Efficacy of pentavalent rotavirus vaccine/severe rotavirus gastroenteritis in infants in developing countries in Asia

The Lancet
Volume 376, Issue 9741, Pages 615 – 623, 21 August 2010

Efficacy of pentavalent rotavirus vaccine against severe rotavirus gastroenteritis in infants in developing countries in Asia: a randomised, double-blind, placebo-controlled trial
K Zaman, Dang Duc Anh, John C Victor, Sunheang Shin, Md Yunus, Michael J Dallas, Goutam Podder, Vu Dinh Thiem, Le Thi Phuong Mai, Stephen P Luby, Le Huu Tho, Michele L Coia, Kristen Lewis, Stephen B Rivers, David A Sack, Florian Schödel, A Duncan Steele, Kathleen M Neuzil, Max Ciarlet

Background

Rotavirus vaccine has proved effective for prevention of severe rotavirus gastroenteritis in infants in developed countries, but no efficacy studies have been done in developing countries in Asia. We assessed the clinical efficacy of live oral pentavalent rotavirus vaccine for prevention of severe rotavirus gastroenteritis in infants in Bangladesh and Vietnam.

Methods

In this multicentre, double-blind, placebo-controlled trial, undertaken in rural Matlab, Bangladesh, and urban and periurban Nha Trang, Vietnam, infants aged 4—12 weeks without symptoms of gastrointestinal disorders were randomly assigned (1:1) to receive three oral doses of pentavalent rotavirus vaccine 2 mL or placebo at around 6 weeks, 10 weeks, and 14 weeks of age, in conjunction with routine infant vaccines including oral poliovirus vaccine. Randomisation was done by computer-generated randomisation sequence in blocks of six. Episodes of gastroenteritis in infants who presented to study medical facilities were reported by clinical staff and from parent recollection. The primary endpoint was severe rotavirus gastroenteritis (Vesikari score ≥11) arising 14 days or more after the third dose of placebo or vaccine to end of study (March 31, 2009; around 21 months of age). Analysis was per protocol; infants who received scheduled doses of vaccine or placebo without intervening laboratory-confirmed naturally occurring rotavirus disease earlier than 14 days after the third dose and had complete clinical and laboratory results were included in the analysis. This study is registered with ClinicalTrials.gov, number NCT00362648.

Findings

2036 infants were randomly assigned to receive pentavalent rotavirus vaccine (n=1018) or placebo (n=1018). 991 infants assigned to pentavalent rotavirus vaccine and 978 assigned to placebo were included in the per-protocol analysis. Median follow up from 14 days after the third dose of placebo or vaccine until final disposition was 498 days (IQR 480—575). 38 cases of severe rotavirus gastroenteritis (Vesikari score ≥11) were reported during more than 1197 person-years of follow up in the vaccine group, compared with 71 cases in more than 1156 person years in the placebo group, resulting in a vaccine efficacy of 48·3% (95% CI 22·3—66·1) against severe disease (p=0·0005 for efficacy >0%) during nearly 2 years of follow-up. 25 (2·5%) of 1017 infants assigned to receive vaccine and 20 (2·0%) of 1018 assigned to receive placebo had a serious adverse event within 14 days of any dose. The most frequent serious adverse event was pneumonia (vaccine 12 [1·2%]; placebo 15 [1·5%]).

Interpretation

In infants in developing countries in Asia, pentavalent rotavirus vaccine is safe and efficacious against severe rotavirus gastroenteritis, and our results support expanded WHO recommendations to promote its global use.

Funding

PATH (GAVI Alliance grant) and Merck.

Statement from the International Symposium on Smallpox Eradication

Sabin Vaccine Institute, Fogarty International Center of the U.S. National Institutes of Health, and Fundação Oswaldo Cruz convened Smallpox Eradication after 30 Years: Lessons, Legacies and Innovations” in Rio de Janeiro, Brazil on 24 August 2010. The meeting involved “global health dignitaries from 33 countries to share global health lessons, legacies and innovations post smallpox eradication.” 2010 marks the 30th anniversary of the Global Commission for the Certification of Smallpox Eradication officially reporting the elimination of smallpox disease. Smallpox remains the only disease to ever have been eradicated.

Dr. Mirta Roses, Director of the Pan American Health Organization, commented, “The eradication of smallpox has rightly been called one of mankind’s greatest achievements. Not only was it an important public health milestone, but it also gave rise to the founding of the Expanded Program on Immunization, which has been instrumental in saving the lives of millions of children around the world. As we have advanced with polio eradication in the Americas, now a global goal, and the elimination of measles and rubella, the Americas are forging a new future in control of vaccine-preventable diseases that sets examples for the rest of the world. We honor the heroes of smallpox eradication and the millions of health workers who toil selflessly every day to bring life-saving vaccines to the remotest corners of the earth, and we urge continued government, NGO, and private sector support for the goals of universal immunization.”

http://www.sabin.org/pressroom/releases/2010/08/24/sabin-vaccine-institute-fogarty-international-center-us-national-insti

Statement from the International Symposium on Smallpox Eradication

After 30 Years: Lessons, Legacies and Innovations

We, the 260 scientists, public health workers, historians and other professionals from 34 countries who participated in the August 24‐27, 2010 Smallpox Eradication Symposium at the Oswaldo Cruz Foundation in Rio de Janeiro, offer the following observations on smallpox eradication:

– First, smallpox eradication removed from the human population a virus that killed an estimated 300 million people in the twentieth century.

– Second, after 1980 smallpox vaccination was stopped saving the great costs of vaccination programs and eliminating the sometimes severe complications of smallpox vaccination.

– Third, the smallpox eradication program inspired a generation of public health practitioners and several major programs such as:

— A wider program of vaccination (The Expanded Program on Immunizations) that has helped achieve high levels of immunization around the world preventing large numbers of deaths of children and adults.

—- Wide-spread use of epidemiological surveillance as a key tool in disease control.

—- Programs that have made great progress toward the global eradication of polio and Guinea Worm and the elimination of measles and rubella from the Americas.

– Fourth, it demonstrated that international cooperation and solidarity can contribute to major public health improvements around the world.

– Finally, since the end of smallpox vaccination an increasing proportion of the population of the world is susceptible to smallpox. Given the current limited supplies of smallpox vaccine, release of smallpox into the environment could cause a catastrophic global epidemic. Further, smallpox virus is known to be held by only two laboratories in the world as authorized by WHO. Although these two laboratories maintain extensive precautions against release of the virus, no containment system is risk-free. In addition, it cannot be ascertained that there are no unauthorized stores of smallpox virus.

More than 15 years have elapsed since the World Health Assembly agreed to postpone the destruction of the smallpox virus. Therefore, in the interest of global security, consideration should now be given to early destruction of existing laboratory stocks of smallpox virus when on-going WHO-sanctioned research is completed on improved vaccines and diagnostics, effective anti-virals, and reliable animal model.

Finally, possession or deployment of the smallpox virus outside the WHO-sanctioned facilities should be designated a crime against humanity.

http://sabin.org/files/uploads/pdfs/Statement%20from%20the%20International%20Symposium%20on%20Smallpox%20Eradication%20After%2030%20Years-%20Lessons%2C%20Legacies%20and%20Innovations.pdf

9th International Rotavirus Symposium: Call to Action

The 9th International Rotavirus Symposium, held at Johannesburg, South Africa released the following Call to Action:

We the Participants of the 9th International Rotavirus Symposium
Considering that:

– Diarrhea is the second greatest killer of children under five worldwide, killing 1.33 million children under five each year;
– Rotavirus is the leading cause of severe diarrheal disease;
– Rotavirus-related diarrheal disease takes the lives of more than 500,000 children under five every year and is responsible for the hospitalization of millions more around the world;
– 85% of rotavirus deaths occur in low income countries in sub-Saharan Africa and Asia;
– A growing body of evidence attests to the safety, efficacy, effectiveness and lifesaving potential of rotavirus vaccines;
– In light of the demonstrated burden of rotavirus disease and the evidence supporting the use of vaccines to reduce that burden, there is a need to increase access to affordable rotavirus vaccines in the developing world;
– In 2009 WHO recommended that rotavirus vaccines be included in every nation’s immunization program;
– Adding rotavirus vaccination in national immunization programs and combining it with appropriate diarrhea control interventions as part of a package of strategies to prevent diarrheal diseases-related deaths would be critical to achieving Millennium Development Goal 4 (MDG 4);
– Prevention and control of diarrheal disease requires collaborative action by national governments, industry, civil society organizations, and international health agencies.

Therefore, We Agree to:
– Continue to support immunization as a common public good worldwide, an economic necessity and a vital political priority;
– Enourage increased vaccine research and expanded surveillance for vaccine preventable diseases;
– Encourage the joint collaboration of national governments, health professionals, bilateral and multilateral agencies, the GAVI Alliance, and the manufacturers of vaccines to facilitate and accelerate the introduction of affordable rotavirus vaccines worldwide;
– Advocate for and raise awareness among public and policy makers of the burden of rotavirus-related diarrheal disease and the value of vaccination;
– Call upon political leaders and decision-makers from developing countries to increase financial support to their national immunization programs;
– Call upon political leaders and decision-makers from developed countries and global – immunization partners to scale-up financial support to the GAVI Alliance.

http://www.sabin.org/pressroom/sabin_news/2010/08/09/9th-international-rotavirus-symposium-call-action

Call to Action PDF: here

WHO Director General announces end of the Phase 6: influenza pandemic alert

WHO Director General Dr. Margaret Chan announced the end of the Phase 6 of the Influenza pandemic alert:

H1N1 in post-pandemic period

The world is no longer in phase 6 of influenza pandemic alert. We are now moving into the post-pandemic period. The new H1N1 virus has largely run its course…

As we enter the post-pandemic period, this does not mean that the H1N1 virus has gone away. Based on experience with past pandemics, we expect the H1N1 virus to take on the behaviour of a seasonal influenza virus and continue to circulate for some years to come.

In the post-pandemic period, localized outbreaks of different magnitude may show significant levels of H1N1 transmission. This is the situation we are observing right now in New Zealand, and may see elsewhere.

In fact, the actions of health authorities in New Zealand, and also in India, in terms of vigilance, quick detection and treatment, and recommended vaccination, provide a model of how other countries may need to respond in the immediate post-pandemic period.

Globally, the levels and patterns of H1N1 transmission now being seen differ significantly from what was observed during the pandemic. Out-of-season outbreaks are no longer being reported in either the northern or southern hemisphere. Influenza outbreaks, including those primarily caused by the H1N1 virus, show an intensity similar to that seen during seasonal epidemics.

During the pandemic, the H1N1 virus crowded out other influenza viruses to become the dominant virus. This is no longer the case. Many countries are reporting a mix of influenza viruses, again as is typically seen during seasonal epidemics.

Recently published studies indicate that 20–40% of populations in some areas have been infected by the H1N1 virus and thus have some level of protective immunity. Many countries report good vaccination coverage, especially in high-risk groups, and this coverage further increases community-wide immunity.

Pandemics, like the viruses that cause them, are unpredictable. So is the immediate post-pandemic period. There will be many questions, and we will have clear answers for only some. Continued vigilance is extremely important, and WHO has issued advice on recommended surveillance, vaccination, and clinical management during the post-pandemic period.

Based on available evidence and experience from past pandemics, it is likely that the virus will continue to cause serious disease in younger age groups, at least in the immediate post-pandemic period. Groups identified during the pandemic as at higher risk of severe or fatal illness will probably remain at heightened risk, though hopefully the number of such cases will diminish.

In addition, a small proportion of people infected during the pandemic, including young and healthy people, developed a severe form of primary viral pneumonia that is not typically seen during seasonal epidemics and is especially difficult and demanding to treat. It is not known whether this pattern will change during the post-pandemic period, further emphasizing the need for vigilance.

As I said, pandemics are unpredictable and prone to deliver surprises. No two pandemics are ever alike. This pandemic has turned out to be much more fortunate than what we feared a little over a year ago.

This time around, we have been aided by pure good luck. The virus did not mutate during the pandemic to a more lethal form. Widespread resistance to oseltamivir did not develop. The vaccine proved to be a good match with circulating viruses and showed an excellent safety profile.

Thanks to extensive preparedness and support from the international community, even countries with very weak health systems were able to detect cases and report them promptly.

Had things gone wrong in any of these areas, we would be in a very different situation today….

http://www.who.int/mediacentre/news/statements/2010/h1n1_vpc_20100810/en/index.html

:: Read the report from the Emergency Committee meeting
:: WHO recommendations for the post-pandemic period
:: Press briefing – audio and video files
:: Surveillance recommendations in the post-pandemic period

GAVI announces Julian Lob-Levyt to step down as CEO

GAVI announced that Julian Lob-Levyt will step down as CEO of the GAVI Alliance in October “to take up a major role in the private sector after leading the public-private global health partnership through nearly six years of growth and innovation.” Dr Lob-Levyt will continue as CEO until October to oversee GAVI’s first Resource Mobilisation Meeting on 6 October at which “existing and potential donors will be asked to pledge additional funds to enable new vaccines against pneumococcal disease and rotavirus diarrhoea to be added to immunisation programmes.” In November, Dr Lob-Levyt, will become Managing Director of DAI Europe and Senior Vice President of DAI, based in London. DAI “has worked in 150 developing and transition countries, providing comprehensive development solutions in areas including HIV/AIDS and avian influenza control, crisis mitigation and stability operations, agriculture and agribusiness, democratic governance and public sector management, private sector development and financial services, economics and trade, water and natural resources management, and energy and climate change.”

Geneva, 11 August 2010: More at: http://www.gavialliance.org/media_centre/press_releases/ceo.php

Gates Foundation announces Grand Challenges Explorations: Round 6

The Bill & Melinda Gates Foundation today announced the opening of Round 6 of Grand Challenges Explorations, described as a US$100 million grant initiative to encourage bold and unconventional global health solutions. Proposals are being accepted until November 2, 2010. Grand Challenges Explorations “offers researchers the chance to win US$100,000 grants to foster innovative projects that could transform health in developing countries. The initiative focuses on areas where creative, unorthodox thinking is most urgently needed. For this round, applicants are asked to focus their proposals on these five topic areas:

– Design New Approaches to Cure HIV Infection;

– Create the Next Generation of Sanitation Technologies;

– Create Low-Cost Cell Phone-Based Applications for Priority Global Health Conditions;

– Create New Technologies for the Health of Mothers and Newborns;

– The Poliovirus Endgame: Create Ways to Accelerate, Sustain and Monitor Eradication.

http://www.gatesfoundation.org/press-releases/Pages/grand-challenges-explorations-round-six-100819.aspx

NIH launched US$100 million research initiative on human immune system changes: infection and vaccination

NIH launched a new nationwide research initiative “to define changes in the human immune system, using human and not animal studies, in response to infection or to vaccination.” Six U. S.-based Human Immune Phenotyping Centers will receive a total of US$100 million over five years to conduct this research. NIAID Director Anthony S. Fauci, M.D. commented, “Recognizing the differences in immune system activity before, during and after exposure to an infectious agent or vaccine will help in the development of safer, more effective therapeutics and vaccines. This research effort also will contribute to the ongoing evolution in our ability to study the immune system.”

Investigators will analyze samples from well-characterized groups, including children, the elderly and people with autoimmune diseases such as lupus. These groups represent diverse populations with respect to age, genetics, gender and ethnicity. The research teams will examine immune system elements of these populations before and after exposure to naturally acquired infections or to vaccines or vaccine components. The profile that will emerge of the body’s response to vaccination will be based on the most sophisticated and comprehensive assays currently available. This will enable new approaches to examining vaccine safety, not just of individual vaccines but of the processes of immunization in general.

The following six core institutions and principal investigators will participate in the inaugural program:

Baylor Research Institute, Dallas – Jacques Banchereau, Ph.D.

Dana-Farber Cancer Institute, Boston – Ellis Reinherz, M.D.

Emory University, Atlanta – Bali Pulendran, Ph.D.

Mayo Clinic, Rochester, Minn. – Gregory Poland, M.D.

Stanford University, Calif. – Mark Davis, Ph.D.

Yale University, New Haven, Conn. – David Hafler, M.D., and Erol Fikrig, M.D.

http://www.nih.gov/news/health/aug2010/niaid-11.htm