A pdf version of Vaccines: The Week in Review 27 June 2011 comprising all the posts below for this date is available here: Vaccines_The Week in Review_27 June 2011
Vaccines from start to finish: harnessing our opportunity
Opening remarks at the Pacific Health Summit:
Dr Margaret Chan, Director-General of the World Health Organization
Seattle, Washington, USA
23 June 2011
“Immunization was on the agenda at the May World Health Assembly, which is attended by delegations from all 193 WHO member states.
The immunization session covered current progress internationally and within countries, expectations for the Decade of Vaccines, and plans for WHO to develop a global vaccine action plan to guide work during the decade.
Well over 50 delegations and representatives of civil society took the floor on this item. For those of you unfamiliar with the workings of Health Assemblies, this number represents an extraordinary level of interest and engagement.
I think a brief summary of these interventions is a good way to give you an overview of what countries themselves see as progress and sources of pride. It also tells you some of their deep-seated concerns, right now and for the future.
Many developing countries are proud of their ownership of national immunization programmes, and many have dedicated budget lines as a formal expression of this commitment.
As we enter this Decade of Vaccines, we heard about great progress and high praise for support from WHO and UNICEF, but especially for the GAVI Alliance.
GAVI operates according to a fundamental principle that resonates extremely well with public health thinking in general and the principles that guide the work of WHO: every child, regardless of where it is born or the wealth of its parents, deserves protection with the best that science can offer.
This is an expression of fairness, and this is a principle that guides much of my own personal work.
With GAVI support, vaccines that prevent pneumonia and diarrhoea, the two biggest childhood killers, are now being rolled out in a number of countries. But these new vaccines are expensive and sustainability is definitely a problem, as stressed by many speakers from the developing world.
As reported, many countries have added yellow fever and hepatitis B vaccines to routine immunization programmes.
We heard first-hand accounts of what the new meningitis vaccine, developed in a project coordinated by WHO and PATH, with support from the Gates Foundation, means for Africa and its people.
Launch of the vaccine, which costs less than 50 cents a dose, a price demanded by African ministers of health, began last December in the three hyper-endemic countries in Africa’s notorious meningitis belt, namely Burkina Faso, Mali, and Niger. By the end of that month, 19.5 million people had been vaccinated in the three countries.
WHO and its partners are currently assessing the impact of these initial mass immunization campaigns, including their safety and efficacy. This is a thorough, systematic assessment, but early results look extremely promising.
Epidemic meningitis is not the biggest killer in Africa, but it is one of the most greatly feared of all diseases. My staff in the field tell me that long lines for vaccination form at the first hint of an epidemic that will leave around 25% of affected children, I mean the ones that survive, permanently impaired with brain damage or profound hearing loss.
For once, Africa is the first to receive the very best technology that the world, working together, can offer.
Ladies and gentlemen,
Delegates gave us two extremely clear messages.
First, the achievement of ambitious, yet fully agreed goals, such as expanded immunization coverage, the introduction of new vaccines, polio eradication, and measles elimination, is directly tied to funds.
We heard compelling pleas to fully replenish GAVI funds so that recent spectacular progress, supported by strong country ownership, does not lose its momentum.
Second, expanded vaccination coverage alone will not help countries reach the MDG for reducing young child mortality. According to the latest UNICEF estimates, some 8.1 million young children died in 2009 from largely preventable causes.
This figure is the lowest recorded in more than six decades. It is a measure of welcome progress, but the figure is still way too high. Immunization is thought to prevent 2 to 3 million childhood deaths each year. Vaccines are magic bullets, yes, but they don’t hit all the enemies that extinguish so many young lives.
Countries reminded us of the critical role of basic primary health care measures, such as oral rehydration therapy, home-based antibiotic treatment for pneumonia, and things so straightforward, yet so difficult for the poor, as adequate nutrition and good hygiene.
The issue of sustainable funding came up over and over again. As I have heard on many occasions, a vaccine that is too expensive for the developing world is worse than no vaccine at all.
Many asked the international community to seek ways to reduce the costs of vaccines, especially the newer ones.
Delegates from the developing world referred to the need for technology transfer and skills training to enable local manufacturing of vaccines, especially in Africa. Some described WHO’s key role in achieving exactly this objective for the local manufacturing of pandemic influenza vaccines.
And what has happened since the May Assembly?
On 6 June, leading drug companies announced dramatic slashes in vaccine prices for the developing world, including a 95% price cut on the new rotavirus vaccine that can prevent diarrhoeal deaths.
On 13 June, donors pledged more than $4 billion to support the work of GAVI, an amount that exceeded anyone’s wildest dreams. This money will certainly hasten the introduction of new vaccines and expand vaccination campaigns in Africa’s meningitis belt, which has 25 countries.
There are critics, of course. Many cite the lack of basic infrastructure for delivering vaccines and the crumbling of public health services, after years of neglect, throughout most of the developing world.
But let me reassure the critics. The strengthening of health systems has moved near the top of the international health agenda. The May Health Assembly adopted no fewer than 5 resolutions setting out ways to build stronger health systems that extend affordable services to the poor.
This is, after all, how health operates in the context of the MDGs, with their overarching goal of poverty reduction. By improving health, you reduce poverty. But to do so, you must reach the poor.
Ladies and gentlemen,
This decade of vaccines has a vision, and vision always feeds that perennial optimism of public health that keeps us going despite the many obstacles and setbacks thrown our way by policies and events beyond our control.
This decade will help realize the full power of immunization to prevent morbidity and mortality. And the young lives saved from death or life-long disability will be numbered in the millions.
Sabin Vaccine Institute announced receipt of a two-year, US$12 million grant from the Bill & Melinda Gates Foundation “to continue development of a vaccine to prevent human hookworm infection, a parasitic disease that affects 600 million people worldwide.” Hookworm infection, most commonly found in sub-Saharan Africa, Southeast Asia and Latin America, is a significant contributor to the global burden of iron-deficiency anemia that disproportionately affects children and women of reproductive age. The infection results in approximately 65,000 deaths and the loss of up to 22 million disability adjusted life years (DALYs) annually. Hookworm is one of the seven most common neglected tropical diseases (NTDs), which together carry a greater health burden than malaria and tuberculosis and rival that of HIV/AIDS.
Sabin also announced that WHO granted prequalification for Typhim Vi, a typhoid Vi polysaccharide vaccine produced by Sanofi Pasteur. This is the first typhoid vaccine to be prequalified by the WHO, “allowing UNICEF, other UN agencies and the Pan American Health Organization Revolving Fund to procure the vaccine. WHO prequalification is also a prerequisite for GAVI Alliance support.” Sabin noted that with at least 200,000 deaths occurring worldwide from typhoid fever each year, and a further 16-33 million people falling ill, use of typhoid vaccines can contribute to achieving the United Nations Millennium Development Goals. Dr. Shyam Raj Upreti, Director of the Child Health Division of the Department of Health Services, Ministry of Health and Population of Nepal, said, “WHO prequalification of a typhoid vaccine will accelerate the availability of this vaccine for children in Nepal and throughout Asia, where the burden of typhoid fever is highest.” http://sabin.org/news-resources/releases/2011/06/23/coalition-against-typhoid-applauds-world-health-organization-preq
J.P. Morgan announced that it will donate £1.5 million to the GAVI Alliance. The donation will be matched by the U.K. government’s newly created matching fund bringing the total to £3 million. GAVI Alliance Board Chair Dagfinn Hoybraten commented, “We are delighted to welcome J.P. Morgan as a Matching Fund partner. We recognise J.P. Morgan’s strong commitment to social finance. This generous investment will help us fulfill our mission to save children’s lives and protect people’s health by increasing access to immunisation in developing countries. On behalf of the children we will vaccinate with these resources, our thanks go out to the people of J.P. Morgan.”
Sanofi Pasteur Limited (Canada) said it opened a C$101 million dollar vaccine research and development facility at Sanofi Pasteur’s Connaught Campus in north Toronto. This new facility “establishes the Connaught Campus as the North American Centre of Excellence in analytical and bioprocessing R&D for Sanofi Pasteur globally (and) solidifies the Toronto site as a national strategic asset for the research, development and manufacturing of vaccines that protect public health – in Canada and around the world.” The province of Ontario contributed C$13.9 million to the project through the Biopharmaceutical Investment Program, part of the Next Generation of Jobs Fund. The new R&D facility, known internally as “Building 95“, “will help the company retain over 300 highly-skilled vaccine research positions and bring many of the company’s accomplished scientists and state-of-the-art technologies under one roof.” Sanofi noted that the site “manufactures many vaccines vital to public health with 94% of its vaccine production being delivered to over 90 countries around the world. http://www.prnewswire.com/news-releases/sanofi-pasteur-opens-100m-rd-centre-in-canada-124348274.html
The Weekly Epidemiological Record (WER) for 24 June 2011, vol. 86, 26 (pp 269–276) includes: Index of countries/areas; Index, Volume 86, 2011, Nos. 1–26 – Subject index; Performance of acute flaccid paralysis (AFP) surveillance and incidence of poliomyelitis, 2011
A selection of items of interest this week from a variety of twitter feeds. This capture is highly selective and by no means intended to be exhaustive.
British Medical Journal
25 June 2011 Volume 342, Issue 7812
Measles outbreak in Europe
Simon Cottrell, Richard John Roberts
BMJ 2011;342:doi:10.1136/bmj.d3724 (Published 15 June 2011)
Despite the current threat in Europe rates of infection are declining globally
Current outbreaks of measles in Europe are a reminder of the important risks of death and serious morbidity associated with measles. Between 2009 and 2010, cases of measles increased dramatically in Europe, with notifications increasing from 7175 to 30 367. 1 In 2010 most reported cases were in Bulgaria (22 005), but there were also 5019 in France, 861 in Italy, 787 in Germany, 406 in Ireland, 397 in the United Kingdom, and 302 in Spain. Of these, 21 877 people were admitted to hospital and 21 died (case fatality 0.69 deaths/1000 reported cases); 71% of people infected were aged under 20 years and 85% were unvaccinated. The World Health Organization has reported outbreaks in 24 European countries already this year. 2 There is little sign of a decrease in cases in 2011, and travel has facilitated transmission between countries. From January to March 2011, 9349 cases were reported, and 18 of 32 reporting countries found that the incidence of measles was higher than during the same period in 2010. 3
Currently the French outbreak is the largest in Europe and it has not yet peaked. Since it began in 2008, France …
Clinical Infectious Diseases
Volume 53 Issue 2 July 15, 2011
Shioko Kawai, Seiichiro Nanri, Eiko Ban, Mikako Inokuchi, Tetsuya Tanaka, Mitsuaki Tokumura, Keiko Kimura, and Norio Sugaya
Influenza Vaccination of Schoolchildren and Influenza Outbreaks in a School
Clin Infect Dis. (2011) 53(2): 130-136 doi:10.1093/cid/cir336
Background. The objective of this retrospective descriptive study was to determine whether the universal influenza vaccination for schoolchildren was effective in controlling influenza outbreaks in a school. A universal vaccination program for schoolchildren was started in Japan in the 1960s, but the government abandoned the program in 1994 because of lack of evidence that the program was effective in preventing influenza in schoolchildren.
Methods. Influenza vaccine coverage rates, total numbers of class cancellation days, and absentee rates were reviewed in a single elementary school during the 24-year period during 1984–2007.
Results. The mean number of class cancellation days and the mean absentee rate in the compulsory vaccination period (1984–1987; mean vaccine coverage rate, 96.5%) were 1.3 days and 2.5%, respectively, and they increased to 8.3 days and 3.2% during the quasi-compulsory vaccination period (1988–1994; vaccine coverage, 66.4%). In the no-vaccination period (1995–1999; vaccine coverage, 2.4%), they were 20.5 days and 4.3%, respectively, and in the voluntary vaccination period (2000–2007; vaccine coverage, 38.9–78.6%), they were 7.0–9.3 days and 3.8%–3.9%. When minor epidemics were excluded, there was a significant inverse correlation between the vaccine coverage rates and both the number of class cancellation days and absentee rates.
Conclusions. The universal influenza vaccination for schoolchildren was effective in reducing the number of class cancellation days and absenteeism in the school.
June 22/29, 2011, Vol 305, No. 24, pp 2493-2592
Health Advocacy Organizations and Evidence-Based Medicine
Sheila M. Rothman
[No abstract: first 150 words per JAMA convention]
Strong and independent not-for-profit advocacy organizations are vital to a democratic society. At their best, they stand apart from the interests of the marketplace and the government, helping to promote diverse public concerns. The scope of their activities is extensive. Some not-for-profit advocacy organizations spearhead campaigns to eliminate discriminatory legislation and improve the life chances of vulnerable groups. Others challenge economic interests to better protect the environment. Still others work to advance civil and human rights.
Health advocacy organizations are part of this sector. They speak for targeted populations affected by a variety of diseases such as epilepsy, breast cancer, mental illness, and autism. They effectively communicate their priorities to legislators, regulators, private and public funders, and the media. Their initiatives often highlight needs that might otherwise be overlooked. However, some health advocacy organizations, as shall be illustrated, are so committed to securing diagnostic and treatment interventions for their targeted …
The Lancet Infectious Disease
Jul 2011 Volume 11 Number 7 Pages 489 – 578
Measles once again
The Lancet Infectious Diseases
An effective vaccine against measles has been available for the past 40 years. Before its introduction in 1963 there were almost 135 million cases of measles and over 6 million measles-related deaths per year. Globally, thanks to this vaccine the number of measles deaths worldwide fell by 78% between 2000 and 2008, from an estimated 733 000 to 164 000.
However, despite these efforts, it is hard to believe that in the 21st century measles remains a leading vaccine-preventable cause of deaths in children younger than 5 years old. The disease is still endemic in many parts of Europe. In the past 2 years, Austria, France, Germany, Ireland, Italy, the Netherlands, Spain, and the UK have all seen outbreaks. In 2010, more than 27 795 cases of measles were reported in Europe, and 21 853 were reported during the 2009—10 outbreak in Bulgaria where 25 people died.
In USA during the 1980s, the number of measles cases was low but a big increase occurred in 1989 with almost 18 000 cases reported. Lack of a second dose of measles, mumps, and rubella (MMR) vaccine could have decreased the level of immunity among the school-age population, among whom most of the cases were reported. Subsequently, two rounds of vaccination were recommended. At the end of 2000, thanks to vaccination, the ongoing transmission of endemic measles was declared eliminated in the USA. However, this year from January 1 to May 20, 118 cases were reported in the USA. 46% of the cases were imported, most from countries in the WHO European region.
Before the era of vaccination, immunity against measles was acquired by natural infection or by protection given by antibodies transmitted from the mother to the fetus during gestation. Measles transmission requires contact between a susceptible person and the infectious secretions of a person with measles. The incidence of measles varies cyclically. Incidence rises as susceptible individuals enter the population. Acquisition of immunity through exposure to the virus or vaccination decreases the number of susceptible individual in the population and measles incidence falls. The interval between epidemic peaks is proportional to the number of susceptible individuals that accumulate over time. In the presence of vaccination, the interval between peaks of disease can be 10 years; without vaccination, the interval can be 3—4 years. A decline in the uptake of immunisation in the past decade has increased the susceptible population and measles has resurged.
Elimination of measles, defined as the interruption of indigenous transmission, is difficult because the disease is very contagious and transmissible before an infected person shows signs of illness. Ideally, two doses of MMR vaccine given to 95% of children are required to halt the spread of the virus. By 2009 only 60% of countries worldwide had achieved 90% coverage with at least one vaccine dose. Difficulty accessing services, religious beliefs, and vaccine scepticism are only part of the reasons for low coverage. Better organisation of the vaccination systems is required—for example, 10% of children receive one dose of vaccine but then miss the second shot. Lack of reminders and difficulty tracking moving families are among the weaknesses of the vaccine system.
However, elimination is not impossible. Measles was eliminated from the Americas in 2000, but progress towards elimination in the European region has faltered. By 2010, 30 of the 53 European countries had reached the target of a measles incidence of fewer than one case per million population. The WHO Europe strategic plan for measles 2010—15 sets targets of 90% measles vaccination coverage, and reductions in the number of cases to fewer than five per million and in mortality by 95% compared with 2000 levels.
Additional effort and resources from European states are needed to reach the above targets. Vaccine acceptability could be improved through better communication with the public. Thought needs to be given to targeted messaging campaigns and perhaps the recruitment of public figures as advocates for vaccination. Catch-up vaccination campaigns outside the routine system are needed to cover susceptible populations. Commitment from governments, donors, and parents is needed to make measles a disease of the past. Despite recent outbreaks, elimination in Europe in the in the next 4 years should be achievable, and would inspire efforts in developing regions, which still have the highest burden of the disease: global eradication of the disease in this generation would spare future generations from this preventable disease.
The Lancet Infectious Disease
Jul 2011 Volume 11 Number 7 Pages 489 – 578
Safety and efficacy of the HVTN 503/Phambili Study of a clade-B-based HIV-1 vaccine in South Africa: a double-blind, randomised, placebo-controlled test-of-concept phase 2b study
Glenda E Gray, Mary Allen, Zoe Moodie, Gavin Churchyard, Linda-Gail Bekker, Maphoshane Nchabeleng, Koleka Mlisana, Barbara Metch, Guy de Bruyn, Mary H Latka, Surita Roux, Matsontso Mathebula, Nivashnee Naicker, Constance Ducar, Donald K Carter, Adrien Puren, Niles Eaton, M Julie McElrath, Michael Robertson, Lawrence Corey, James G Kublin, on behalf of the HVTN 503/Phambili study team
The MRKAd5 HIV-1 vaccine did not prevent HIV-1 infection or lower viral-load setpoint; however, stopping our trial early probably compromised our ability to draw conclusions. The high incidence rates noted in South Africa highlight the crucial need for intensified efforts to develop an efficacious vaccine.
The Lancet Infectious Disease
Jul 2011 Volume 11 Number 7 Pages 489 – 578
Rationale for pertussis booster vaccination throughout life in Europe
Fred Zepp, Ulrich Heininger, Jussi Mertsola, Ewa Bernatowska, Nicole Guiso, John Roord, Alberto E Tozzi, Pierre Van Damme
Although the introduction of universal pertussis immunisation in infants has greatly reduced the number of reported cases in infants and young children, disease incidence has been increasing in adolescents and adults in recent years. This changing epidemiological pattern is probably largely attributable to waning immunity after natural infection or vaccination. Furthermore, improved diagnostic testing, active surveillance, changes in disease susceptibility, vaccine characteristics, and increased awareness of the disease might also be contributing factors.
Volume 474 Number 7352 pp419-536 23 June 2011
Vaccine trial’s ethics criticized
Collapsed trial fuels unfounded vaccine fears.
A clinical trial that came under fire in India threatens to have a dual legacy: inflaming unfounded fears about a lifesaving vaccine and raising new questions about the management of medical research in the country. After four teenage girls taking part in a test of human papillomavirus (HPV) vaccines died last year, the Indian government faced accusations that its citizens were being used as guinea pigs to test dangerous vaccines. A scientific investigation has exonerated the vaccines but uncovered a more familiar problem in India: ethical irregularities.
The study, funded by the Bill & Melinda Gates Foundation and run by the international health charity PATH and the Indian Council of Medical Research (ICMR), vaccinated more than 23,000 girls aged 10–14 against HPV, which can cause cervical cancer. The vaccines — Merck’s Gardasil and GlaxoSmithKline’s Cervarix — are already in widespread use in the developed world, and the study was designed to assess the feasibility of launching an HPV-immunization programme in the Indian health system. The researchers hoped to gauge public acceptance of the vaccines and assess the costs of administering it in different parts of the country.
A committee of three scientists from the All India Institute of Medical Sciences (AIIMS) in New Delhi, commissioned by the government to look into the trial, confirmed that the deaths were not linked to the vaccines — two of the girls died of poisoning, one of drowning and the fourth of a fever. But its report, leaked to India’s media last month, said that the study involved several serious ethical violations. According to media reports, participants were recruited from vulnerable tribal populations, consent was improperly obtained — headmasters of the girls’ schools signed the forms — and adverse events were poorly recorded…
Science Translational Medicine
22 June 2011 vol 3, issue 88
Immunogenicity of the Tuberculosis Vaccine MVA85A Is Reduced by Coadministration with EPI Vaccines in a Randomized Controlled Trial in Gambian Infants
Martin O. C. Ota, Aderonke A. Odutola, Patrick K. Owiafe, Simon Donkor, Olumuyiwa A. Owolabi, Nathaniel J. Brittain, Nicola Williams, Sarah Rowland-Jones, Adrian V. S. Hill, Richard A. Adegbola, and Helen McShane
22 June 2011: 88ra56
New tuberculosis vaccines are urgently needed to curtail the current epidemic. MVA85A is a subunit vaccine that could enhance immunity from BCG vaccination. To determine MVA85A safety and immunogenicity as well as interactions with other routine vaccines administered in infancy, we randomized healthy 4-month-old infants who had received Bacille Calmette-Guérin at birth to receive Expanded Program on Immunization (EPI) vaccines alone, EPI and MVA85A simultaneously, or MVA85A alone. Adverse events were monitored throughout. Blood samples obtained before vaccination and at 1, 4, and 20 weeks after vaccination were used to assess safety and immunogenicity. The safety profile of both low and standard doses was comparable, but the standard dose was more immunogenic and therefore was selected for the second stage of the study. In total, 72 (first stage) and 142 (second stage) infants were enrolled. MVA85A was safe and well tolerated and induced a potent cellular immune response. Coadministration of MVA85A with EPI vaccines was associated with a significant reduction in MVA85A immunogenicity, but did not affect humoral responses to the EPI vaccines. These results provide important information regarding timing of immunizations, which is required for the design of infant efficacy trials with MVA85A, and suggest that modifications to the standard EPI schedule may be required to incorporate a new generation of T cell–inducing vaccines.
Science Translational Medicine
22 June 2011 vol 3, issue 88
Leveraging Crowdsourcing to Facilitate the Discovery of New Medicines
Thea C. Norman, Chas Bountra, Aled M. Edwards, Keith R. Yamamoto, and Stephen H. Friend
22 June 2011: 88mr1
Gloomy predictions about the future of pharma have forced the industry to investigate alternative models of drug discovery. Public-private partnerships (PPPs) have the potential to revitalize the discovery and development of first-in-class therapeutics. The new PPP Arch2POCM hopes to foster biomedical innovation through precompetitive validation of pioneer therapeutic targets for human diseases. In this meeting report, we capture insights garnered from the April 2011 Arch2POCM conference.
Volume 29, Supplement 1, Pages A1-A50 (1 July 2011)
Transfer of Technology for Pandemic Influenza Vaccine Production in Developing Countries
Edited by Ray Spier
[13 articles covering this theme are presented in this supplement; the first two articles are included below]
WHO initiative to increase global and equitable access to influenza vaccine in the event of a pandemic: Supporting developing country production capacity through technology transfer
Martin Friede, Laszlo Palkonyay, Claudia Alfonso, Yuri Pervikov, Guido Torelli, David Wood, Marie Paule Kieny
Should a highly pathogenic avian influenza virus, such as the H5N1 virus type currently circulating in birds, become transmissible among humans, an effective vaccine, rapidly available in vast quantities, would be the best tool to prevent high case-fatalities and the breakdown of health and social services. The number of vaccine doses that could be produced on demand has risen sharply over the last few years; however, it is still alarmingly short of the 13 billion doses that would be needed if two doses were required to protect fully the world’s population. Most developing countries would be last in the queue to benefit from a pandemic vaccine. The World Health Organization, together with governments, the pharmaceutical industry and other stakeholders, has been implementing the global pandemic influenza action plan to increase vaccine supply since 2006. Building capacity in developing countries to manufacture influenza vaccine is an integral part of this plan, as well as research and development into more efficacious technologies, e.g. those that allow significant dose-sparing. To this end, the influenza vaccine technology transfer initiative was launched in 2007 and, to date, vaccine manufacturers in 11 developing countries have received grants to acquire the capacity to produce inactivated or live attenuated influenza vaccine for their populations. In addition, a centralized ‘hub’ has been established to facilitate training in the new technologies for scientists and regulators in the countries. This supplement of Vaccine is devoted to showcasing the interim results of the WHO initiative and the impressive progress made by the developing country manufacturers.
Th pdf version of Vaccines: The Week in Review 20 June 2011, comprising the posts below on this date, is available here: Vaccines_The Week in Review_20 June 2011
The GAVI Alliance pledging conference – Saving children’s lives – resulted in donors committing US$ 4.3 billion, exceeding an initial target of $3.7 billion, “enabling GAVI to reach more children faster than planned and to accelerate the introduction of new vaccines.” A portion of the pledges are conditional upon GAVI raising additional funds from new donors in the future. Today’s pledges bring GAVI’s total available resources for the period 2011 to 2015 to $ 7.6 billion.
Download the press release and tables showing a breakdown of donor pledges from the conference, and a composition of pledges for 2011-2015 (PDF – 192K)
GAVI has provided a summary of publications and documents related to the pledging conference at:
Speech: GAVI Replenishing Event
Anthony Lake, UNICEF Executive Director at London, 13 June 2011
USAID announced the U.S. pledge to GAVI of US$450 million over the next 3 years, subject to congressional approval. Dr. Rajiv Shah, Administrator of the U.S. Agency for International Development (USAID), commented, ”…At a time when budgets around the world are being scrutinized, this partnership with donor and host country governments, civil society and private sector partners ensures our development dollars have the greatest impact. Not only is our commitment inspiring the generosity of other donors, it helps ensure the quantities of vaccine needed to obtain lower prices, allowing us to save even more lives.” He also noted that “within the next year, the U.S. Government will host a high-level conference to assess progress against achieving impact based on the immunization pledges made here today.”
The Special Programme for Research and Training in Tropical Diseases based at WHO and co-sponsored by UNICEF, UNDP, the World Bank and WHO – was awarded the 2011 Gates Award for Global Health. The “world’s largest public health prize” was presented to TDR Director Dr Robert Ridley who commented, “This award represents the culmination of 36 years of history. Researchers from all over the world have worked with us to find improved health solutions for people in poor countries. The long-term commitments from our donors have led to major progress against many infectious diseases of poverty.”
Speech: Success, shocks, surprises, and moral vindication
Dr Margaret Chan, Director-General of the World Health Organization
Address at the Chatham House event on the increasing importance of global health in international affairs, London, UK; 13 June 2011
HHS in the U.S., through the National Prevention, Health Promotion, and Public Health Council, announced the release of the National Prevention Strategy, described as a comprehensive plan that will help increase the number of Americans who are healthy at every stage of life. The National Prevention Strategy “recognizes that good health comes not just from receiving quality medical care, but also from clean air and water, safe outdoor spaces for physical activity, safe worksites, healthy foods, violence-free environments and healthy homes. Prevention should be woven into all aspects of our lives, including where and how we live, learn, work and play. Everyone—businesses, educators, health care institutions, government, communities and every single American—has a role in creating a healthier nation.”
The full report is available at: http://www.healthcare.gov/center/councils/nphpphc/strategy/report.pdf
The report addresses vaccines in Strategic Directions No. 6 (p.20): Enhance coordination and integration of clinical, behavioral, and complementary health strategies:
The Federal Government will:
Develop new and improved vaccines, enhance understanding of the safety of vaccines and vaccination practices, support informed vaccine decision-making, and improve access to and better use of recommended vaccines.
The MMWR Weekly for June 17, 2011 / Vol. 60 / No. 23 includes:
Place of Influenza Vaccination Among Adults — United States, 2010–11 Influenza Season
WHO Europe: WHO Epidemiological Brief 15: Measles outbreaks and response to importation of wild poliovirus; Measles outbreaks continue
By the end of April 2011, the Region had reported more than 11 000 confirmed cases of measles. Over 75% of these cases are not immunized against measles. While western Europe is particularly affected by outbreaks, it is clear that the problem of measles outbreaks is not confined to any specific country or subregion.
Response to importation of wild poliovirus
Genetic analysis of the virus that caused the 2010 polio outbreak in Tajikistan and neighbouring countries has shed light on the possible origin and date of introduction, namely an importation of WPV1 of a South Asia (SOAS) genotype, which most likely occurred in late 2009 or early 2010. As part of the continued response to the outbreak, seven Member States have synchronized their supplementary immunization activities (SIAs). These campaigns have resulted in 15 rounds of polio immunization (mOPV and tOPV) and targeted more than 18 million children.
The Weekly Epidemiological Record (WER) for 17 June 2011, vol. 86, 25 (pp 257–268) includes: Soil-transmitted helminthiases: estimates of the number of children needing preventive chemotherapy and number treated, 2009
267 Monthly report on dracunculiasis cases, January–April 2011 http://www.who.int/entity/wer/2011/wer8625.pdf
A selection of items of interest this week from a variety of twitter feeds. This capture is highly selective and by no means intended to be exhaustive.
British Medical Journal
18 June 2011 Volume 342, Issue 7811
H1N1 influenza in pregnant women
K S Joseph, Robert M Liston
BMJ 2011;342:doi:10.1136/bmj.d3237 (Published 14 June 2011)
Vaccination is the key to mitigating the higher incidence of adverse outcomes
Although the 2009 H1N1 pandemic proved to be more benign than anticipated, it had a substantial effect on pregnant women. In the linked cohort study (doi: 10.1136/bmj.d3214 ), Pierce and colleagues report the perinatal outcomes of 256 pregnant women admitted to hospital with H1N1 influenza in the United Kingdom. 1
The study found that pregnant women admitted to hospital with H1N1 influenza had significantly higher rates of adverse pregnancy outcomes than uninfected pregnant women. These included three to four times higher rates of preterm birth, four to five times higher rates of stillbirth, and four to six times higher rates of neonatal death. 1 These high rates of adverse perinatal outcomes were consistent with those reported in a population based study from the United States, 2 which also found a high maternal death rate (five deaths in 489 pregnant women admitted to hospital). Presumably, details of specific maternal complications and causes of death will be forthcoming …
Global health diplomacy: how foreign policy can influence health
BMJ 2011;342:doi:10.1136/bmj.d3154 (Published 10 June 2011)
June 2011; Volume 30, Issue 6
Strategies For The ‘Decade Of Vaccines’
Vaccination: Facts Alone Do Not Policy Make
Deadly Choices: How The Anti-Vaccine Movement Threatens Us All by Paul A. Offit New York (NY): Basic Books, 2011 288 pp., $27.50
The Panic Virus: A True Story Of Medicine, Science, And Fear by Seth Mnookin New York (NY): Simon and Schuster, 2011 488 pp.; $26.99
If biomedical scientists, physicians, or experts in health policy were asked what they base their clinical or policy recommendations on, one would probably hear references to facts, data, evidence, and confirmed findings. Little would be said about values—but they must be at the center of any discussion. These two books make this point clearly.
Evidence-based medicine began as an effort to identify and examine regional variations in clinical practice with the goal of increasing safety and efficacy. The field has evolved into a full-fledged ideological movement that demands that clinical practice and policies rest on solid, objective evidence for their warrant and reimbursement. 1 Evidence surely is necessary and desirable in trying to decide what to do about health care at the bedside, in the legislature, or in the boardroom. But it is not sufficient. 2 Nowhere is this more in evidence than in the running battle about vaccination in the United States.
Two recent books lay out the facts about vaccine efficacy and safety. One, Deadly Choices: How the Anti-Vaccine Movement Threatens Us All, is by Paul A. Offit, a physician and infectious disease expert at the Children’s Hospital of Philadelphia. The other, by writer and editor Seth Mnookin, is The Panic Virus: A True Story of Medicine, Science, and Fear.
Offit does yeoman’s duty in showing that worries about vaccine safety rest firmly on a vast pile of nonsense, duplicity, hype, and deeply flawed science. He tracks the history of vaccine opposition from its start among the conscientious objectors to smallpox vaccine in Britain in the nineteenth century down to the gaggle of celebrities and media lights who lead the movement today. If you want a solid grasp of the worries, fears, misunderstandings, and ideology that have inspired a small minority of people to vocally oppose …
Health Economics, Policy and Law
Volume 6 – Issue 03 – 2011 http://journals.cambridge.org/action/displayIssue?jid=HEP&tab=currentissue
Should health authorities offer risk-sharing contracts to pharmaceutical firms? A theoretical approach
Fernando Antonanzas, Carmelo Juarez-Castello and Roberto Rodriguez-Ibeas
In this paper, we characterise the risk-sharing contracts that health authorities can design when they face a regulatory decision on drug pricing and reimbursement in a context of uncertainty. We focus on two types of contracts. On the one hand, the health authority can reimburse the firm for each treated patient regardless of health outcomes (non risk-sharing). Alternatively, the health authority can pay for the drug only when the patient is cured (risk-sharing contract). The optimal contract depends on the trade-off between the monitoring costs, the marginal production cost and the utility derived from treatment. A non-risk-sharing agreement will be preferred by the health authority, if patients who should not be treated impose a relatively low cost to the health system. When this cost is high, the health authority would prefer a risk-sharing agreement for relatively low monitoring costs.
Journal of Infectious Diseases
Volume 204 Issue 2 July 15, 2011
Editor’s Choice: The Nonspecific Effects of Vaccines and the Expanded Program on Immunization
J Infect Dis. (2011) 204(2): 182-184 doi:10.1093/infdis/jir244
(See the article by Aaby et al, on pages 245–52 .)
There is now clear evidence that the simplistic conventional model of immunization is invalid [ 1]. We can no longer assume that a vaccine acts independently of other vaccines, or that it influences only infections caused by the target disease. Strong evidence from randomized trials suggests that bacillus Calmette-Guérin vaccine (BCG) reduces mortality from infections other than tuberculosis and that measles vaccine reduces mortality from infections other than measles [ 1– 4]. However, there is worrying evidence that whole-cell diphtheria-tetanus-pertussis vaccine (DTP) may increase mortality from infections other than diphtheria, tetanus, or pertussis in high-mortality areas [ 1, 3– 8]. These nonspecific effects of BCG, measles vaccine, and DTP are generally stronger in girls, appear to be maximal in the first 6 months after immunization, and are largely determined by the most recent vaccine administered [ 1].
Randomized trials show that measles vaccine has strong nonspecific effects. Providing it is not given after vitamin A or followed by DTP, measles vaccine reduces mortality from diseases other than measles by 45% (95% confidence interval [CI], 14%–65%) when given at 4.5 months of age [ 9], and by 47% (95% CI, 23%–63%) when given to girls at 9 to 10 months of age [ 1].
In this issue of the Journal, Aaby et al present further evidence, from Guinea-Bissau, that BCG has potent nonspecific effects on mortality [ 4]. Low-birth-weight neonates were randomized to receive BCG at birth or via the routine immunization program at an older age (median, 7.7 weeks). The biological effects of BCG are shown by the outcome during the first 4 weeks after randomization, before children in either group had been given DTP and when few …
[Free full text: http://jid.oxfordjournals.org/content/204/2/182.full ]
New England Journal of Medicine
June 16, 2011 Vol. 364 No. 24
The Polio Endgame
Bruce Aylward, M.D., and Tadataka Yamada, M.D.
N Engl J Med 2011; 364:2273-2275June 16, 2011
[Free full text]
Infection with poliovirus can have devastating consequences, including paralysis and death. In 1988, a year when an estimated 350,000 or more children were paralyzed by polio, the World Health Assembly initiated a global effort to eradicate the infection once and for all. It was an audacious undertaking, given that the virus circulates largely undetected, requires laborious cell-culture techniques to confirm infection, and is tackled with vaccines that provide imperfect protection in the gut.
Initially, the number of polio cases and countries with infections fell rapidly, particularly as financing and political support increased in the mid-1990s. The last case of paralytic poliomyelitis caused by the serotype 2 wild poliovirus was detected in 1999. The number of new polio cases caused by the two remaining wild serotypes had decreased by 99% between 1988 and 2005, but progress had stalled and there was a danger of failure when wild polio viruses were reintroduced into large areas of Africa and Asia. By the end of 2009, sustained investments in innovation had produced a new bivalent oral poliovirus vaccine (OPV)1 and novel tactics for reaching children who had been missed consistently by vaccination campaigns. A new independent monitoring process was established for overseeing the program and guiding course corrections. Since January 2010, new polio cases have decreased by 95% in the world’s largest remaining reservoirs of indigenous virus in northern India and northern Nigeria; the number of cases caused by serotype 3 has fallen by 92% globally; and most countries where poliovirus had been reintroduced have again become polio-free
Declines in the intensity of poliovirus transmission in India and Nigeria are key to interrupting wild poliovirus globally, since viruses originating in these countries have been responsible for all the recent importation-associated outbreaks in previously polio-free countries. Besides India and Nigeria, indigenous polioviruses now survive only in Pakistan and one part of Afghanistan, with just eight other countries currently responding to outbreaks caused by imported viruses. However, in three of these countries — Angola, Chad, and the Democratic Republic of Congo — transmission was reestablished (i.e., at least one imported virus continued to circulate for more than 12 months). All three countries then became secondary wild-poliovirus reservoirs, with onward spread to other previously polio-free countries. The logistic challenges of reaching more than 90% of young children in mass OPV immunization campaigns in countries with reestablished transmission are similar in scale to those faced in the remaining countries with endemic disease, where conflict, insecurity, and weak public services complicate eradication operations.
Although there is still much distance to cover to eradicate the remaining wild polioviruses, recent progress has generated new confidence in the eradication effort, and talk of the polio “endgame” has intensified. However, preventing new polio outbreaks in a “post-eradication era” will require more than biocontainment measures to prevent the reintroduction of wild virus from laboratory stocks or sites where inactivated (Salk) polio vaccine (IPV) is produced. Achieving a polio-free world will eventually require stopping routine immunization with OPV and eliminating vaccine-derived polioviruses (VDPVs), particularly circulating VDPVs, which are Sabin-strain viruses that have acquired both neurovirulence and the capacity to circulate.2
Of the three risks associated with OPV, the most frequently realized one is vaccine-associated paralytic poliomyelitis (VAPP). This risk will disappear with the cessation of use of OPV. Outbreaks caused by circulating VDPVs are rarer than VAPP cases, but new diagnostic tests have confirmed their regular emergence, particularly that of serotype 2 circulating VDPVs, which were found in eight of the nine countries reporting VDPV outbreaks between 2008 and 2010. The persistence of such an outbreak for more than 4 years in Nigeria highlights the importance of reducing the risk of VDPV outbreaks when OPV use ceases and of actively managing any persisting outbreaks.
The rarest risk associated with OPV use is chronic VDPV excretion by people with severe primary B-cell immune disorders. All but one of these chronic immunodeficiency-associated VDPVs to date have occurred in industrialized countries that no longer use OPV. However, people with such infections may excrete virulent virus for years and are themselves at risk for fatal disease (see Brief Report by DeVries et al. in this issue of the Journal, pages 2316–2323). Although industrialized countries now use IPV and will therefore no longer generate new immunodeficiency-associated VDPVs, additional strategies and tools are required to mitigate the associated risk. Ongoing studies in nine low- and low-middle-income countries should help to inform more robust surveillance and, if necessary, case-management strategies for chronic immunodeficiency-associated VDPVs in such settings.
Stopping routine immunization with OPV globally after wild poliovirus is eradicated will eliminate VAPP immediately and halt the generation of new circulating and immunodeficiency-associated VDPVs. The challenge will be to synchronize global cessation of OPV immunization and then manage the transition, potentially lasting several years, to the point where residual VDPVs have been eliminated. Five years ago, the tools for executing this endgame didn’t exist. Today, 12 monovalent OPVs, at least 1 for each serotype, are licensed, and a global stockpile is being built to facilitate a rapid response to any circulating VDPVs that persist after OPV immunization ceases.
It is important to decrease the risk of emergence and transmission of circulating VDPVs in low-income countries, as well as the transmission of any wild viruses introduced through breaks in laboratory containment. Low-cost solutions have been sought to facilitate routine immunization with IPV in such settings and thereby maintain some immunity to polio through at least the first 5 to 10 years after cessation of OPV administration, when risk would probably be highest. It now appears increasingly feasible to create an IPV administration schedule that costs no more than existing OPV schedules, through some combination of reducing the number of doses, delivering one fifth the amount of antigen per dose by intradermal administration, using adjuvants, and introducing seed strains (e.g., Sabin strains) that can be produced safely by low-cost manufacturers in developing countries.3,4 To help address the problem of chronic shedding of immunodeficiency-associated VDPV and reduce the potential for emergence of resistance, there are at least two antiviral candidates in early stages of development. Given the potentially fatal outcome of chronic infection, the availability of such treatments should also facilitate screening of at-risk but asymptomatic people.
Of course, none of these tools is perfect. Using monovalent OPVs to combat residual circulating VDPVs incurs the small risk of generating a new circulating VDPV — a risk that could increase with time after OPV use ceases. Since IPV does not induce the same level of intestinal mucosal immunity as OPV, we don’t yet know how effective IPV would be in terminating transmission of a circulating VDPV in tropical settings. Even if an antiviral drug is successfully developed, viral resistance may be encountered in the treatment of chronic shedders of immunodeficiency-associated VDPVs. Further research is providing additional tools and strategies that may be necessary for managing the risks in the posteradication era. Already the availability of these new tools has allowed serious discussions to begin regarding replacing trivalent OPV with bivalent OPV in routine vaccination programs, to take advantage of the apparent eradication of wild poliovirus type 2 and eliminate the VDPV risks associated with continued routine use of live vaccines with a type 2 component.
Uncertainties about the risks associated with cessation of OPV use have contributed to arguments that continued OPV immunization might be a more prudent approach to the polio endgame. However, there is accumulating evidence that intelligent application of innovative tools and strategies has shifted the balance of risk so that sustaining routine OPV immunization after the eradication of wild-type virus would present a greater risk to society and cost much more5 than eventual cessation of OPV immunization as a critical step in eradicating all polio disease.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
From the World Health Organization, Geneva (B.A.); and the Bill and Melinda Gates Foundation, Seattle (T.Y.).
New England Journal of Medicine
June 16, 2011 Vol. 364 No. 24
Intussusception Risk and Health Benefits of Rotavirus Vaccination in Mexico and Brazil
Manish M. Patel, Vesta Richardson López-Collada, Marília Mattos Bulhões, Lucia Helena De Oliveira, Aurora Bautista Márquez, Brendan Flannery, Marcelino Esparza-Aguilar, Ernesto Isaac Montenegro Renoiner, María Edilia Luna-Cruz, Helena Keico Sato, Luz del Carmen Hernández-Hernández, Gerardo Toledo-Cortina, Magdalena Cerón-Rodríguez, Neydi Osnaya-Romero, Mario Martínez-Alcazar, Rocío Gabriela Aguinaga-Villasenor, Arturo Plascencia-Hernández, Francisco Fojaco-González, Guillermo Hernández-Peredo Rezk, Sixto Fortino Gutierrez-Ramírez, Roberto Dorame-Castillo, Rogelio Tinajero-Pizano, Bernice Mercado-Villegas, Marilia Reichelt Barbosa, Eliane Mara Cesário Maluf, Lucimar Bozza Ferreira, Francisca Maria de Carvalho, Ana Rosa dos Santos, Eduardo Dolabella Cesar, Maria Elisa Paula de Oliveira, Carmem Lúcia Osterno Silva, Maria de los Angeles Cortes, Cuauhtemoc Ruiz Matus, Jacqueline Tate, Paul Gargiullo, and Umesh D. Parashar
N Engl J Med 2011; 364:2283-2292June 16, 2011
Because postlicensure surveillance determined that a previous rotavirus vaccine, RotaShield, caused intussusception in 1 of every 10,000 recipients, we assessed the association of the new monovalent rotavirus vaccine (RV1) with intussusception after routine immunization of infants in Mexico and Brazil.
Full Text of Background…
We used case-series and case–control methods to assess the association between RV1 and intussusception. Infants with intussusception were identified through active surveillance at 69 hospitals (16 in Mexico and 53 in Brazil), and age-matched infants from the same neighborhood were enrolled as controls. Vaccination dates were verified by a review of vaccination cards or clinic records.
Full Text of Methods…
We enrolled 615 case patients (285 in Mexico and 330 in Brazil) and 2050 controls. An increased risk of intussusception 1 to 7 days after the first dose of RV1 was identified among infants in Mexico with the use of both the case-series method (incidence ratio, 5.3; 95% confidence interval [CI], 3.0 to 9.3) and the case–control method (odds ratio, 5.8; 95% CI, 2.6 to 13.0). No significant risk was found after the first dose among infants in Brazil, but an increased risk, albeit smaller than that seen after the first dose in Mexico — an increase by a factor of 1.9 to 2.6 — was seen 1 to 7 days after the second dose. A combined annual excess of 96 cases of intussusception in Mexico (approximately 1 per 51,000 infants) and in Brazil (approximately 1 per 68,000 infants) and of 5 deaths due to intussusception was attributable to RV1. However, RV1 prevented approximately 80,000 hospitalizations and 1300 deaths from diarrhea each year in these two countries.
Full Text of Results…
RV1 was associated with a short-term risk of intussusception in approximately 1 of every 51,000 to 68,000 vaccinated infants. The absolute number of deaths and hospitalizations averted because of vaccination far exceeded the number of intussusception cases that may have been associated with vaccination. (Funded in part by the GAVI Alliance and the U.S. Department of Health and Human Services.)
Full Text of Discussion…
New England Journal of Medicine
June 16, 2011 Vol. 364 No. 24
Immunogenicity and Safety of a Meningococcal A Conjugate Vaccine in Africans
Samba O. Sow, M.D., Brown J. Okoko, M.D., M.P.H., Aldiouma Diallo, M.D., M.P.H., Simonetta Viviani, M.D., Ray Borrow, Ph.D., George Carlone, Ph.D., Milagritos Tapia, M.D., Adebayo K. Akinsola, M.D., Pascal Arduin, M.Sc., Helen Findlow, Ph.D., Cheryl Elie, M.Sc., Fadima Cheick Haidara, M.D., Richard A. Adegbola, Ph.D., F.R.C.Path., Doudou Diop, M.D., Varsha Parulekar, M.Sc., Julie Chaumont, M.Sc., Lionel Martellet, M.A., Fatoumata Diallo, M.D., Olubukola T. Idoko, M.D., Yuxiao Tang, Ph.D., Brian D. Plikaytis, M.Sc., Prasad S. Kulkarni, M.D., Elisa Marchetti, Ph.D., F. Marc LaForce, M.D., and Marie-Pierre Preziosi, M.D., Ph.D.
N Engl J Med 2011; 364:2293-2304June 16, 2011
New England Journal of Medicine
June 16, 2011 Vol. 364 No. 24
Vaccine-Derived Poliomyelitis 12 Years after Infection in Minnesota
Aaron S. DeVries, M.D., M.P.H., Jane Harper, M.S., Andrew Murray, M.P.H., Catherine Lexau, Ph.D., M.P.H., Lynn Bahta, B.S.N., Jaime Christensen, B.S., Elizabeth Cebelinski, B.S., Susan Fuller, M.B.S., Susan Kline, M.D., M.P.H., Gregory S. Wallace, M.D., M.P.H., Jing H. Shaw, M.D., Cara C. Burns, Ph.D., and Ruth Lynfield, M.D.
N Engl J Med 2011; 364:2316-2323June 16, 2011
A 44-year-old woman with long-standing common variable immunodeficiency who was receiving intravenous immune globulin suddenly had paralysis of all four limbs and the respiratory muscles, resulting in death. Type 2 vaccine-derived poliovirus was isolated from stool. The viral capsid protein VP1 region had diverged from the vaccine strain at 12.3% of nucleotide positions, and the two attenuating substitutions had reverted to the wild-type sequence. Infection probably occurred 11.9 years earlier (95% confidence interval [CI], 10.9 to 13.2), when her child received the oral poliovirus vaccine. No secondary cases were identified among close contacts or 2038 screened health care workers. Patients with common variable immunodeficiency can be chronically infected with poliovirus, and poliomyelitis can develop despite treatment with intravenous immune globulin.
New England Journal of Medicine
June 16, 2011 Vol. 364 No. 24
Rotavirus Vaccination and Intussusception — Act Two
Harry B. Greenberg, M.D.
N Engl J Med 2011; 364:2354-2355June 16, 2011
[Free full text]
The development of vaccines has been a triumph of modern medicine.1 In addition to the eradication of smallpox and the near-eradication of polio, the past 30 years has seen an impressive decline in many vaccine-preventable diseases, including measles, hepatitis B virus, serious pneumococcal infection, hemophilus influenza, and, recently, rotavirus. Vaccination has been an enormously powerful force for health improvement because of the large societal benefits provided with remarkably small risks. However, some have expressed worry that current vaccines are dangerous and represent a considerable threat to the health of the recipients.2 These concerns often do not include an analysis of the benefits as well as the risks of a given vaccine.
Rotavirus infection is the most important cause of severe diarrheal disease in young children. In less-developed countries, rotavirus accounts for more than 500,000 childhood deaths annually; in developed countries, rotavirus is an infrequent cause of death but a common cause of hospitalizations and outpatient visits. RotaShield, a rotavirus vaccine composed of four human×simian reassortants (RV4), was recommended for universal pediatric use in the United States in 1998. Within a year, after the vaccine had been given to more than 500,000 children, it was found to cause a transient increased risk of intussusception (estimated to occur in 1 child in 10,000) in the first 10 days after the initial vaccination. It was rapidly withdrawn from the market before there was an opportunity for a detailed public discussion of the risks and benefits surrounding its use.3
Two second-generation rotavirus vaccine candidates (one composed of five human×animal reassortants [RV5] and the other a monovalent attenuated human rotavirus vaccine [RV1]) were in development in 1999 and, after 7 additional years of study, were licensed in the United States and other countries. Both second-generation vaccines are efficacious, and both underwent extensive safety trials (together involving more than 130,000 subjects); no association with intussusception was detected in these trials.4 In the 4 years since RV1 and RV5 were licensed, we have witnessed a substantial reduction in the rates of hospitalization and death from rotavirus in both developed and less-developed countries.5 As part of the postlicensure safety follow-up, the possible effect of the widespread use of RV1 and RV5 on intussusception rates has been monitored in the United States and abroad. In this issue of the Journal, Patel et al.6 report the results of safety assessments of RV1 in Mexico and Brazil.
RV1 was found to be associated with a small excess risk of intussusception (approximately 1 in 51,000 vaccinated children) in Mexico in the first week after the initial vaccination. The timing of the excess risk is similar to that originally seen with RV4 and corresponds to the peak timing of vaccine replication. A smaller excess risk was observed after the second RV1 dose, but this occurred during the second and third week after vaccination and its significance is unclear. Interestingly, in Brazilian children receiving RV1, a smaller excess risk of intussusception was observed (approximately 1 in 68,000 vaccinated children) and then only in the first week after the second dose. The reasons for these differences in timing and rate are not clear but might include the fact that in Brazil, but not in Mexico, the first dose of RV1 was administered with the oral poliovirus vaccine, which suppresses rotavirus vaccine replication. Recent preliminary studies from Australia also suggest a link between RV5 and intussusception.7 Hence, we can infer from these studies that any orally administered live rotavirus vaccines will probably carry some detectable risk of intussusception, that the risks associated with RV4 were not unique, and that the risk of intussusception seems to be small. Since RV1 was originally derived from a virulent human rotavirus, it is likely that natural, wild-type rotavirus infection is also associated with intussusception at a very low frequency.
A likely reason that the very large prelicensure safety trials of RV1 and RV5 did not detect an intussusception signal is that they were simply underpowered to pick up rare events occurring at rates below 1 in 50,000. The study by Patel et al. was insufficiently powered to determine whether the risk of intussusception associated with RV1 in infants receiving their first vaccination after 15 weeks of age was increased, as has been suggested previously in the case of recipients of RV4. Whether the various licensed or candidate live, attenuated rotavirus vaccines — or natural rotavirus infection, for that matter — actually carry different intrinsic risks of intussusception cannot be determined with the current data, but given the ability of viral strains to have distinct pathogenic phenotypes, this possibility is plausible. We do not know whether the temporally associated increase in the rate of intussusception in the first week after vaccination actually translates into an increase in the overall attributable risk of intussusception from rotavirus vaccine or whether there might be a compensatory decrease in the rates of intussusception at later times after vaccination, as was hinted in the original data from the RV1 safety trials, which showed a significant decrease in intussusceptions among children who received the vaccine as compared with those who received placebo during the year-long follow-up.8 Since RV1 and RV5 both efficiently prevent natural rotavirus infection, it is plausible that vaccination might reduce the overall intussusception burden if wild-type infection was also responsible for some sporadic cases.
The study by Patel et al. contextualizes the risks associated with RV1 vaccination and its increasingly well-documented and substantial benefits. It is crucial that the medical community in general, and the vaccine establishment in particular, work to better educate the public to the fact that virtually all beneficial interventions, including vaccination, come with some risk and that the key issue is to ensure that the ratio of benefit to risk is most favorable. As Patel and colleagues point out, in Mexico alone, RV1 vaccination would be expected to prevent 663 childhood deaths and 11,551 hospitalizations, while causing 41 excess hospitalizations and 2 additional deaths due to intussusception. Similar favorable ratios of benefit to risk would be expected to be found in virtually all less-developed countries, in which diarrheal disease remains a leading cause of death. A favorable ratio would probably also be present with RV4. Rotavirus infection is now a rare cause of death in the United States but remains a very common cause of hospitalization and physician visits.9 Intussusception is also a rare cause of death in the United States and other developed countries. Given the low rates of intussusception associated with rotavirus vaccine that were observed in Mexico and Brazil, as well as the possibility that rotavirus vaccination might actually reduce the absolute rate of intussusception, it seems both appropriate and advisable to continue to recommend the rotavirus vaccine for children in both the developed and the developing world, on the basis of the increasingly well documented and substantial benefits.10
Disclosure forms provided by the author are available with the full text of this article at NEJM.org.
From the Stanford University School of Medicine, Stanford, CA.
July 1, 2011 – Volume 29 – Issue 7 pp: 549-635
Presenting Evidence and Summary Measures to Best Inform Societal Decisions When Comparing Multiple Strategies
Eckermann, Simon; Willan, Andrew R.
Pharmacoeconomics. 29(7):563-577, July 1, 2011.
(Accessed 19 June 2011: database unavailable)
Global Protection and the Health Impact of Migration Interception
Zachary Steel, Belinda J. Liddell, Catherine R. Bateman-Steel, Anthony B. Zwi Policy Forum, published 14 Jun 2011
– The volume of international travel and irregular migration places pressure on states to maintain orderly migration programs. Interception strategies are increasingly used by states to halt the movement of irregular migrants, including asylum seekers.
– ome strategies, such as immigration detention, pose a serious threat to health and mental health. Others, such as the use of visa restrictions or other pre-emptive interception measures, have a potentially large impact on migrants’ health and welfare by forcing people to remain in settings where they face the chance of persecution.
– Interception can also promote humanitarian outcomes. Refugee camps, for example, address immediate protection, safety, and service needs of forcibly displaced persons, but they have limits as long-term solutions.
– Migration interception practices are a major global determinant of health and mental health. Health professionals must remain engaged in discussions about migration and humanitarian protection to ensure a broader consideration of the health impact of these practices.
17 June 2011 vol 332, issue 6036, pages 1345-1468
Policy Forum – Infectious Disease
Solving the Sisyphean Problem of Malaria in Zanzibar
David L. Smith, Justin M. Cohen, Bruno Moonen, Andrew J. Tatem, Oliver J. Sabot, Abdullah Ali, and Sultan M. Mugheiry
Science 17 June 2011: 1384-1385.
The Global Malaria Action Plan (GMAP), a consensus framework for coordinated action, aims to end malaria deaths by 2015 and eventually to eradicate malaria (1). The plan calls for universal access to effective antimalarial drugs and universal coverage with appropriate vector interventions. Strategic planning for how best to reach these goals has been left to individual countries, some of which have already made plans to eliminate malaria, i.e., to rid their countries of malaria parasites and to suppress transmission from imported malaria (travelers carrying malaria infections from one region into another) so that locally acquired cases are rare (2). Critics have argued that plans for national elimination distract attention and resources from the priority of reducing malaria’s heavy burden in sub-Saharan Africa (3) and that a better strategy would be “control,” i.e., reducing malaria to a minor public health problem. These sides reflect the bipolar history of antimalaria efforts. When funding collapsed for a previous attempt to eradicate malaria, control defined the malaria agenda through decades of neglect. Control and elimination are often presented as opposite sides of a debate over how to allocate billions of dollars allocated globally for malaria aid. But a recent study in Zanzibar (4) concluded the dichotomy was false. A more urgent problem is continuity. How can enthusiasm for funding malaria be sustained?
Tropical Medicine & International Health
July 2011 Volume 16, Issue 7 Pages 773–903
Achieving STOP TB Partnership goals: perspectives on development of new diagnostics, drugs and vaccines for tuberculosis (pages 819–827)
Peter Mwaba, Ruth McNerney, Martin Peter Grobusch, Justin O’Grady, Matthew Bates, Nathan Kapata, Markus Maeurer and Alimuddin Zumla
Article first published online: 13 APR 2011 | DOI: 10.1111/j.1365-3156.2011.02777.x
Global eradication of tuberculosis (TB) depends on identification and treatment of all active TB cases and of the two billion people who are estimated to be latently infected with Mycobacterium tuberculosis. The past decade has seen a renaissance of scientific activities and funder investment into development of new TB drugs, diagnostics, biomarkers and vaccines. This viewpoint critically summarises the promising portfolio of more accurate TB diagnostics, new TB drugs and vaccines that have been endorsed by the STOP TB Partnership. Increasing numbers of Phase 2 and 3 drug, vaccine and diagnostic clinical trials in high-TB endemic areas reflect substantial progress towards attaining Global STOP-TB Partnership targets. Achievement of STOP-TB Partnership goals will crucially depend on political will and serious investment by funders and developing country governments into improving delivery of better health services and living conditions for their people. Long-term sustainability of any newer tools implemented at point of care is essential.
Tropical Medicine & International Health
July 2011 Volume 16, Issue 7 Pages 773–903
Clustered lot quality assurance sampling: a pragmatic tool for timely assessment of vaccination coverage (pages 863–868)
K. Greenland, M. Rondy, A. Chevez, N. Sadozai, A. Gasasira, E. A. Abanida, M. A. Pate, O. Ronveaux, H. Okayasu, B. Pedalino and L. Pezzoli
Article first published online: 11 APR 2011 | DOI: 10.1111/j.1365-3156.2011.02770.x
Objectives To evaluate oral poliovirus vaccine (OPV) coverage of the November 2009 round in five Northern Nigeria states with ongoing wild poliovirus transmission using clustered lot quality assurance sampling (CLQAS).
Methods We selected four local government areas in each pre-selected state and sampled six clusters of 10 children in each Local Government Area, defined as the lot area. We used three decision thresholds to classify OPV coverage: 75–90%, 55–70% and 35–50%. A full lot was completed, but we also assessed in retrospect the potential time-saving benefits of stopping sampling when a lot had been classified.
Results We accepted two local government areas (LGAs) with vaccination coverage above 75%. Of the remaining 18 rejected LGAs, 11 also failed to reach 70% coverage, of which four also failed to reach 50%. The average time taken to complete a lot was 10 h. By stopping sampling when a decision was reached, we could have classified lots in 5.3, 7.7 and 7.3 h on average at the 90%, 70% and 50% coverage targets, respectively.
Conclusions Clustered lot quality assurance sampling was feasible and useful to estimate OPV coverage in Northern Nigeria. The multi-threshold approach provided useful information on the variation of IPD vaccination coverage. CLQAS is a very timely tool, allowing corrective actions to be directly taken in insufficiently covered areas.
Value in Health
June 2011, Vol. 14, No. 4
Cost-Effectiveness of a Recommendation of Universal Mass Vaccination for Seasonal Influenza in the United States
Karen M. Clements, ScD; Jeremy Chancellor, MSc; Kristin Nichol, MD, MPH, MBA; Kelly DeLong; David Thompson, PhD
published online 06 June 2011.
We evaluated the cost-effectiveness of universal mass vaccination (UMV) against influenza compared with a targeted vaccine program (TVP) for selected age and risk groups in the United States.
We modeled costs and outcomes of seasonal influenza with UMV and TVP, taking a societal perspective. The US population was stratified to model age-specific (< 5, 5–17, 18–49, 50–64, and 65+ years) vaccine coverage and efficacy. Probability of influenza-related illness (ILI) and complications, health-care utilization, costs, and survival were estimated. For a season’s intervention, ILI cases in that year, lifetime costs (2008 US$), and quality-adjusted life years (QALYs) lost (both discounted at 3% per annum) were calculated for each policy and used to derive incremental cost-effectiveness ratios. A range of sensitivity and alternative-scenario analyses were conducted.
In base-case analyses, TVP resulted in 63 million ILI cases, 859,000 QALYs lost, and $114.5 billion in direct and indirect costs; corresponding estimates for UMV were 61 million cases, 825,000 QALYs lost, and $111.4 billion. UMV was therefore estimated to dominate TVP, saving $3.1 billion and 34,000 QALYs. In probabilistic sensitivity analyses, UMV was dominant in 82% and dominated in 0% of iterations. In alternative-scenario analyses, UMV dominated TVP when lower estimates of vaccine coverage were used. Lower estimates of ILI risk among unvaccinated, vaccine effectiveness, and risk of complications resulted in ICERs of $2800, $8100, and $15,900 per QALY gained, respectively, for UMV compared with TVP.
UMV against seasonal influenza is cost saving in the United States under reasonable assumptions for coverage, cost, and efficacy.
Value in Health
June 2011, Vol. 14, No. 4
Conjoint Analysis Applications in Health—a Checklist: A Report of the ISPOR Good Research Practices for Conjoint Analysis Task Force
This report presents a checklist for good research practices of conjoint analysis in health care applications.
The application of conjoint analysis (including discrete-choice experiments and other multiattribute stated-preference methods) in health has increased rapidly over the past decade. A wider acceptance of these methods is limited by an absence of consensus-based methodological standards.
The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Good Research Practices for Conjoint Analysis Task Force was established to identify good research practices for conjoint-analysis applications in health.
The task force met regularly to identify the important steps in a conjoint analysis, to discuss good research practices for conjoint analysis, and to develop and refine the key criteria for identifying good research practices. ISPOR members contributed to this process through an extensive consultation process. A final consensus meeting was held to revise the article using these comments, and those of a number of international reviewers.
Task force findings are presented as a 10-item checklist covering: 1) research question; 2) attributes and levels; 3) construction of tasks; 4) experimental design; 5) preference elicitation; 6) instrument design; 7) data-collection plan; 8) statistical analyses; 9) results and conclusions; and 10) study presentation. A primary question relating to each of the 10 items is posed, and three sub-questions examine finer issues within items.
Although the checklist should not be interpreted as endorsing any specific methodological approach to conjoint analysis, it can facilitate future training activities and discussions of good research practices for the application of conjoint-analysis methods in health care studies.
Value in Health
June 2011, Vol. 14, No. 4
Health Policy Analysis
Pharmaceutical Priority Setting and the Use of Health Economic Evaluations: A Systematic Literature Review
Factors that seem to support the increased use of health economic evaluations are well-developed frameworks for evaluations, the presence of health economic skills, and an explicit priority setting process.
To investigate which factors and criteria are used in priority setting of pharmaceuticals, in what contexts health economic evaluations are used, and barriers to the use of health economic evaluations at micro, meso, and macro health-care levels.
The search for empirical articles was based on the MeSH index (Medical Substance Heading), including the search terms “economic evaluation,” “cost-effectiveness analysis,” “cost-utility analysis,” “cost-benefit analysis,” “pharmacoeconomic,” AND “drug cost(s),” AND “eligibility determination,” AND “decision-making,” AND “rationing,” AND formulary. The following databases were searched: PubMed, EconLit, Cochrane, Web of Science, CINAHL, and PsycINFO. More than 3100 studies were identified, 31 of which were included in this review.
The use of health economic evaluations at all three health-care levels was investigated in three countries (United States [US], United Kingdom [UK], and Sweden). Postal and telephone survey methods dominated (n = 17) followed by interviews (n = 13), document analysis (n = 10), and observations of group deliberations (n = 9). The cost-effectiveness criterion was most important at the macro level. A number of contextual uses of health economic evaluations were identified, including importantly the legitimizing of decisions, structuring the priority-setting process, and requesting additional budgets to finance expensive pharmaceuticals.
Factors that seem to support the increased use of health economic evaluations are well-developed frameworks for evaluations, the presence of health economic skills, and an explicit priority-setting process. Differences in how economic evaluations are used at macro, meso, and micro levels are attributed to differences in the preconditions at each level.
The pdf version of Vaccines: The Week in Review 13 June 2011, comprising the posts below for this date, is available here: Vaccines_The Week in Review_13 June 2011
The GAVI Alliance pledging conference – Saving children’s lives – is underway in London with coverage via twitter at #4mlives and @GAVIAlliance, and at GAVI’s website: http://www.gavialliance.org/about/pledging_conference/index.php. GAVI has provided a summary of publications and documents related to the pledging conference at:
Initial pledge activity has included “a ten-fold increase in Australia’s commitment to GAVI, which will reach AUS$200 million between 2011 and 2013.” Anglo-American PLC pledged US$1 million per year for three years and Absolute Return for Kids (ARK) pledged £1 million “to purchase vaccines to combat deadly rotavirus in Zambia.”
GAVI announced that it achieved commitments from two emerging market vaccine manufacturers to lower prices for pentavalent vaccine, and that developed country manufacturers have also offered price reductions on rotavirus and HPV vaccines. GAVI said that Serum Institute and Panacea Biotec have committed to price reductions on their pentavalent vaccines. Serum announced it “would continue to provide the most competitive pricing and encouraged other manufacturers to follow its lead.” Panacea Biotec committed to lower its prices by up to 15%. GSK offered to provide the rotavirus vaccine to GAVI at $2.50 per dose, or $5 to fully immunise a child, in response to a current tender administered by UNICEF, representing a 67% reduction in the current lowest available public price. GAVI said Merck has also stated that it will offer its rotavirus vaccine to UNICEF at discounted prices. The GAVI announcement also noted that Merck announced it will offer GAVI the HPV vaccine at a reduced price of US$ 5 per dose, a 67% reduction in the current lowest public price. The price offer is the first of its kind for developing countries. GAVI also noted that Crucell and Sanofi Pasteur will extend GAVI prices on their pentavalent vaccines to the 16 countries currently expected to graduate from GAVI support. Sanofi Pasteur confirmed that this would also apply to its yellow fever vaccine and the rotavirus vaccine being developed by its subsidiary Shantha. The announcements build on similar commitments made to graduating countries by Pfizer and GSK to provide the same access to pneumococcal conjugate vaccines through the Advance Market Commitment, GAVI said.
Helen Evans, GAVI interim CEO, said, “These are promising offers that demonstrate industry commitment to work towards affordable and sustainable prices for life-saving vaccines in developing countries. We congratulate all manufacturers who have responded to our call in the lead up to the pledging conference. We will continue to drive for sustainable prices, while ensuring procurement of innovative, appropriate, quality vaccines to meet GAVI country needs.”
The Lancet Series: New Decade of Vaccines
Launched in London on June 9, 2011
Vaccines are undoubtedly one of the best investments in health. Immunisation programmes have contributed enormously to reducing the burden of infectious diseases, and are responsible for much of the falling rates of morbidity and mortality worldwide. In December 2010, global health leaders committed to making the next 10 years the Decade of Vaccines – to ensure discovery, development, and delivery of lifesaving vaccines globally, especially to the poorest countries. This Series looks at every aspect of this medical technology, including the developments expected over the coming decade and what we can expect from translation of the latest vaccine science. Improving vaccine coverage and financing of both existing and newer vaccines together with how we communicate the benefits of vaccines and ensure public trust and confidence, are also examined.
The next decade of vaccines: societal and scientific challenges
E Richard Moxon, Claire-Anne Siegrist
Full Text | PDF
Vaccines against microbial diseases have improved the health of millions of people. In the next decade and beyond, many conceptual and technological scientific advances offer extraordinary opportunities to expand the portfolio of immunisations against viral and bacterial diseases and to pioneer the first vaccines against human parasitic and fungal diseases. Scientists in the public and private sectors are motivated as never before to bring about these innovations in immunisation. Many societal factors threaten to compromise realisation of the public health gains that immunisation can achieve in the next decade and beyond—understanding these factors is imperative. Vaccines are typically given to healthy individuals and safety issues loom high on the list of public concerns. The public needs to regain confidence in immunisation and trust the organisations responsible for the research, development, and implementation of vaccines. In the past, by use of a judicious amalgam of knowledge and empiricism, successful vaccines were largely developed by microbiologists who identified antigens that induced immune responses to conserved pathogen components. In the future, vaccines need to be developed against deadly diseases for which this strategy is often not feasible because of the extensive antigenic variability of relevant pathogens. High microbial diversity means that immunity after natural infection is often ineffective for prevention of disease on subsequent exposure, for example in HIV infection and malaria. Additionally, vaccines need to be generated to protect the people who are most vulnerable because of age or underlying diseases. Thus, in the future, a much deeper understanding of the immunological challenges—including the diversifying role of host genetics and environmental factors, leading perhaps to more personalised approaches—will be the touchstone for rational design and development of adjuvants that result in novel safe and effective vaccines.
Vaccine discovery and translation of new vaccine technology
Rino Rappuoli, Steven Black, Paul Henri Lambert
Full Text | PDF
An unprecedented increase in new vaccine development has occurred over the past three decades. This activity has resulted in vaccines that protect against an increased range of vaccine-preventable diseases, vaccines that reduce the number of required injections, and vaccines with improved safety and purity. New methods of discovery, such as reverse vaccinology, structural biology, and systems biology, promise new vaccines for different diseases and efficient development pathways for these vaccines. We expect development of vaccines not only for infectious diseases in children but also for healthy adults, pregnant women, and elderly people, and for new indications such as autoimmune disease and cancer. We have witnessed a concomitant development of new technology for assessment of vaccine safety to rapidly identify potential safety issues. Success of these new approaches will depend on effective implementation of vaccination programmes, creative thinking on the part of manufacturers and regulators as to how best to ensure that safe and effective vaccines are available in a timely manner, and improvement of public awareness about the benefits and risks of new vaccines in a way that encourages confidence in vaccines.
Vaccine production, distribution, access, and uptake
Jon Smith, Marc Lipsitch, Jeffrey W Almond
Full Text | PDF
For human vaccines to be available on a global scale, complex production methods, meticulous quality control, and reliable distribution channels are needed to ensure that the products are potent and effective at the point of use. The technologies used to manufacture different types of vaccines can strongly affect vaccine cost, ease of industrial scale-up, stability, and, ultimately, worldwide availability. The complexity of manufacturing is compounded by the need for different formulations in different countries and age-groups. Reliable vaccine production in appropriate quantities and at affordable prices is the cornerstone of developing global vaccination policies. However, to ensure optimum access and uptake, strong partnerships are needed between private manufacturers, regulatory authorities, and national and international public health services. For vaccines whose supply is insufficient to meet demand, prioritisation of target groups can increase the effect of these vaccines. In this report, we draw from our experience of vaccine development and focus on influenza vaccines as an example to consider production, distribution, access, and other factors that affect vaccine uptake and population-level effectiveness.
The future of immunisation policy, implementation, and financing
Orin S Levine, David E Bloom, Thomas Cherian, Ciro de Quadros, Samba Sow, John Wecker, Philippe Duclos, Brian Greenwood
Full Text | PDF
Vaccines have already saved many lives and they have the potential to save many more as increasingly elaborate technologies deliver new and effective vaccines against both infectious diseases—for which there are currently no effective licensed vaccines—such as malaria, tuberculosis, and HIV and non-infectious diseases such as hypertension and diabetes. However, these new vaccines are likely to be more complex and expensive than those that have been used so effectively in the past, and they could have a multifaceted effect on the disease that they are designed to prevent, as has already been seen with pneumococcal conjugate vaccines. Deciding which new vaccines a country should invest in requires not only sound advice from international organisations such as WHO but also a well informed national immunisation advisory committee with access to appropriate data for local disease burden. Introduction of vaccines might need modification of immunisation schedules and delivery procedures. Novel methods are needed to finance the increasing number of new vaccines that have the potential to save lives in countries that are too poor to afford them. Here, we discuss some options.
Addressing the vaccine confidence gap
Heidi J Larson, Louis Z Cooper, Juhani Eskola, Samuel L Katz, Scott Ratzan
Full Text | PDF
Vaccines—often lauded as one of the greatest public health interventions—are losing public confidence. Some vaccine experts have referred to this decline in confidence as a crisis. We discuss some of the characteristics of the changing global environment that are contributing to increased public questioning of vaccines, and outline some of the specific determinants of public trust. Public decision making related to vaccine acceptance is neither driven by scientific nor economic evidence alone, but is also driven by a mix of psychological, sociocultural, and political factors, all of which need to be understood and taken into account by policy and other decision makers. Public trust in vaccines is highly variable and building trust depends on understanding perceptions of vaccines and vaccine risks, historical experiences, religious or political affiliations, and socioeconomic status. Although provision of accurate, scientifically based evidence on the risk—benefit ratios of vaccines is crucial, it is not enough to redress the gap between current levels of public confidence in vaccines and levels of trust needed to ensure adequate and sustained vaccine coverage. We call for more research not just on individual determinants of public trust, but on what mix of factors are most likely to sustain public trust. The vaccine community demands rigorous evidence on vaccine efficacy and safety and technical and operational feasibility when introducing a new vaccine, but has been negligent in demanding equally rigorous research to understand the psychological, social, and political factors that affect public trust in vaccines.
Related Articles published in The Lancet
Making new vaccines affordable: a comparison of financing processes used to develop and deploy new meningococcal and pneumococcal conjugate vaccines
James R Hargreaves, Brian Greenwood, Charles Clift, Akshay Goel, Anne Roemer-Mahler, Richard Smith, David L Heymann
Full Text | PDF
Mechanisms to increase access to health products are varied and controversial. Two innovative mechanisms have been used to accelerate the development of low-price supply lines for conjugate vaccines. The Meningitis Vaccine Project is a so-called push mechanism that facilitated technology transfer to an Indian company to establish capacity to manufacture a vaccine. The Advanced Market Commitment for pneumococcal vaccines is a so-called pull mechanism that guarantees companies a supplement paid in addition to the purchase price for vaccines for a specific period. We compare these approaches, identifying key dimensions of each and considering their potential for replication. We also discuss issues that the Global Alliance for Vaccines and Immunisation (GAVI) face now that these new vaccines are available. Progress towards GAVI’s strategic aims is needed and funding is crucial. Approaches that decrease the financial pressure on GAVI and greatly increase political and financial engagement by low-income countries should also be considered.
June 2011; Volume 30, Issue 6
Strategies For The ‘Decade Of Vaccines’
From The Editor-in-Chief
Vaccines, Children, And Fulfilling Human Potential
Health Aff June 2011 30:1006; doi:10.1377/hlthaff.2011.0562
Slow Going For The Global Health Initiative
Health Aff June 2011 30:1007-1009; doi:10.1377/hlthaff.2011.0460
The program of US foreign assistance to advance health and health care in developing countries survived the 2011 budget battles, but it continues to face other challenges.
The Priceless Payoff
During The ‘Decade Of Vaccines,’ The Lives Of 6.4 Million Children Valued At $231 Billion Could Be Saved
Sachiko Ozawa, Meghan L. Stack, David M. Bishai, Andrew Mirelman, Ingrid K. Friberg, Louis Niessen, Damian G. Walker, and Orin S. Levine
Health Aff June 2011 30:1010-1020; doi:10.1377/hlthaff.2011.0381
Governments constantly face the challenge of determining how much they should spend to prevent premature deaths and suffering in their populations. In this article we explore the benefits of expanding the delivery of life-saving vaccines in seventy-two low- and middle-income countries, which we estimate would prevent the deaths of 6.4 million children between 2011 and 2020. We present the economic benefits of vaccines by using a “value of statistical life” approach, which is based on individuals’ perceptions regarding the trade-off between income and increased risk of mortality. Our analysis shows that the vaccine expansion described above corresponds to $231 billion (uncertainty range: $116–$614 billion) in the value of statistical lives saved. This analysis complements results from analyses based on other techniques and is the first of its kind for immunizations in the world’s poorest countries. It highlights the major economic benefits made possible by improving vaccine coverage.
Estimated Economic Benefits During The ‘Decade Of Vaccines’ Include Treatment Savings, Gains In Labor Productivity
Meghan L. Stack, Sachiko Ozawa, David M. Bishai, Andrew Mirelman, Yvonne Tam, Louis Niessen, Damian G. Walker, and Orin S. Levine
Health Aff June 2011 30:1021-1028; doi:10.1377/hlthaff.2011.0382
In 2010 the Bill & Melinda Gates Foundation announced a $10 billion commitment over the next ten years to increase access to childhood vaccines in the world’s poorest countries. The effort was labeled the “Decade of Vaccines.” This study estimates both the short- and long-term economic benefits from the introduction and increased use of six vaccines in seventy-two of the world’s poorest countries from 2011 to 2020. Increased rates of vaccination against pneumococcal and Haemophilus influenzae type b pneumonia and meningitis, rotavirus, pertussis, measles, and malaria over the next ten years would save 6.4 million lives and avert 426 million cases of illness, $6.2 billion in treatment costs, and $145 billion in productivity losses. Monetary estimates based on this type of analysis can be used to determine the return on investment in immunization from both the international community and local governments, and they should be considered in policy making.
ANALYSIS & COMMENTARY: The Moral Case For The Routine Vaccination Of Children In Developed And Developing Countries
Health Aff June 2011 30:1029-1033; doi:10.1377/hlthaff.2011.0301
In developed countries some parents have decided not to provide routine vaccinations for their children, while in many developing countries there are inadequate rates of vaccination for various reasons. The consequences for children, and members of the community in which they live, can be significant and even tragic. Although some parents may worry that vaccines will harm their child, there is a broader moral case for vaccination that parents and policy makers should consider. This case has four components: benefits and harms, best interests, community benefits, and justice. This moral case should be central to deliberations about vaccination by parents and policy makers.
Challenges For Science & Business
ANALYSIS & COMMENTARY: A Global Road Map Is Needed For Vaccine Research, Development, And Deployment
Health Aff June 2011 30:1034-1041; doi:10.1377/hlthaff.2011.0391
The world is witnessing a tremendous interest in the discovery, development, and use of vaccines as an important contributor to disease prevention and control. However, current global vaccine efforts are not coordinated, and they face many challenges. One is scientific: Most vaccines in use today are based on the scientific knowledge of past centuries. To usher in a new era, there is an urgent need to draw upon new science and scientific disciplines and recruit a new generation of talent trained in the basic and computational sciences of the twenty-first century. In addition, a global road map is urgently needed for making the scientific discoveries necessary to produce new vaccines; developing these into effective vaccines; and drawing up priorities and undertaking the necessary planning for rolling out these vaccines in developing countries. The developing countries themselves must play the lead role in these activities and contribute their own resources as well. This article aims to initiate a wide-ranging debate and discussion that will ultimately result in some agreement on the future of vaccine development and deployment.
ANALYSIS & COMMENTARY: Vaccines As A Global Imperative—A Business Perspective
Health Aff June 2011 30:1042-1048; doi:10.1377/hlthaff.2011.0338
During the past thirty years, vaccines have experienced a renaissance. Advances in science, business, and distribution have transformed the field to the point where vaccines are recognized as a “best buy” in global health, a driver of pharmaceutical industry growth, and a key instrument of international development. With many new vaccines available and others on the horizon, the global community will need to explore new ways of ensuring access to vaccines in developing nations. So-called tiered pricing, which makes vaccines available at different prices for countries at different levels of economic development; innovative financing mechanisms such as advance market commitments or offers of long-term and high-volume contracts to vaccine producers; and technology transfers such as sharing intellectual property and production techniques among companies and countries can all play a part in bringing new life-saving vaccines for pneumonia, rotavirus, malaria, and other diseases to developing countries.
Fighting Critical Diseases
Eliminating Epidemic Group A Meningococcal Meningitis In Africa Through A New Vaccine
F. Marc LaForce and Jean-Marie Okwo-Bele
Health Aff June 2011 30:1049-1057; doi:10.1377/hlthaff.2011.0328
A new affordable vaccine against Group A meningococcus, the most common cause of large and often fatal African epidemics of meningitis, was introduced in Burkina Faso, Mali, and Niger in 2010. Widespread use of the vaccine throughout much of Africa may prevent more than a million cases of meningitis over the next decade. The new vaccine is expected to be cost-saving when compared to current expenditures on these epidemics; for example, an analysis shows that introducing it in seven highly endemic countries could save $350 million or more over a decade. International donors have already committed funds to support the new vaccine’s introduction in Burkina Faso, Niger, and Mali, but an estimated US$400 million is needed to fund mass immunization campaigns in people ages 1–29 over six years in all twenty-five countries of the African meningitis belt. The vaccine’s low cost—less than fifty cents per dose—makes it possible for the affected countries themselves to purchase vaccines for future birth cohorts.
ANALYSIS & COMMENTARY: Product Development Partnerships Hit Their Stride: Lessons From Developing A Meningitis Vaccine For Africa
David M. Bishai, Claire Champion, Michael E. Steele, and Lindsay Thompson
Health Aff June 2011 30:1058-1064; doi:10.1377/hlthaff.2011.0295
The Meningitis Vaccine Project, a so-called product development partnership, developed a new vaccine against bacterial meningitis, an inflammation of brain tissues that causes an estimated 10,000 deaths among African children and young people each year. The vaccine—known as MenAfriVac and specifically targeted for use in low-income countries in Africa—was designed to be made available to governments at a price of fifty cents per dose. The Meningitis Vaccine Project is an example of how product development partnerships have reinvigorated research on vaccines for neglected diseases. These partnerships disperse the multiple tasks of product development across a network of partners that are best suited for each task. The vaccine was rapidly embraced by African health officials, and in its first few weeks on the market, in late 2010, more than nineteen million people in Burkina Faso, Mali, and Niger were vaccinated.
Producing A Successful Malaria Vaccine: Innovation In The Lab And Beyond
Christian Loucq, Ashley Birkett, David Poland, Carla Botting, Julia Nunes, and Sally Ethelston
Health Aff June 2011 30:1065-1072; doi:10.1377/hlthaff.2011.0356
With approximately 225 million new cases and 800,000 deaths annually, malaria exacts a tremendous toll—mostly on African children under the age of five. Late-stage trials of an advanced malaria vaccine candidate—which, if approved, would become the world’s first malaria vaccine—are under way, and it may be ready for use by 2015. This article recounts the pivotal roles in that achievement played by collaborations of nonprofit organizations, pharmaceutical companies, private and public donors, and countries whose citizens would benefit most directly from a vaccine. Just as it takes a village to raise a child, it has taken a huge number of stakeholders around the world to reach this point. Developing even more effective vaccines for malaria and other diseases will require continued hard work and creative thinking from scientists, regulators, and policy makers.
The Challenges Of Developing New Tuberculosis Vaccines
Lewellys F. Barker, Annmarie E. Leadman, and Bartholt Clagett
Health Aff June 2011 30:1073-1079; doi:10.1377/hlthaff.2011.0303
The World Health Organization estimates that tuberculosis is causing nearly two million deaths annually, mostly in developing countries. Widespread administration of the current tuberculosis vaccine to newborns is not a reliable route for preventing the disease in adults, the population that drives the epidemic. Several new vaccine candidates are in development, and a few have entered clinical trials. However, the field faces formidable scientific and policy challenges. A collaborative approach to solving scientific, policy, and resource obstacles—as well as new partnerships among emerging economies and vaccine development organizations—will be critical to developing a new tuberculosis vaccine that could achieve its public health potential to save lives and reduce the burden of disease.
A Handful Of ‘Antipoverty’ Vaccines Exist For Neglected Diseases, But The World’s Poorest Billion People Need More
Health Aff June 2011 30:1080-1087; doi:10.1377/hlthaff.2011.0317
So-called neglected tropical diseases are the most common infections of the world’s poor. Almost all of the “bottom billion”—the 1.4 billion people who live below the poverty level defined by the World Bank—suffer from one or more neglected diseases including hookworm infection, sleeping sickness, or Chagas disease. These diseases are actually a cause of poverty because of their adverse effects on child growth and development and worker productivity. Vaccines to combat such diseases have come to be known as “antipoverty vaccines.” Unfortunately, the recent surge in the development and delivery of vaccines to combat the major childhood killers—such as pneumococcal pneumonia and measles—has bypassed neglected diseases. Nevertheless, some vaccines for these neglected diseases are now entering the clinical pipeline. In this article I describe how some antipoverty vaccine development is proceeding and offer recommendations for stimulating further development such as through pooled funding for innovation, developing-country manufacturers, and public-private partnerships for product development.
Providing Vaccines Against Human Papillomavirus To Adolescent Girls In The Americas: Battling Cervical Cancer, Improving Overall Health
Silvana Luciani, Elisa Prieto-Lara, and Andrea Vicari
Health Aff June 2011 30:1089-1095; doi:10.1377/hlthaff.2011.0315
Vaccines against the human papillomavirus (HPV)—the primary cause of cervical cancer—target adolescent girls, many of whom have limited contact with health services. Countries in the Americas are beginning to use HPV vaccines to increase the impact of cervical cancer programs and as an entry point to broader health services for girls. This strategy opens new opportunities to improve lifelong health habits; encourage regular cervical cancer screening and treatment, when necessary; and offer associated services such as reproductive health and nutrition guidance. Some of the early experiences with this strategy illustrate challenges and opportunities that may arise with other new vaccines.
People & Places
Health Aff June 2011 30:1088; doi:10.1377/hlthaff.2011.0513
Peter Hotez and his Sabin Vaccine Institute seek to end preventable illness among the world’s impoverished people.
India’s Vaccine Deficit: Why More Than Half Of Indian Children Are Not Fully Immunized, And What Can—And Should—Be Done
Ramanan Laxminarayan and Nirmal Kumar Ganguly
Health Aff June 2011 30:1096-1103; doi:10.1377/hlthaff.2011.0405
Although India is a leading producer and exporter of vaccines, the country is home to one-third of the world’s unimmunized children. Fewer than 44 percent of India’s young children receive the full schedule of immunizations. India’s vaccine deficit has several causes: little investment by the government; a focus on polio eradication at the expense of other immunizations; and low demand as a consequence of a poorly educated population and the presence of anti-vaccine advocates. In this article we describe India’s vaccine deficit and recommend that the government move quickly to increase spending on, and otherwise strengthen, national immunization programs.
ANALYSIS & COMMENTARY: Challenges To Building Capacity For Evidence-Based New Vaccine Policy In Developing Countries
Jon Kim Andrus, Barbara Jauregui, Lúcia Helena De Oliveira, and Cuauhtémoc Ruiz Matus
Health Aff June 2011 30:1104-1112; doi:10.1377/hlthaff.2011.0361
There are many challenges to ensuring that people in developing countries have equitable access to new vaccines. Two of the most important are having the capacity to make evidence-based new vaccine policy decisions in developing countries, and then when appropriate actually distributing those new vaccines to those who will most benefit from them. Based on our review of the Pan American Health Organization’s ProVac Initiative in the Americas, we found that when national governments in developing countries develop the expertise to make the best technical decisions about immunization programs; take responsibility for helping to pay for and distribute vaccines; and are supported by strong partnerships with international organizations, they succeed in saving more lives more quickly.
ANALYSIS & COMMENTARY: Vaccine Supply Chains Need To Be Better Funded And Strengthened, Or Lives Will Be At Risk
Judith R. Kaufmann, Roger Miller, and James Cheyne
Health Aff June 2011 30:1113-1121; doi:10.1377/hlthaff.2011.0368
In the next decade, at least twelve additional vaccines that target such diseases as typhoid, malaria, and dengue will become available to lower- and middle-income countries. These vaccines must travel along what are called supply chains, which include all personnel, systems, equipment, and activities involved in ensuring that vaccines are effectively delivered from the point of production to the people who need them. But for various reasons, supply chains are already strained in many developing countries, and the potential inability to distribute new vaccines will place lives at risk. Among the many steps needed to strengthen the global vaccine supply chain, we suggest that the international community pursue improved coordination between organizations that donate and ship vaccines and the host-country officials who receive and distribute the vaccines, as well as better training for supply-chain managers.
An Analysis Of How The GAVI Alliance And Low- And Middle-Income Countries Can Share Costs Of New Vaccines
Helen Saxenian, Santiago Cornejo, Kira Thorien, Robert Hecht, and Nina Schwalbe
Health Aff June 2011 30:1122-1133; doi:10.1377/hlthaff.2011.0332
Immunization is one of the “best buys” in global health. However, for the poorest countries, even modest expenditures may be out of reach. The GAVI Alliance is a public-private partnership created to help the poorest countries introduce new vaccines. Since 2008 GAVI has required that countries cover a share of the cost of vaccines introduced with GAVI support. To determine how much countries can contribute to the cost of vaccines—without displacing spending on other essential programs—we analyzed their fiscal capacity to contribute to the purchase of vaccines over the coming decade. For low-income countries, external financing will be required to purchase vaccines supported by GAVI, so co-financing needs to be modest. Relatively better-off “intermediate” countries could support initially modest but gradually increasing co-financing levels. The countries soon to graduate from GAVI can generally afford to follow a rapid path to self-sufficiency. Co-financing for these countries needs to ramp up so that national budgets fully cover the costs of the new generation of vaccines once GAVI support ends.
Creating Sustainable Financing And Support For Immunization Programs In Fifteen Developing Countries
Michael McQuestion, Devendra Gnawali, Clifford Kamara, Helene Mambu-Ma-Disu, Jonas Mbwangue, and Ciro de Quadros
Health Aff June 2011 30:1134-1140; doi:10.1377/hlthaff.2011.0265
Immunization programs are important tools for reducing child mortality, and they need to be in place for each new generation. However, most national immunization programs in developing countries are financially and organizationally weak, in part because they depend heavily on funding from foreign sources. Through its Sustainable Immunization Financing Program, launched in 2007, the Sabin Vaccine Institute is working with fifteen African and Asian countries to establish stable internal funding for their immunization programs. The Sabin program advocates strengthening immunization programs through budget reforms, decentralization, and legislation. Six of the fifteen countries have increased their national immunization budgets, and nine are preparing legislation to finance immunization sustainably. Lessons from this work with immunization programs may be applicable in other countries as well as to other health programs.
Issues For The United States
The Benefits To All Of Ensuring Equal And Timely Access To Influenza Vaccines In Poor Communities
Bruce Y. Lee, Shawn T. Brown, Rachel R. Bailey, Richard K. Zimmerman, Margaret A. Potter, Sarah M. McGlone, Philip C. Cooley, John J. Grefenstette, Shanta M. Zimmer,
William D. Wheaton, Sandra Crouse Quinn, Ronald E. Voorhees, and Donald S. Burke
Health Aff June 2011 30:1141-1150; doi:10.1377/hlthaff.2010.0778
When influenza vaccines are in short supply, allocating vaccines equitably among different jurisdictions can be challenging. But justice is not the only reason to ensure that poorer counties have the same access to influenza vaccines as do wealthier ones. Using a detailed computer simulation model of the Washington, D.C., metropolitan region, we found that limiting or delaying vaccination of residents of poorer counties could raise the total number of influenza infections and the number of new infections per day at the peak of an epidemic throughout the region—even in the wealthier counties that had received more timely and abundant vaccine access. Among other underlying reasons, poorer counties tend to have high-density populations and more children and other higher-risk people per household, resulting in more interactions and both increased transmission of influenza and greater risk for worse influenza outcomes. Thus, policy makers across the country, in poor and wealthy areas alike, have an incentive to ensure that poorer residents have equal access to vaccines.
Confidence About Vaccines In The United States: Understanding Parents’ Perceptions
Allison Kennedy, Katherine LaVail, Glen Nowak, Michelle Basket, and Sarah Landry
Health Aff June 2011 30:1151-1159; doi:10.1377/hlthaff.2011.0396
The United States has made tremendous progress in using vaccines to prevent serious, often infectious, diseases. But concerns about such issues as vaccines’ safety and the increasing complexity of immunization schedules have fostered doubts about the necessity of vaccinations. We investigated parents’ confidence in childhood vaccines by reviewing recent survey data. We found that most parents—even those whose children receive all of the recommended vaccines—have questions, concerns, or misperceptions about them. We suggest ways to give parents the information they need and to keep the US national vaccination program a success.
The 2011 United Nations High Level Meeting on AIDS, held in New York, “launched a Global Plan that will make significant strides towards eliminating new HIV infections among children by 2015 and keeping their mothers alive.” Michel Sidibé. Executive Director of UNAIDS, said, “We believe that by 2015 children everywhere can be born free of HIV and that their mothers can remain healthy. This new global plan is realistic, it is achievable and it is driven by the most affected countries.” The United States President’s Emergency Plan for AIDS Relief (PEPFAR) announced an additional US$75 million to preventing mother-to-child transmission of HIV (PMTCT) efforts. This funding will be on top of the approximately US$300 million that PEPFAR already provides annually for PMTCT. The Bill & Melinda Gates Foundation pledged US$40 million, Chevron committed to US$20 million and Johnson & Johnson pledged US$15 million.