Predictors of administration and attitudes about pneumo, Hib and rotas vaccines among pediatricians in India:

Volume 30, Issue 24, Pages 3489-3722 (21 May 2012)

Regular Papers
Predictors of administration and attitudes about pneumococcal, Haemophilus influenzae type b and rotavirus vaccines among pediatricians in India: A national survey
Original Research Article
Pages 3541-3545
Lisa M. Gargano, Naveen Thacker, Panna Choudhury, Paul S. Weiss, Karen Pazol, Sunil Bahl, Hamid S. Jafari, Manisha Arora, Walter A. Orenstein, James M. Hughes, Saad B. Omer

According to the World Health Organization in 2008, pneumonia accounted for 20% of deaths and diarrheal diseases accounted for 13% of deaths among children under 5 in India. Vaccines are available for Streptococcus pneumoniae (pneumococcal conjugate vaccine (PCV)), Haemophilus influenzae type b (Hib vaccine), and rotavirus. Barriers to including these vaccines in routine immunization schedule in India include potential negative impacts on fragile existing immunization programs and cost. Pediatricians who are members of the Indian Academy of Pediatrics (IAP) are important stakeholders for vaccine delivery and maintaining public confidence in vaccines.

A random sample of 785 pediatricians belonging to IAP was selected for the survey conducted from June 2009 to June 2010. Descriptive analyses using sampling weights were performed to evaluate the distributions of variables assessing vaccine-related attitudes and behaviors among pediatricians. Logistic regression was used to assess factors associated with routine vaccine use.

The majority of pediatricians reported administering PCV (85.6%), Hib (95.9%), and rotavirus (80.2%) vaccine selectively or routinely. Pediatricians who had high perceived disease susceptibility were 2.42 times more likely to report routine administration of Hib vaccine (OR 2.42, 95% CI 1.24, 4.74). Pediatricians who had high perceived Hib vaccine efficacy were 4.74 times more likely to administer Hib vaccine routinely (OR 4.74, 95% CI 2.09, 10.74). Perceptions of disease susceptibility and severity or of vaccine safety and efficacy were not associated with routine administration of PCV or rotavirus vaccine.

Understanding predictors of routine use of a new vaccine could help focus interventions to improve the routine use of other vaccines. The importance of perceived susceptibility to and severity of diseases caused by S. pneumoniae, Hib, and rotavirus and perceived efficacy and safety of the vaccines by pediatricians presents an opportunity to design strategies to build support for new vaccine introduction and may have important implications for national immunization policy in India.

Factors associated with HPV vaccine uptake in teenage girls: systematic review

Volume 30, Issue 24, Pages 3489-3722 (21 May 2012)

Regular Papers
Factors associated with HPV vaccine uptake in teenage girls: A systematic review
Original Research Article
Pages 3546-3556
Sharon J.M. Kessels, Helen S. Marshall, Maureen Watson, Annette J. Braunack-Mayer, Rob Reuzel, Rebecca L. Tooher

Since 2006 Human papillomavirus (HPV) vaccination has become available to adolescent girls and women in an increasing number of countries, to protect against the virus causing cervical cancer. The vaccine series is offered in three doses over 6 months, and this study aimed to identify factors associated with initiation and/or completion of the 3 dose series in (pre-) adolescent girls. Previous studies have considered intention to vaccinate rather than actual vaccination uptake.

A systematic search of Medline, Medline in process, Embase and CINAHL, from 2006 to March 2011 for articles related to HPV-vaccine uptake among adolescent girls and factors potentially associated with uptake yielded 25 studies.

The majority of studies were surveys or retrospective reviews of data, only 5 studies reported data on program completion. Most were conducted in the United States (20/25). Higher vaccine uptake was associated with having health insurance, of older age, receipt of childhood vaccines, a higher vaccine related knowledge, more healthcare utilization, having a healthcare provider as a source of information and positive vaccine attitudes. In US settings, African American girls were less likely to have either initiated or completed the three dose vaccination series.

HPV vaccination programs should focus on narrowing disparities in vaccine receipt in ethnic and racial groups and on providing correct information by a reliable source, e.g. healthcare providers. School-based vaccination programs have a high vaccine uptake. More studies are required to determine actual vaccine course completion and factors related to high uptake and completion, and information from a broader range of developed and developing settings is needed.

Emotional benefits of influenza vaccination and vaccination intentions among (HCW) healthcare personnel

Volume 30, Issue 24, Pages 3489-3722 (21 May 2012)

Regular Papers
The expected emotional benefits of influenza vaccination strongly affect pre-season intentions and subsequent vaccination among healthcare personnel
Original Research Article
Pages 3557-3565
Mark G. Thompson, Manjusha J. Gaglani, Allison Naleway, Sarah Ball, Emily M. Henkle, Leslie Z. Sokolow, Beth Brennan, Hong Zhou, Lydia Foster, Carla Black, Erin D. Kennedy, Sam Bozeman, Lisa A. Grohskopf, David K. Shay

The relative importance of different attitudes in predicting vaccination among healthcare personnel (HCP) is unclear. We hypothesized that HCP who feel at risk without vaccination or say they would regret not getting vaccinated would be more likely to get vaccinated than HCP who do not expect these emotional benefits.

A prospective cohort of 1544 HCP with direct patient care was enrolled from September 18 to December 18, 2010 at Scott & White Healthcare in Texas and Kaiser Permanente Northwest in Oregon and Washington. An Internet-based questionnaire assessed pre-season intention to be vaccinated and included 12 questions on attitudes about vaccination: single-item measures of perceived susceptibility and vaccine effectiveness, 5 items that were summed to form a concerns about vaccine scale, and 5 items summed to form an emotional benefits of vaccination scale. Influenza vaccination status for the 2010–2011 season and for 5 prior seasons was confirmed by medical record extraction.

There were significant differences between vaccinated and unvaccinated HCP on all attitude items; 72% of vaccinated HCP agreed that they “worry less about getting the flu” if vaccinated, compared to only 26% of the unvaccinated (odds ratio = 7.4, 95% confidence interval = 5.8–9.5). In a multivariate model, the emotional benefits scale was the strongest predictor of 2010–2011 seasonal influenza vaccination, after adjusting for other attitude measures, prior vaccination history, and pre-season intention to be vaccinated. The predictive value of the emotional benefits scale was strongest for HCP with low pre-season intention to be vaccinated, where HCP vaccine receipt was 15% versus 83% for those with low versus high scores on the emotional benefits scale.

The expected emotional benefits of vaccination strongly affect seasonal influenza vaccination among HCP, even after taking into account other attitudes, pre-season intentions, and prior vaccination history. These attitudes are promising targets for future vaccination campaigns.

Invasive meningococcal disease in England and Wales: Implications for the introduction of new vaccines

Volume 30, Issue 24, Pages 3489-3722 (21 May 2012)

Regular Papers
Invasive meningococcal disease in England and Wales: Implications for the introduction of new vaccines
Original Research Article
Pages 3710-3716
Shamez N. Ladhani, Jessica S. Flood, Mary E. Ramsay, Helen Campbell, Stephen J. Gray, Edward B. Kaczmarski, Richard H. Mallard, Malcolm Guiver, Lynne S. Newbold, Ray Borrow

A number of meningococcal vaccines have either been recently licensed or are in late-phase clinical trials. To inform national vaccination policy, it is important to define the burden of disease and the potential impact of any new vaccine. This study describes the epidemiology of invasive meningococcal disease across all age groups in England and Wales for recent epidemiological years between 2006 and 2010. The Health Protection Agency (HPA) conducts enhanced national meningococcal surveillance through a combination of clinical and laboratory reporting. Between 2006/07 and 2010/11, the average annual incidence of invasive meningococcal disease across all age groups was 2.0/100,000. Capsular group B (MenB) accounted for 87% (4777/5471) cases, with an overall incidence of 1.8/100,000. The highest MenB incidence observed among infants (36.2/100,000) where cases increased from birth to 5 months of age then gradually declined. An annual average of 245 MenB cases occurred in infants (135 in those aged ≤6 months) representing 26% (and 14%) of all MenB cases, respectively. After infancy, MenB rates declined until the age of 12 years, rising to a second smaller peak at 18 years. MenB case fatality ratio (CFR) was 5.2% (247/4777 cases) overall and was highest among ≥65 year-olds (28/161; 17.4%). The largest number of deaths (n = 125), however, occurred among <5 year-olds. Clonal complexes cc269 and cc41/44 each accounted for around a third of cases across the age groups. Other capsular groups rarely caused invasive disease, although capsular group Y (MenY) cases more than doubled from 35 in 2006/07 to 86 in 2010/11. Thus, universal meningococcal vaccination with an effective broad-spectrum formulation has potential to prevent most disease, particularly if the vaccine is immunogenic early in infancy, but, there is currently little justification for routine quadrivalent ACWY conjugate vaccination in the UK, although the increase in MenY disease warrants continued surveillance.

Adherence to rotavirus vaccination schedules among infants in managed care in U.S.

Volume 30, Issue 24, Pages 3489-3722 (21 May 2012)

Regular Papers
Rotavirus vaccine series completion and adherence to vaccination schedules among infants in managed care in the United States
Original Research Article
Pages 3717-3722
Girishanthy Krishnarajah, Elizabeth J. Davis, Ying Fan, Baudouin A. Standaert, Ami R. Buikema

Two rotavirus vaccines are currently approved in the United States: 3-dose RotaTeq (RV5; Merck & Co., Inc., Whitehouse Station, NJ, USA) is administered at ages 2, 4, and 6 months; and 2-dose Rotarix (RV1; GlaxoSmithKline, Research Triangle Park, NC, USA) is administered at ages 2 and 4 months. Our objective was to compare rotavirus vaccine series completion and dosing schedule compliance between cohorts of infants who received these vaccines.

Infants aged less than 1 year who initiated a rotavirus vaccine series between 01 January 2009 and 30 June 2009 were identified in US health insurance claims data. Cohorts were formed based on vaccine brand use. Series completion and compliance with the FDA-approved and ACIP-recommended harmonized schedules were analyzed descriptively and a log binomial model was used to estimate the difference in series completion by vaccine brand while adjusting for demographic variables.

Among infants in the RV1 and RV5 cohorts (N = 55,584), 84.3% completed a full series. A greater proportion of the RV1 cohort than the RV5 cohort completed their series (91.0% vs. 83.4%; P < 0.001; multivariate-adjusted relative risk 1.07; 95% CI 1.06–1.08). In the RV1 and RV5 cohorts, respectively, 75.0% and 59.5% of infants were fully compliant with the FDA-approved administration schedule for their vaccine (P < 0.001); 83.3% and 76.4% of infants were fully compliant with the harmonized schedule (P < 0.001).

Draft global vaccine action plan: 65th World Health Assembly – A65/22

Editor’s Note: The draft of the Global Vaccine Action Plan (GVAP) developed by the Decade of Vaccines Collaboration was posted as part of the 65th World Health Assembly meeting documentation  The 39-page document is available as a pdf here:  We extract the “Continuing Momentum…” and “Action by the Health Assembly” sections below.

Provisional agenda item 13.12 11 May 2012
Draft global vaccine action plan

Extract (full text)

100. Ensuring success throughout the Decade of Vaccines requires additional focus and action beyond the development of the draft global vaccine action plan. Four critical sets of activities will be required in order to translate the action plan into actions and results: development of tools for translation of the plan; development of a complete accountability framework; securing commitments from the stakeholder community; and communicating Decade of Vaccines opportunities and challenges.

101. Tools are needed that provide the full thinking behind the draft global vaccine action plan, together with details, in order to enable implementation. The production, publication and communication of these tools will help stakeholders better understand how to translate the actions recommended in the action plan into the local context.

102. The draft global vaccine action plan lays the groundwork for an accountability framework, which will be finalized with more detailed roles and responsibilities for stakeholders, a complete set of indicators, the methodology and data sources for each indicator detailed and baselines established where required. Investments are needed to improve data quality and develop more robust in-country monitoring and evaluation systems. Regular audits should be conducted to verify data quality. Progress should be reviewed annually, beginning in 2013, by country, the WHO regional committees and the Health Assembly.

103. Commitments aligned to the draft global vaccine action plan from countries, civil society organizations, multilateral agencies, development partners and vaccine manufacturers can transform the action plan from a document to a movement. Efforts to build these commitments and a strategy for coordinating them will be required at the global, regional and country levels. Appropriate channels must be identified and targeted communications developed to ensure that Decade of Vaccines messages reach and resonate with all stakeholders.

104. The period of time immediately following the Sixty-fifth World Health Assembly will be critical for ensuring that the agenda-setting translates into effective action. Key opportunities to sustain and build on the current momentum during the remainder of 2012 include the WHO regional committee meetings, the meeting of the Board of the GAVI Alliance, the UNICEF Executive Board meeting, the GAVI Alliance Partners’ Forum and the Child Survival: A Call to Action summit.

105. The Decade of Vaccines collaboration is a time-limited effort that ends with the completion of the draft global vaccine action plan and related activities identified above. There will be no new structure to support the implementation phase of the Decade of Vaccines/global vaccine action plan. Lead stakeholders need to assume ownership to support implementation and progress monitoring.

106. WHO will play a leadership role for the action plan as the normative lead agency in global health, including the defining of norms and standards for production and quality control of vaccines, as well for strengthening immunization delivery, programme monitoring and surveillance systems. In collaboration with other stakeholders, the WHO Secretariat will also advocate for and provide technical support to Member States in promoting greater country ownership, creating synergies between immunization and other primary health-care programmes and implementing research, notably to increase programme efficiencies and impact.


107. The Health Assembly is invited to adopt the resolution on World Immunization Week recommended by the Executive Board in resolution EB130.R12.

108. It is further invited to consider the following draft resolution:
The Sixty-fifth World Health Assembly,
– Having considered the report on the draft global vaccine action plan;1
– Recognizing the importance of immunization as one of the most cost-effective interventions in public health which should be recognized as a core component of the human right to health;
– Acknowledging the remarkable progress made in immunization in several countries to ensure that every eligible individual is immunized with all appropriate vaccines, irrespective of geographic location, age, gender, disability, educational level, socioeconomic level, ethnic group or work condition;
– Applauding the contribution of successful immunization programmes in achieving global health goals, in particular in reducing childhood mortality and morbidity, and their potential for reducing mortality and morbidity across the life-course;
– Noting that the introduction of new vaccines targeted against several important causes of major killer diseases such as pneumonia, diarrhoea and cervical cancer can be used as a catalyst to scale up complementary interventions and create synergies between primary health care programmes; and that beyond the mortality gains, these new vaccines will prevent morbidity with resulting economic returns even in countries that have already succeeded in reducing mortality;
– Concerned that, despite the progress already made, disease eradication and elimination goals such as the eradication of poliomyelitis, the elimination of measles, rubella, and maternal and neonatal tetanus cannot be met without achieving and sustaining high and equitable coverage;
– Concerned that low- and middle-income countries where the adoption of available vaccines has been slower may not have the opportunity to access newer and improved vaccines expected to become available during this decade;
– Alarmed that globally routine immunization services are not reaching one child in five, and that substantial gaps persist in routine immunization coverage within countries;

Recalling resolutions WHA58.15 and WHA61.15 on the global immunization strategy,
1. ENDORSES the Global Vaccine Action Plan;
2. URGES Members States:
(1) to apply the vision and the strategies of the Global Vaccine Action Plan to develop the vaccines and immunization components of their national health strategy and plans, according to the epidemiological situation in their respective countries;
(2) to commit themselves to allocating adequate human and financial resources to achieve the immunization goals and other relevant key milestones;
(3) to report every year to the regional committees during a dedicated Decade of Vaccines session, on lessons learnt, progress made, remaining challenges and updated
actions to reach the national immunization targets;

3. REQUESTS the Director-General:
(1) to foster alignment and coordination of global immunization efforts by all stakeholders in support of the implementation of the Global Vaccine Action Plan;

(2) to identify human and financial resources for the provision of technical support in order to implement the national plans of the Global Vaccine Action Plan and monitor their impact;

(3) to monitor progress and report annually, through the Executive Board, to the Health Assembly, until the Seventy-first World Health Assembly, on progress towards
achievement of global immunization targets, as a substantive agenda item, utilizing the proposed accountability framework to guide discussions and future actions.

New collaboration to advance research on therapeutic vaccine for Chagas disease

    A new collaboration was announced to help advance research towards the development of a therapeutic vaccine for Chagas disease. The collaboration involves Baylor College of Medicine and SouthWest Electronic Energy Medical Research Institute, and “allots $250,000 per year for two years to support ongoing efforts at BCM in the research and development of a vaccine for Chagas disease, a tropical disease spread by insects that is an important cause of heart disease in South and Central America. This therapeutic vaccine would work to treat individuals already affected by this disease, which is common in those living in poverty.” Dr. Peter Hotez, dean of the newly established Baylor College of Medicine National School of Tropical Medicine and Texas Children’s Hospital Endowed Chair of Tropical Pediatrics, commented, “Chagas disease is one of the most devastating diseases of poverty in Latin America and the Caribbean region, including new foci in the Amazon Region. Chagas disease has also emerged in Texas and elsewhere in the U.S. There is an urgent need to develop new therapeutics for this infection, including a therapeutic vaccine.” SouthWest Electronic Energy recently established its Medical Research Institute under the leadership of company chairman and CEO Len Benckenstein. The goal of the Medical Research Institute is to collaborate directly in the active conduct of medical research with the most talented and productive medical researchers available.

PATH wins two Gates Grand Challenges Explorations grants to innovate delivery and management of vaccine supplies

PATH said it received two Grand Challenges Explorations grants from the Gates Foundation to explore new ways to deliver and manage vaccine supplies. Each winning proposal receives US$100,000. The first grant supports a PATH project to advance the development of a protective liner for vaccine carriers. The liner is prefilled with a newly developed material derived from biomass known as an engineered phase-change material. It can prevent vaccines from freezing during transport to remote locations while also extending the cooling capacity of vaccine carriers. The low-cost liner will use the novel phase-change material to protect vaccines from temperature extremes. The nontoxic material helps stabilize the temperature inside the carrier as frozen ice packs gradually warm, buffering vaccines from freezing temperatures. The liner can be retrofitted for use in existing carriers. PATH will work with companies that make vaccine carriers to conduct lab and field tests and develop product specifications that can be shared broadly with manufacturers. The second grant-funded project will assess the feasibility of using bar code technology to improve vaccine inventory management and supply forecasting when introducing new vaccines in low-income countries.

Global Fund “finds” about $1.6 billion in additional funding for 2012-14

Global Fund News Flash: Issue 01
Posted on Thursday, 10 May 2012

Extract (full text)
Available Funding
We start with a piece of very good news: a financial forecast by the Global Fund surprised everyone by finding that about $1.6 billion in additional funding will be available in the 2012-14 period for investment in projects that save lives. There were many factors that piled up on the plus side of the ledger, but most of the reasons grew out of tough choices that the Board made last year. A back-to-basics approach, focusing on the core business of managing grants, with common sense management, has created a situation where good things happen. Many of our friends noticed. Some got more generous. Others found they could speed up existing plans to make a donation. Still others jumped in for the first time. What the new forecast means is that in addition to the $616 million in funding for existing programs, known in Global Fund-speak as the ‘Transitional Funding Mechanism,’ there is another billion dollars for new grants. This has no effect on the $7 billion in grants that were already approved and scheduled to be disbursed over the next 18 months or so. But it means we can now help fund new projects that are designed to meet the most pressing need for service. Our mission statement sums it up best: We are investing the world’s money, to save lives.

Transformation in 90 Days
Gabriel Jaramillo, who became General Manager in February, 2012, reported to the Board of the Global Fund at its meeting today about the transformation he has led in his 90 days on the job. The place is not really the same as it was before he arrived. A full 245 jobs were eliminated. And 189 new positions were created, almost all in grant management. Net-net, it’s only an 8 percent drop. But inside the building, it felt like an earthquake. Now that the aftershocks have died down, the change is evident. It’s all about grant management. The division reset its priorities, with three ‘High Impact’ teams that concentrate on the countries with most of the disease burden, meaning the ones that require the most intensive work. Two other teams concentrate on smaller countries so every region gets the attention it needs. A reorganization like this can create more cohesion, by breaking down internal barriers. Plus, new executive committees make for better oversight and course correction. Jaramillo’s approach is that common sense rules.

PAHO Director receives Peru Order of Merit

      PAHO Director Dr. Mirta Roses Periago received Order of Merit in the Grade of Grand Officer from the government of Peru. The award resolution recognizes that Dr. Roses Periago “has led important and recognized efforts throughout Latin America, that have contributed substantially to improving health policies in Peru” and stressed “the high professional performance, specifically in the areas of immunization, malaria and tobacco control.  These results have been properly applied and incorporated in public health policies in Peru.”

WHO Fact sheet N°286: Measles

WHO Fact sheet N°286: Measles
April 2012

Key Facts
– Measles is one of the leading causes of death among young children even though a safe and cost-effective vaccine is available.

– In 2010, there were 139 300 measles deaths globally – nearly 380 deaths every day or 15 deaths every hour.

– More than 95% of measles deaths occur in low-income countries with weak health infrastructures.

– Measles vaccination resulted in a 74% drop in measles deaths between 2000 and 2010 worldwide.

– In 2010, about 85% of the world’s children received one dose of measles vaccine by their first birthday through routine health services – up from 72% in 2000.

Twitter Watch [accessed 12 May 2012 – 16:46]

Twitter Watch [accessed 12 May 2012 – 16:46]
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.

EndPolioNow @EndPolioNow
Amazing photos from the @UNICEF polio vaccination campaigns in South Sudan
2:16 PM – 12 May 12

Good wknd reading: Monitoring the Fight – blog on new estimates of global child mortality, & what they mean:
9:00 AM – 12 May 12

Dagfinn Høybråten @Hoybraten
We are closer than ever to beating #polio, but the funding shortfall may undermine the progress against the disease.
Retweeted by GAVI Alliance
1:15 AM – 12 May 12

PATH @PATHtweets
Congratulations to Dr. F. Marc LaForce for winning the prestigious Sabin Gold Medal Award!
Retweeted by GAVI Alliance
5:46 PM – 7 May 12

UNICEF USA@unicefusa
The @UPS Dir. of Humanitarian Logistics blogs about how logistical expertise helps @UNICEF in times of crisis #SahelNOW
Retweeted by UNICEF
9:02 AM – 10 May 12

How do #globalhealth workers deliver diff #vaccines w/ consistency? Expert group talking primary containers
9:00 AM – 10 May 12

The Global Fund @globalfundnews
#GlobalFund forecasts $1.6b in available funds for 2012-2014 reflects strategic choices by board, renewed confidence
3:56 AM – 10 May 12

Report: Ranking Vaccines: A Prioritization Framework (SMART)

Report: Ranking Vaccines: A Prioritization Framework – Phase I: Demonstration of Concept and a Software Blueprint

“As a number of diseases emerge or reemerge, thus stimulating new vaccine development opportunities to help prevent those diseases, it can be especially difficult for decision makers to know where to invest their limited resources. Therefore, it is increasingly important for decision makers to have the tools that can assist and inform their vaccine prioritization efforts. Ranking Vaccines: A Prioritization Framework describes a decision-support model and the blueprint of software called Strategic Multi-Attribute Ranking Tool for Vaccines, or SMART Vaccines, that should help decision makers prioritize new vaccines by accounting for demographic, economic, health, scientific, business, programmatic, social, policy and related factors. This study is being conducted in two phases. The first phase report which is being released describes a model—tested with three vaccine candidates—that can ultimately be used to prioritize new vaccines. Thus, this report describes a product that is purposefully midstream in development. In the next phase of this work, the committee will obtain feedback on the model from stakeholders to enhance SMART Vaccines. Moreover, the second phase of this study will test the model with three additional vaccines candidates.”

Read the Report >>

Report: Assembling the pharmaceutical R&D puzzle for needs in the developing world.

Report: Assembling the pharmaceutical R&D puzzle for needs in the developing world.
Pugatch Consilium – Meir Perez Pugatch, Rachel Chu & David Torstensson
May 2012

New report offers a blueprint to boost research and development (R&D) for diseases of the developing world

The IFPMA announced a new study was released “reviewing initiatives to encourage research and development (R&D) for diseases such as HIV, tuberculosis, malaria and neglected tropical diseases.” The report introduces “a blueprint based on six enabling factors that comprise: identification of gaps in the R&D process, mitigation of risk and cost of R&D, ability to translate research into clinical outcomes, sustainability of funding for specific disease areas, effective access to new medicines, and compatibility with different R&D mechanisms.” The report also provides a review of key mechanisms currently being discussed by global health policymakers which “delink the cost of R&D from the price of medicines, such as open databases, research grants, and advanced market commitments.”  The report’s authors conclude that multiple mechanisms are required to effectively address diverse R&D needs of the developing world.


Biosecurity and Censorship: the H5N1 Influenza Controversy

Journal of Infectious Diseases
Volume 205 Issue 11 June 1, 2012

Biosecurity and Censorship: the H5N1 Influenza Controversy
Martin S. Hirsch

In this issue of The Journal of Infectious Diseases (JID), 3 short articles by leaders in influenza virus research and/or biosecurity discuss current controversies regarding experiments with bioengineered H5N1 influenza virus. Sander Herfst and colleagues, the creators of an H5N1 virus strain with increased …

Sander Herfst, Albert D. M. E. Osterhaus, and Ron A. M. Fouchier
The Future of Research and Publication on Altered H5N1 Viruses
J Infect Dis. (2012) 205(11): 1628-1631 first published online March 27, 2012 doi:10.1093/infdis/jis257
a href=””>Abstract

Nicole M. Bouvier
The Science of Security Versus the Security of Science
J Infect Dis. (2012) 205(11): 1632-1635 first published online March 27, 2012 doi:10.1093/infdis/jis256

Michael T. Osterholm and David A. Relman
Creating a Mammalian-Transmissible A/H5N1 Influenza Virus: Social Contracts, Prudence, and Alternative Perspectives
J Infect Dis. (2012) 205(11): 1636-1638 first published online March 27, 2012 doi:10.1093/infdis/jis259

Comment: Re-engineering the European Union Clinical Trials Directive

The Lancet  
May 12, 2012  Volume 379  Number 9828  p1763 – 1850  e50 – 51

Re-engineering the European Union Clinical Trials Directive
MJH Kenter, AF Cohen

The European Union Clinical Trials Directive 2001/20/EC (EU CTD), which was introduced in 2004 for drug trials, aims to protect European citizens who take part in research, safeguard data quality, and harmonise the review of clinical trials. Unfortunately, the directive is based on an ill-defined, two-tier assessment system in which two review bodies—a national competent authority and a research ethics committee (REC)—both evaluate the same clinical trial application in every member state. The European Commission is currently considering a revision of the EU CTD, but this will simply build further on the current directive’s flawed foundations.

Perspective: Measles in the 21st Century

New England Journal of Medicine
May 10, 2012  Vol. 366 No. 19

Measles in the 21st Century
E. Kim Mulholland, M.D., Ulla Kou Griffiths, M.Sc., and Robin Biellik, Ph.D.
N Engl J Med 2012; 366:1755-1757May 10, 2012

This article has no abstract; the first 100 words appear below.
Barely 20 years ago, such a high proportion of childhood deaths globally was attributable to measles that the going estimate of more than 1 million measles-related deaths per year was almost certainly an underestimate. Pediatric wards in the developing world were filled with patients with measles and its complications, and measles continued to be a major cause of blindness globally. All this occurred despite the remarkable progress that had been achieved during the 1980s in bringing routine immunizations, including a single dose of measles vaccine, to the poorest countries of the world, culminating in the achievement of the global Universal . . .

Disease Control: Epidemiological and Economic Factors

PLoS One
[Accessed 12 May 2012];jsessionid=577FD8B9E1F322DAA533C413369CD6F3.ambra01?field=date

Understanding Disease Control: Influence of Epidemiological and Economic Factors
Katarzyna Oleś, Ewa Gudowska-Nowak, Adam Kleczkowski
PLoS ONE: Research Article, published 09 May 2012 10.1371/journal.pone.0036026

We present a model of disease transmission on a regular and small world network and compare different control options. Comparison is based on a total cost of epidemic, including cost of palliative treatment of ill individuals and preventive cost aimed at vaccination or culling of susceptible individuals. Disease is characterized by pre-symptomatic phase, which makes detection and control difficult. Three general strategies emerge: global preventive treatment, local treatment within a neighborhood of certain size and only palliative treatment with no prevention. While the choice between the strategies depends on a relative cost of palliative and preventive treatment, the details of the local strategy and, in particular, the size of the optimal treatment neighborhood depend on the epidemiological factors. The required extent of prevention is proportional to the size of the infection neighborhood, but depends on time till detection and time till treatment in a non-nonlinear (power) law. The optimal size of control neighborhood is also highly sensitive to the relative cost, particularly for inefficient detection and control application. These results have important consequences for design of prevention strategies aiming at emerging diseases for which parameters are not necessarily known in advance.

Development Assistance for Health and Government Health Spending

PLoS Medicine
(Accessed 12 May 2012)

Does Development Assistance for Health Really Displace Government Health Spending? Reassessing the Evidence
Rajaie Batniji, Eran Bendavid Essay, published 08 May 2012

Summary Points
– At the core of the current aid debate is the question of whether development assistance for health provided to developing country governments increases health expenditures.

– It has recently been suggested that development assistance for health to governments leads to a displacement of government spending, reinforcing skepticism about health aid.

– Here we examine a database of public financing for health from 1995 to 2006 and demonstrate that prior conclusions drawn from these data are unstable and driven by outliers.

– While government spending may be displaced by development assistance for health in some settings, the evidence is not robust and is highly variable across countries. We recommend

WHO: European Region – Update on measles and rubella, polio

WHO Epidemiological Brief 23: European Region – Update on measles and rubella, regional and global polio outbreak status

Measles and rubella
Incomplete reporting makes it difficult to provide an accurate number of measles cases for 2012, thus far. The officially reported number of cases (4 463) is much lower than the actual number, with the Ukrainian Ministry of Health, for example, reporting nearly 8 000 cases on its web site. Romania continues to report the highest number of rubella cases in the Region, as it faces an ongoing outbreak.

The European Region has retained its polio-free status after a 2010 polio outbreak, but remains at risk of the poliovirus importation while polio is still endemic in countries like Afghanistan and Pakistan. A recent outbreak in China, which is no longer considered active, offers a sobering illustration of this risk.  Consequently, it is critical to maintain high quality AFP, enterovirus and environmental surveillance in the Region to ensure early detection of wild poliovirus importation.

TuBerculosis Vaccine Initiative (TBVI) and Aeras announce vaccines MOU

The TuBerculosis Vaccine Initiative (TBVI) and Aeras announced a new memorandum of understanding “to enhance and strengthen collaborative efforts to advance the world’s most promising TB vaccine candidates.” Aeras is “a nonprofit global TB vaccine biotech based in the US and South Africa” and TBVI is “a pan-European TB vaccine research foundation based in the Netherlands.” The relationship “will address significant scientific opportunities and challenges described in Tuberculosis Vaccines: A Strategic Blueprint for the Next Decade” – a unified global strategy published last month in the journal Tuberculosis which provides a comprehensive approach for developing and introducing safe and effective TB vaccines over the next decade.” Jim Connolly, President and CEO of Aeras, said, “Without new TB vaccines, we cannot end this epidemic. TB vaccine development is particularly complex and costly, and to achieve our mission it is critical to bring together the best and brightest minds in the field. Aeras is looking forward to expanding our collaboration with TBVI, whose role has been pivotal in fueling the quality of research in Europe and the development of promising new vaccine candidates.” Dr. Jelle Thole, Director of TBVI, said, “Aeras has deep experience with preclinical and clinical evaluation of TB vaccine candidates and expertise in identifying promising vaccines. This provides important added value to our know-how. Together we are able to develop vaccines as cost-effectively and efficiently as possible, moving seamlessly from early laboratory research through clinical development to licensure, to deliver vaccines to communities that need their protection.”

Sabin Gold Medal to Dr. F. Marc LaForce

Event: Annual Albert B. Sabin Gold Medal Award Ceremony

The 19th annual Albert B. Sabin Gold Medal Award Ceremony will be held May 7, 2012 in Baltimore, Maryland. This year the award ceremony will honor Dr. F. Marc LaForce for his contributions to the development of a new vaccine for epidemic meningitis in Africa. The Gold Medal Award has been awarded annually since 1994 and is given to a distinguished member of the research community who has made extraordinary contributions in the field of vaccinology or a complementary field. Each recipient is a role model for young researchers, someone whose career has saved lives through the development and use of vaccines. The Medal is the highest scientific honor given by the Sabin Vaccine Institute and commemorates the legacy of the late Dr. Albert B. Sabin. This prestigious award is presented by the Sabin Vaccine Institute (Sabin) as part of the National Foundation for Infectious Diseases (NFID) annual conference in Baltimore, Maryland.

PATH – WHO (MVP) win 2012 Vaccine Industry Excellence Award

   PATH and the World Health Organization (WHO) were named winners of the 2012 Vaccine Industry Excellence Award for best vaccine partnership in recognition of the Meningitis Vaccine Project (MVP) that led to the introduction of a new meningitis A vaccine. Created in 2001, MVP developed MenAfriVac™, “a revolutionary vaccine that protects people against deadly meningitis A and could end a century of meningitis epidemics in sub-Saharan Africa. Since its introduction in 2010, more than 54 million Africans across six countries have received the vaccine. Not a single case of group A meningococcal meningitis has been reported among those vaccinated.” MVP, a partnership between PATH and WHO, is funded by the Bill & Melinda Gates Foundation and involves dozens of partner organizations working together across four continents. MVP “marks the first time a philanthropic foundation has joined with public- and private-sector organizations as well as nongovernmental organizations to create a vaccine that would not otherwise have been developed by the private sector.”

PATH’s Malaria Vaccine Initiative received an honorable mention in the same category for its public-private partnership with GSK Biologicals. That collaboration is supporting the development of RTS,S, a malaria vaccine candidate that could add a powerful, complementary tool for the control of malaria in Africa. The Malaria Vaccine Initiative was established at PATH in 1999 with the mission to accelerate the development of malaria vaccines and ensure their availability and accessibility in the developing world. The collaboration with GSK Biologicals began in 2001.

The Vaccine Industry Excellence Awards “are organized by Terrapinn and sponsored by Novartis Vaccines to recognize outstanding achievements by organizations and individuals in the vaccine industry. Nominees are judged on their strategic potential to the industry and potential to address unmet needs, among other criteria.” The awards were presented at the 12th World Vaccine Congress in Washington, DC, on April 11.

MMWR Weekly for May 4, 2012

The MMWR Weekly for May 4, 2012 / Vol. 61 / No. 17 includes:

Imported Human Rabies in a U.S. Army Soldier — New York, 2011

Comparison of Meningococcal Disease Surveillance Systems — United States, 2005–2008

Notes from the Field: Identification of Vibrio cholerae Serogroup O1, Serotype Inaba, Biotype El Tor Strain — Haiti, March 2012
On October 20, 2010, an outbreak of cholera was confirmed in Haiti for the first time in more than a century. As of April 10, 2012, a total of 534,647 cases, 287,656 hospitalizations, and 7,091 deaths have been reported in Haiti as a result of the outbreak (1). The Vibrio cholerae strain that caused the Haiti epidemic has been characterized as toxigenic V. cholerae, serogroup O1, serotype Ogawa, biotype El Tor (2).

Recently, two V. cholerae isolates collected on March 12 and 13, 2012, in Anse Rouge, Artibonite Department, were characterized at the National Public Health Laboratory in Haiti as non-Ogawa serotypes. The isolates subsequently were confirmed by CDC to belong to the Inaba serotype. By molecular analyses (pulsed-field gel electrophoresis, multilocus variable number of tandem repeat analysis, and virulence gene sequencing [ctxB and tcpA]), these two isolates are indistinguishable from the currently circulating V. cholerae serotype Ogawa strain in Haiti. The molecular analyses conducted to date suggest that they arose from serotype switching, which is a commonly observed phenomenon in cholera epidemics, often driven by population immunity to the circulating serotype. Further characterization efforts are ongoing.  Finding these two isolates does not change current clinical management guidelines (3)…

…The two World Health Organization prequalified vaccines provide protection against the Ogawa and Inaba serotypes. In addition, the cholera rapid diagnostic tests detect all O1 serogroup infections, including Ogawa and Inaba serotypes.

This serotype conversion illustrates the increasing diversity of V. cholerae in Haiti (2) and emphasizes the importance of continued public health surveillance by the National Public Health Laboratory and CDC, which are partnering to establish a laboratory-enhanced sentinel surveillance system for a range of infectious diseases, including cholera and other diarrheal diseases. The system will provide data to determine the burden of diarrheal disease attributable to cholera and to help direct prevention efforts and programs to reduce morbidity and mortality from cholera in Haiti

Twitter Watch [accessed 5 May 2012 – 14:42]

Twitter Watch [accessed 5 May 2012 – 14:42]
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.

Shot@Life ‏ @ShotAtLife
What can you commit? We’re kicking-off the campaign with a goal to vaccinate 1,000 children by Mother’s Day. Will you help us? #vaccineswork
10:51 AM – 26 Apr 12

HarvardPublicHealth @HarvardHSPH
CDC reports cholera in Haiti has changed, a sign that it is becoming endemic #globalhealth
10:21 AM – 5 May 12

GAVI Alliance @GAVIAlliance
@MeaslesRubella provided indispensable funding 4 Nepal & Myanmar campaigns. But success also depends on vaccine heroes.
3:35 AM – 5 May 12

Sandra Rotman Centre @srcglobal
“The challenge now is to stimulate public demand for vaccinations”: Southern Vaccine Advocacy Challenge
4:21 PM – 4 May 12

PAHO/WHO @pahowho
Top #PAHOWHO officials meet #Gates Foundation counterparts public health priorities
2:13 PM – 4 May 12

UofT Bioethics @utjcb
Anant Bhan, MHSc grad, has a new publication, “Clinical trial ethics in India: One step forward, two steps back”.
Retweeted by Sandra Rotman Centre
12:39 PM – 2 May 12

ECDC Eurovaccine @Eurovaccine
Helpful reading: 7 key reasons to immunise from @WHO_Europe #EuropeDoctorsMeet #immuniseEurope
5:07 AM – 4 May 12

Public health experts, doctors & patients discuss role of doctors in childhood #vaccination, 4May w/ @CPME_Europa.Follow #EuropeDoctorsMeet
3:39 AM – 3 May 12

Report: Ethical and Scientific Issues in Studying the Safety of Approved Drugs

Report: Ethical and Scientific Issues in Studying the Safety of Approved Drugs

Institute of Medicine (IOM); 1 May 2012

Prescription drugs are crucial for preventing and treating diseases and improving the public’s health, but they can also have unintended harmful effects. Often, their benefits and risks cannot be fully identified until after a drug has been used by a large, diverse group of patients over time. The passage of the Food and Drug Administration Act in 2007 provides the Food and Drug Administration (FDA) with additional postmarketing regulatory tools to better protect the health of the public, including the authority to require manufacturers to continue studying drugs that are being marketed. The FDA asked the IOM to evaluate the scientific and ethical aspects of conducting safety studies for approved drugs. The IOM recommends implementing a life cycle approach to drug safety oversight that could allow the FDA to better anticipate post-approval research needs and improve drug safety for all Americans.

Read the Report >>

Editorial: Establishing an evidence base for e-health

Bulletin of the World Health Organization
Volume 90, Number 5, May 2012, 321-400

Special theme: e-health
Establishing an evidence base for e-health: the proof is in the pudding
Najeeb Al-Shorbaji & Antoine Geissbuhler
Bulletin of the World Health Organization 2012;90:322-322A. doi: 10.2471/BLT.12.106146

Seven years have passed since the World Health Assembly adopted resolution WHA58.28 urging the World Health Organization and its Member States1 to endorse e-health as a way to strengthen health systems. In defining e-health as “the cost-effective and secure use of information and communication technologies in support of health and health-related fields”, the resolution offered a definition that was comprehensive and generic, yet specific enough for researchers wishing to evaluate the impact of e-health to know what to evaluate. Specifically, the resolution urged Member States to “mobilize multisectoral collaboration for determining evidence-based e-health standards and norms, to evaluate e-health activities, and to share the knowledge of cost-effective models, thus ensuring quality, safety and ethical standards and respect for the principles of confidentiality of information, privacy, equity and equality”.

This theme issue has three main objectives, as explained in a call for papers2 published in June 2011:

– to provide an authoritative, critical and independent overview of current knowledge about appropriate, trans-disciplinary methods and applications in e-health;

– to include contributors from developing countries, who seldom have the opportunity to publish in international journals;

– to strengthen the commitment of high-level decision-makers to address e-health interoperability issues and seek to widened the application of e-health.

Researchers, academicians and practitioners from all over the world responded to the call for papers with more than 90 submissions, 14 of which are published here.

Van Gemert-Pijnen et al.’s editorial3 makes a worthy point: e-health development must be holistic, evidence-based and people-centred; it must take into account how people live within their own environments and respond to stakeholders’ needs. In the research section that follows, Wootton et al.4 examine the characteristics of long-running telemedicine networks and conclude that “improved collaboration between networks could help attenuate the lack of resources […] and improve sustainability”. In a study of the health-related uses of information and communication technologies (ICT) in low- and middle-income countries, Lewis et al.5 find three leading purposes: to extend geographic access to health care, to improve data management, and to facilitate communication between patients and physicians outside the physician’s office. The authors highlight the need for more sustainable sources of funding, greater support for the adoption of new technologies, and better ways to evaluate impact. A review by Piette et al.6 of the published literature on e-health systems of three types – systems facilitating clinical practice, institutional systems and systems facilitating care at a distance – shows that e-health can improve clinical care in low- and middle-income countries, but that more research is needed on its economic benefits and impact on patient health.

In a revealing Perspective, Thirumurthy & Lester7 find evidence that mobile health (m-health) can enable behaviour change and improve health outcomes in resource-limited settings. Van Heerden et al.8 argue, in the same section, that the real challenge for the deployment of e-health lies in establishing country-level best practices that are both cost-effective and supported by rigorous research and evaluation. Policy-makers and funders must promote, legislate and fund programmes and interventions that integrate and build upon a common m-health framework. Kwankam9 identifies further challenges facing e-health: creating a platform for knowledge sharing; scaling up interventions; designing integrated e-health systems; conducting professional training on e-health; integrating e-health into the social and economic context, and building ICT into the health systems of the future.

Alkmim et al.,10 in a Lesson from the field, describe a telehealth network in Brazil and how in just five years there was a notable increase in the number of professionals trained in telehealth and in the number of electrocardiograms and teleconsultations performed through the network. The authors caution, however, that to succeed, a telehealth service needs to be collaborative, to meet the real needs of local health professionals, to employ a simple technology and to have at least some face-to-face components. According to Braa et al.11, data use workshops have strengthened the health management information systems by improving the quality of public health data in Zanzibar, United Republic of Tanzania. In Madagascar,12 Rajatonirina et al. found evidence of improved disease surveillance capacity despite resource constraints owing to an innovative sentinel system based on a short message service.

The factors promoting or inhibiting the implementation of e-health systems were the subject of a systematic review, by Mair et al.,13 that shows a growing research emphasis on “workability”, or the work that health professionals must undertake to make e-health systems function well in practice. The review also points to the need for more research on the impact of e-health services on everyday clinical practice.

This theme issue highlights what we have learnt from e-health projects throughout the world in terms of feasibility, acceptance and impact on processes. The recipe may seem familiar and replicable, but the proof is in the pudding, in the clear demonstration that e-health can result in economic benefits and improve health outcomes. Programme evaluators and implementers face the challenge of generating such evidence, a prerequisite for the widespread adoption of e-health.14

Global Health and Human Rights Database

Health and Human Rights
Vol 13, No 2 (2011) December
[Reviewed earlier]

Papers in Press  (Issue 14.1, June 2012)
Bridging international law and rights-based litigation: Mapping health-related rights through the development of the Global Health and Human Rights Database
Benjamin Mason Meier, Helena Nygren-Krug, Oscar A. Cabrera, Ana Ayala, Lawrence O. Gostin

The O’Neill Institute for National and Global Health Law at Georgetown University, the World Health Organization, and the Lawyers Collective have come together to develop a searchable Global Health and Human Rights Database that maps the intersection of health and human rights in judgments, international and regional instruments, and national constitutions. Where states long remained unaccountable for violations of health-related human rights, litigation has arisen as a central mechanism in an expanding movement to create rights-based accountability. Facilitated by the incorporation of international human rights standards in national law, this judicial enforcement has supported the implementation of rights-based claims, giving meaning to states’ longstanding obligations to realize the highest attainable standard of health. Yet despite these advancements, there has been insufficient awareness of the international and domestic legal instruments enshrining health-related rights and little understanding of the scope and content of litigation upholding these rights. As this accountability movement evolves, the Global Health and Human Rights Database seeks to chart this burgeoning landscape of international instruments, national constitutions, and judgments for health-related rights. Employing international legal research to document and catalogue these three interconnected aspects of human rights for the public’s health, the Database’s categorization by human rights, health topics, and regional scope provides a comprehensive means of understanding health and human rights law. Through these categorizations, the Global Health and Human Rights Database serves as a basis for analogous legal reasoning across states to serve as precedents for future cases, for comparative legal analysis of similar health claims in different country contexts, and for empirical research to clarify the impact of human rights judgments on public health outcomes.

Lessons learned and applied…Vaccines in the 21st century

Human Vaccines & Immunotherapeutics (formerly Human Vaccines)
Volume 8, Issue 5  May 2012

Lessons learned and applied: What the 20th century vaccine experience can teach us about vaccines in the 21st century
Corey Joseph Hebert, Corey Hall and La’ Nyia J. Odoms

Abstract    Open Access Article
Most vaccines available in the United States have been incorporated into vaccination schedules for infants and young children, age groups particularly at risk of contracting infectious diseases. High universal vaccination coverage is responsible for substantially reducing or nearly eliminating many of the diseases that once killed thousands of children each year in the US…

Potential of a recombinant pandemic influenza vaccine produced in tobacco plants

Human Vaccines & Immunotherapeutics (formerly Human Vaccines)
Volume 8, Issue 5  May 2012

Research Papers
The human potential of a recombinant pandemic influenza vaccine produced in tobacco plants
Asne Jul-Larsen, Abdullah Madhun, Karl Brokstad, Emanuele Montomoli, Vidadi Yusibov and Rebecca Cox

Abstract   Open Access Article
Rapid production of influenza vaccine antigen is an important challenge when a new pandemic occurs. Production of recombinant antigens in plants is a quick, cost effective and up scalable new strategy for influenza vaccine production. In this study, we have characterized a recombinant influenza haemagglutinin antigen (HAC1) that was derived from the 2009 pandemic H1N1 virus and expressed in tobacco plants. Volunteers vaccinated with the 2009 pH1N1 oil-in-water adjuvanted vaccine provided serum and lymphocyte samples that were used to study the immunogenic properties of the HAC1 antigen in vitro. By 7 d post vaccination, the vaccine fulfilled the licensing criteria for antibody responses to the HA detected by haemagglutination inhibition and single radial hemolysis. By ELISA and ELISPOT analysis we showed that HAC1 was recognized by specific serum antibodies and antibody secreting cells, respectively. We conducted a kinetic analysis and found a peak of serum HAC1 spec antibody response between day 14 and 21 post vaccination by ELISA. We also detected elevated production of IL-2 and IFNγ and low frequencies of CD4+ T cells producing single or multiple Th1 cytokines after stimulating PBMCs (peripheral blood mononuclear cells) with the HAC1 antigen in vitro. This indicates that the antigen can interact with T cells, although confirming an effective adjuvant would be required to improve the T-cell stimulation of plant based vaccines. We conclude that the tobacco derived recombinant HAC1 antigen is a promising vaccine candidate recognized by both B- and T cells.

Cholera vaccine: New preventive tool for endemic countries

Human Vaccines & Immunotherapeutics (formerly Human Vaccines)
Volume 8, Issue 5  May 2012

Cholera vaccine: New preventive tool for endemic countries
Ramesh Verma, Pardeep Khanna and Suraj Chawla

Cholera is a major global public health problem and remains an important threat in almost every developing country, especially in areas where population overcrowding and poor sanitation are common, such as slums and refugee camps. Cholera is one of the most dreaded diseases in the world, in some cases leading to death within 24 h if left untreated. Without treatment, severe infection has a mortality rate of 30–50%. In 2007, WHO recorded 177,963 cholera cases and 4,031 deaths worldwide. However, the estimated actual burden of cholera is in the vicinity of 3 to 5 million cases and 100 000 to 130 000 deaths per year. The disease is endemic to parts of Africa, Asia, the Middle East and South America.1 Large outbreaks are common after natural disasters or in populations displaced by war, where there is inadequate sewage disposal and contaminated water. In India, during the 10-y period (1997–2006) studied, the states having the highest number of reported outbreaks were West Bengal, Orissa, Maharashtra and Kerala, which together accounted for 60% of all reported outbreaks. A review of cholera cases in India reported to WHO from 2003–2007 showed that the numbers were in the few thousands with a case fatality rate of < 1%. However, it is believed that the number of cholera cases and deaths occurring annually in India is much greater than the number reported. A literature review covering a four-year period from 2003 to 2006 found reported cholera outbreaks in 18 of the 35 States and Union Territories of India. Of these, 11 had cholera outbreaks reported for multiple years. Vietnam has produced a cheaper variant of killed whole-cell vaccine devoid of the B subunit. This vaccine contains both Vibrio cholerae O1 and O139, and provides 50 per cent protection for at least three years after vaccination. For endemic cholera, population-level immunity is relatively high, making control possible with relatively low vaccine coverage levels. This vaccine should be used in areas where cholera is endemic, particularly in those at risk of outbreaks, in conjunction with other prevention and control strategies.

Clinical Trial Registeries – Evolution and Characteristics

May 2, 2012, Vol 307, No. 17, pp 1775-1877

Original Contributions
Characteristics of Clinical Trials Registered in, 2007-2010
Robert M. Califf, Deborah A. Zarin, Judith M. Kramer, Rachel E. Sherman, Laura H. Aberle, Asba Tasneem
JAMA. 2012;307(17):1838-1847.doi:10.1001/jama.2012.3424

Context  Recent reports highlight gaps between guidelines-based treatment recommendations and evidence from clinical trials that supports those recommendations. Strengthened reporting requirements for studies registered with enable a comprehensive evaluation of the national trials portfolio.

Objective  To examine fundamental characteristics of interventional clinical trials registered in the database.

Methods  A data set comprising 96 346 clinical studies from was downloaded on September 27, 2010, and entered into a relational database to analyze aggregate data. Interventional trials were identified and analyses were focused on 3 clinical specialties—cardiovascular, mental health, and oncology—that together encompass the largest number of disability-adjusted life-years lost in the United States.

Main Outcome  Measures Characteristics of registered clinical trials as reported data elements in the trial registry; how those characteristics have changed over time; differences in characteristics as a function of clinical specialty; and factors associated with use of randomization, blinding, and data monitoring committees (DMCs).

Results  The number of registered interventional clinical trials increased from 28 881 (October 2004–September 2007) to 40 970 (October 2007–September 2010), and the number of missing data elements has generally declined. Most interventional trials registered between 2007 and 2010 were small, with 62% enrolling 100 or fewer participants. Many clinical trials were single-center (66%; 24 788/37 520) and funded by organizations other than industry or the National Institutes of Health (NIH) (47%; 17 592/37 520). Heterogeneity in the reported methods by clinical specialty; sponsor type; and the reported use of DMCs, randomization, and blinding was evident. For example, reported use of DMCs was less common in industry-sponsored vs NIH-sponsored trials (adjusted odds ratio [OR], 0.11; 95% CI, 0.09-0.14), earlier-phase vs phase 3 trials (adjusted OR, 0.83; 95% CI, 0.76-0.91), and mental health trials vs those in the other 2 specialties. In similar comparisons, randomization and blinding were less frequently reported in earlier-phase, oncology, and device trials.

Conclusion  Clinical trials registered in are dominated by small trials and contain significant heterogeneity in methodological approaches, including reported use of randomization, blinding, and DMCs.

The Evolution of Trial Registries and Their Use to Assess the Clinical Trial Enterprise
Kay Dickersin, Drummond Rennie
JAMA. 2012;307(17):1861-1864.doi:10.1001/jama.2012.4230

The original purpose of registries of clinical trials was to reveal the existence of all trials, published or not, to investigators and systematic reviewers. Trials left unpublished because results were unfavorable to their sponsors, or simply because investigators never submitted them to journals for publication, could then be discovered, the trial investigators contacted, and the available trial evidence involving medical interventions could then be assessed. This would help eliminate publication bias, shown originally in the 1980s,1 demonstrated by Simes2 to affect the treatment of patients, and later revealed to be widespread by the expanding efforts of the Cochrane Collaboration. A seemingly arcane statistical point became a pressing clinical problem.

Although the 1997 US Food and Drug Administration Modernization Act (FDAMA)3 established a US-based trial registry,, the mandated content was narrowly defined by law, and trial investigators, whether funded by commercial sponsors, government agencies, or academic institutions, …

Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets

Volume 485 Number 7396 pp5-142  3 May 2012

Advance Online Publication (AOP)
Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets

Masaki Imai, Tokiko Watanabe, Masato Hatta, Subash C. Das, Makoto Ozawa, Kyoko Shinya, Gongxun Zhong, Anthony Hanson, Hiroaki Katsura, Shinji Watanabe, Chengjun Li, Eiryo Kawakami, Shinya Yamada, Maki Kiso, Yasuo Suzuki, Eileen A. Maher, Gabriele Neumann & Yoshihiro Kawaoka

Highly pathogenic avian H5N1 influenza A viruses occasionally infect humans, but currently do not transmit efficiently among humans. The viral haemagglutinin (HA) protein is a known host-range determinant as it mediates virus binding to host-specific cellular receptors1, 2, 3. Here we assess the molecular changes in HA that would allow a virus possessing subtype H5 HA to be transmissible among mammals. We identified a reassortant H5 HA/H1N1 virus—comprising H5 HA (from an H5N1 virus) with four mutations and the remaining seven gene segments from a 2009 pandemic H1N1 virus—that was capable of droplet transmission in a ferret model. The transmissible H5 reassortant virus preferentially recognized human-type receptors, replicated efficiently in ferrets, caused lung lesions and weight loss, but was not highly pathogenic and did not cause mortality. These results indicate that H5 HA can convert to an HA that supports efficient viral transmission in mammals; however, we do not know whether the four mutations in the H5 HA identified here would render a wholly avian H5N1 virus transmissible. The genetic origin of the remaining seven viral gene segments may also critically contribute to transmissibility in mammals. Nevertheless, as H5N1 viruses continue to evolve and infect humans, receptor-binding variants of H5N1 viruses with pandemic potential, including avian–human reassortant viruses as tested here, may emerge. Our findings emphasize the need to prepare for potential pandemics caused by influenza viruses possessing H5 HA, and will help individuals conducting surveillance in regions with circulating H5N1 viruses to recognize key residues that predict the pandemic potential of isolates, which will inform the development, production and distribution of effective countermeasures.

Opinion: The WHO must reform for its own health

Nature Medicine
May 2012, Volume 18 No 5 pp631-834

The WHO must reform for its own health – p646
Tikki Pang & Laurie Garrett

The World Health Organization (WHO) is facing an unprecedented crisis that threatens its position as the premier international health agency. To ensure its leading role, it must rethink its internal governance and revamp its financing mechanisms.

04 May 2012

Pediatrics Perspective: Inside Millennium Development Goal 4

May 2012, VOLUME 129 / ISSUE 5

Pediatrics Perspective
Inside Millennium Development Goal 4
Jonathan M. Spector
Pediatrics 2012; 129:805-808

Context and Extract
This Pediatrics Perspectives column traces the origins of the promises and commitments made to decrease global under-5 mortality. The disparities that exist worldwide are extraordinarily large, although significant progress has been made since the establishment of the Millennium Development Goals (MDGs). Dr Spector traces the origins and challenges of Goal 4 (of 8) that relate specifically to this issue. Although overall survival rates are improving, outcome gaps in under-5 mortality have widened between rich and poor nations. Clearly, the MDGs must be looked at as a large package. There are specific measurements for each goal, but success in 1 area influences the outcomes in the others. Our advocacy efforts should focus on improving the lives of the world’s poorest people broadly. World leaders have committed to achieving the MDGs by 2015. We all need to use our influence and personal resources to push the international community to succeed in eliminating extreme poverty and hunger everywhere, ultimately allowing for elimination of the growing health disparities among the affluent and poorest nations.
—Jay E. Berkelhamer, MD
Editor, Global Health Perspectives

The Millennium Development Goals (MDGs) have been dubbed the “world’s biggest promise.”1 At the turn of the 21st century, 189 (now 192) United Nations (UN) member states agreed to support the most comprehensive poverty reduction objectives ever established (Table 1).2,3 Child mortality is addressed through Goal 4: reduction of the global under-5 mortality rate (U5MR) by two-thirds between 1990 and 2015, equivalent to an annual drop rate of 4.3% (Table 2).4 In 1990, the U5MR was estimated at 84 of 1000 live births, and 11.9 million largely preventable child deaths took place. If MDG 4 could be achieved, 30 million children would be saved by 2015.2 Since their launch, the MDGs have been …

Measles-Containing Vaccines and Febrile Seizures in Children Age 4 to 6 Years

May 2012, VOLUME 129 / ISSUE 5

Measles-Containing Vaccines and Febrile Seizures in Children Age 4 to 6 Years
Nicola P. Klein, Edwin Lewis, Roger Baxter, Eric Weintraub, Jason Glanz, Allison Naleway, Lisa A. Jackson, James Nordin, Tracy Lieu, Edward A. Belongia, and Bruce Fireman
Pediatrics 2012; 129:809-814

BACKGROUND: In the United States, children receive 2 doses of measles-mumps-rubella vaccine (MMR) and varicella vaccine (V), the first between ages 1 to 2 years and the second between ages 4 to 6 years. Among 1- to 2-year-olds, the risk of febrile seizures 7 to 10 days after MMRV is double that after separate MMR + V. Whether MMRV or MMR + V affects risk for febrile seizure risk among 4- to 6-year-olds has not been reported.

METHODS: Among 4- to 6-year-old Vaccine Safety Datalink members, we identified seizures in the emergency department and hospital from 2000 to 2008 and outpatient visits for fever from 2006 to 2008 during days 7 to 10 and 0 to 42 after MMRV and MMR + V. Incorporating medical record reviews, we assessed seizure risk after MMRV and MMR + V.

RESULTS: From 2006 through 2008, 86 750 children received MMRV; from 2000 through 2008, 67 438 received same-day MMR + V. Seizures were rare throughout days 0 to 42 without peaking during days 7 to 10. There was 1 febrile seizure 7 to 10 days after MMRV and 0 after MMR + V. Febrile seizure risk was 1 per 86 750 MMRV doses (95% confidence interval, 1 per 3 426 441, 1 per 15 570) and 0 per 67 438 MMR + V doses (1 per 18 282).

CONCLUSIONS: This study provides reassurance that MMRV and MMR + V were not associated with increased risk of febrile seizures among 4- to 6-year-olds. We can rule out with 95% confidence a risk greater than 1 febrile seizure per 15 500 MMRV doses and 1 per 18 000 MMR + V doses.

Commentary: Why Do Pertussis Vaccines Fail?

May 2012, VOLUME 129 / ISSUE 5

Why Do Pertussis Vaccines Fail?
James D. Cherry
Pediatrics 2012; 129:968-970

During the 2010 pertussis epidemic in California, there was considerable concern in the press and in public health communications about the possible contribution of vaccine failures to the problem.1,2.

…The first reason, and perhaps the most important one, is that our estimates of vaccine efficacy have been inflated because of case definition.3–11 At the time of the pediatric diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine efficacy trials in the early 1990s, it was hoped that a universal case definition could be developed so that the results of the various trials could be compared. To this end, the World Health Organization (WHO) case definition was developed.3 The primary case definition required laboratory confirmation and ≥21 days of paroxysmal cough. I was a member of the WHO committee and disagreed with the primary case definition because it was clear at that time that this definition would eliminate a substantial number of cases and therefore inflate reported efficacy values.4–11 Nevertheless, the Center for Biologics Evaluation and Research of the Food and Drug Administration accepted this definition, and package inserts of the US-licensed DTaP vaccines reflect this. For example, Infanrix (containing 25 μg pertussis toxin [PT], 25 μg filamentous hemagglutinin [FHA], and 8 μg pertactin [PRN]) and Daptacel (containing 10 μg PT, 5 μg FHA, 5 μg fimbriae [FIM]-2/3, and 3 μg …

Pediatric Clinical Trial Registration and Trial Results: An Urgent Need for Improvement

May 2012, VOLUME 129 / ISSUE 5

Pediatric Clinical Trial Registration and Trial Results: An Urgent Need for Improvement
Scott C. Denne
Pediatrics 2012; 129:e1320-e1321

Performing research studies in children to evaluate drugs and other therapies is critical to providing proper pediatric medical care. For too long, medication use in children has been limited to extrapolation from adult studies or off-label use for indications that have not been properly evaluated in children. It has been less than 20 years since practical measures have been put in place to ensure that the necessary research evaluating therapies is more consistently carried out in children. Prompted by the American Academy of Pediatrics and other pediatric organizations, the Food and Drug Administration (FDA) in 1997 and the National Institutes of Health (NIH) in 1998 initiated policies designed to increase the number of children in research studies, including drug trials.1,2 Along with subsequent legislation, including the Best Pharmaceuticals for Children Act (2002), and the Pediatric Research Equity Act (2007), the initiatives by the FDA and …

Learning from Hackers: Open-Source Clinical Trials

Science Translational Medicine
2 May 2012 vol 4, issue 132

Learning from Hackers: Open-Source Clinical Trials
Adam G. Dunn, Richard O. Day, Kenneth D. Mandl, and Enrico Coiera
2 May 2012: 132cm5

Open sharing of clinical trial data has been proposed as a way to address the gap between the production of clinical evidence and the decision-making of physicians. A similar gap was addressed in the software industry by their open-source software movement. Here, we examine how the social and technical principles of the movement can guide the growth of an open-source clinical trial community.