the village level ranging from 0 to 100% for both diseases. Two districts passed the threshold of 10% for active trachoma, but the cluster survey indicated this was because of misclassification bias and that the real prevalence was <1%.

Conclusion  Results of this mapping were used by the MoH and partners to plan integrated mass drug administration (MDA). Mass drug administration for trachoma was not implemented as no district passed the threshold requiring public health intervention.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 30, Issue 33 pp. 4897-5058 (13 July 2012)

Brief Communications
Development and technology transfer of Haemophilus influenzae type b conjugate vaccines for developing countries
Pages 4897-4906
Michel Beurret, Ahd Hamidi, Hans Kreeftenberg

Abstract
This paper describes the development of a Haemophilus influenzae type b (Hib) conjugate vaccine at the National Institute for Public Health and the Environment/Netherlands Vaccine Institute (RIVM/NVI, Bilthoven, The Netherlands), and the subsequent transfer of its production process to manufacturers in developing countries. In 1998, at the outset of the project, the majority of the world’s children were not immunized against Hib because of the high price and limited supply of the conjugate vaccines, due partly to the fact that local manufacturers in developing countries did not master the Hib conjugate production technology. To address this problem, the RIVM/NVI has developed a robust Hib conjugate vaccine production process based on a proven model, and transferred this technology to several partners in India, Indonesia, Korea and China. As a result, emerging manufacturers in developing countries acquired modern technologies previously unavailable to them. This has in turn facilitated their approach to producing other conjugate vaccines. As an additional spin-off from the project, a World Health Organization (WHO) Hib quality control (QC) course was designed and conducted at the RIVM/NVI, resulting in an increased regulatory capacity for conjugate vaccines in developing countries at the National Regulatory Authority (NRA) level. For the local populations, this has translated into an increased and sustainable supply of affordable Hib conjugate-containing combination vaccines. During the course of this project, developing countries have demonstrated their ability to produce large quantities of high-quality modern vaccines after a successful transfer of the technology.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 30, Issue 33 pp. 4897-5058 (13 July 2012)

Reviews
New technologies for new influenza vaccines
Review Article
Pages 4927-4933
Alan Shaw

Abstract
The currently available influenza vaccines were developed in the 1930s through the 1960s using technologies that were state-of-the art for the times. Decades of advancement in virology and immunology have provided the tools for making better vaccines against influenza. We now have the means to make vaccines that address some of the shortcomings of the original products, in particular performance in the elderly.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 30, Issue 33 pp. 4897-5058 (13 July 2012)

Regular Papers
Human papillomavirus vaccination and sexual behaviour: Cross-sectional and longitudinal surveys conducted in England
Original Research Article
Pages 4939-4944
Alice S. Forster, Laura A.V. Marlow, Judith Stephenson, Jane Wardle, Jo Waller

Abstract
Objective
To examine whether HPV vaccination influences sexual behaviour in adolescent girls, either by giving them a ‘green light’ to have sex, or because perceived protection afforded by the vaccine permits compensatory risky sexual behaviour.

Design
Cross-sectional and longitudinal surveys.

Setting
Seven English schools.

Main outcome measures
Self-reported sexual behaviour.

Participants
The cross-sectional survey included 1053 girls (mean age 17.1 years) who had (n = 433 recruited in March 2010) or had not (n = 620 recruited in March 2009) been offered the HPV vaccine. The longitudinal survey included 407 girls (mean age 17.5 years) who had been offered HPV vaccination and had either received at least one dose (n = 148) or had not received any doses (n = 259).

Results
In the cross-sectional survey, the group of girls who had been offered the HPV vaccine were no more likely to be sexually active than the group of girls who had not been offered the HPV vaccine. In the longitudinal survey, the vaccinated group were no more likely to have changed their condom use or increased their total number of sexual partners than the unvaccinated group.

Conclusions
Neither being offered the HPV vaccine nor receiving it affected sexual behaviour

Vaccine
http://www.sciencedirect.com/science/journal/0264410X

Volume 30, Issue 33 pp. 4897-5058 (13 July 2012)
Febrile events including convulsions following the administration of four brands of 2010 and 2011 inactivated seasonal influenza vaccine in NZ infants and children: The importance of routine active safety surveillance
Original Research Article
Pages 4945-4952
Helen Petousis-Harris, Tracey Poole, Nikki Turner, Gary Reynolds

Abstract
Objective
To evaluate and compare rates of febrile events, including febrile convulsion, following immunisation with four brands of inactivated 2010 and 2011 influenza vaccine in NZ infants and children.

Design
Retrospective telephone surveys of parents of infants and children who received at least one dose of the vaccines of interest.

Setting
184 NZ General Practices who received the vaccines of interest.

Participants
Recipients of 4088 doses of trivalent inactivated vaccines Fluvax®, Vaxigrip®, Influvac® and Fluarix® and/or monovalent Celvapan. Vaccinees were identified via the electronic Practice Management System and contacted consecutively.

Main outcome measures
Primary outcome was febrile convulsive seizure. Secondary outcomes were presence of fever plus other organ system specific symptoms.

Results
The parental response rate was 99%. Of 4088 doses given, 865 were Fluvax®, 2571 Vaxigrip®, 204 Influvac®, 438 Fluarix® and 10 Celvapan. Three febrile convulsions followed Fluvax®, a rate of 35 per 10,000 doses. No convulsions occurred following any dose of the other vaccines. There were nine febrile events that included rigors, all following Fluvax®. Fever occurred significantly more frequently following administration of Fluvax® compared with the other brands of vaccines (p < 0.0001) and Fluvax recipients were more likely to seek medical attention. Influvac® also had higher rates of febrile reactions (OR 0.54, 0.36–0.81) than the other two brands Vaxigrip® (OR 0.21, 0.16–0.27) and Fluarix® (OR 0.10, 0.05–0.20). After multivariable analysis vaccine, European ethnicity and second dose of vaccine were significantly associated with reporting of fever within 24 h of vaccination.

Conclusions
Influenza vaccines have different rates of reactogenicity in children which varies between ethnic groups. High rates of febrile convulsions and reactions in children receiving Fluvax® and to a lesser extent the higher fever rates in those receiving Influvac® compared with the other two brands of influenza vaccines in this study suggests that reactogenicity profiles need to be considered prior to national policy advice each season. The risk-benefit profile in children might not be equally favourable for all licensed paediatric influenza vaccines. More attention needs to be given to comparative research for all trivalent seasonal vaccines, and with all strain changes.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 30, Issue 33 pp. 4897-5058 (13 July 2012)

Capacity for a global vaccine safety system: The perspective of national regulatory authorities
Original Research Article
Pages 4953-4959
Janice E. Graham, Alexander Borda-Rodriguez, Farah Huzair, Emily Zinck

Abstract
Confidence in vaccine safety is critical to national immunization strategies and to global public health. To meet the Millenium Development Goals, and buoyed by the success of new vaccines produced in developing countries, the World Health Organization has been developing a strategy to establish a global system for effective vaccine pharmacovigilance in all countries. This paper reports the findings of a qualitative survey, conducted for the WHO Global Vaccine Safety Blueprint project, on the perspectives of national regulatory authorities responsible for vaccine safety in manufacturing and procuring countries. Capacity and capabilities of detecting, reporting and responding to adverse events following immunization (AEFI), and expectations of minimum capacity necessary for vaccine pharmacovigilance were explored. Key barriers to establishing a functional national vaccine safety system in developing countries were identified. The lack of infrastructure, information technology for stable communications and data exchange, and human resources affect vaccine safety monitoring in developing countries. A persistent “fear of reporting” in several low and middle income countries due to insufficient training and insecure employment underlies a perceived lack of political will in many governments for vaccine pharmacovigilance. Regulators recommended standardized and internationally harmonized safety reporting forms, improved surveillance mechanisms, and a global network for access and exchange of safety data independent of industry.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 30, Issue 33 pp. 4897-5058 (13 July 2012)

Increasing adolescent immunization by webinar: A brief provider intervention at federally qualified health centers
Original Research Article
Pages 4960-4963
Jennifer L. Moss, Paul L. Reiter, Amanda Dayton, Noel T. Brewer

Abstract
Objective
To evaluate a brief intervention to increase provision of adolescent vaccines at health centers that reach the medically underserved.

Method
In April 2010, clinical coordinators from 17 federally qualified health centers (serving 7827 patients ages 12–17) participated in a competition to increase uptake of recommended adolescent vaccines: tetanus, diphtheria, and pertussis booster; meningococcal conjugate; and human papillomavirus. Vaccination coordinators attended a webinar that reviewed provider-based changes recommended by the CDC’s Assessment, Feedback, Incentives, and eXchanges (AFIX) program and received weekly follow-up emails. Data on vaccine uptake came from the North Carolina Immunization Registry.

Results
Uptake of targeted adolescent vaccines increased during the one-month intervention period by about 1–2% (all p < .05). These small but reliable increases were greater than those observed for non-targeted vaccines (measles, mumps, and rubella; hepatitis B; and varicella).

Conclusion
This AFIX webinar led to small increases in provision of targeted adolescent vaccines over a one-month period. Similar, sustainable programs at healthcare facilities, including federally qualified health centers that function as safety net providers for medically underserved populations could help reach populations with great need.

Vaccine
http://www.sciencedirect.com/science/journal/0264410X
Volume 30, Issue 33 pp. 4897-5058 (13 July 2012)

School-located influenza immunization programs: Factors important to parents and students
Original Research Article
Pages 4993-4999
Amy B. Middleman, Mary B. Short, Jean S. Doak

Abstract
Purpose
To describe both parent and student perspectives on the importance of various programmatic factors when deciding to participate in a school-located immunizations program (SLIP) for influenza vaccine.

Method
Questionnaires were distributed to middle- and high-school students and their parents; the document assessed demographic data, influenza vaccination history, and the importance of various factors in their decision to participate in a potential SLIP for influenza vaccine. Factor analysis created six primary factors of importance related to programming: (1) safety/trust; (2) outbreaks (representing imminent threat of disease, an environmental factor associated with program timing); (3) issues of site implementation; (4) public health benefits; (5) record-keeping; (6) medical/emotional support.

Results
Participants included 621 students and 579 parents; 566 student/parent dyads were included. Most respondents were female, felt it is important to be immunized against the flu, and received the influenza vaccine in the past. Fewer than 50% had received the intranasal vaccine. More parents (67%) than students (46%) expressed a general willingness to consent to utilizing a SLIP. The programmatic factors associated with public health were second only to safety/trust factors as the most important to parents and students when considering participation in a SLIP. Demographic variables were found to be associated with the importance ratings of program factors associated with participation in a SLIP.

Conclusions
When considering possible participation in SLIPs, parents and students consider programmatic factors associated with safety/trust and public health benefits to be of the greatest importance. Further study will be needed to develop effective and culturally sensitive messaging that targets and emphasizes these factors to potentially increase participation in SLIPS.

Vaccine
Volume 30, Issue 32 pp. 4709-4896 (6 July 2012)

Meeting Reports
Research priorities for global measles and rubella control and eradication
Pages 4709-4716
James L. Goodson, Susan Y. Chu, Paul A. Rota, William J. Moss, David A. Featherstone, Maya Vijayaraghavan, Kimberly M. Thompson, Rebecca Martin, Susan Reef, Peter M. Strebel

Abstract
In 2010, an expert advisory panel convened by the World Health Organization to assess the feasibility of measles eradication concluded that (1) measles can and should be eradicated, (2) eradication by 2020 is feasible if measurable progress is made toward existing 2015 measles mortality reduction targets, (3) measles eradication activities should occur in the context of strengthening routine immunization services, and (4) measles eradication activities should be used to accelerate control and elimination of rubella and congenital rubella syndrome (CRS). The expert advisory panel also emphasized the critical role of research and innovation in any disease control or eradication program. In May 2011, a meeting was held to identify and prioritize research priorities to support measles and rubella/CRS control and potential eradication activities. This summary presents the questions identified by the meeting participants and their relative priority within the following categories: (1) measles epidemiology, (2) vaccine development and alternative vaccine delivery, (3) surveillance and laboratory methods, (4) immunization strategies, (5) mathematical modeling and economic analyses, and (6) rubella/CRS control and elimination.

Vaccine
Volume 30, Issue 32 pp. 4709-4896 (6 July 2012)

Pneumococcal vaccines WHO position paper – 2012 – Recommendations
Pages 4717-4718
WHO Publication

Abstract
This article presents the World Health Organization (WHO) recommendations on the use of pneumococcal vaccines excerpted from the Pneumococcal vaccines WHO position paper – 2012 recently published in the Weekly Epidemiological Record . The current document replaces the position paper on the use 7-valent pneumococcal conjugate vaccine published in 2007 . Incorporating the most recent developments in the field of pneumococcal vaccines this position paper focuses on the currently available 10-valent and 13-valent conjugate vaccines and their introduction and use in national immunization programmes. It also deals with the 23-valent polysaccharide vaccine, though in less detail than provided in the April 2008 position paper which remains valid . Footnotes to this paper provide a number of core references including references to grading tables that assess the quality of scientific evidence for a few key conclusions.

In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO’s current position on the use of vaccines worldwide. This paper reflects the recommendations of the WHO’s Strategic Advisory Group of Experts (SAGE) on immunization. Recommendations on the use of pneumococcal vaccines were discussed by SAGE at its meetings in November 2006 (conjugate vaccine) and April 2008 (polysaccharide vaccine) and most recently in November 2011.

Vaccine
Volume 30, Issue 32 pp. 4709-4896 (6 July 2012)

Reviews
Factors influencing pandemic influenza vaccination of healthcare workers—A systematic review
Review Article
Pages 4733-4743
Chatura Prematunge, Kimberly Corace, Anne McCarthy, Rama C. Nair, Renee Pugsley, Gary Garber

Abstract
Introduction
Maintaining the health and availability of Health care workers (HCW) is an essential component of pandemic preparedness. A key to protecting HCW during the H1N1 pandemic was influenza vaccination. Numerous researchers have reported on factors influencing H1N1 vaccination behaviour in various HCW groups. This systematic review aims to inform future influenza vaccine interventions and pandemic planning processes via the examination of literature in HCW H1N1 vaccination, in order to identify factors that are (1) unique to pandemic influenza vaccination and (2) similar to seasonal influenza vaccination research.

Methods
We conducted a comprehensive review of literature (MEDLINE, PubMed, EMBASE, PsycINFO, CINHAL, AMED, Cochrane Library, ProQuest, and grey literature sources) published between January 2005 and December 2011 to identify studies relevant to HCW pH1N1 vaccine uptake/refusal.

Results
20 publications sampling HCW from different geographic regions are included in this review. H1N1 vaccine coverage was found to be variable (9–92%) across HCW populations, and self-reported vaccine status was the most frequently utilized predictor of pandemic vaccination. HCW were likely to accept the H1N1 vaccine if they perceived, (1) the H1N1 vaccine to be safe, (2) H1N1 vaccination to be effective in preventing infection to self and others (i.e. loved ones, co-workers and patients), and (3) H1N1 was a serious and severe infection. Positive cues to action, such as the access of scientific literature, trust in public health communications and messaging, and encouragement from loved ones, physicians and co-workers were also found to influence HCW H1N1 uptake. Previous seasonal influenza vaccination was found to be an important socio-demographic predictor of vaccine uptake. Factors unique to HCW pandemic vaccine behaviour are (1) lack of time and vaccine access related barriers to vaccination, (2) perceptions of novel and rapid pandemic vaccine formulation, and (3) the strong role of mass media on vaccine uptake.

Conclusions
Many of the factors that influenced HCW pandemic vaccination decisions have previously been reported in seasonal influenza vaccination literature, but some factors were unique to pandemic vaccination. Future influenza vaccine campaigns should emphasize the benefits of vaccination and highlight positive cues to vaccination, while addressing barriers to vaccine uptake in order to improve vaccine coverage among HCW populations. Since pandemic vaccination factors tend be similar among different HCW groups, successful pandemic vaccination strategies may be effective across numerous HCW populations in pandemic scenarios.

Vaccine
Volume 30, Issue 32 pp. 4709-4896 (6 July 2012)

Uptake of pandemic influenza (H1N1)-2009 vaccines in Brazil, 2010
Review Article
Pages 4744-4751
Carla Magda Allan S. Domingues, Wanderson Kleber de Oliveira, For the Brazilian Pandemic Influenza Vaccination Evaluation Team

Abstract
In 2010, the Brazilian Ministry of Health organized a mass vaccination campaign of selected priority groups in response to the 2009 H1N1 influenza pandemic. The campaign was conducted in six phases from March to July, 2010. Priority groups included healthcare professionals, indigenous persons, pregnant women, young children, persons with chronic illnesses and otherwise healthy adults 20–39 years of age. Over 89 million doses of pandemic influenza vaccines were administered, surpassing immunization targets among several priority groups, including healthcare professionals. We reviewed strategies used in Brazil to promote vaccination against pandemic influenza as well as factors external to the campaign that may have contributed to vaccine uptake among priority groups.

Vaccine
Volume 30, Issue 32 pp. 4709-4896 (6 July 2012)

Current issues with the immunization program in Japan: Can we fill the “vaccine gap”?
Review Article
Pages 4752-4756
Akihiko Saitoh, Nobuhiko Okabe

Abstract
The “vaccine gap” is a term which has been used in Japan to indicate that the current immunization program is behind compared to the programs in other developed countries. The current national immunization program (NIP) which was established under the Japanese Immunization Law includes only six vaccines (eight targeted diseases), and the rest of available vaccines have been categorized as voluntary vaccines, which require out-of-pocket expense in order for the patients to receive them. This has led the vaccination rates for the voluntary vaccines remaining low, and the incidence of the target diseases remaining high. In addition, there are a few domestic rules that exist for immunizations including (1) subcutaneous injection is the standard method of vaccination, (2) the thigh is not considered to be the common site of vaccination in infants, and (3) the intervals of administration of inactivated and live vaccines are strictly determined by law. Along with the “vaccine gap” and the domestic rules, some movements to improve our current NIP are underway; including increased calls to change the NIP from civilians and professionals, the establishment of a group by the representatives from 13 medical professional societies asking the government to consider the immunization policy a “national policy” and seeking the establishment of a new and reorganized national immunization technical advisory group (NITAG). In addition, the Vaccination Subcommittee of Health Sciences Council was formed in the government to reform the current Immunization Law and NIP, which established a new national program for three voluntary vaccines funded by a temporary budget. We hope these new movements will fill the “vaccine gap” and that the NITAG will help ensure that vaccine policy becomes a national policy, and will provide necessary vaccinations without out-of-pocket expense to protect children in Japan from vaccine preventable diseases.

Vaccine
Volume 30, Issue 32 pp. 4709-4896 (6 July 2012)

Two decades of hepatitis B vaccination in mentally retarded patients: Effectiveness, antibody persistence and duration of immune memory
Original Research Article
Pages 4757-4761
Tessa Braeckman, Koen Van Herck, Wolfgang Jilg, Tanja Bauer, Pierre Van Damme

Abstract
Introduction
Institutionalized mentally retarded subjects are well-known to be at-risk for HBV infection. We studied the persistence of vaccine-induced anti-HBs antibodies and the robustness of the HBsAg-specific immune memory in this population, 18–20 years after the first vaccine dose.

Materials and methods
Non-immune residents of 4 institutions were immunized in 1984–1986. In 2004, 207 subjects were bled to determine humoral and cellular immune memory. Immune response to a booster dose was evaluated in subjects with anti-HBs level <100 IU/L.

Results
Four subjects showed anti-HBc seroconversion, without clinical implications. Pre-booster anti-HBs levels <100 IU/L were found in 45 subjects (22%); 34/39 (87%) responded with a rapid and high anti-HBs titer to the booster dose. Robust T and B cell memory was present pre- and post-booster.

Discussion and conclusion
Overall results confirm that hepatitis B vaccines are highly effective and immunogenic, and confer long-term persistence of antibodies and immune memory in an at-risk population.

Vaccine
Volume 30, Issue 32 pp. 4709-4896 (6 July 2012)

Psychosocial determinants of parents’ intention to vaccinate their newborn child against hepatitis B
Original Research Article
Pages 4771-4777
Irene A. Harmsen, Mattijs S. Lambooij, Robert A.C. Ruiter, Liesbeth Mollema, Jorien Veldwijk, Yolanda J.W.M. van Weert, Gerjo Kok, Theo G.W. Paulussen, G. Ardine de Wit, Hester E. de Melker

Abstract
From October 2011, The Netherlands started to vaccinate all newborns against hepatitis B. The aim of the present study was to get insight in the psychosocial factors that determine parents’ intention to vaccinate their child against hepatitis B, and to test whether intention to vaccinate is a good predictor of actual vaccination behaviour. In total, 2000 parents of newborns (0–2 weeks old) received a self-report questionnaire measuring intention towards hepatitis B vaccination and its psychosocial determinants (response rate 45.6%). Participants were invited for follow-up research and subsequently offered the opportunity to have their child vaccinated against hepatitis B. The findings showed that the large majority of parents intend to vaccinate their child against hepatitis B. The intention to vaccinate was most strongly determined by parents’ attitude towards hepatitis B vaccination, which in turn was positively associated with perceived benefits of the vaccination and perceptions of the child’s susceptibility to hepatitis B. The majority of the 246 parents that accepted the invitation for a follow-up study had their child vaccinated (83.7%). Intention was found to be a significant predictor of vaccination behaviour although less strong than expected. It is concluded that Dutch parents were positive towards hepatitis B vaccination in terms of both intention and behaviour. To further sustain parents’ positive attitudes towards hepatitis B vaccination, educational campaigns should strengthen the benefits of vaccination along with emphasizing the child’s risk to hepatitis B infection.

Vaccine
Volume 30, Issue 32 pp. 4709-4896 (6 July 2012)

Survey of the prevalence of immunization non-compliance due to needle fears in children and adults
Original Research Article
Pages 4807-4812
Anna Taddio, Moshe Ipp, Suganthan Thivakaran, Ali Jamal, Chaitya Parikh, Sarah Smart, Julia Sovran, Derek Stephens, Joel Katz

Abstract
Needle fears are a documented barrier to immunization in children and adults. There is a paucity of data, however, regarding the prevalence of needle fears and their impact on immunization compliance. In this cross-sectional survey, a convenience sample of parents (n = 883) and children (n = 1024) attending a public museum in Toronto, Canada answered questions about needle fears and non-compliance with immunization due to needle fear. Altogether, 24% of parents and 63% of children reported a fear of needles. Needle fear was the primary reason for immunization non-compliance for 7% and 8% of parents and children, respectively. Interventions aimed at improving education about, and access to, analgesic interventions during immunization injections performed in childhood are recommended in order to prevent the development of needle fears and vaccine non-compliance.

Vaccine
Volume 30, Issue 32 pp. 4709-4896 (6 July 2012)

Nurses’ vaccination against pandemic H1N1 influenza and their knowledge and other factors
Original Research Article
Pages 4813-4819
Jing Zhang, Alison E. While, Ian J. Norman

Abstract
This study aimed to estimate the vaccination coverage against the pandemic H1N1 influenza in a group of nurses and determine the factors associated with their vaccination behaviours. An anonymous, self-administered questionnaire was distributed to a convenience sample of nurses who were enrolled on continuing professional education courses in a university in London. The survey response rate was 77.7% (n = 522). A total of 172 (35.2%) nurses reported receiving the pandemic H1N1 vaccine in the 2009–2010 influenza season and only 22.3% of them had the intent to accept the vaccine in the next season. Compared to nurses with low knowledge scores, those with high knowledge scores were more likely to receive the pandemic H1N1 vaccine (p = 0.017), recommend the vaccine to their patients (p = 0.003), and have the willingness to recommend vaccination to patients in the future (p = 0.009). There was a higher vaccination rate among nurses with higher risk perception scores than with lower scores (p = 0.001). A small, positive correlation between H1N1 knowledge and risk perception scores was identified (p < 0.001) indicating that a high knowledge level was associated with high levels of risk perception. More male nurses received the H1N1 vaccine than females (p < 0.001) and there were a significant differences in the uptake among nurses from different clinical specialty groups (p < 0.001). About half of the vaccinated nurses reported the intent to be vaccinated again but only 8.1% of the unvaccinated nurses had the intent to receive the vaccine in the next season (p < 0.001). The pandemic H1N1 2009 influenza vaccination coverage among this nurse sample was sub-optional. Lack of knowledge and risk perception were predictors associated with the nurses’ vaccination behaviours. The identified knowledge items should be addressed in future vaccination campaigns. The hindrances associated with continuing vaccination decision-making and factors contributing to the different vaccination coverage among clinical specialty groups require further exploration.

Vaccine
Volume 30, Issue 32 pp. 4709-4896 (6 July 2012)

Early-life and contemporaneous nutritional and environmental predictors of antibody response to vaccination in young Gambian adults
Original Research Article
Pages 4842-4848
Sophie E. Moore, Anna A. Richards, David Goldblatt, Lindsey Ashton, Shousun Chen Szu, Andrew M. Prentice

Abstract
Recent research links nutritional exposures early in life with alterations in functional immunity that persist beyond childhood. Here we investigate predictors of antibody response to polysaccharide vaccines in a cohort of Gambian adults with detailed records from birth and early infancy available. 320 adults were given a single dose of a Vi polysaccharide vaccine for Salmonella typhi and a 23-valent capsular polysaccharide pneumococcal vaccine. Anti-Vi antibody levels and antibodies against 4 pneumococcal serotypes (1, 5, 14 and 23F) were measured in serum samples collected at baseline and then 14 days following vaccination and compared to data available from birth and early infancy. Post-vaccination antibody titres to serotype 14 of the pneumococcal vaccine were negatively associated with rate of growth from birth to three months of age, infant weight at 12 months of age and season of birth, but no other associations were observed with early-life exposures. The strongest predictor of antibody levels was pre-vaccination antibody titres, with adult height and serum neopterin levels at time of vaccination also implicated. The current study does not support the hypothesis that nutritional exposures early in life consistently compromise antibody response to polysaccharide vaccines administered in young adulthood.

Vaccine
Volume 30, Issue 32 pp. 4709-4896 (6 July 2012)

Economic modelling assessment of the HPV quadrivalent vaccine in Brazil: A dynamic individual-based approach
Original Research Article
Pages 4866-4871
Tazio Vanni, Paula Mendes Luz, Anna Foss, Marco Mesa-Frias, Rosa Legood

Abstract
We examined the cost-effectiveness of the quadrivalent HPV vaccine for the pre-adolescent female population of Brazil. Using demographic, epidemiological and cancer data, we developed a dynamic individual-based model representing the natural history of HPV/cervical cancer as well as the impact of screening and vaccination programmes. Assuming the current screening strategies, we calculated the incremental cost-effectiveness ratio (ICER) for cohorts with and without vaccination taking into account different combinations of vaccination coverage (50%, 70%, 90%) and cost per vaccinated woman (US$25, US$55, US$125, US$556). The results varied from cost-saving (coverage 50% or 70% and cost per vaccinated woman US$25) to 5950 US$/QALY (coverage 90% and cost per vaccinated 556 US$). In a scenario in which a booster shot was needed after 10 years in order to secure lifelong protection, the ICER resulted in 13,576 US$/QALY. Considering the very cost-effective and cost-effective thresholds based on Brazil’s GDP per capita, apart from the booster scenario which would be deemed cost-effective, all the other scenarios would be deemed very cost-effective. Both the cost per dose of vaccine and discount rate (5%) had an important impact on the results. Vaccination in addition to the current screening programme is likely to save years of life and, depending on the cost of vaccination, may even save resources. Price negotiations between governments and manufacturers will be paramount in determining that the vaccine not only represents good value for money, but is also affordable in middle-income countries like Brazil.

Vaccine
Volume 30, Issue 32 pp. 4709-4896 (6 July 2012)

Cost of production of live attenuated dengue vaccines: A case study of the Instituto Butantan, Sao Paulo, Brazil
Original Research Article
Pages 4892-4896
R.T. Mahoney, D.P. Francis, N.M. Frazatti-Gallina, A.R. Precioso, I. Raw, P. Watler, P. Whitehead, S.S. Whitehead

Abstract
Background
A vaccine to prevent dengue disease is urgently needed. Fortunately, a few tetravalent candidate vaccines are in the later stages of development and show promise. But, if the cost of these candidates is too high, their beneficial potential will not be realized. The price of a vaccine is one of the most important factors affecting its ultimate application in developing countries. In recent years, new vaccines such as those for human papilloma virus and pneumococcal disease (conjugate vaccine) have been introduced with prices in developed countries exceeding $50 per dose. These prices are above the level affordable by developing countries. In contrast, other vaccines such as those against Japanese encephalitis (SA14-14-2 strain vaccine) and meningitis type A have prices in developing countries below one dollar per dose, and it is expected that their introduction and use will proceed more rapidly. Because dengue disease is caused by four related viruses, vaccines must be able to protect against all four. Although there are several live attenuated dengue vaccine candidates under clinical evaluation, there remains uncertainty about the cost of production of these tetravalent vaccines, and this uncertainty is an impediment to rapid progress in planning for the introduction and distribution of dengue vaccines once they are licensed.

Method
We have undertaken a detailed economic analysis, using standard industrial methodologies and applying generally accepted accounting practices, of the cost of production of a live attenuated vaccine, originally developed at the US National Institutes of Health (National Institute of Allergy and Infectious Diseases), to be produced at the Instituto Butantan in Sao Paulo, Brazil. We determined direct costs of materials, direct costs of personnel and labor, indirect costs, and depreciation. These were analyzed assuming a steady-state production of 60 million doses per year.

Results
Although this study does not seek to compute the price of the final licensed vaccine, the cost of production estimate produced here leads to the conclusion that the vaccine can be made available at a price that most ministries of health in developing countries could afford. This conclusion provides strong encouragement for supporting the development of the vaccine so that, if it proves to be safe and effective, licensure can be achieved soon and the burden of dengue disease can be reduced.

Washington Post
http://www.washingtonpost.com/
Accessed 23 June 2012

National
Texas A&M awarded federal biodefense contract to develop vaccines in event of pandemic

AUSTIN, Texas — The Texas A&M University System will be the home of one of three national biodefense centers to help the country quickly develop vaccines in the event of a pandemic and strategies for responding to bioterrorism.
Associated Press,  AP   JUN 18

Editor’s Notes:

– Email Summary: Vaccines: The Week in Review is available as a weekly email summary: please send your request to david.r.curry@centerforvaccineethicsandpolicy.org.

– pdf version: A pdf of the current issues is available here: Vaccines_The Week in Review_16 June 2012

– Twitter: Readers can also follow developments on twitter: @vaxethicspolicy.

– Support: If you would like to join the growing list of individuals who support this service and its contribution to their roles in public health, clinical practice, government, IGOs/NGOs, research, industry and academia, please visit this page at The Wistar Institute, our co-founder and fiduciary. Thank you…

Pakistani militant leader warns polio vaccination teams to stay away unless drone strikes stop

By Associated Press, Updated: Saturday, June 16, 12:17 PM

[Full text]

PESHAWAR, Pakistan — A militant commander in northwest Pakistan warned polio vaccination teams on Saturday to stay away from the territory he controls near the Afghan border, saying he would not allow immunizations until U.S. drone attacks in the country are stopped.

The statement by Hafiz Gul Bahadur is an obstacle to efforts to beat polio on Pakistan, one of only three nations where the virus is endemic.

The threat came in a pamphlet distributed Saturday in markets in the troubled North Waziristan tribal region. “We don’t want benefits from well-wishers who spend billions to save children from polio, which can affect one or two out of hundreds of thousands, while on the other hand the same well-wisher (America) with the help of its slave (Pakistan’s government) kills hundreds of innocent tribesmen including old women and children by unleashing numerous drone attacks,” it said.

The pamphlet also said spies could enter the region under the cover of vaccination teams to get information for the United States about “holy warriors.” It said teams who disregarded his warning would be responsible for any consequences.

The polio virus, which usually infects children living in unsanitary conditions, attacks the nerves and can kill or paralyze.

Bahadur is believed to have a truce with the Pakistani army, while he focuses on attacks against U.S. and NATO troops across the Afghan border. Some of his fighters have recently been killed in the U.S. drone attacks, which Pakistan’s government also opposes.

Washington has refused to stop the strikes, which it holds are an essential weapon against militants. It is widely believed in Pakistan that most of the dead are civilians, but villagers living near the sites of a number of major strikes told the The Associated Press in a report published earlier this year that a significant majority of those killed were combatants.

The region’s top health official Mohammed Sadiq said that teams had completed an initial round of anti-polio vaccinations, but would not start another round of the campaign that was scheduled to begin from June 20. He said 162,000 children were to be immunized.

Sadiq said they had informed Pakistani authorities and the World Health Organization about the warning.

Copyright 2012 The Associated Press. All rights reserved.

UNICEF Press release 14 June 2012

Extract
World unites to accelerate progress in ending preventable child deaths
WASHINGTON, D.C.– Today over 80 governments and a multitude of partners from the private sector, civil society, and faith-based organizations gather at the Child Survival Call to Action – a high-level forum convened by the governments of Ethiopia, India and the United States, in collaboration with UNICEF, to launch a sustained, global effort to save children’s lives.

Over the past 40 years, new vaccines, improved health care practices, investments in education, and the dedication of governments, civil society and other partners have contributed to reducing the number of child deaths by more than 50 per cent.

Still, millions of children – most of them in Sub-Saharan Africa and South Asia – die every year from largely preventable causes before reaching their fifth birthdays.  In 2010, this translated to 57 children dying for every 1,000 live births.

The Call to Action challenges the world to reduce child mortality to 20 or fewer child deaths per 1,000 live births in every country by 2035.  Reaching this historic target will save an additional 45 million children’s lives by 2035, bringing the world closer to the ultimate goal of ending preventable child deaths.

Modelling shows that this goal can be reached by greater effort across five key areas:

1. Geography: Increasing efforts in the 24 countries that account for 80 percent  of under-five deaths.
2. High Burden Populations:  Focusing country health systems on scaling-up access for underserved populations, to include rural and low income groups
3. High Impact Solutions:  Addressing the five causes that account for nearly 60 per cent of child deaths: pneumonia, diarrhea, malaria, pre-term births and intrapartum (around the time of childbirth)
4. Education for Women and Girls: Investing beyond health programs to include educating girls, empowering women, and promoting inclusive economic growth
5. Mutual Accountability: Unifying around a shared goal and using common metrics to track progress

At the Call to Action, governments and partners are being asked to pledge their support for A Promise Renewed , a commitment to work together on sharpening national plans for child survival, monitoring results, and focusing greater attention on the most disadvantaged and vulnerable children.

“We have the tools, the treatments, and the technology to save millions of lives every year, and there is no excuse not to use them,” said UNICEF Executive Director Anthony Lake.  “To renew our promise to the world’s children, we have to focus on the leading causes of child mortality like diarrhea, pneumonia and malaria, scaling up coverage of high-impact, low-cost treatments, sparking greater innovation, and spurring greater political will to reach the hardest to reach children. The grand goal of preventing child deaths must be our common cause.”…

http://www.unicef.org/media/media_62629.html

    The GAVI Alliance said it will provide up to an additional US$162 million to control and prevent outbreaks in developing countries. GAVI “will exceptionally make” up to US$107 million available for measles control and prevention in six high-risk countries: Afghanistan, Chad, DR Congo, Ethiopia, Nigeria and Pakistan.  A further US$ 55 million will be offered through the Measles & Rubella Initiative for rapid response vaccination campaigns in GAVI-eligible countries where outbreaks occur. The increased measles support, between now and 2017, will strengthen routine immunisation systems.

http://www.gavialliance.org/library/news/press-releases/2012/gavi-boosts-global-response-to-measles-outbreaks/

    The U.S. Food and Drug Administration (FDA) announced approval of Menhibrix, a combination vaccine for infants and children ages 6 weeks through 18 months, for prevention of invasive disease caused by Neisseria meningitidis serogroups C and Yand Haemophilus influenzae type b. Ther vaccine is manufactured by GlaxoSmithKline Biologicals, based in Rixensart, Belgium. Karen Midthun, M.D., director of the FDA’s Center for Biologics Evaluation and Research, said, “With today’s approval of Menhibrix, there is now a combination vaccine that can be used to prevent potentially life-threatening Hib disease and two types of meningococcal disease in children. It is the first meningococcal vaccine that can be given starting as young as six weeks of age.”

The safety of Menhibrix was evaluated in about 7,500 infants and toddlers in the U.S., Mexico and Australia. Common adverse reactions reported after administration of Menhibrix were pain, redness and swelling at the injection site, irritability and fever. Menhibrix is given as a four-dose series at 2, 4, 6 and 12 through 15 months of age. The first dose may be given as early as 6 weeks of age. The fourth dose may be given as late as 18 months of age.

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm308350.htm

   The Sabin Vaccine Institute said it began vaccinating participants for a Phase 1 clinical trial of a novel human hookworm vaccine in partnership with the George Washington University and the Children’s National Medical Center,. The trial will investigate the Na-GST-1 antigen developed by the Sabin Vaccine Institute Product Development Partnership (Sabin PDP) to prevent hookworm infections in endemic areas. Dr. Peter Hotez, president of the Sabin Vaccine Institute and director of the Sabin Vaccine Institute and Texas Children’s Hospital Center for Vaccine Development, said, “This trial signifies the great progress global health leaders are making to help combat diseases of poverty. This trial helps advance our goal to develop a safe, efficacious and low-cost vaccine to reduce the global burden of human hookworm, which infects nearly 600 million people worldwide.” This study will help to quickly determine the optimal vaccine formulation for future clinical testing of the Na-GST-1 antigen. A critical component of the vaccine being tested is a novel adjuvant developed by the Infectious Disease Research Institute (IDRI) of Seattle, Washington. The adjuvant, GLA-AF, could potentially help to stimulate the immune system for an improved specific antibody response to the vaccine antigen.

Established in 2000 with funding from the Bill & Melinda Gates Foundation and with additional support from the Dutch Ministry of Foreign Affairs, the Brazilian Ministry of Health, the George Washington University, and the Children’s National Clinical and Translational Science Institute, the Sabin PDP is “the first and only program that aims to reduce the prevalence of human hookworm infection by developing the world’s first vaccine targeting the disease.”

http://www.sabin.org/news-resources/in-news/2012/06/13/clinical-trial-human-hookworm-vaccine-begins-children%E2%80%99s-national-m

Meeting: Coalition against Typhoid (CaT)
June 13, 2012 – Bangkok, Thailand

The Coalition against Typhoid (CaT), an initiative of the Sabin Vaccine Institute, brought together global health leaders from across Asia to discuss the high burden of endemic typhoid and the growing number of typhoid outbreaks in the region. Experts called on policymakers and ministries of health to make typhoid vaccination a priority in their countries.

“Pediatric associations and others across the region recognize typhoid’s serious impact, particularly the rising and widespread threat of drug resistant typhoid. Many – including India and Indonesia – have made recommendations supporting the use of typhoid vaccines.” said Dr. Lalitha Mendis, Chairperson of the Technical Consultative Group on immunization for the World Health Organization’s (WHO) South East Asia Regional Office (SEARO) in New Delhi and immediate past President of the Sri Lanka Medical Council. “National stakeholders and policy makers should review the evidence and discuss the adoption of typhoid vaccines.”

Despite a WHO recommendation and the prioritization of typhoid vaccines for “immediate” implementation at a 2009 WHO SEARO meeting, many countries in Asia have yet to recommend or introduce typhoid vaccines.

More about the typhoid burden in Asia and a full list of speakers: http://coalitionagainsttyphoid.org/.

http://www.sabin.org/news-resources/in-news/2012/06/13/health-experts-highlight-growing-typhoid-pandemic-asia

NIH announced that five more pharmaceutical companies join Discovering New Therapeutic Uses for Existing Molecules program, an initiative to “help scientists research promising new treatments for patients. Funding and molecular compound information is available now for the initial phase of the recently unveiled program. This NIH-industry collaboration will match researchers with 58 compounds to test ideas for new therapeutic uses. Since the launch of the program last month, the total number of compounds the companies are making available has more than doubled. Abbott, Bristol-Myers Squibb Company, GlaxoSmithKline, Janssen Pharmaceutical Research & Development, L.L.C., and Sanofi have joined Pfizer, AstraZeneca, and Eli Lilly and Company. The NIH’s new National Center for Advancing Translational Sciences (NCATS) created the Therapeutics Discovery program “to help re-engineer the research pipeline. By crowdsourcing compounds that already have cleared several key steps in the development process, including safety testing in humans, scientists nationwide have the opportunity to contribute their expertise to advancing these resources for new disease therapies.” The eight participating companies will provide their compounds and related data, which were determined by the NIH to meet specific eligibility criteria. For example, each compound must have advanced to clinical studies but been unsuccessful in its original therapeutic indication or not pursued for business reasons. Preliminary information about the compounds, including mechanism of action, route of administration, and any limitations in use based on safety and tolerability, are available at http://ncats.nih.gov/therapeutics-directory.html.

http://www.nih.gov/news/health/jun2012/ncats-12.htm

The Weekly Epidemiological Record (WER) for 15 June 2012, vol. 87, 24 (pp 233–240) includes: Review of the 2011–2012 winter influenza season, northern hemisphere
http://www.who.int/entity/wer/2012/wer8724.pdf

Twitter Watch [accessed 16 June 2012 – 16:17]
Items of interest from a variety of twitter feeds associated with immunization, vaccines and global public health. This capture is highly selective and is by no means intended to be exhaustive.

Gates Health ‏@gateshealth
The Polio End Game. “The World is closer than ever to eradicating the polio virus.” (via @washingtonpost) http://cot.ag/LRX5Ee
Retweeted by GAVI Alliance
12:51 PM – 15 Jun 12

GAVI Alliance ‏@GAVIAlliance
Child Survival Call to Action meeting sees governments and CSOs pledge to end preventable child deaths – http://ht.ly/bCKNX #5thBDay
2:45 PM – 16 Jun 12

Doctors w/o Borders ‏@MSF_USA
Fighting Neglect: A new report from @msf_access on neglected tropical diseases (#NTDs) http://bit.ly/Nsqiay
9:13 AM – 16 Jun 12

GAVI Alliance @GAVIAlliance
“U.S. Leadership at Home Is Saving Lives Around the World” – Read @GAVISeth latest blog: http://ht.ly/bCqY2 via @HuffingtonPost
7:00 AM – 16 Jun 12

PAHO/WHO ‏@pahowho
“Water and Sustainable Development: The Elimination of #Cholera on the Island of Hispaniola” Tue 19JUN #pahowho http://bit.ly/LSmoGv @rio+20
3:14 PM – 15 Jun 12

APHA ‏@PublicHealth
Washington state’s whooping cough epidemic surpassed 2K cases this week & is upping vaccination demand: http://goo.gl/tSk9u
2:52 PM – 15 Jun 12

Partners In Health ‏@PIH
Vaccination is key to preventing child deaths. Example: @PIH‘s #Haiti #cholera vaccination effort. http://ow.ly/bAr30 #Promise4Children
2:00 PM – 15 Jun 12

WHO/Europe ‏@WHO_Europe
New WHO/Europe report released on urban dimension & role of local gov on social determinants of health http://bit.ly/L9OFar #healthycities
Retweeted by Health Evidence
8:13 AM – 15 Jun 12

UNICEF‏@UNICEF
‘Today, we all are launching Committing to Child Survival: A Promise Renewed’ -Anthony Lake #promise4children
4:33 PM – 14 Jun 12

Report: Building a Future for Women and Children: The 2012 Report
The Partnership (PMNCH) for Maternal, Newborn and Child Health
June 2012

Countdown’s new report, Building a Future for Women and Children: The 2012 Report, highlights country progress—and obstacles to progress—towards achieving Millennium Development Goals (MDGs) 4 and 5 to reduce child mortality and improve maternal health. It focuses, like previous Countdown reports, on evidence-based solutions—health interventions proven to save lives—and on the health systems, policies, financing and other factors that affect the equitable delivery of these lifesaving interventions to women and children. Updated country profiles for 75 Countdown countries were published together with the report. Country-by-country data gathered and analyzed for the 2012 report highlight progress, and show where greater efforts are needed, in the 75 countries that account for more than 95% of all maternal and child deaths:

Annual maternal deaths are down by 47 percent over the past two decades. Nine Countdown countries are on track to meet MDG 5, but more than a third of the Countdown countries have made little, if any progress. In efforts to reduce deaths of children under age 5, 23 Countdown countries are expected to achieve MDG 4. But 13 countries have made no progress in reducing child deaths…

…High coverage levels for vaccines (averaging over 80%) and rapid progress in distribution of insecticide-treated bed nets show what is possible with political commitment and financial investment, but progress is much slower for skilled attendant at birth and other interventions that require a strong health system…

Countdown to 2015 is a multi-disciplinary, multi-institutional collaboration that tracks, stimulates, and supports country progress on maternal, newborn, and child survival. It calls on governments and development partners to be accountable, identifies knowledge gaps, and proposes new actions to achieve MDGs 4 and 5, to reduce child mortality and improve maternal health. It presents data on coverage levels, trends, and equity of coverage for health interventions proven to improve reproductive, maternal, newborn and child health, as well as on critical determinants of coverage including health systems functionality, health policies, and financing.

http://www.who.int/pmnch/topics/part_publications/countdown_2012_report/en/index.html

Report: Fighting Neglect: Finding ways to manage and control visceral leishmaniasis, human African trypanosomiasis and Chagas disease

MSF, June 2012

Abstract

“Fighting Neglect” charts MSF’s 25 years of experience in diagnosing and treating Chagas disease, sleeping sickness, and kala azar, in Latin America, Sub-Saharan Africa, South Asia and the Caucasus. It examines past, present, and future management of the diseases and shows that treatment is possible even with existing diagnostic tools and medicines. However, additional research and development toward new and more effective diagnostics and treatments are desperately needed to address the overwhelming neglect of people whose needs fail to be met by pharmaceutical companies. It will take increased political will among international donors and national governments where these diseases are endemic to improve access to quality life-saving treatment.

Report pdf: http://www.msfaccess.org/sites/default/files/MSF_assets/NegDis/Docs/NTD_Report_FightingNeglect_ENG_2012.pdf

Report: The International Compilation of Human Research Standards
A listing of over 1,000 laws, regulations, and guidelines on human subjects protections in over 100 countries and from several international organizations. Many of the listings embed hyperlinks to the source document. These laws, regulations, and guidelines are classified into six categories:
– General, i.e., applicable to most or all types of human subjects research
– Drugs and Devices
– Research Injury
– Privacy/Data Protection
– Human Biological Materials
– Genetic
– Embryos, Stem Cells, and Cloning

Disclaimer: Though this Compilation contains information of a legal nature, it has been developed for informational purposes only and does not constitute legal advice or opinions as to the current operative laws, regulations, or guidelines of any jurisdiction. In addition, because new laws, regulations, and guidelines are issued on a continuing basis, this Compilation is not an exhaustive source of all current applicable laws, regulations, and guidelines relating to international human subject research protections. While reasonable efforts have been made to assure the accuracy and completeness of the information provided, researchers and other individuals should check with local authorities and/or research ethics committees before starting research activities.

Document: http://www.hhs.gov/ohrp/international/intlcompilation/intlcompil2012.doc.doc

http://www.hhs.gov/ohrp/international/intlcompilation/intlcompilation.html

British Medical Journal
16 June 2012 (Vol 344, Issue 7861)
http://www.bmj.com/content/344/7861

Feature
Infectious Disease
Trials at the ready: preparing for the next pandemic
BMJ 2012; 344 doi: 10.1136/bmj.e2982 (Published 3 May 201
Ed Yong, Science writer

Extract
Researchers have previously struggled to carry out clinical trials on epidemics and the drugs used to treat them. Ed Yong finds out about the scientists who are changing that by planning ahead…

In 2009 the world squandered a prime opportunity to study a harmful virus. From March a strain of H1N1 influenza virus swept the globe, reaching six continents in three months. It infected between 11% and 21% of all the people on the planet, and gave us the perfect chance to learn more about a virus that has been troubling humanity for centuries. But we failed to make the most of it and, to date, still know surprisingly little about how to treat the pandemic strain.

The problem is that while viruses are fast and adaptable, clinical research is lumbering and cumbersome. Epidemics tend to arrive with little warning, spread quickly, and end abruptly. By contrast, clinical trials can take months to plan. Forms must be designed to record the right data and ethical approval must be sought. By the time would-be researchers can vault over these obstacles the epidemic is history.

This explains why, during the 2009 A/H1N1 influenza pandemic, virtually no patients were enrolled in a randomised controlled trial designed to identify the best ways of treating the infection. Such trials are the gold standard of medicine and the best way of getting rigorous evidence for a treatment’s effectiveness. During the pandemic millions of people were treated with the front line drug oseltamivir (Tamiflu). But the only evidence that oseltamivir actually saved lives came from retrospective observational studies, with all the biases they entail. To this date, serious questions remain about the drug’s effectiveness. “A Tamiflu trial during the last pandemic would have resol

Emerging Infectious Diseases
Volume 18, Number 7—July 2012
http://www.cdc.gov/ncidod/EID/index.htm

Perspective
World Health Organization Perspective on Implementation of International Health Regulations
M. Hardiman

Abstract
In 2005, the International Health Regulations were adopted at the 58th World Health Assembly; in June 2007, they were entered into force for most countries. In 2012, the world is approaching a major 5-year milestone in the global commitment to ensure national capacities to identify, investigate, assess, and respond to public health events. In the past 5 years, existing programs have been boosted and some new activities relating to International Health Regulations provisions have been successfully established. The lessons and experience of the past 5 years need to be drawn upon to provide improved direction for the future.

Assessment of Public Health Events through International Health Regulations, United States, 2007–2011
K. S. Kohl et al.

Abstract
Under the current International Health Regulations, 194 states parties are obligated to report potential public health emergencies of international concern to the World Health Organization (WHO) within 72 hours of becoming aware of an event. During July 2007–December 2011, WHO assessed and posted on a secure web portal 222 events from 105 states parties, including 24 events from the United States. Twelve US events involved human influenza caused by a new virus subtype, including the first report of influenza A(H1N1)pdm09 virus, which constitutes the only public health emergency of international concern determined by the WHO director-general to date. Additional US events involved 5 Salmonella spp. outbreaks, botulism, Escherichia coli O157:H7 infections, Guillain-Barré syndrome, contaminated heparin, Lassa fever, an oil spill, and typhoid fever. Rapid information exchange among WHO and member states facilitated by the International Health Regulations leads to better situation awareness of emerging threats and enables a more coordinated and transparent global response.

International Health Regulations—What Gets Measured Gets Done
K. Ijaz et al.

Abstract
The global spread of severe acute respiratory syndrome highlighted the need to detect and control disease outbreaks at their source, as envisioned by the 2005 revised International Health Regulations (IHR). June 2012 marked the initial deadline by which all 194 World Health Organization (WHO) member states agreed to have IHR core capacities fully implemented for limiting the spread of public health emergencies of international concern. Many countries fell short of these implementation goals and requested a 2-year extension. The degree to which achieving IHR compliance will result in global health security is not clear, but what is clear is that progress against the threat of epidemic disease requires a focused approach that can be monitored and measured efficiently. We developed concrete goals and metrics for 4 of the 8 core capacities with other US government partners in consultation with WHO and national collaborators worldwide. The intent is to offer an example of an approach to implementing and monitoring IHR for consideration or adaptation by countries that complements other frameworks and goals of IHR. Without concrete metrics, IHR may waste its considerable promise as an instrument for global health security against public health emergencies.

Research

Validity of International Health Regulations in Reporting Emerging Infectious Diseases
M. Edelstein et al.

Abstract
Understanding which emerging infectious diseases are of international public health concern is vital. The International Health Regulations include a decision instrument to help countries determine which public health events are of international concern and require reporting to the World Health Organization (WHO) on the basis of seriousness, unusualness, international spread and trade, or need for travel restrictions. This study examined the validity of the International Health Regulations decision instrument in reporting emerging infectious disease to WHO by calculating its sensitivity, specificity, and positive predictive value. It found a sensitivity of 95.6%, a specificity of 38%, and a positive predictive value of 35.5%. These findings are acceptable if the notification volume to WHO remains low. Validity could be improved by setting more prescriptive criteria of seriousness and unusualness and training persons responsible for notification. However, the criteria should be balanced with the need for the instrument to adapt to future unknown threats.

Costing Framework for International Health Regulations (2005)
R. Katz et al.

Abstract
The revised International Health Regulations (IHR [2005]) conferred new responsibilities on member states of the World Health Organization, requiring them to develop core capacities to detect, assess, report, and respond to public health emergencies. Many countries have not yet developed these capacities, and poor understanding of the associated costs have created a barrier to effectively marshaling assistance. To help national and international decision makers understand the inputs and associated costs of implementing the IHR (2005), we developed an IHR implementation strategy to serve as a framework for making preliminary estimates of fixed and operating costs associated with developing and sustaining IHR core capacities across an entire public health system. This tool lays the groundwork for modeling the costs of strengthening public health systems from the central to the peripheral level of an integrated health system, a key step in helping national health authorities define necessary actions and investments required for IHR compliance.

Emerging Infectious Diseases
Volume 18, Number 7—July 2012
http://www.cdc.gov/ncidod/EID/index.htm

Book Reviews
Infectious Disease: A Geographic Guide and Atlas of Human Infectious Diseases
– Eskild Petersen, Lin H. Chen, and Patricia Schlangenhauf, editors
Infectious Disease: A Geographic Guide, Wiley-Blackwell, Oxford, UK, 2011
ISBN: 978-0-470-65529-0
Pages: 480; Price: US $84.95
– Heiman F.L. Wertheim, Peter Horby, and John P. Woodall, editors
Atlas of Human Infectious Diseases, Wiley-Blackwell, Oxford, UK, 2012
ISBN: 978-1-4051-8440-3
Pages: 306; Price: US $130.00
Infectious Disease: A Geographic Guide and Atlas of Human Infectious Diseases, 2 books recently published by Wiley-Blackwell, deliver to the global medicine bookshelf diagnostic adjuncts for expatriate clinicians and those who see immigrants or returning travelers, while also serving as pretravel references on regional disease risk and authoritative sources for anyone needing infectious diseases information. Mary Wilson, who contributed to the first book and wrote the foreword for the second, filled a similar need in 1991 with A World Guide to Infections. Now these new books remind us that even in the age of near–real-time, electronic references, a printed volume to hold in one’s hands can be an unmatched resource.

Emerging Infectious Diseases
Volume 18, Number 7—July 2012
http://www.cdc.gov/ncidod/EID/index.htm

Book Review
– Nancy Leys Stepan
Eradication: Ridding the World of Diseases Forever?
Cornell University Press, Ithaca, NY, USA, 2011
ISBN-10: 0801450586
ISBN-13: 978-0801450587
Pages: 272; Price: US $35.00

Public health, like any dynamic field filled with social reformers, scientists, and passionate believers, generates conflicting views, approaches, and goals. Thus, on domestic and global fronts, public health advocates compete for priority and resources for vertical (single-disease) versus horizontal (infrastructure or systems) programs; infectious diseases versus noncommunicable diseases; targeting diseases to improve health versus emphasizing the role of economic development or social determinants; and primary health care versus eradicating diseases.

Eradication: Ridding the World of Diseases Forever? by Nancy Leys Stepan provides a rich context for the role of eradication historically and conceptually in public health and, along the way, touches on many of the fault lines that stress and enrich public health. The depth and breadth of the author’s approach also enrich her book and broaden its appeal to readers whose interests go beyond the topic of disease eradication and include public health history, governance, leadership, philosophy, and dependence on multiple disciplines.

Global Health Governance
Volume V, Issue 1: Fall 2011
http://blogs.shu.edu/ghg/

The Global Governance of Bioethics: Negotiating UNESCO’s Universal Declaration on Bioethics and Human Rights (2005)
Adèle Langlois

Abstract
UNESCO’s Universal Declaration on Bioethics and Human Rights (2005) was drawn up by an independent panel of experts (the International Bioethics Committee) and negotiated by member states. UNESCO aimed for a participatory and transparent drafting process, holding national and regional consultations and seeking the views of various interest groups, including religious and spiritual ones. Furthermore, reflecting UNESCO’s broad interpretation of bioethics, the IBC included medics, scientists, lawyers and philosophers among its membership. Nevertheless, several potential stakeholders—academic scientists and ethicists, government policy-makers and NGO representatives—felt they had not been sufficiently consulted or even represented during the Declaration’s development. Better communications and understanding within and between national, regional and international layers of governance would help to avoid a recurrence of this problem in future negotiations.

Global Health Governance
Volume V, Issue 1: Fall 2011
http://blogs.shu.edu/ghg/
Are the ‘Good Times’ Over? Looking to the Future of Global Health Governance
Owain David Williams and Simon Rushton

Abstract
After ten years of unprecedented attention and funding for global health, and a simultaneous increase in the range and number of institutions involved in global health governance, we have arrived at what seems to be a watershed moment. This paper assesses the future of global health governance in this context. In particular, the financial crisis, the rise of middle- income powers, and changes in US domestic politics are all viewed as injecting new fault lines and dynamics into the existing system of governance. Although the impacts of these changes are likely to be profound, the paper argues that the private and hybrid public-private institutions that have become prominent in global health governance in the last decade will continue to play a central role in tackling a narrowly delineated range of global health problems, albeit with potentially fewer resources. Indeed the trend for a greater emphasis on ‘private’ forms of authority seems likely to become further entrenched by the financial crisis-engendered emphasis on the delivery of efficient global health interventions.

Health and Human Rights
Vol 14, No 1 (2012)
http://hhrjournal.org/index.php/hhr

Pillars for progress on the right to health: Harnessing the potential of human rights through a Framework Convention on Global Health
Eric A. Friedman, Lawrence O. Gostin

Abstract
Ever more constitutions incorporate the right to health, courts continue to expand
their right to health jurisprudence, and communities and civil society increasingly turn to the right to health in their advocacy. Yet the right remains far from being realized. Even with steady progress on numerous fronts of global health, vast inequities at the global and national levels persist, and are responsible for millions of deaths annually. We propose a four-part approach to accelerating progress towards fulfilling the right to health: 1) national legal and policy reform, incorporating right to health obligations and principles including equity, participation, and accountability in designing, implementing, and monitoring the health sector, as well as an all-of-government approach in advancing the public’s health; 2) litigation, using creative legal strategies, enhanced training, and promotion of progressive judgments to increase courts’ effectiveness in advancing the right to health; 3) civil society and community engagement, empowering communities to understand and claim this right and building the capacity of right to health organizations; and 4) innovative global governance for health, strengthening World Health Organization leadership on health and human rights, further clarifying the international right to health, ensuring sustained and scalable development assistance, and conforming other international legal regimes (e.g., trade, intellectual property, and finance) to health and human rights norms. We offer specific steps to advance each of these areas, including how a new global health treaty, a Framework Convention on Global Health, could help construct these four pillars.

Health Policy and Planning
Volume 27 Issue 4 July 2012
http://heapol.oxfordjournals.org/content/current

Review
David Berlan and Jeremy Shiffman
Holding health providers in developing countries accountable to consumers: a synthesis of relevant scholarship
Health Policy Plan. (2012) 27(4): 271-280 doi:10.1093/heapol/czr036

Abstract
Health care providers in low-income countries often treat consumers poorly. Many providers do not consider it their responsibility to listen carefully to consumer preferences, to facilitate access to care, to offer detailed information, or to treat patients with respect. A lack of provider accountability to health consumers may have adverse effects on the quality of health care they provide, and ultimately on health outcomes.

This paper synthesizes relevant research on health provision in low-, middle- and high-income countries with the aim of identifying factors that shape health provider accountability to consumers, and discerning promising interventions to enhance responsiveness. Drawing on this scholarship, we develop a framework that classifies factors into two categories: those concerning the health system and those that pertain to social influences. Among the health systems factors that may shape provider accountability are oversight mechanisms, revenue sources, and the nature of competition in the health sector—all influences that may lead providers to be accountable to entities other than consumers, such as governments and donors. Among the social factors we explore are consumer power, especially information levels, and provider beliefs surrounding accountability.

Evidence on factors and interventions shaping health provider accountability is thin. For this reason, it is not possible to draw firm conclusions on what works to enhance accountability. This being said, research does suggest four mechanisms that may improve provider responsiveness:

– Creating official community participation mechanisms in the context of health service decentralization;

– Enhancing the quality of health information that consumers receive;

– Establishing community groups that empower consumers to take action;

– Including non-governmental organizations in efforts to expand access to care.

This synthesis reviews evidence on these and other interventions, and points to future research needs to build knowledge on how to enhance health provider accountability to consumers.

International Journal of Infectious Diseases
Volume 16, Issue 7, Pages e469-e572 (July 2012)
http://www.sciencedirect.com/science/journal/12019712

Perspective
The discovery of viruses: advancing science and medicine by challenging dogma
Pages e470-e473
Andrew W. Artenstein

Summary
The discovery of viruses in the final years of the nineteenth century represented the culmination of two decades of work on tobacco mosaic disease by three botanical scientists. Eventually their discovery led to a paradigm shift in scientific thought, but it took more than 20 years to appreciate its implications because it was inconsistent with the prevailing dogma of the time—Koch’s postulates. Although these ‘rules’ were actually conceived of as guidelines upon which to establish microbial causality and their implementation resulted in many new discoveries, they also had the unintended effect of limiting the interpretation of novel findings. However, by challenging existing dogma through rigorous scientific observation and sheer persistence, the investigators advanced medicine and heralded new areas of discovery.

JAMA   
June 13, 2012, Vol 307, No. 22
http://jama.ama-assn.org/current.dtl

Viewpoint | June 13, 2012
Adaptive Clinical Trials – A Partial Remedy for the Therapeutic Misconception?
William J. Meurer, MD, MS; Roger J. Lewis, MD, PhD; Donald A. Berry, PhD

Extract
There is a common “therapeutic misconception” among patients considering participation in clinical trials.1 Some trial participants and family members believe that the goal of a clinical trial is to improve their outcomes—a misperception often reinforced by media advertising of clinical research.2 Clinical trials have primarily scientific aims and rarely attempt to collectively improve the outcomes of their participants. The overarching goal of most clinical trials is to evaluate the effect of a treatment on disease outcomes.3 Comparisons are usually made with placebo for conditions having no established treatments and with standard care for conditions having effective treatments. Any benefit to an individual trial participant is a chance effect of randomization and the true, but unknown, relative effects of the treatments. Available evidence is conflicting regarding whether patients receive some benefit from simply participating in a clinical trial.3 Thus, even though serving as a research participant is essentially an altruistic activity, many clinical trial volunteers do not participate in research out of altruism.4 An adaptive clinical trial design can be used to increase the likelihood that study participants will benefit by being in a clinical trial…

Viewpoint | June 13, 2012
Adaptive Trials in Clinical Research – Scientific and Ethical Issues to Consider
Rieke van der Graaf, PhD; Kit C. B. Roes, PhD; Johannes J. M. van Delden, MD, PhD

Extract
Interest in the use of adaptive trial design has increased among clinical investigators, pharmaceutical companies, and regulatory authorities. Adaptive trials are randomized clinical trials that allow for adaptations in the study design while the study is being conducted. Modifications as a study is being conducted can include changes in sample size, adjustments in medication dosage, or changes in the number of treatment groups.   Adaptive trials can often decrease drug development time, which can have clinical and economic advantages.

Adaptive trials also have certain ethical advantages because fewer participants are assigned to the inferior procedure or drug compared with trials with fixed designs. For instance, in the ASTIN trial, researchers conducted an adaptive phase 2 dose response trial to determine whether a neutrophil inhibitory factor improved recovery in patients with acute ischemic stroke; it did not. However, this trial needed to enroll 966 patients, compared with the need to enroll 1080 patients if a traditional design had been used. Furthermore, the adaptive design made it possible to stop the trial early for futility.1

However, certain features of adaptive trials may create some potential scientific and ethical challenges.2 This Viewpoint explores several ethical issues that researchers and participants in adaptive trials should consider…

Nature  
Volume 486 Number 7402 pp157-286  14 June 2012
http://www.nature.com/nature/current_issue.html

Nature | News
Cholera vaccine deployed to control African outbreak
Patients in Guinea are first in Africa to be given oral vaccination during an epidemic.
Gozde Zorlu

11 June 2012
For the first time, health officials in West Africa have begun a vaccination campaign to try to control cholera during an active epidemic.

In collaboration with the Ministry of Health in Guinea, the charity Médecins Sans Frontières (MSF; also known as Doctors Without Borders) has been administering the cholera vaccine Shanchol in the region of Boffa, 150 kilometres northwest of the country’s capital, Conakry. The programme began in late April, with patients receiving a two-dose oral vaccine. In total, almost 150,000 people received at least one dose of vaccine, and just over 110,000 people received a second dose.

Iza Ciglenecki, project manager for diarrhoeal diseases at MSF, ran the campaign in Guinea. She hopes that the results will lead to more widespread use of the vaccine in epidemics. “Until very recently, no one was using this as an extra tool to control cholera,” she says. “We hope to add to the evidence base regarding this vaccine to help develop an intervention criteria for the control of cholera in outbreaks.”

The programme follows on the heels of two modelling studies, published in the journal PLoS Neglected Tropical Diseases last year, which suggested that cholera vaccines were beneficial after outbreaks occurred in Vietnam and Zimbabwe1, 2. But more information is needed on how and when to administer the vaccine, explains Ciglenecki.

Surveillance systems in Boffa have been strengthened to enable the MSF to monitor the Guinean epidemic and to assess the effectiveness of the vaccine over the next six months.

William Perea of the Control of Epidemic Diseases Unit at the World Health Organization (WHO) in Geneva, Switzerland, is watching the intervention closely. Alongside other control measures such as cleaning up the water supply, the WHO now recommends using available cholera vaccines to control outbreaks. Opinions were divided among vaccination experts at the start of the 2010 cholera epidemic in Haiti regarding vaccine efficacy and availability. There were also concerns that time and resources would be better spent on improving water and sanitation systems than on vaccines (see ‘Would cholera vaccines have helped in Haiti?’).

Time for action

The real issue now is not the vaccine, but the mechanism by which to deliver a vaccination programme in response to an outbreak, says Perea. “We know enough about the vaccine to say it is very likely to work, but in the field where you have to respond quickly, other elements will come into consideration,” he says. “So we need to make sure we collect data and do the necessary work to make sure that the cholera vaccine will have an impact in these situations. It is time to stop talking and time to start acting.”

A WHO technical group has recommended that cholera vaccine is stockpiled ready for use in response to outbreaks, says Perea. To fund this, the organization needs to gain support from major donors, such as the GAVI Alliance in Geneva and the Bill & Melinda Gates Foundation in Seattle, Washington. Perea hopes that a stockpile will be established by January 2013, but acknowledged that it may take longer.

Meanwhile, in Haiti, the organization Partners in Health, headquartered in Boston, Massachusetts, has implemented a cholera vaccination programme to protect the thousands of people still at risk of cholera from the epidemic that broke out in the wake of the 2010 earthquake. After several delays, the programme started in April this year. Vaccine uptake has been good so far, and the results of the programme will be known by the end of September, according to Louise Ivers, chief of mission for Partners in Health in Haiti.

Ivers is excited about the MSF vaccination campaign in Guinea and hopes that the two organizations can learn from each other. “We have a vaccine that is pretty good but it is not used,” she says. “So the more information we can gather to help inform public health officials and ministries of health on the use of vaccine in the field, the better”.

Ivers explains that the most important objectives are to show that a sufficient number of patients will come back for their second dose of vaccine, and that the logistical and supply systems are able to deliver the vaccines successfully.

Cholera experts are agreed on the need to tackle the root of the problem: improving water and sanitation systems in countries where these are lacking. But because this can take a significant amount of investment, in terms of time and resources, a vaccine can offer protection during an outbreak. “It’s a good tool, we have to use it,” says Perea.

Nature

doi:10.1038/nature.2012.10801

References

Reyburn, R. et al. PLoS Negl. Trop. Dis. 5, e952 (2011).

Anh, D. D. et al. PLoS Negl. Trop. Dis. 5, e1006 (2011).

New England Journal of Medicine
June 14, 2012  Vol. 366 No. 24
http://content.nejm.org/current.shtml

Review Article
Guillain–Barré Syndrome
Nobuhiro Yuki, M.D., Ph.D., and Hans-Peter Hartung, M.D.

Extract
The Guillain–Barré syndrome, which is characterized by acute areflexic paralysis with albuminocytologic dissociation (i.e., high levels of protein in the cerebrospinal fluid and normal cell counts), was described in 1916.1 Since poliomyelitis has nearly been eliminated, the Guillain–Barré syndrome is currently the most frequent cause of acute flaccid paralysis worldwide and constitutes one of the serious emergencies in neurology. A common misconception is that the Guillain–Barré syndrome has a good prognosis — but up to 20% of patients remain severely disabled and approximately 5% die, despite immunotherapy.2 The Miller Fisher syndrome, which is characterized by ophthalmoplegia, ataxia, and areflexia, was . .

PLoS Medicine
(Accessed 16 June 2012)
http://www.plosmedicine.org/article/browse.action?field=date

Protecting Clinical Trial Participants and Protecting Data Integrity: Are We Meeting the Challenges?
Susan S. Ellenberg
Essay, published 12 Jun 2012
doi:10.1371/journal.pmed.1001234

Summary Points
– Although there is substantial consensus regarding the need for interim monitoring of certain types of trials, there is controversy about specific aspects of data monitoring.

– Approaches to ensuring independence of those who perform the interim monitoring and confidentiality of interim data vary substantially by type of trial and trial funder.

– The “independent statistician” model, involving a separate statistician to analyze interim data and report to the data monitoring committee (DMC), remains controversial but provides important protections of data integrity.

– Early stopping guidelines should be clearly understood and accepted by all parties, and only deviated from if there are unexpected findings that confound the overall benefit-risk assessment at interim analysis.

– Liability of DMC members is an important concern that has not been dealt with adequately by either commercial or government trial sponsors.