Vaccines: The Week in Review 22 December 2012

Editor’s Notes:

– Vaccines: The Week in Review will resume publication on 5 January 2013 following a holiday break next week

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pdf version: A pdf of the current issues is available here: Vaccines_The Week in Review_22 December 2012_PDF

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UNICEF, WHO condemn attacks on polio health workers in Pakistan

UNICEF, WHO Joint Statements: Attacks on polio health workers in Pakistan
19 December 2012 – ISLAMABAD
UNICEF and The World Health Organization join the government and people of Pakistan in condemning the multiple attacks on health workers in the past week.

Those killed or injured, many of whom are women, are among hundreds of thousands of heroes who work selflessly to eradicate polio and provide other health services to children in Pakistan. Such attacks deprive children in Pakistan of their right to basic life-saving health interventions and place them at risk for a disease that causes lifelong disability.

In light of the prevailing security situation, WHO and UNICEF Pakistan are implementing additional security protocols to ensure the safety and security of their polio workers.

UNICEF, WHO and all our partners in Pakistan express our deepest sympathy to the families of the health workers who were killed or injured. We remain committed to supporting the Government and the people of Pakistan in their efforts to rid the country of polio.

18 December 2012
WHO and UNICEF join the Government of Pakistan and the provinces of Sindh and Khyber Pakhtunkhwa in condemning the multiple attacks that have killed six health workers in the past 24 hours.

At least six people working on a polio vaccination campaign have been reported shot dead in several locations in Pakistan – Gadap, Landi, Baldia and Orangi towns of Karachi city, Sindh Province and Peshawar, Khyber Pakhtunkhwa Province. Those killed were among thousands who work selflessly across Pakistan to eradicate polio.

The Government of Pakistan and the affected provinces have temporarily suspended the vaccination campaign due to concerns over safety of health workers.

Such attacks deprive Pakistan’s most vulnerable populations – especially children – of basic life-saving health interventions. We call on the leaders of the affected communities and everyone concerned to do their utmost to protect health workers and create a secure environment so that we can meet the health needs of the children of Pakista

Polio is a highly infectious disease caused by a virus that can cause permanent paralysis in a matter of hours. Safe and effective vaccines protect children from the disease. Currently the disease remains endemic in only three countries: Afghanistan, Nigeria and Pakistan.

WHO, UNICEF and all their partners in Pakistan and globally express their deepest sympathy to the families of the health workers. We remain committed to supporting the Government of Pakistan and the people of Pakistan in their efforts to rid the country of polio and other diseases.

UN Condemns deadly attacks on polio workers in Pakistan


GPEI Update: Polio this week – As of 18 Dec 2012

Update: Polio this week – As of 18 Dec 2012
Global Polio Eradication Initiative

[Editor’s Extract]
See joint statement by WHO, UNICEF

– Two new WPV cases were reported in the past week (1 WPV1 from Kano and 1 WPV3 from Yobe), bringing the total number of WPV cases for 2012 to 119. The WPV1 from Kano is the most recent in the country and had onset of paralysis on 20 November.

Horn of Africa
– Efforts are continuing to stop an ongoing cVDPV2 outbreak in Kenya and parts of Somalia (in a Somali refugee camp in Dadaab, Kenya, and Kismayo, south-central Somalia)…”

Aeras CEO Jim Connolly to step down

Aeras announced that Jim Connolly will step down as CEO effective January 31, 2013 but remain active on its Board of Directors. Aeras Chief Scientific Officer Dr. Tom Evans will serve as interim CEO, starting on February 1, 2013, while the Board of Directors selects a permanent successor. Aeras describes itself as “a non-profit product development organization dedicated to the development of effective tuberculosis (TB) vaccines and biologics to prevent TB across all age groups in an affordable and sustainable manner.”


GSK said that the FDA approved FLUARIX QUADRIVALENT (Influenza Virus Vaccine) for the immunisation of children (three years and older) and adults to help prevent disease caused by seasonal influenza (flu) virus subtypes A and type B contained in the vaccine. Fluarix Quadrivalent is the first intramuscular vaccine to cover against four influenza strains. Dr. Leonard Friedland , VP and Head, GSK North America Vaccines Clinical Development and Medical Affairs, said, “Trivalent influenza vaccines have helped protect millions of people against flu, but in six of the last 11 flu seasons, the predominant circulating influenza B strain was not the strain that public health authorities selected. Fluarix Quadrivalent will help protect individuals against both B strains and from a public-health standpoint, can help decrease the burden of disease.”

WHO: Global Immunization News December 2012

WHO: Global Immunization News   December 2012

– Djibouti celebrates Introduction of Pneumococcal vaccine in the National Immunization programme

– Growing Consensus on Strengthening National Vaccine Delivery Systems

– Timor-Leste launches introduction of new vaccine as part of intensification of routine immunization

– Review of National Immunization Programme in Tajikistan, 19-28 November 2012

– Eastern Mediterranean is the first WHO region launching Vaccine Safety E-learning course CD

– New technology for producing thermostable INFLUENZA vaccines

– The 2nd Hands-on Training Course to Implement Real-time Polymerase Chain Reaction (PCR) Technique for Rapid Detection and Characterization of Polioviruses in the Western Pacific Region

– 18th Meeting of the Regional Commission for the Certification of Poliomyelitis Eradication in the Western Pacific Region

– First meeting on seasonal influenza vaccines in Western Pacific Region

– IPV recommended for countries to mitigate risks and consequences associated with OPV2 withdrawal

– Global Invasive Bacterial Vaccine Preventable Diseases Surveillance Meeting

– SOUTH EAST ASIA countries share experiences on intensification of routine immunization at GAVI Partners’ Forum

– National Polio Committees develop action plans for 2013 in Ouagadougou, Burkina Faso

– Immunizations Systems and Technologies for Tomorrow

IVAC – Costing Dengue Cases and Outbreaks: A Guide to Current Practices and Procedures

IVAC: Costing Dengue Cases and Outbreaks: A Guide to Current Practices and Procedures
December 20, 2012

“In response to the growing need to answer the question of cost in order to weigh the benefits of future introduction of vaccines against dengue, IVAC convened an expert panel in March 2012 to discuss and develop a standardized methodology for estimating costs of dengue in the Americas. The resulting guidelines aim to ensure robust assessment of the economic burden of dengue infections and to make the results of future dengue cost studies more comparable among Latin American countries.”

Contributing factors to influenza vaccine uptake in general hospitals: an explorative management questionnaire study from the Netherlands

BMC Public Health
(Accessed 22 December 2012)

Research article
Contributing factors to influenza vaccine uptake in general hospitals: an explorative management questionnaire study from the Netherlands
Josien Riphagen-Dalhuisen, Joep CF Kuiphuis, Arjen R Procé, Willem Luytjes, Maarten J Postma, Eelko Hak BMC Public Health 2012, 12:1101 (21 December 2012)

Abstract (provisional)
The influenza vaccination rate in hospitals among health care workers in Europe remains low. As there is a lack of research about management factors we assessed factors reported by administrators of general hospitals that are associated with the influenza vaccine uptake among health care workers.

All 81 general hospitals in the Netherlands were approached to participate in a self-administered questionnaire study. The questionnaire was directed at the hospital administrators. The following factors were addressed: beliefs about the effectiveness of the influenza vaccine, whether the hospital had a written policy on influenza vaccination and how the hospital informed their staff about influenza vaccination. The questionnaire also included questions about mandatory vaccination, whether it was free of charge and how delivered as well as the vaccination campaign costs. The outcome of this one-season survey is the self-reported overall influenza vaccination rate of health care workers.

In all, 79 of 81 hospitals that were approached were willing to participate and therefore received a questionnaire. Of these, 42 were returned (response rate 52%). Overall influenza vaccination rate among health care workers in our sample was 17.7% (95% confidence interval: 14.6% to 20.8%). Hospitals in which the administrators agreed with positive statements concerning the influenza vaccination had a slightly higher, but non-significant, vaccine uptake. There was a 9% higher vaccine uptake in hospitals that spent more than [euro sign]1250,- on the vaccination campaign (24.0% versus 15.0%; 95% confidence interval from 0.7% to 17.3%).

Agreement with positive statements about management factors with regard to influenza vaccination were not associated with the uptake. More economic investments were related with a higher vaccine uptake; the reasons for this should be explored further.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

Indigenous populations health protection: A Canadian perspective

BMC Public Health
(Accessed 22 December 2012)

Indigenous populations health protection: A Canadian perspective
Katya L Richardson, Michelle S Driedger, Nick J Pizzi, Jianhong Wu, Seyed M Moghadas BMC Public Health 2012, 12:1098 (20 December 2012)

Abstract (provisional)
The disproportionate effects of the 2009 H1N1 pandemic on many Canadian Aboriginal communities have drawn attention to the vulnerability of these communities in terms of health outcomes in the face of emerging and reemerging infectious diseases. Exploring the particular challenges facing these communities is essential to improving public health planning. In alignment with the objectives of the Pandemic Influenza Outbreak Research Modelling (Pan-InfORM) team, a Canadian public health workshop was held at the Centre for Disease Modelling (CDM) to: (i) evaluate post-pandemic research findings; (ii) identify existing gaps in knowledge that have yet to be addressed through ongoing research and collaborative activities; and (iii) build upon existing partnerships within the research community to forge new collaborative links with Aboriginal health organizations. The workshop achieved its objectives in identifying main research findings and emerging information post pandemic, and highlighting key challenges that pose significant impediments to the health protection and promotion of Canadian Aboriginal populations. The health challenges faced by Canadian indigenous populations are unique and complex, and can only be addressed through active engagement with affected communities. The academic research community will need to develop a new interdisciplinary framework, building upon concepts from ‘Communities of Practice’, to ensure that the research priorities are identified and targeted, and the outcomes are translated into the context of community health to improve policy and practice.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

Personal View – Polio eradication was an ideological project

British Medical Journal
22 December 2012 (Vol 345, Issue 7888)

Views & Reviews – Personal View
Polio eradication was an ideological project
BMJ 2012; 345 doi: (Published 19 December 2012)
Cite this as: BMJ 2012;345:e8545

In the 1980s, why was polio, with its rather small mortality rate, chosen for a worldwide “eradication” campaign, when other infectious diseases such as measles, pneumonia, and diarrhoea causing infections each killed millions of children a year? It had little to do with the priorities of most developing countries where polio was endemic. It was more to do with the ideology of a small number of powerful and well placed players in global public health who were dedicated to the concept of so called eradication as perhaps the major tool for international public health.1

Many of these people had been involved in the successful campaign to eradicate smallpox. However, after that great achievement near consensus had formed in public health circles that primary healthcare (including routine immunisation) rather than vertical eradication campaigns should be the focus of global and national efforts. It looked as though smallpox would be the first and last human disease to be eradicated.

Those who I would call “eradicationists” had to find a disease that could be quickly…

Emerging Infectious Diseases Volume 19, Number 1—January 2013

Emerging Infectious Diseases
Volume 19, Number 1—January 2013

Invasive Pneumococcal Disease after Routine Pneumococcal Conjugate Vaccination in Children, England and Wales
S. N. Ladhani et al.
Nonvaccine serotypes occur more often among children with comorbid conditions.

Vaccination and Tick-borne Encephalitis, Central Europe
F. X. Heinz et al.
Tick-borne encephalitis is a disease of the brain caused by a virus found in many parts of Europe as well as central and eastern Asia. As the name indicates, the virus is spread by tick bites. The number of people infected each year varies according to complex interactions involving the ticks’ environment, the weather, and human socioeconomic and vaccination status. To determine how well vaccine protects against the disease, researchers compared the number of cases in 3 neighboring countries in which vaccination coverage differs but many other factors remain the same: Austria (where more than three quarters of the population are vaccinated) and Slovenia and the Czech Republic (where less than one quarter of the population are vaccinated). They found far fewer cases in Austria, indicating that vaccination is an excellent way to prevent this disease.

Novel Framework for Assessing Epidemiologic Effects of Influenza Epidemics and Pandemics
C. Reed et al.
Organizing and prioritizing data collection may lead to informed assessment and guide decision making.

Human rights and health systems development: Confronting the politics of exclusion and the economics of inequality

Health and Human Rights
Vol 14, No 2 (2012)

Human rights and health systems development: Confronting the politics of exclusion and the economics of inequality
Paul Farmer, Duncan Maru

The social movements of the last two decades have fostered a rights-based approach to health systems development within the global discourse on national and international health governance. In this piece, we discuss ongoing challenges in the cavernous “implementation gap”—translating legislative human rights victories into actual practice and delivery. Using accompaniment as an underlying principle, we focus primarily on constructing effective, equitable, and accountable public sector health systems. Public sector health care delivery is challenged by increasingly exclusive politics and inequitable economic policies that fundamentally limit the participatory power of marginalized citizens. Finally, we discuss the role of implementation science in closing the delivery gap in human rights practice.

Experimental Malaria Vaccine

December 19, 2012, Vol 308, No. 23

Global Health
Experimental Malaria Vaccine
M. J. Friedrich
JAMA. 2012;308(23):2449. doi:10.1001/jama.2012.128613.

An experimental malaria vaccine given to African infants younger than 12 weeks reduced the risks of clinical and severe malaria only by about one-third, reports an international team of researchers (The RTS,S Clinical Trials Partnership. N Engl J Med. doi: 10.1056/NEJMoa1208394 [published online November 9, 2012]).

In the phase 3 trial, 6537 infants who were between 6 and 12 months old at the time of the first vaccination received 3 doses of either the RTS,S/AS01 candidate vaccine or a nonmalaria comparator vaccine at 1-month intervals along with standard childhood vaccines. An analysis of the incidence of malaria in infants for 12 months after the third vaccine dose found that the RTS,S/AS01 vaccine reduced the risk of detectable malaria and severe malaria by 31% and 37%, respectively, compared with controls…

Impact of the demand for ‘proxy assent’ on recruitment to a randomised controlled trial of vaccination testing in care homes

Journal of Medical Ethics
January 2013, Volume 39, Issue 1

Research ethics
Impact of the demand for ‘proxy assent’ on recruitment to a randomised controlled trial of vaccination testing in care homes
Paul James Whelan, Rebecca Walwyn, Fiona Gaughran, Alastair Macdonald
J Med Ethics 2013;39:36-40 Published Online First: 1 September 2012 doi:10.1136/medethics-2011-100119

Legal frameworks are in place to protect those who lack the capacity to consent to research, such as the Mental Capacity Act in the UK. Assent is sought instead from a proxy, usually a relative. However, the same legislation may, perversely, affect the welfare of those who lack capacity and of others by hindering the process of recruitment into otherwise potentially beneficial research. In addition, the onus of responsibility is moved from those who know most about the study (ie, the scientific community) to those who know less (the proxies). In this paper, we describe the characteristics of a sample at different stages of the recruitment process of an influenza vaccine-based randomised control trial in elderly care home residents (the FEVER study). 62% (602/968) of potential subjects lacked capacity but only 29% (80/277) of those actually randomised. Older age, being female and living in an Elderly Mentally Ill care home were the only variables associated with lacking capacity. Considering this was a study based in a care home setting where the prevalence of dementia approximates 80%, the trial, like many others, was thus significantly biased. We believe that difficulties seeking proxy assent contributed significantly to this problem. Further thought should be given to how assent to enter research for those who lack capacity should be provided, and we suggest avenues for further discussion such as independent risk/benefit expert panels.

Comment: Mapping the terrain of investment in global infectious diseases

The Lancet Infectious Disease
Jan 2013  Volume 13  Number 1  p1 – 96

Mapping the terrain of investment in global infectious diseases
Yiannis Kyratsis, Raheelah Ahma

The limited resources available for research into global infectious diseases make the setting of priorities inevitable. The priorities of funding agencies largely dictate the type of research done, as well as the health issues and diseases studied.1 Global health research governance needs to be transparent while the funders make difficult choices with the aim of channelling funds where most needed. This openness is crucial for maintaining public confidence and continued support. Defining public need is not straightforward.

Comment: Low effectiveness undermines promotion of seasonal influenza vaccine

The Lancet Infectious Disease
Jan 2013  Volume 13  Number 1  p1 – 96

Low effectiveness undermines promotion of seasonal influenza vaccine
Angus Nicoll, Marc Sprenger

In 2011, a systematic review1 showed low effectiveness (panel) (often less than 60%) of seasonal influenza vaccines in the protection of risk groups—ie, individuals most at risk of severe disease from infection. The Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE) project4—a publicly funded network supported by the European Centre for Disease Prevention and Control (ECDC) and EU member states—monitors the effectiveness of influenza vaccines every year, and in April, 2012, showed a low early season effectiveness of 43% of the 2011–12 influenza vaccine in the risk groups in eight European countries.

UK investments in global infectious disease research 1997–2010: a case study

The Lancet Infectious Disease
Jan 2013  Volume 13  Number 1  p1 – 96

UK investments in global infectious disease research 1997–2010: a case study
Michael G Head, Joseph R Fitchett, Mary K Cooke, Fatima B Wurie, Andrew C Hayward, Rifat Atun

Infectious diseases account for 15 million deaths per year worldwide, and disproportionately affect young people, elderly people, and the poorest sections of society. We aimed to describe the investments awarded to UK institutions for infectious disease research.

We systematically searched databases and websites for information on research studies from funding institutions and created a comprehensive database of infectious disease research projects for the period 1997—2010. We categorised studies and funding by disease, cross-cutting theme, and by a research and development value chain describing the type of science. Regression analyses were reported with Spearman’s rank correlation coefficient to establish the relation between research investment, mortality, and disease burden as measured by disability-adjusted life years (DALYs).

We identified 6170 funded studies, with a total research investment of UK£2·6 billion. Studies with a clear global health component represented 35·6% of all funding (£927 million). By disease, HIV received £461 million (17·7%), malaria £346 million (13·3%), tuberculosis £149 million (5·7%), influenza £80 million (3·1%), and hepatitis C £60 million (2·3%). We compared funding with disease burden (DALYs and mortality) to show low levels of investment relative to burden for gastrointestinal infections (£254 million, 9·7%), some neglected tropical diseases (£184 million, 7·1%), and antimicrobial resistance (£96 million, 3·7%). Virology was the highest funded category (£1 billion, 38·4%). Leading funding sources were the Wellcome Trust (£688 million, 26·4%) and the Medical Research Council (£673 million, 25·8%).

Research funding has to be aligned with prevailing and projected global infectious disease burden. Funding agencies and industry need to openly document their research investments to redress any inequities in resource allocation.


Nature Editorial: Global Burden of Disease 2010

Volume 492 Number 7429 pp311-462  20 December 2012

Nature | Editorial
A burden weighed
Despite some shortcomings, a global study of health metrics should be applauded.
18 December 2012

The best evidence-based health policies are made on the basis of thorough and regular updates of the global burden of disease. Aid agencies need to know how and where to target their funding and monitor impact. Knowledge of what sickens and kills people can help health-care providers and researchers to tailor their priorities to needs and to long-term trends in the health of populations. Yet in many poor areas of the world, basic systems such as death certification are lacking, and quality health-care data are scarce and scattered. At national, regional and global levels, collection of comprehensive health metrics is too often the poor cousin in health care and in health research. The result is a shortage of high-quality, comparable and readily accessible data.

For these reasons, the publication in The Lancet last week of the Global Burden of Disease 2010 study (GBD 2010) should be applauded. The study is an unprecedented five-year effort by hundreds of researchers in dozens of countries worldwide, who made a huge effort to track down, collate and analyse surveys, as well as published and unpublished health-care data. Led by the Institute for Health Metrics and Evaluation at the University of Washington in Seattle, they have produced a vast smorgasbord of global estimates of the burden of multiple diseases, injuries, risk factors and chronic complications (see page 322).

The findings capture the world’s health status in impressive detail, and highlight significant trends, including how, in almost all countries, life expectancies are rapidly converging towards the long lives previously enjoyed only by the richest. The study also charts the demise of major causes of global health burden such as infectious diseases and maternal and child mortality, although these continue to blight many poorer countries, particularly in sub-Saharan Africa.

People benefit from longer lives but they are increasingly experiencing a downside. They spend many of those extra years in ill health, often with more than one illness, which creates large costs for health-care systems. The study found that age-related illnesses include not only the usual suspects such as cancers and heart disease, but also a host of conditions that rarely kill but often disable, such as mental illness and musculoskeletal disorders.

“The GBD 2010 should be required reading for health leaders and research administrators.”

Health-care systems and research agendas must adapt accordingly; for example, health-care providers must learn how to manage the high costs of tackling this new disease landscape. The GBD 2010 should be required reading for health leaders and research administrators, and should lead them to re-examine how well current research portfolios match emerging trends in the burden of sickness and disease.

The GBD 2010 is far from perfect. Some of the underlying data are weak — for example, they may be scarce, unreliable or unstandardized — and in places the study relies heavily on sophisticated modelling to eke out meaning. To its credit, it has tried to provide transparency in the form of quantitative indicators as to the robustness — or otherwise — of each of its estimates. Given such caveats, some of its findings will inevitably be dubious. Malaria researchers have vigorously contested the GBD’s assertion earlier this year that malaria killed twice as many people in 2010 as previously thought, but the study stands by its data (see Nature; 2012).

Such disagreements are inevitable in any complex, large-scale, international collaborative undertaking of this kind, particularly in areas where uncertainties in the data are highest. Such health metrics are also highly political, because they can affect the direction of national and international health-care and research funds, where there is much turf to fight over. But, ultimately, the findings of the GBD 2010, however imperfect, provide a robust basis and analytical framework for further research and health policies that is better than anything that went before. That its findings and methodologies will be challenged and debated in the months and years to come is not only healthy, but how science works. The way forward is to rework and build on the foundations that have been laid.


Vaccines, Thimerosal, SAGE Recommendation

December 2012, VOLUME 130 / ISSUE 6

Early Releases
Global Vaccination Recommendations and Thimerosal
Walter A. Orenstein, Jerome A. Paulson, Michael T. Brady, Louis Z. Cooper, and Katherine Seib
Pediatrics peds.2012-1760; Published online December 17, 2012 (10.1542/peds.2012-1760)

“…Global removal of thimerosal has the potential to adversely affect the worldwide vaccine supply. In recent reports given to WHO, estimates were presented by acknowledged experts on the impact of global removal of thimerosal; some estimates were based on expert opinion

but had the advantage of input from other experts within the context of 3 WHO technical consultations or expert advisory meetings. The increases in manufacturing cost vary greatly from country to country, ranging from 200% to .500%.22–25 Single-dose vials would reduce manufacturing capacity and increase the amount of transportation and storage space required more than threefold. The resulting cold-chain requirements would be untenable in many areas of the world because of programmatic challenges and increased workload.22,24,25  Furthermore, single-dose packaging produces more waste (both vaccine and CO2 emissions). 22,24,26 The continued benefits of thimerosal use in vaccine manufacturing clearly outweigh any perceived risks.

WHO’s Strategic Advisory Group of Experts on Immunization27 recently recommended that this part of the ban be removed from the UNEP treaty28 and we concur.29 This is an exciting time for global immunization programs. Global immunization efforts are being supported worldwide by many organizations, including the US government as both humanitarian and protective measures. 30 As advocates for the health of all children, we strongly support these efforts also. Immunization prevents approx. 2.5 million deaths a year globally. Millions more deaths could be prevented if global immunization efforts are bolstered.31 The preponderance of available evidence has failed to demonstrate serious harm associated with thimerosal in vaccines. As such, we extend our strongest support to the recent Strategic Advisory Group of Experts recommendations to retain the use of thimerosal in the global vaccine supply.

Ban on Thimerosal in Draft Treaty on Mercury: Why the AAP’s Position in 2012 Is So Important
Louis Z. Cooper and Samuel L. Katz
Pediatrics peds.2012-1823; Published online December 17, 2012 (10.1542/peds.2012-1823)
Full Text (PDF)

STATEMENT OF ENDORSEMENT: Recommendation of WHO Strategic Advisory Group of Experts (SAGE) on Immunization
Pediatrics peds.2012-2262; Published online December 17, 2012 (10.1542/peds.2012-2262)
Full Text (PDF)

Global Justice and the Proposed Ban on Thimerosal-Containing Vaccines
Katherine King, Megan Paterson, and Shane K. Green
Pediatrics peds.2012-2976; Published online December 17, 2012 (10.1542/peds.2012-2976)
Full Text (PDF)

Influenza Vaccination Guidelines and Vaccine Sales in Southeast Asia: 2008–2011

PLoS One
[Accessed 22 December 2012]

Influenza Vaccination Guidelines and Vaccine Sales in Southeast Asia: 2008–2011
Vinay Gupta, Fatimah S. Dawood, Charung Muangchana, Phan Trong Lan, Anonh Xeuatvongsa, Ly Sovann, Remigio Olveda, Jeffery Cutter, Khin Yi Oo, Theresia Sandra Diah Ratih, Chong Chee Kheong, Bryan K. Kapella, Paul Kitsutani, Andrew Corwin, Sonja J. Olsen
Research Article | published 21 Dec 2012 | PLOS ONE 10.1371/journal.pone.0052842

Southeast Asia is a region with great potential for the emergence of a pandemic influenza virus. Global efforts to improve influenza surveillance in this region have documented the burden and seasonality of influenza viruses and have informed influenza prevention strategies, but little information exists about influenza vaccination guidelines and vaccine sales.

To ascertain the existence of influenza vaccine guidelines and define the scope of vaccine sales, we sent a standard three-page questionnaire to the ten member nations of the Association of Southeast Asian Nations. We also surveyed three multinational manufacturers who supply influenza vaccines in the region.

Vaccine sales in the private sector were <1000 per 100,000 population in the 10 countries. Five countries reported purchasing vaccine for use in the public sector. In 2011, Thailand had the highest combined reported rate of vaccine sales (10,333 per 100,000). In the 10 countries combined, the rate of private sector sales during 2010–2011 (after the A(H1N1)2009pdm pandemic) exceeded 2008 pre-pandemic levels. Five countries (Indonesia, Malaysia, Singapore, Thailand and Vietnam) had guidelines for influenza vaccination but only two were consistent with global guidelines. Four recommended vaccination for health care workers, four for elderly persons, three for young children, three for persons with underlying disease, and two for pregnant women.

The rate of vaccine sales in Southeast Asia remains low, but there was a positive impact in sales after the A(H1N1)2009pdm pandemic. Low adherence to global vaccine guidelines suggests that more work is needed in the policy arena.

A Year On, the H5N1 Debate Remains Infectious, With No End in Sight

21 December 2012 vol 338, issue 6114, pages 1497-1676

News – Breakthrough of the Year
A Year On, the H5N1 Debate Remains Infectious, With No End in Sight
David Malakoff

After two science teams showed how to make the H5N1 avian influenza virus—which typically kills birds—transmissible among mammals in late 2011, a contentious debate began among scientists, government officials, the media, and the public about “dual-use” research: Were scientists potentially opening the door to a deadly human pandemic? Are there flaws in efforts to prevent dangerous agents from escaping from unsafe laboratories or falling into the hands of terrorists? In January, researchers agreed to a voluntary, temporary moratorium on many H5N1 experiments. Now, more than a year after the H5N1 controversy erupted, there is still no clear international consensus on which kinds of studies are worth the risk, or how potentially dangerous results should be reviewed or safely communicated to the public and public health experts

Tackling Meningitis in Africa

21 December 2012 vol 338, issue 6114, pages 1497-1676

Perspective – History of Science
Tackling Meningitis in Africa
Halla Thorsteinsdóttir1, Tirso W. Sáenz2

The United States is currently in the midst of a meningitis outbreak (with at least 36 deaths) as the result of fungal contamination of steroid injections to relieve back pain (1). In Africa’s so-called “meningitis belt,” outbreaks of meningitis are a regular occurrence, killing thousands and infecting tens of thousands each year. In 2009, about 5300 people died of meningitis and 88,000 were infected with the disease (2). The meningitis belt stretches from Senegal in the West to Ethiopia in the East and includes around 300 million people. Sanofi Pasteur had provided Africa with a meningitis vaccine for decades but because of reduced supplies in 2006 and 2007, and a threat of increased incidences of the disease, the World Health Organization (WHO) made a call for additional vaccine providers (3). But it wasn’t multinational companies from wealthy nations that responded, but two Latin American countries that answered the call. What brought Brazil and Cuba together in this seemingly unlikely collaboration?

Hidden Killers: Human Fungal Infections

Science Translational Medicine
19 December 2012 vol 4, issue 165

Review – Medical Mycology
Hidden Killers: Human Fungal Infections
Gordon D. Brown, David W. Denning, Neil A. R. Gow, Stuart M. Levitz, Mihai G. Netea, and Theodore C. White
19 December 2012: 165rv13

Although fungal infections contribute substantially to human morbidity and mortality, the impact of these diseases on human health is not widely appreciated. Moreover, despite the urgent need for efficient diagnostic tests and safe and effective new drugs and vaccines, research into the pathophysiology of human fungal infections lags behind that of diseases caused by other pathogens. In this Review, we highlight the importance of fungi as human pathogens and discuss the challenges we face in combating the devastating invasive infections caused by these microorganisms, in particular in immunocompromised individuals.

Correlates of seasonal flu vaccination among U.S. home health aides

Volume 31, Issue 2, Pages 279-438 (2 January 2013)

Brief Report
Correlates of seasonal flu vaccination among U.S. home health aides
Pages 287-290
Alberto Juan Caban-Martinez, Anna Arlinghaus, Silje E. Reme

Home health aides (HAs) receive limited training and reach many older patient populations highly susceptible to influenza virus. We sought to examine socio-demographic correlates of seasonal flu vaccination receipt among HAs.

We analyzed data from the 2007 U.S. National Home Health Aide Survey, a nationally representative sample of HAs reporting on occupational status, job and demographic characteristics and receipt of seasonal flu vaccine (n = 3377).

Seasonal flu vaccine receipt was low among all types of HAs (43.9%). After adjustment for socio-demographic indicators (i.e. age, gender, race and health insurance), home health, home care, hospice and personal care attendants were significantly less likely to report receiving seasonal flu vaccine as compared to licensed nursing assistants (adjusted odds ratio, AOR = 0.42, 95% CI [0.20–0.85]; 0.41, [0.17–0.99]; 0.50, [0.26–0.97], and 0.53, [0.26–0.99], respectively).

Targeted effective vaccination campaigns are needed to improve vaccination rates among home health aides.

Sustained high influenza vaccination rates and decreased safety concerns among pregnant women during the 2010–2011 influenza season

Volume 31, Issue 2, Pages 279-438 (2 January 2013)

Sustained high influenza vaccination rates and decreased safety concerns among pregnant women during the 2010–2011 influenza season
Original Research Article
Pages 362-366
M. Drees, B. Tambourelli, A. Denstman, W. Zhang, R. Zent, P. McGraw, D.B. Ehrenthal

Intense efforts to vaccinate pregnant women against 2009 H1N1 influenza resulted in much higher vaccine uptake than previously reported. We surveyed postpartum women to determine whether high vaccination rates were sustained during the 2010–11 influenza season.

We performed cross-sectional surveys of postpartum women delivering at our institution during February–April 2010 and February–March 2011. The surveys ascertained maternal characteristics, history of influenza vaccination, and reasons for lack of vaccination.

During the 2010–11 season, 165 (55%) of 300 women surveyed reported receiving influenza vaccination, compared to 191 of 307 (62%) during 2009–10 (p = 0.08). Vaccination by an obstetrical provider was common, but decreased compared to 2009–10 (60% vs. 71%, p = 0.04). While most women (76%) in 2010–11 reported that their provider recommended influenza vaccination, significantly more reported lack of discussion about vaccination (24% vs. 11%, p < 0.01) compared to 2009–10. Vaccine safety concerns were cited by most (66%) women declining vaccination during 2009–10 but only 27% of women who declined in 2010–11.

The vaccination rate among pregnant women at our institution was relatively sustained, although fewer providers appear to be discussing influenza vaccination in pregnancy. Concern about vaccine safety, the primary barrier during 2009–10, was much less prominent.

Prevalence, incidence and persistence of genital HPV infections in a large cohort of sexually active young women in the Netherlands

Volume 31, Issue 2, Pages 279-438 (2 January 2013)

Prevalence, incidence and persistence of genital HPV infections in a large cohort of sexually active young women in the Netherlands
Original Research Article
Pages 394-401
M. Mollers, J. Boot Hein, J. Vriend Henrike, J. King Audrey, V.F. van den Broek Ingrid, E.A.M. van Bergen Jan, A.T.P. Brink Antoinette, F.G. Wolffs Petra, J.P.A. Hoebe Christian, J.L.M. Meijer Chris, A.B. van der Sande Marianne, E. de Melker Hester

We assessed age- and type-specific HPV prevalence, incidence and persistence and their associated risk factors in young women prior to vaccination, to enable monitoring of the impact of introduction of HPV vaccination in the years before participation in the cervical screening program.

The HPV status was assessed in 3282 women aged 16–29 who participated in a Chlamydia trachomatis screening implementation program, of which 2014 women (61%) participated in two rounds (one year apart). Self-collected vaginal swab were analyzed by SPF10 LiPA on the presence of HPV DNA. Risk factors for prevalent, incident and persistent HPV infections were calculated using generalized estimating equation.

The prevalence of any HPV in the first round amounted to 54%, while 34% of the women who participated in the second round had a persistent infection and 45% an incident infection. The five most common HPV types found in this study were HPV16, −51, −52, −31 and −53. HPV16 and/or HPV18 prevalence, incidence and persistence in the second round were 15%, 8% and 9%, respectively and for HPV6 and/or HPV11 6%, 4% and 2%, respectively. Relatively to other HPV genotypes, hrHPV types were found more often as a persistent infection than as an incident infection. Furthermore, there is an age-dependent increase within this age range for persistent infections but not for incident infections.

The HPV prevalence (54%), incidence (45%) and persistence (34%) is high among sexually active young women in the Netherlands. The different HPV type distribution and risk factors for prevalent, incident and persistent infections, as well as the observed age-trends should be taken into account in interpreting data obtained after vaccine introduction. Repeating measurements post-immunization are particularly relevant until the age when screening starts (i.e. 30 years in the Netherlands).

How cost effective is universal varicella vaccination in developing countries? A case-study from Colombia

Volume 31, Issue 2, Pages 279-438 (2 January 2013)

How cost effective is universal varicella vaccination in developing countries? A case-study from Colombia
Original Research Article
Pages 402-409
Angel Paternina-Caicedo, Fernando De la Hoz-Restrepo, Oscar Gamboa-Garay, Carlos Castañeda-Orjuela, Martha Velandia-González, Nelson Alvis-Guzmán

Varicella vaccination has not been introduced worldwide, especially in developing countries. The present study assesses the potential epidemiological and economic impact of one-dose and two-dose varicella vaccination schemes in Colombia, a south American upper middle-income country.

A decision-tree based model was developed. Varicella cases were estimated based on previous reports of seropositivity within the country. Cost per life-year gained (LYG) was the main outcome measure. Costs from the health care system perspective were expressed in 2008 American dollars. Deterministic and probabilistic sensitivity analyses were performed.

In Colombia, there would be 700,197 varicella cases in an average year plus 60 yearly deaths without vaccination. It was estimated that health care costs for all cases during 30 years period could be around US $88,734,735 (with discount). Cost per LYG of one-dose vaccination was US $2519 and using a two-dose scheme was US $5728.

Factors affecting repeated influenza vaccination among older people in Taiwan

Volume 31, Issue 2, Pages 279-438 (2 January 2013)

Factors affecting repeated influenza vaccination among older people in Taiwan
Original Research Article
Pages 410-416
Yu-Chia Chang, Nicole Huang, Long-Sheng Chen, Shang-Wei Hsu, Yiing-Jenq Chou

This study identifies factors that influence repeated influenza vaccination among people aged 65 years and older in Taiwan.

Data of this retrospective cohort study were drawn from the 2005 National Health Interview Survey and the 2005–2007 National Health Insurance claims data; a sample of 1384 older people was analyzed. The pattern of repeated influenza vaccination was divided into 3 groups: unvaccinated all 3 years, vaccinated 1–2 times over 3 years, and vaccinated all 3 years. Multinomial logistic regression analyses were performed.

Only 20.6% of older people were vaccinated all 3 years. Those 70–74 years of age (odds ratio [OR] = 1.81), living in rural areas (OR = 2.47), having one (OR = 2.07) or more (OR = 2.41) chronic conditions, frequent outpatient visits (OR = 1.48), and undergoing preventive health examinations (OR = 2.22) were more likely to have repeated vaccinations. However, those with difficulties performing one or more activities of daily living (ADL difficulty) (OR = 0.41) and seeking care from alternative medicine (OR = 0.48) were less likely to undergo regular vaccinations.

The repeated influenza vaccination rates in our Taiwan sample were far from optimal. Factors identified in this analysis may help to improving influenza vaccination programs.

Inquiry into the Relationship between Equity Weights and the Value of the QALY

Value in Health
Vol 15 | No. 8 | December 2012 | Pages 991-1192

Inquiry into the Relationship between Equity Weights and the Value of the QALY
Ana Bobinac, N. Job A. van Exel, Frans F.H. Rutten, Werner B.F. Brouwer

A commonly held view of the decision rule in economic evaluations in health care is that the final incremental cost-effectiveness ratio needs to be judged against some threshold, which is equal for all quality-adjusted life-year (QALY) gains. This reflects the assumption that “a QALY is a QALY” no matter who receives it, or the equity notion that all QALY gains are equally valuable, regardless of the context in which they are realized. If such an assumption does not adequately reflect the distributional concerns in society, however, different thresholds could be used for different QALY gains, whose relative values can be seen as “equity weights.”

Our aim was to explore the relationship between equity or distributional concerns and the social value of QALYs within the health economics literature. In light of the empirical interest in equity-related concerns as well as the nature and height of the incremental cost-effectiveness ratio threshold, this study investigates the “common ground” between the two streams of literature and considers how the empirical literature estimating the incremental cost-effectiveness ratio threshold treats existing distributional considerations.

From Google Scholar…

From Google Scholar+: Dissertations, Theses, Selected Journal Articles

A human papillomavirus public vaccination program in Taiwan: The Kinmen County experience
CC Lee, TS Chen, TZ Wu, LM Huang – Journal of the Formosan Medical Association, 2012
… The Bureau established a committee to promote public awareness, coordinate with the
schools, arrange for the administration of the vaccine, establish a vaccination registry, and
develop a plan for follow-up and assessment. … Vaccine administration. …

Ali Salanti receives Phase II Grand Challenges Explorations Funding
K Storm – 2012
… Associate Professor Ali Salanti will continue to pursue an innovative global health
research project, titled “Novel combinatorial vaccine to protect women against cervical
cancer and placental malaria”. Associate professor Ali Salanti. …

Cost-Minimization Analysis of the US Army Accession Screening and Immunization Program
J Tzeng, C Jankosky, H Hughes – Military Medicine, 2012
… Jankosky, MC USN*; Hayley Hughes, DrPH, MPH†: 1: *Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Room A1040, 4301 Jones
Bridge Road, Bethesda, MD 20814-4712.; 2: †Military Vaccine (MILVAX) Agency, 7700 …

Monitoring adverse events following immunisation in developing countries: experience from human papillomavirus vaccination demonstration projects
KM Jain, P Paul, DS LaMontagne – Sexual Health, 2012
… This paper discusses retrospective reports by parents and guardians of girls experiencing AEFIs during human papillomavirus (HPV) vaccine demonstration projects in Uganda and Vietnam. … Conclusions: AEFIs reported were similar to Phase III vaccine trials. ..

Pakistan Polio Workers Attacked Dec 2012 – General Media Coverage, Opinion

Accessed 22 December 2012
Pakistani attacks on aid workers
Killing disease – Grisly attacks in Pakistan target those doing good to children
Dec 22nd 2012 | ISLAMABAD | from the print edition

ON DECEMBER 18th five health workers, all women, were gunned down in Pakistan in carefully planned and co-ordinated shootings. They were administering polio vaccinations. The following day a vaccination supervisor and her driver were killed. Several health workers are critically injured. The youngest killed was a 17-year-old in the north-western town of Peshawar. Others were working in poor, ethnic Pushtun districts in the southern megacity of Karachi, where polio workers have already been killed this year. The Pakistani Taliban or allied groups are the murderers, and they have now caused the UN to suspend its campaign to eradicate polio in Pakistan.

The country is one of only three countries left where polio is endemic, leading the world in 2011 in cases of the crippling childhood disease. It had been making progress in 2012. The country, backed by the UN, was striving urgently to immunise 34m children. Almost all the polio cases are among Pushtuns, who live mainly in north-west Pakistan or in Karachi. They also form the main ethnic group in the Pakistani Taliban.

The extremists spread the rumour that polio drops are a Western conspiracy to sterilise Muslims. As it is, the credibility of health workers has been badly shaken by the revelation in 2011 that the CIA had recruited a Pakistani doctor, Shakil Afridi. He set up a fake vaccination programme, for hepatitis B, as part of the hunt that finally killed Osama bin Laden. Militants also use polio to press the government. They say they will refuse to allow immunisations in North or South Waziristan, part of the wild tribal areas, unless attacks by unmanned American drone aircraft are stopped.

The climate for humanitarian workers has not been improved by the authorities. They have harassed aid professionals, restricting their movements and limiting visas, fearing that spies lurk among them. In 2012 the Red Cross halted much of its work in Pakistan after a British doctor was kidnapped in the western city of Quetta and beheaded.

The prime minister, Raja Pervez Ashraf, insists that “we will stay the course until polio is wiped out”. If the country fails, new generations of children will have their lives blighted by this wholly preventable disease.

New Yorker
Accessed 22 December 2012
December 18, 2012
The C.I.A. and the Polio Murders
Posted by Michael Specter

Scientists, with the help of public-health workers, have managed to wipe just two diseases from the face of the earth: smallpox and rinderpest (otherwise known as cattle plague). This year, it had begun to look as if we would soon add another name to that list, a virus that has been a paralytic threat for millennia: polio.

The effort took a devastating step backward yesterday, with the news that six public-health workers were killed in Pakistan; all had been administering polio vaccines. Earlier this year, the World Health Organization declared the eradication of polio to be a world-wide health emergency (a designation which makes it easier to release funds). It did so primarily because the end seemed in sight. Just three countries continue to report infections: Pakistan,  Afghanistan, and Nigeria. As soon as the news of the murders spread, however, the health minister for Pakistan’s southern Sindh Province put a halt to the vaccination program, which had employed more than twenty-four thousand aid workers. The risks of this detour, which will leave tens of thousands of people vulnerable to new infections, cannot be overstated.

Nobody has yet claimed responsibility for the coördinated attacks, but the Taliban has opposed polio vaccination vigorously. Taliban leaders have issued several religious edicts saying that the U.S. runs a spy network under the guise of a vaccine program. Now, there is no question that this is a depraved, heartless, and sickening act. But, as I wrote in a post here more than a year ago, the claim about the C.I.A. is not entirely untrue. In 2011, American intelligence, in a stunning display of arrogance, stupidity, or both, faked a vaccination drive as a cover for its attempt to pin down the location of Osama bin Laden. (The idea was to get DNA samples from the children in the Abbottabad compound while injecting them with a dummy vaccine, and then compare them to those of bin Laden’s relatives.) There is a history here, and somebody in the American intelligence community should have known it. The world was close to eradication in 2004 as well. Then several mullahs in northern Nigeria campaigned against polio vaccinations—claiming they were part of a Western plot. The result was that people who were infected went to Mecca on the hajj and spread their disease to people from many countries.

Pakistan’s attitude toward those who are associated with the C.I.A. has not exactly been a secret. After the raid on bin Laden’s compound, the doctor who tried to obtain the DNA was arrested and sentenced to thirty-three years in prison. I don’t mean to lay these crimes on anyone other than the murderers. But the sickness and death caused by a renewed polio epidemic in South Asia would make today’s tragedy seem small. Again, we should hold the killers responsible for this terrible reversal. But at least some of blame lies in the swamplands of Langley, Virginia.

Read more:

New York Times
Accessed 22 December 2012.
Female Vaccination Workers, Essential in Pakistan, Become Prey
Published: December 20, 2012

Accessed 22 December 2012
FEATURE-Violence, fear & suspicion imperil Pakistan’s war on polio
Sat Dec 22, 2012 8:34pm EST
– Conspiracy theories undermine anti-polio fight
– Health workers afraid to go to work
– High stakes in fight against a crippling disease
By Mehreen Zahra-Malik

Washington Post
Accessed 22 December 2012
Michael Gerson, Opinion Writer
In Pakistan, Taliban makes healers the targets
The murder of nine polio vaccination workers during 48 hours in Pakistan has all the hallmarks of a Taliban operation: coordinated, ruthless and monstrous. The attacks have succeeded in shutting down an anti-polio campaign in Pakistan’s largest city, Karachi, and other areas…

Twitter Watch [accessed 22 December 2012 – 16:17]

Twitter Watch [accessed 22 December 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.

Key public health milestones were reached in 2012, incl the end of polio transmission in India. 2012 in review: 
8:50 AM – 21 Dec 12

WHO interview regarding attacks on health workers in Pakistan  #ProtectHealthWorkers (VIDEO)
WHO: Dr Bruce Aylward interview regarding attacks on health workers…
During the week of 18 December 2012, at least six people working on a polio vaccination campaign have been reported shot dead in several locations in Pakistan…
8:32 AM – 21 Dec 12

‘My family is very scared’. Female Pakistani #polio workers speak out on recent attacks. Via @BBC  #protecthealthworkers
8:15 AM – 21 Dec 12

Via @AP, Pakistani #polio workers get police protection  #protecthealthworkers
Pakistani polio workers get police protection
LAHORE, Pakistan (AP) — Under police guard, thousands of health workers pressed on with a polio immunization program Thursday after nine were killed elsewhere in Pakistan by suspected militants who…
7:39 AM – 21 Dec 12

Female Vaccination Workers, Essential in Pakistan, Become Prey
One of Pakistan’s most crucial public health campaigns has been plunged into crisis after militants killed nine volunteers over the course of a three-day polio vaccination drive.
7:30 AM – 21 Dec 12

Pakistan made tremendous progress over past 18 months in eradicating #polio. Polio cases are down 65% compared to 2011 #ProtectHealthWorkers
1:51 AM – 21 Dec 12

Pakistan: Progress in #polio eradication has been possible only with engagement and leadership of all levels of government and civil society
1:47 PM – 20 Dec 12

Killing, hurting, threatening health workers is endangering the health of children and their families #protecthealthworkers
1:10 PM – 20 Dec 12

Sabin Vaccine Inst.  @sabinvaccine
Polio and vaccine diplomacy in Pakistan …
6:07 AM – 20 Dec 12

GAVI Alliance ‏@GAVIAlliance
Read @GAVIAlliance CEO @GAVISeth latest paper expressing his initial views on the post-2015 development agenda: 
5:20 AM – 20 Dec 12

Angus Thomson @ThomsonAngus
‘Successful immunization comes from successful partnerships’ – Mike Watson at #GAVIPartners Forum, Tanzania  #vaccines
Retweeted by GAVI Alliance
2:04 AM – 20 Dec 12

Vaccines: The Week in Review 15 December 2012

Editor’s Notes:

Email Summary: Vaccines: The Week in Review is available as a weekly email summary: please send your request to

pdf version: A pdf of the current issues is available here: Vaccines_The Week in Review_15 December 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…

UN announces Hispanola cholera initiative intergating oral cholera vaccine

The United Nations announced a new initiative valued at over US$2.2 billion over 10 years to help eliminate cholera in Haiti and the Dominican Republic (Hispaniola). Secretary-General Ban Ki-moon commented, “The new initiative will invest in prevention, treatment, and education – it will take a holistic approach to tackling the cholera challenge. The main focus is on the extension of clean drinking water and sanitation systems – but we are also determined to save lives now through the use of an oral cholera vaccine. Because global vaccines are in short supply, we will first target high-risk areas: densely populated urban areas and rural areas far removed from health services. As production increases, the vaccine effort will expand its reach.” Launched at UN Headquarters in New York in the presence of government officials from the two countries, the new initiative will support an existing campaign – known as the Initiative for the Elimination of Cholera in the Island of Hispaniola – established almost a year ago by the Presidents of Haiti and the Dominican Republic.

The UN chief said resources will be critical, with Haiti needing almost US$500 million over the next two years to carry out its national implementation plan for the disease. Noting that the relevant humanitarian appeals are less than half-funded, Mr. Ban said he will “use every opportunity” in the months ahead to mobilize more funding. “Today I am pleased to announce that $215 million in existing funds from bilateral and multilateral donors will be used to support the initiative. I thank the donor community for this generous commitment. The United Nations will do its part. We are committing $23.5 million, building on the $118 million the UN system has spent on the cholera response to date.”

GSK partners with Vodafone to focus mobile technology on immunization in Africa

GSK announced that it has formed a partnership with Vodafone to “harness innovative mobile technology to help vaccinate more children against common infectious diseases in Africa.” GSK said the initial focus of the new partnership will be a one-year pilot vaccination project in Mozambique, supported by Save the Children and run in collaboration with the Mozambique Ministry of Health. The project aims “to establish if mobile technology solutions could increase the proportion of children covered by vaccination in Mozambique by an additional 5-10% through helping to encourage mothers to take up vaccination services, support health workers, improve record keeping, and enable better management of vaccine stock.”  Sir Andrew Witty, CEO of GSK, said, “Innovative technologies – whether mobile devices, medicines or vaccines – are helping to transform global health. Organisations such as UNICEF and GAVI have played a key role in making vaccines much more accessible in Africa but barriers still exist which stop children from benefitting from basic immunisation. This new partnership combines GSK’s expertise, knowledge and resources with those of Vodafone with the potential to deliver life-saving vaccines to tens of thousands more children in Mozambique. Our hope is that together we will create a sustainable and scalable model which could ultimately be replicated to help more children live healthy lives across developing countries.”

GSK and Vodafone said the pilot will use mobile technology to address barriers to increased take-up of vaccines in Mozambique in three key ways:
– Mothers and caregivers will be registered on a Mozambique Ministry of Health database and alerted by SMS to the availability and importance of lifesaving vaccinations against common childhood diseases. Mothers will be able to schedule vaccination appointments by SMS and receive notifications of past and future vaccinations to ensure children complete the full schedule and become fully immunised.
– Health workers will be provided with smartphones with software allowing them to contact mothers, view and record vaccination histories, schedule vaccinations and report on follow-up visits.
– Healthcare facilities will be prompted to regularly report on crucial vaccination stock levels by SMS. This will enable critical supply chain management and the availability of vaccines when and where they are needed, particularly in rural areas.

The pilot will include up to 100 clinics and will be independently tested to prove its impact, effectiveness and cost benefits. To ensure open access, the platform will be available to caregivers across any mobile network and can be used to increase take-up of any selected vaccine.

WHO Statement: Global Burden of Disease Study (2010)

[Editor’s Note: The Lancet published a landmark set of articles and associated commentary in this week’s edition under the collective title “Global Burden of Disease 2010”. The article summaries are captured in a separate post below. The WHO statement on the work is presented here.]

WHO Statement
13 December 2012

WHO welcomes the data gathering and methodological innovations of the Global Burden of Disease 2010 (GBD) which has relied on the contributions of many researchers and scientists, including some from WHO.

In some areas, there was close collaboration between the Institute for Health Metrics and Evaluation (IHME) and WHO staff and the GBD results are similar to WHO’s recent estimates. In other areas, the results of the GBD differ substantially from existing analyses done by WHO and other United Nations agencies at global, regional and country levels. In yet many other areas, the GBD results update, and are broadly similar to, previous WHO analyses.

Academic institutions such as IHME have a strong interest in developing novel, cutting-edge methods for their research. This can result in scientific advances which may influence official UN statistics, once replicated and evaluated by other experts.

In an effort to provide the world with the best possible comparable global health statistics, WHO will host a meeting in February 2013 to take stock of existing and new approaches in global health estimation and to discuss ways to improve current practices.

Participants will include chairs of key WHO disease expert groups, relevant UN agencies, donors and representatives from countries and academia, including IHME.

Producing internationally comparable statistics

WHO is accountable to Member States and works closely with them to produce internationally comparable statistics that adhere to agreed criteria and methodologies. We work continuously with experts from academic institutions to develop and improve our methods and to take into account new developments in data and analytic methods. We anticipate that we will make use of many of the GBD analyses, and that others will influence further research and scientific debate towards improving global health estimates.

Improving health information systems

The real need is to improve the accuracy of global health data so that we no longer have to rely so much on statistical modelling to estimate the disease burden. Currently only 34 countries – representing 15% of the world’s population – produce high quality cause-of-death data and almost all of these are in Europe and the Americas. WHO is committed to working closely with developing countries to improve their health information systems including birth and death registration.

UN General Assembly Encourages Member States to Plan, Pursue Transition towards Universal Coverage (12 December 2012)

UN: Adopting Consensus Text, General Assembly Encourages Member States to Plan, Pursue Transition of National Health Care Systems towards Universal Coverage (12 December 2012)
Sixty-seventh General Assembly
53rd Meeting (AM)

“Recognizing the intrinsic role of health in achieving international development goals, the General Assembly today – through the unanimous adoption of a resolution on global health and foreign policy – encouraged Governments to plan or pursue the transition towards universal access to affordable and quality health-care services.

“By that text, the Assembly, calling for more attention to health as an important cross-cutting policy issue, urged Member States, civil society and international organizations to incorporate universal health coverage in the international development agenda and in the implementation of the internationally agreed development goals, including the Millennium Development Goals.

“The Assembly also recognized that improving social protection towards universal coverage “is an investment in people that empowers them to adjust to changes in the economy and the labour market and helps support a transition to a more sustainable, inclusive and equitable economy”.  As such, while planning or pursuing the transition towards universal coverage, Member States were encouraged to continue investing in health-delivery systems to increase and safeguard the range and quality of services and meet the health needs of their populations.

“Further, Member States were encouraged to recognize the links between the promotion of universal health coverage and other foreign policy issues, such as the social dimension of globalization, inclusive and equitable growth and sustainable development…”

Speech: The place of health on the post-2015 development agenda – Dr. Margaret Chan, WHO

Speech: The place of health on the post-2015 development agenda
Dr Margaret Chan
Director-General of the World Health Organization
Opening remarks at an informal Member State consultation on health in the post-2015 development agenda
Geneva, Switzerland
14 December 2012

“…I am further aware of how much the world has changed in just the past decade. All around the world, health is being shaped by the same powerful forces, like demographic ageing, rapid urbanization, and the globalization of unhealthy lifestyles. The distinctions between health problems in wealthy and resource-constrained countries have become blurred.

“In such a world situation, a compact, like the MDGs, between the haves and the have-nots loses some of its power to capture current challenges to development and shape their solutions.

“As a string of global crises demonstrated, this is a world in which the international systems that govern trade, financial markets, and business relations can have a greater impact on the opportunities of citizens, also for better health, than the policies of their sovereign governments.

“Chronic noncommunicable diseases have overtaken infectious diseases as the leading cause of mortality worldwide. Health has moved into a new political space in which the main causes of ill health and premature death have their roots in non-health sectors beyond the direct purview of health officials.

Ladies and gentlemen,

“I have personal views about the place of health in the post-2015 agenda. This is no secret. I regard universal health coverage as the single most powerful concept that public health has to offer. It is inclusive. It unifies services and delivers them in a comprehensive and integrated way, based on primary health care.

“I will say no more. The purpose of this meeting is to listen to you and benefit from your thinking and experience.

“Just one final comment. Any new goals must have unbeatable political appeal. Without strong political commitment, no goal on the new agenda can leverage real progress.”

IFFIm debt ratings affirmed by Fitch

Fitch Ratings affirmed the International Finance Facility for Immunisation’s (IFFIm) Long-term Issuer Default Rating (IDR) at ‘AAA’ with a Negative Outlook and Short-term IDR at ‘F1+’.

The affirmation is largely based on the strong support and committed grant payments from IFFIm’s donor countries, and particularly from its two largest donors, the UK (‘AAA’/Negative) and France (‘AAA’/Negative). Other donors include the government of Australia (‘AAA’/Stable), Italy (‘A-‘/Negative), the Netherlands (‘AAA’/Stable), Norway (‘AAA’/Stable), South Africa (‘BBB+’/Negative), Spain (‘BBB’/Negative) and Sweden (‘AAA’/Stable). Support from donors is strong because of their high overall credit quality and the legally binding nature of donors’ commitments. In Fitch’s opinion, repudiation of these commitments would impose severe reputational damage.

Funds raised by IFFIm on the financial markets are disbursed as grants to GAVI, a global health partnership committed to improving access to immunisation for children in impoverished countries, which in turn distributes them to recipient countries. IFFIm has enjoyed strong participation from the international community. The number of donor countries has increased to nine from six since its creation in 2006. IFFIm’s resources essentially consist of grants, which have been pledged by donors at inception, and are disbursed over a period of up to 23 years.   They also include interest on funds raised on the market and held in trust as a liquidity buffer. New pledges have been received since then, including USD144m from Australia and Italy in 2011. At end-June 2011, the fair value of pledges receivable amounted to USD3.4bn; based on end-October 2012 figures. The UK is the largest contributor, with 47.5% of total pledges, followed by France, with 27.4%.

Global Fund welcomes Japan’s final tranche of US$343 million; releases Governance handbook

The Global Fund said it “welcomed the payment by Japan of the second and final tranche of its total 2012 contribution of US$ 343 million, the highest annual amount that Japan has ever made in 10 years of vigorous support…” The payment of the second tranche of US$ 127 million follows a first payment of US$ 216 million which was made in March. Gabriel Jaramillo, General Manager of the Global Fund, said, “Japan has once more shown with this vote of confidence in the Global Fund that it is a leader in the fight against disease.”

   The Global Fund made its new Governance Handbook available to the public, noting that it was “conceived primarily as an operations guide for members of the Global Fund Board, (and) lays out with clarity and precision the Fund’s various structures and operations.” Comprised of ten PDF documents, the Handbook can be found here:

Weekly Epidemiological Record (WER) for 14 December 2012

The Weekly Epidemiological Record (WER) for 14 December 2012, vol. 87, 51/52 (pp. 509–526) includes:

– Global Polio Eradication Initiative: 7th meeting of the Independent Monitoring Board
– Establishing surveillance for acute meningitis and encephalitis syndromes through expansion of poliomyelitis and measles surveillance networks in Bangladesh, China and India, 2006–2008
– Chagas disease – factsheet
– Index of countries/areas
– Index, Volume 87, 2012, Nos. 1–52

GPEI: Update: Polio this week – As of 12 Dec 2012

Update: Polio this week – As of 12 Dec 2012
Global Polio Eradication Initiative

[Editor’s Extract]
– A report on polio eradication was prepared for next month’s WHO Executive Board (EB) meeting in Geneva, Switzerland. The EB is expected to focus its discussions on the progress and remaining challenges associated with the emergency action plans and to review the endgame strategy. The full report in English is available here [see also excerpt below]
– Two polio vaccinators were killed in Afghanistan last week in separate incidents, underlining the dangerous conditions that health and humanitarian workers face in many countries. These tragic events further underline the truly heroic and courageous efforts of the front-line health workers, often working under very dangerous conditions, all in efforts to protect children from lifelong polio-paralysis.

– One new WPV case was reported in the past week (WPV1 from Hilmand), bringing the total number of WPV cases for 2012 to 34. It is the most recent case in the country, and had onset of paralysis on 19 November…

– Seven new WPV cases were reported in the past week (2 cases of WPV1 from Katsina, 1 WPV1 from Kaduna, 1 WPV1 from Kano, 1 WPV1 from FCT, 1 WPV3 from Taraba, and 1 WPV3 from Yobe), bringing the total number of WPV cases for 2012 to 118. The WPV1 from Kaduna is the most recent in the country and had onset of paralysis on 17 November.
– The 2 new WPV3 cases reported are particularly concerning, as Nigeria is now the only country in the world reporting cases due to this strain over the past six months. Taraba’s previous WPV3 case dates back to July, and a comprehensive outbreak response is urgently needed…

– No new WPV cases were reported in the past week. The most recently reported WPV case occurred in Federally Administered Tribal Areas (WPV1) with onset of paralysis on 10 November. The total number of WPV cases for 2012 remains 56.
– However, two new circulating vaccine-derived poliovirus type 2 (cVDPV2) cases were reported in the past week from Killa Abdullah in Balochistan, bringing the total number of cVDPV2 cases to 12 (all from the greater Quetta area of Balochistan)…

Horn of Africa
– Efforts are continuing to stop an ongoing cVDPV2 outbreak in Kenya and parts of Somalia (in a Somali refugee camp in Dadaab, Kenya, and Kismayo, south-central Somalia)…”

Excerpt from Poliomyelitis: intensification of the global eradication initiative
Report by the Secretariat to the WHO Executive Board
14 December 2012
“9. The importance of withdrawing the type 2 component of oral poliovirus vaccine as soon as possible from routine immunization programmes globally was reinforced by the detection in 2012 of five outbreaks of poliomyelitis due to circulating type 2 vaccine-derived polioviruses. The outbreaks left 37 children paralysed in the following six countries: Chad, Democratic Republic of the Congo, Kenya, Nigeria, Pakistan and Somalia. Two of these outbreaks, in Nigeria and Somalia, involve the continuing transmission of a type 2 virus for a period exceeding 36 months. Interrupting the outbreak in central southern Somalia continues to be complicated by the ban on mass vaccination campaigns in areas controlled by Al-Shabaab militants.”

Meeting: Strengthening the Mechanisms to Plan, Coordinate, Finance, and Execute Research and Development to Meet Health Needs in Developing Countries

Meeting: Strengthening the Mechanisms to Plan, Coordinate, Finance, and Execute Research and Development to Meet Health Needs in Developing Countries
Washington, DC, on December 18th, 2012

The HHS Office of Global Health requested that the IOM Board on Global Health plan a meeting on strengthening the mechanisms to plan, coordinate, finance, and execute research and development to meet health needs in developing countries. Discussion issues could include approaches to research priority setting, an enumeration of leading gaps in global health R&D, R&D planning and costing, the private sector role in global health R&D, the creation of effective global health research networks, the building of R&D capacity in developing countries, innovations in financing the global health R&D enterprise, and principles of global health R&D management.

As part of this meeting, there will be a listening session open to the public. Members of the public are invited to offer brief 5-minute remarks on the Consultative Expert Working Group’s report and the US Government role in the process. The meeting will be held at the US National Academies’ Keck Center in Washington, DC, on December 18 at 4 pm. Registration is required, and attendance can be in person or by phone.

More Information >>
Register for the Meeting >>

Conference: Lives in the Balance: Delivering Medical Innovations for Neglected Patients and Populations

Conference: Lives in the Balance: Delivering Medical Innovations for Neglected Patients and Populations
December 13-14, 2012

“Various R&D initiatives, including product development partnerships, have begun to fill previously abandoned or non-existent drug development pipelines, with a limited number of new funding opportunities provided by a group of public and philanthropic donors.
“While progress has been made, where do we stand today? Are urgent R&D needs indeed being met? How can we accelerate the delivery of medical innovations to neglected patients?

Lives in the Balance aims to bring together key actors in global public health to reflect on progress and shortcomings, consider the evidence and report on analyses of recent data, and chart out ways to effectively tackle current challenges by drawing on lessons from the past decade.
“A broad range of scientists and medical professionals from countries hard hit by neglected diseases; policy-makers; academics; non-profit R&D initiatives; the pharmaceutical and biotechnology sectors; donors; civil society organizations; and medical journalists and editors will come together to review the current scientific and policy landscapes and pinpoint the remaining gaps as well as new opportunities for progress in the delivery of medical innovation to neglected patients.

Conference Background Report: Medical Innovations for Neglected Patients

Research: Falsified Medicines and the Global Public’s Health

Research: Falsified Medicines and the Global Public’s Health
Commissioned by the IFPMA and was independently prepared by researchers at the University College London (UCL) School of Pharmacy and the international research agency Matrix Insight.

“The new report focuses on the need for high quality information about the scale of harm caused by medicine falsification. Past studies found that 15 to 50 percent of anti-malarial treatments purchased in parts of Asia and Africa to be counterfeit, and data overall suggest that falsified products may account for nearly one percent of global medicine sales. While people in less developed communities are at greater risk than in richer ones, falsified therapies are regularly reported in virtually every country from the US and EU to the poorest sub-Saharan nations. They also affect every major therapeutic category…

The new report’s key conclusions include:
– An increasing number of governments (including China, India, Brazil, Russia and Nigeria) has, through their actions, recognized the need for effective measures against medicines falsification, which involves deliberately misrepresenting products’ origins and circumventing regulatory controls designed to assure treatment safety and effectiveness.

– The World Health Organization is uniquely placed to add value to governments’ efforts to protect against all forms of pharmaceutical crime, along with those of local regulators and other national and international agencies. More investment is needed to not only quantify medicines falsification but to provide early warning of potentially hazardous products as soon as they are detected in legitimate supply chains.

– All relevant stakeholders should be able and willing to participate in appropriate preventive activities at all levels. The new UCL/Matrix analysis emphasizes the need for more collaborative action between all stakeholders involved in better medicines use. At worst, unresolved disputes between vested interests may cost lives which responsible global action could have saved.

Regional inequality and vaccine uptake: a multilevel analysis of the 2007 Welfare Monitoring Survey in Malawi

BMC Public Health
(Accessed 15 December 2012)

Research article
Regional inequality and vaccine uptake: a multilevel analysis of the 2007 Welfare Monitoring Survey in Malawi
Dawit Shawel Abebe, Vibeke Oestreich Nielsen, Jon Erik Finnvold BMC Public Health 2012, 12:1075 (13 December 2012)

Abstract (provisional)
A significant part of childhood mortality can be prevented given the existence of a well functioning health care system that can deliver vaccines to children during their first year of life. This study assesses immunization differentials between regions in Malawi, and attempts to relate regional disparities in immunization to factors on individual, household and village level.

We used data from the 2007 Welfare Monitoring Survey which includes 18 251 children ages 10–60 months. Multilevel logistic regression models were applied for data analysis.

Major differences in full vaccine coverage (children receiving all of the 9 recommended vaccines) were documented between the 27 official regions, called districts, of Malawi. The vaccine coverage among regions varied from 2 % to 74 % when all children 10 — 60 months old were included. Vaccine coverage was significantly higher for women that had their delivery attended by a midwife/nurse, or gave birth at a hospital or maternity clinic. Regions with a high percentage of deliveries attended by health personnel were also characterized by a higher coverage. Characteristics of health care utilization on the individual level could in part account for the observed regional variations in coverage.

Several factors related to socio-demographic characteristics of individuals and households were significantly correlated with coverage (child’s age, illiteracy, income, water and sanitary conditions), implying a lower coverage among the most vulnerable parts of the population. However, these factors could only to a minor extent account for the regional variation in coverage.

The persistent regional inequalities suggest that the low immunization coverage in Malawi is less likely to be a result of geographical clustering of social groups with difficult level-of living conditions. Although the mean vaccine coverage in Malawi is low, some regions have succeeded in reaching a relatively high proportion of their children. The relative success of some regions implies that there is a substantial potential for political intervention to improve vaccine coverage. One important negative implication of regional inequality is the presence of clusters with under-vaccinated children, leading to an increased vulnerability during outbreaks of vaccine-preventable diseases.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

Global Burden of Disease Study 2010 (GBD 2010)

The Lancet  
Dec 15, 2012  Volume 380  Number 9859  p2053 – 2260

GBD 2010: understanding disease, injury, and risk
Richard Horton
Publication of the Global Burden of Disease Study 2010 (GBD 2010) is a landmark event for this journal and, we hope, for health. The collaboration of 486 scientists from 302 institutions in 50 countries has produced an important contribution to our understanding of present and future health priorities for countries and the global community.

From new estimates to better data
Margaret Chan
The Global Burden of Disease Study 2010 (GBD 2010) in The Lancet represents an unprecedented effort to improve global and regional estimates of levels and trends in the burden of disease. Accurate assessment of the global, regional, and country health situation and trends is critical for evidence-based decision making for public health. WHO therefore warmly welcomes GBD 2010, which was undertaken by the Institute for Health Metrics and Evaluation (IHME) with its partners and draws on the contributions of many scientists, including those who work in WHO programmes.

Data for better health—and to help end poverty
Jim Yong Kim
The World Bank Group welcomes the publication of the new Global Burden of Disease Study (GBD). The Bank commissioned the first GBD in 1990, and continues to make extensive use of this signal contribution to global health. Like its predecessors, the new, methodologically updated GBD 2010 marks a milestone in global health knowledge and our capacity for evidence-based action. It will once again set the terms of health policy, planning, and funding discussions for years to come.

GBD 2010: a multi-investigator collaboration for global comparative descriptive epidemiology
Christopher JL Murray, Majid Ezzati, Abraham D Flaxman, Stephen Lim, Rafael Lozano, Catherine Michaud, Mohsen Naghavi, Joshua A Salomon, Kenji Shibuya, Theo Vos, Alan D Lopez
The data, methods, and findings of the Global Burden of Disease Study 2010 (GBD 2010) are described in detail in The Lancet. This large collaboration is an evolution of a body of work that began with GBD 1990.1 The number of diseases, injuries, and risk factors evaluated and the geographical units of analysis have greatly expanded in the past 20 years, and change over time has been assessed. Nevertheless, GBD 2010 follows the basic principles of GBD 1990: trying to use all the relevant published and unpublished evidence; capturing fatal and non-fatal health outcomes with comparable metrics; and separating epidemiological assessment from advocacy concerns or entanglement of agendas.

GBD 2010: design, definitions, and metrics
Christopher JL Murray, Majid Ezzati, Abraham D Flaxman, Stephen Lim, Rafael Lozano, Catherine Michaud, Mohsen Naghavi, Joshua A Salomon, Kenji Shibuya, Theo Vos, Daniel Wikler, Alan D Lopez
The Global Burden of Diseases, Injuries, and Risk Factors (GBD) enterprise is a systematic, scientific effort to quantify the comparative magnitude of health loss due to diseases, injuries, and risk factors by age, sex, and geography for specific points in time. The GBD construct of the burden of disease is health loss, not income or productivity loss.1 For decision makers, health-sector leaders, researchers, and informed citizens, the GBD approach provides an opportunity to see the big picture, to compare diseases, injuries, and risk factors, and to understand in a given place, time, and age-sex group what are the most important contributors to health loss.

Age-specific and sex-specific mortality in 187 countries, 1970–2010: a systematic analysis for the Global Burden of Disease Study 2010
Haidong Wang, Laura Dwyer-Lindgren, Katherine T Lofgren, Julie Knoll Rajaratnam, Jacob R Marcus, Alison Levin-Rector, Carly E Levitz, Alan D Lopez, Christopher JL Murray
Estimation of the number and rate of deaths by age and sex is a key first stage for calculation of the burden of disease in order to constrain estimates of cause-specific mortality and to measure premature mortality in populations. We aimed to estimate life tables and annual numbers of deaths for 187 countries from 1970 to 2010.

We estimated trends in under-5 mortality rate (children aged 0—4 years) and probability of adult death (15—59 years) for each country with all available data. Death registration data were available for more than 100 countries and we corrected for undercount with improved death distribution methods. We applied refined methods to survey data on sibling survival that correct for survivor, zero-sibling, and recall bias. We separately estimated mortality from natural disasters and wars. We generated final estimates of under-5 mortality and adult mortality from the data with Gaussian process regression. We used these results as input parameters in a relational model life table system. We developed a model to extrapolate mortality to 110 years of age. All death rates and numbers have been estimated with 95% uncertainty intervals (95% UIs).

From 1970 to 2010, global male life expectancy at birth increased from 56·4 years (95% UI 55·5—57·2) to 67·5 years (66·9—68·1) and global female life expectancy at birth increased from 61·2 years (60·2—62·0) to 73·3 years (72·8—73·8). Life expectancy at birth rose by 3—4 years every decade from 1970, apart from during the 1990s (increase in male life expectancy of 1·4 years and in female life expectancy of 1·6 years). Substantial reductions in mortality occurred in eastern and southern sub-Saharan Africa since 2004, coinciding with increased coverage of antiretroviral therapy and preventive measures against malaria. Sex-specific changes in life expectancy from 1970 to 2010 ranged from gains of 23—29 years in the Maldives and Bhutan to declines of 1—7 years in Belarus, Lesotho, Ukraine, and Zimbabwe. Globally, 52·8 million (95% UI 51·6—54·1 million) deaths occurred in 2010, which is about 13·5% more than occurred in 1990 (46·5 million [45·7—47·4 million]), and 21·9% more than occurred in 1970 (43·3 million [42·2—44·6 million]). Proportionally more deaths in 2010 occurred at age 70 years and older (42·8% in 2010 vs 33·1% in 1990), and 22·9% occurred at 80 years or older. Deaths in children younger than 5 years declined by almost 60% since 1970 (16·4 million [16·1—16·7 million] in 1970 vs 6·8 million [6·6—7·1 million] in 2010), especially at ages 1—59 months (10·8 million [10·4—11·1 million] in 1970 vs 4·0 million [3·8—4·2 million] in 2010). In all regions, including those most affected by HIV/AIDS, we noted increases in mean ages at death.

Despite global and regional health crises, global life expectancy has increased continuously and substantially in the past 40 years. Yet substantial heterogeneity exists across age groups, among countries, and over different decades. 179 of 187 countries have had increases in life expectancy after the slowdown in progress in the 1990s. Efforts should be directed to reduce mortality in low-income and middle-income countries. Potential underestimation of achievement of the Millennium Development Goal 4 might result from limitations of demographic data on child mortality for the most recent time period. Improvement of civil registration system worldwide is crucial for better tracking of global mortality.

Bill & Melinda Gates Foundation.

Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010
Rafael Lozano et al

Reliable and timely information on the leading causes of death in populations, and how these are changing, is a crucial input into health policy debates. In the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010), we aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex.

We attempted to identify all available data on causes of death for 187 countries from 1980 to 2010 from vital registration, verbal autopsy, mortality surveillance, censuses, surveys, hospitals, police records, and mortuaries. We assessed data quality for completeness, diagnostic accuracy, missing data, stochastic variations, and probable causes of death. We applied six different modelling strategies to estimate cause-specific mortality trends depending on the strength of the data. For 133 causes and three special aggregates we used the Cause of Death Ensemble model (CODEm) approach, which uses four families of statistical models testing a large set of different models using different permutations of covariates. Model ensembles were developed from these component models. We assessed model performance with rigorous out-of-sample testing of prediction error and the validity of 95% UIs. For 13 causes with low observed numbers of deaths, we developed negative binomial models with plausible covariates. For 27 causes for which death is rare, we modelled the higher level cause in the cause hierarchy of the GBD 2010 and then allocated deaths across component causes proportionately, estimated from all available data in the database. For selected causes (African trypanosomiasis, congenital syphilis, whooping cough, measles, typhoid and parathyroid, leishmaniasis, acute hepatitis E, and HIV/AIDS), we used natural history models based on information on incidence, prevalence, and case-fatality. We separately estimated cause fractions by aetiology for diarrhoea, lower respiratory infections, and meningitis, as well as disaggregations by subcause for chronic kidney disease, maternal disorders, cirrhosis, and liver cancer. For deaths due to collective violence and natural disasters, we used mortality shock regressions. For every cause, we estimated 95% UIs that captured both parameter estimation uncertainty and uncertainty due to model specification where CODEm was used. We constrained cause-specific fractions within every age-sex group to sum to total mortality based on draws from the uncertainty distributions.

In 2010, there were 52·8 million deaths globally. At the most aggregate level, communicable, maternal, neonatal, and nutritional causes were 24·9% of deaths worldwide in 2010, down from 15·9 million (34·1%) of 46·5 million in 1990. This decrease was largely due to decreases in mortality from diarrhoeal disease (from 2·5 to 1·4 million), lower respiratory infections (from 3·4 to 2·8 million), neonatal disorders (from 3·1 to 2·2 million), measles (from 0·63 to 0·13 million), and tetanus (from 0·27 to 0·06 million). Deaths from HIV/AIDS increased from 0·30 million in 1990 to 1·5 million in 2010, reaching a peak of 1·7 million in 2006. Malaria mortality also rose by an estimated 19·9% since 1990 to 1·17 million deaths in 2010. Tuberculosis killed 1·2 million people in 2010. Deaths from non-communicable diseases rose by just under 8 million between 1990 and 2010, accounting for two of every three deaths (34·5 million) worldwide by 2010. 8 million people died from cancer in 2010, 38% more than two decades ago; of these, 1·5 million (19%) were from trachea, bronchus, and lung cancer. Ischaemic heart disease and stroke collectively killed 12·9 million people in 2010, or one in four deaths worldwide, compared with one in five in 1990; 1·3 million deaths were due to diabetes, twice as many as in 1990. The fraction of global deaths due to injuries (5·1 million deaths) was marginally higher in 2010 (9·6%) compared with two decades earlier (8·8%). This was driven by a 46% rise in deaths worldwide due to road traffic accidents (1·3 million in 2010) and a rise in deaths from falls. Ischaemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), lower respiratory infections, lung cancer, and HIV/AIDS were the leading causes of death in 2010. Ischaemic heart disease, lower respiratory infections, stroke, diarrhoeal disease, malaria, and HIV/AIDS were the leading causes of years of life lost due to premature mortality (YLLs) in 2010, similar to what was estimated for 1990, except for HIV/AIDS and preterm birth complications. YLLs from lower respiratory infections and diarrhoea decreased by 45—54% since 1990; ischaemic heart disease and stroke YLLs increased by 17—28%. Regional variations in leading causes of death were substantial. Communicable, maternal, neonatal, and nutritional causes still accounted for 76% of premature mortality in sub-Saharan Africa in 2010. Age standardised death rates from some key disorders rose (HIV/AIDS, Alzheimer’s disease, diabetes mellitus, and chronic kidney disease in particular), but for most diseases, death rates fell in the past two decades; including major vascular diseases, COPD, most forms of cancer, liver cirrhosis, and maternal disorders. For other conditions, notably malaria, prostate cancer, and injuries, little change was noted.

Population growth, increased average age of the world’s population, and largely decreasing age-specific, sex-specific, and cause-specific death rates combine to drive a broad shift from communicable, maternal, neonatal, and nutritional causes towards non-communicable diseases. Nevertheless, communicable, maternal, neonatal, and nutritional causes remain the dominant causes of YLLs in sub-Saharan Africa. Overlaid on this general pattern of the epidemiological transition, marked regional variation exists in many causes, such as interpersonal violence, suicide, liver cancer, diabetes, cirrhosis, Chagas disease, African trypanosomiasis, melanoma, and others. Regional heterogeneity highlights the importance of sound epidemiological assessments of the causes of death on a regular basis.

Bill & Melinda Gates Foundation.

Common values in assessing health outcomes from disease and injury: disability weights measurement study for the Global Burden of Disease Study 2010
Joshua A Salomon et al

Measurement of the global burden of disease with disability-adjusted life-years (DALYs) requires disability weights that quantify health losses for all non-fatal consequences of disease and injury. There has been extensive debate about a range of conceptual and methodological issues concerning the definition and measurement of these weights. Our primary objective was a comprehensive re-estimation of disability weights for the Global Burden of Disease Study 2010 through a large-scale empirical investigation in which judgments about health losses associated with many causes of disease and injury were elicited from the general public in diverse communities through a new, standardised approach.

We surveyed respondents in two ways: household surveys of adults aged 18 years or older (face-to-face interviews in Bangladesh, Indonesia, Peru, and Tanzania; telephone interviews in the USA) between Oct 28, 2009, and June 23, 2010; and an open-access web-based survey between July 26, 2010, and May 16, 2011. The surveys used paired comparison questions, in which respondents considered two hypothetical individuals with different, randomly selected health states and indicated which person they regarded as healthier. The web survey added questions about population health equivalence, which compared the overall health benefits of different life-saving or disease-prevention programmes. We analysed paired comparison responses with probit regression analysis on all 220 unique states in the study. We used results from the population health equivalence responses to anchor the results from the paired comparisons on the disability weight scale from 0 (implying no loss of health) to 1 (implying a health loss equivalent to death). Additionally, we compared new disability weights with those used in WHO’s most recent update of the Global Burden of Disease Study for 2004.

13 902 individuals participated in household surveys and 16 328 in the web survey. Analysis of paired comparison responses indicated a high degree of consistency across surveys: correlations between individual survey results and results from analysis of the pooled dataset were 0·9 or higher in all surveys except in Bangladesh (r=0·75). Most of the 220 disability weights were located on the mild end of the severity scale, with 58 (26%) having weights below 0·05. Five (11%) states had weights below 0·01, such as mild anaemia, mild hearing or vision loss, and secondary infertility. The health states with the highest disability weights were acute schizophrenia (0·76) and severe multiple sclerosis (0·71). We identified a broad pattern of agreement between the old and new weights (r=0·70), particularly in the moderate-to-severe range. However, in the mild range below 0·2, many states had significantly lower weights in our study than previously.

This study represents the most extensive empirical effort as yet to measure disability weights. By contrast with the popular hypothesis that disability assessments vary widely across samples with different cultural environments, we have reported strong evidence of highly consistent results.

Bill & Melinda Gates Foundation.

Healthy life expectancy for 187 countries, 1990–2010: a systematic analysis for the Global Burden Disease Study 2010
Joshua A Salomon, Haidong Wang, Michael K Freeman, Theo Vos, Abraham D Flaxman, Alan D Lopez, Christopher JL Murray

Healthy life expectancy (HALE) summarises mortality and non-fatal outcomes in a single measure of average population health. It has been used to compare health between countries, or to measure changes over time. These comparisons can inform policy questions that depend on how morbidity changes as mortality decreases. We characterise current HALE and changes over the past two decades in 187 countries.

Using inputs from the Global Burden of Disease Study (GBD) 2010, we assessed HALE for 1990 and 2010. We calculated HALE with life table methods, incorporating estimates of average health over each age interval. Inputs from GBD 2010 included age-specific information for mortality rates and prevalence of 1160 sequelae, and disability weights associated with 220 distinct health states relating to these sequelae. We computed estimates of average overall health for each age group, adjusting for comorbidity with a Monte Carlo simulation method to capture how multiple morbidities can combine in an individual. We incorporated these estimates in the life table by the Sullivan method to produce HALE estimates for each population defined by sex, country, and year. We estimated the contributions of changes in child mortality, adult mortality, and disability to overall change in population health between 1990 and 2010.

In 2010, global male HALE at birth was 58·3 years (uncertainty interval 56·7—59·8) and global female HALE at birth was 61·8 years (60·1—63·4). HALE increased more slowly than did life expectancy over the past 20 years, with each 1-year increase in life expectancy at birth associated with a 0·8-year increase in HALE. Across countries in 2010, male HALE at birth ranged from 27·9 years (17·3—36·5) in Haiti, to 68·8 years (67·0—70·4) in Japan. Female HALE at birth ranged from 37·1 years (26·9—43·7) in Haiti, to 71·7 years (69·7—73·4) in Japan. Between 1990 and 2010, male HALE increased by 5 years or more in 42 countries compared with 37 countries for female HALE, while male HALE decreased in 21 countries and 11 for female HALE. Between countries and over time, life expectancy was strongly and positively related to number of years lost to disability. This relation was consistent between sexes, in cross-sectional and longitudinal analysis, and when assessed at birth, or at age 50 years. Changes in disability had small effects on changes in HALE compared with changes in mortality.

HALE differs substantially between countries. As life expectancy has increased, the number of healthy years lost to disability has also increased in most countries, consistent with the expansion of morbidity hypothesis, which has implications for health planning and health-care expenditure. Compared with substantial progress in reduction of mortality over the past two decades, relatively little progress has been made in reduction of the overall effect of non-fatal disease and injury on population health. HALE is an attractive indicator for monitoring health post-2015.

The Bill & Melinda Gates Foundation

Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010
Theo Vos et al

Non-fatal health outcomes from diseases and injuries are a crucial consideration in the promotion and monitoring of individual and population health. The Global Burden of Disease (GBD) studies done in 1990 and 2000 have been the only studies to quantify non-fatal health outcomes across an exhaustive set of disorders at the global and regional level. Neither effort quantified uncertainty in prevalence or years lived with disability (YLDs).

Of the 291 diseases and injuries in the GBD cause list, 289 cause disability. For 1160 sequelae of the 289 diseases and injuries, we undertook a systematic analysis of prevalence, incidence, remission, duration, and excess mortality. Sources included published studies, case notification, population-based cancer registries, other disease registries, antenatal clinic serosurveillance, hospital discharge data, ambulatory care data, household surveys, other surveys, and cohort studies. For most sequelae, we used a Bayesian meta-regression method, DisMod-MR, designed to address key limitations in descriptive epidemiological data, including missing data, inconsistency, and large methodological variation between data sources. For some disorders, we used natural history models, geospatial models, back-calculation models (models calculating incidence from population mortality rates and case fatality), or registration completeness models (models adjusting for incomplete registration with health-system access and other covariates). Disability weights for 220 unique health states were used to capture the severity of health loss. YLDs by cause at age, sex, country, and year levels were adjusted for comorbidity with simulation methods. We included uncertainty estimates at all stages of the analysis.

Global prevalence for all ages combined in 2010 across the 1160 sequelae ranged from fewer than one case per 1 million people to 350 000 cases per 1 million people. Prevalence and severity of health loss were weakly correlated (correlation coefficient −0·37). In 2010, there were 777 million YLDs from all causes, up from 583 million in 1990. The main contributors to global YLDs were mental and behavioural disorders, musculoskeletal disorders, and diabetes or endocrine diseases. The leading specific causes of YLDs were much the same in 2010 as they were in 1990: low back pain, major depressive disorder, iron-deficiency anaemia, neck pain, chronic obstructive pulmonary disease, anxiety disorders, migraine, diabetes, and falls. Age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010. Regional patterns of the leading causes of YLDs were more similar compared with years of life lost due to premature mortality. Neglected tropical diseases, HIV/AIDS, tuberculosis, malaria, and anaemia were important causes of YLDs in sub-Saharan Africa.

Rates of YLDs per 100 000 people have remained largely constant over time but rise steadily with age. Population growth and ageing have increased YLD numbers and crude rates over the past two decades. Prevalences of the most common causes of YLDs, such as mental and behavioural disorders and musculoskeletal disorders, have not decreased. Health systems will need to address the needs of the rising numbers of individuals with a range of disorders that largely cause disability but not mortality. Quantification of the burden of non-fatal health outcomes will be crucial to understand how well health systems are responding to these challenges. Effective and affordable strategies to deal with this rising burden are an urgent priority for health systems in most parts of the world.

Bill & Melinda Gates Foundation.

Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010
Christopher J L Murray et al

Measuring disease and injury burden in populations requires a composite metric that captures both premature mortality and the prevalence and severity of ill-health. The 1990 Global Burden of Disease study proposed disability-adjusted life years (DALYs) to measure disease burden. No comprehensive update of disease burden worldwide incorporating a systematic reassessment of disease and injury-specific epidemiology has been done since the 1990 study. We aimed to calculate disease burden worldwide and for 21 regions for 1990, 2005, and 2010 with methods to enable meaningful comparisons over time.

We calculated DALYs as the sum of years of life lost (YLLs) and years lived with disability (YLDs). DALYs were calculated for 291 causes, 20 age groups, both sexes, and for 187 countries, and aggregated to regional and global estimates of disease burden for three points in time with strictly comparable definitions and methods. YLLs were calculated from age-sex-country-time-specific estimates of mortality by cause, with death by standardised lost life expectancy at each age. YLDs were calculated as prevalence of 1160 disabling sequelae, by age, sex, and cause, and weighted by new disability weights for each health state. Neither YLLs nor YLDs were age-weighted or discounted. Uncertainty around cause-specific DALYs was calculated incorporating uncertainty in levels of all-cause mortality, cause-specific mortality, prevalence, and disability weights.

Global DALYs remained stable from 1990 (2·503 billion) to 2010 (2·490 billion). Crude DALYs per 1000 decreased by 23% (472 per 1000 to 361 per 1000). An important shift has occurred in DALY composition with the contribution of deaths and disability among children (younger than 5 years of age) declining from 41% of global DALYs in 1990 to 25% in 2010. YLLs typically account for about half of disease burden in more developed regions (high-income Asia Pacific, western Europe, high-income North America, and Australasia), rising to over 80% of DALYs in sub-Saharan Africa. In 1990, 47% of DALYs worldwide were from communicable, maternal, neonatal, and nutritional disorders, 43% from non-communicable diseases, and 10% from injuries. By 2010, this had shifted to 35%, 54%, and 11%, respectively. Ischaemic heart disease was the leading cause of DALYs worldwide in 2010 (up from fourth rank in 1990, increasing by 29%), followed by lower respiratory infections (top rank in 1990; 44% decline in DALYs), stroke (fifth in 1990; 19% increase), diarrhoeal diseases (second in 1990; 51% decrease), and HIV/AIDS (33rd in 1990; 351% increase). Major depressive disorder increased from 15th to 11th rank (37% increase) and road injury from 12th to 10th rank (34% increase). Substantial heterogeneity exists in rankings of leading causes of disease burden among regions.

Global disease burden has continued to shift away from communicable to non-communicable diseases and from premature death to years lived with disability. In sub-Saharan Africa, however, many communicable, maternal, neonatal, and nutritional disorders remain the dominant causes of disease burden. The rising burden from mental and behavioural disorders, musculoskeletal disorders, and diabetes will impose new challenges on health systems. Regional heterogeneity highlights the importance of understanding local burden of disease and setting goals and targets for the post-2015 agenda taking such patterns into account. Because of improved definitions, methods, and data, these results for 1990 and 2010 supersede all previously published Global Burden of Disease results.

Bill & Melinda Gates Foundation.

A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010
Stephen S Lim et al

Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time.

We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden.

In 2010, the three leading risk factors for global disease burden were high blood pressure (7·0% [95% uncertainty interval 6·2—7·7] of global DALYs), tobacco smoking including second-hand smoke (6·3% [5·5—7·0]), and alcohol use (5·5% [5·0—5·9]). In 1990, the leading risks were childhood underweight (7·9% [6·8—9·4]), household air pollution from solid fuels (HAP; 7·0% [5·6—8·3]), and tobacco smoking including second-hand smoke (6·1% [5·4—6·8]). Dietary risk factors and physical inactivity collectively accounted for 10·0% (95% UI 9·2—10·8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water and sanitation accounting for 0·9% (0·4—1·6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania.

Worldwide, the contribution of different risk factors to disease burden has changed substantially, with a shift away from risks for communicable diseases in children towards those for non-communicable diseases in adults. These changes are related to the ageing population, decreased mortality among children younger than 5 years, changes in cause-of-death composition, and changes in risk factor exposures. New evidence has led to changes in the magnitude of key risks including unimproved water and sanitation, vitamin A and zinc deficiencies, and ambient particulate matter pollution. The extent to which the epidemiological shift has occurred and what the leading risks currently are varies greatly across regions. In much of sub-Saharan Africa, the leading risks are still those associated with poverty and those that affect children.

Bill & Melinda Gates Foundation.

A Phase 3 Trial of RTS,S/AS01 Malaria Vaccine in African Infants

New England Journal of Medicine
December 13, 2012  Vol. 367 No. 24

Original Articles
A Phase 3 Trial of RTS,S/AS01 Malaria Vaccine in African Infants
The RTS,S Clinical Trials Partnership

The candidate malaria vaccine RTS,S/AS01 reduced episodes of both clinical and severe malaria in children 5 to 17 months of age by approximately 50% in an ongoing phase 3 trial. We studied infants 6 to 12 weeks of age recruited for the same trial.

We administered RTS,S/AS01 or a comparator vaccine to 6537 infants who were 6 to 12 weeks of age at the time of the first vaccination in conjunction with Expanded Program on Immunization (EPI) vaccines in a three-dose monthly schedule. Vaccine efficacy against the first or only episode of clinical malaria during the 12 months after vaccination, a coprimary end point, was analyzed with the use of Cox regression. Vaccine efficacy against all malaria episodes, vaccine efficacy against severe malaria, safety, and immunogenicity were also assessed.

The incidence of the first or only episode of clinical malaria in the intention-to-treat population during the 14 months after the first dose of vaccine was 0.31 per person-year in the RTS,S/AS01 group and 0.40 per person-year in the control group, for a vaccine efficacy of 30.1% (95% confidence interval [CI], 23.6 to 36.1). Vaccine efficacy in the per-protocol population was 31.3% (97.5% CI, 23.6 to 38.3). Vaccine efficacy against severe malaria was 26.0% (95% CI, −7.4 to 48.6) in the intention-to-treat population and 36.6% (95% CI, 4.6 to 57.7) in the per-protocol population. Serious adverse events occurred with a similar frequency in the two study groups. One month after administration of the third dose of RTS,S/AS01, 99.7% of children were positive for anti-circumsporozoite antibodies, with a geometric mean titer of 209 EU per milliliter (95% CI, 197 to 222).

The RTS,S/AS01 vaccine coadministered with EPI vaccines provided modest protection against both clinical and severe malaria in young infants. (Funded by GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative; RTS,S number, NCT00866619.)

Malaria Vaccine Trials — Beyond Efficacy End Points
J.P. Daily

Extract [First 100 words]

Plasmodium falciparum infection, malaria, continues to cause more than 1 million childhood deaths each year.1 In addition, millions of nonlethal infections affect communities on an economic basis and inhibit children from reaching their full developmental potential.2 The creation of an effective vaccine has been a long-sought, elusive goal.

The first results of the phase 3 trial of the candidate malaria vaccine RTS,S/AS01, which is being conducted in seven African countries, were reported for children 5 to 17 months of age at enrollment, with a vaccine efficacy of 56% against all clinical malaria infections and 47% against severe malaria during a . . .