A new report from the International Vaccine Access Center (IVAC) at Johns Hopkins University finds that despite major reductions in pneumonia and diarrhea deaths globally, progress has been slow in the highest-burden countries. The Pneumonia and Diarrhea Progress Report evaluates the progress made by the fifteen highest-burden countries in implementing high-impact interventions from the Global Action Plan on Pneumonia and Diarrhea (GAPPD), and highlights countries making strides toward reducing child mortality from pneumonia and diarrhea.
ROTA Council members Duncan Steele and Umesh Parashar served as two of the guest editors in this month’s The Pediatric Infectious Disease Journal supplement on rotavirus disease burden in Africa. Drs. Parashar and Steele co-authored the introductory article ”Preparing for the Scale-up of Rotavirus Vaccine Introduction in Africa: Establishing Surveillance Platforms to Monitor Disease Burden and Vaccine Impact,” one of several articles they contributed to in the supplement, which appeared in the January 2014 issue of The Pediatric Infectious Disease Journal. Council member George Armah also contributed to a study in the supplement, about rotavirus disease burden in Enugu, Nigeria.
This supplement appeared in The Pediatric Infectious Disease Journal, 2014 Jan 33;1(1) pp: S1-S106. Guest Editors: Mwenda, Jason M.; Tate, Jacqueline E.; Steele, A. Duncan; Parashar, Umesh D.
Read more about the supplement in PATH’s RotaFlash.
This paper appeared in Human Vaccines & Immunotherapeutics, 2013 Aug 16;9(11). Authors: Nelson EA, de Quadros CA, Santosham M, Parashar UD, Steele D.
A two-page summary of the paper can be found here.
Despite a WHO recommendation in 2009, reaffirmed in 2013, that all countries should consider introducing rotavirus vaccines into their National Immunization Programs, as of June 2013 only 45 have done so. One major consideration appears to have been the costs of the vaccine to countries. Of concern, is that Asian countries have been slow to introduce rotavirus vaccines despite having robust data that could inform the decision-making process. Although decisions on new vaccine introduction are very complex and vary by country and region, economic evaluations are often pivotal once vaccine efficacy and safety has been established, and disease burden documented and communicated. Unfortunately, with private sector list prices of vaccines often used in economic evaluations, rather than a potential public health sector pricing structure, policy-makers may defer decisions on rotavirus vaccine introduction based on the belief that “the vaccine price is too high,” even though this might be based on erroneous data. The Pan American Health Organization’s Revolving Fund provides one example of how vaccine price can be made more competitive and transparent through a regional tendering process. Other mechanisms, such as tiered pricing and UNICEF procurement, also exist that could help Asian and other countries move forward more quickly with rotavirus vaccine introduction.
This post first appeared on SciDev.Net.
[LA PAZ] A WHO-recommended vaccine for rotavirus infection has proved effective in Bolivia, the first low-income country to introduce it, researchers have reported.
Rotavirus is the leading cause of diarrhoea-related deaths in most of the developing world. The WHO recommends two vaccines for all children worldwide — RV1, which targets one strain of the virus and is given in two doses, and RV5, a three-dose vaccine targeting five strains.
In 2008, RV1 was added to Bolivia’s routine immunisation schedule, with doses recommended for all children at two and four months. Bolivia was the first country that receives support from the Global Alliance for Vaccines and Immunisation to use the vaccine.
Until now there has been a lack of data on whether RV1 is as effective in the real-life conditions of lower-middle income countries — particularly those with lots of children dying from rotavirus infections — as it has been in clinical trials.
The study, published in The British Medical Journal last month (19 June), analysed hospitalisations at six hospitals in Bolivia between March 2010 and June 2011. It found that RV1 prevented 69-77 per cent of rotavirus hospitalisations.
Manish Patel, lead author of the study and a researcher at the National Center for Immunization and Respiratory Diseases at the US Centers for Disease Control and Prevention (CDC), tells SciDev.Net that the results of the trial were “quite similar to the clinical trial results from lower-mortality middle- and high-income settings in the Americas”.
Other studies have shown that overall the vaccine has performed better in upper-middle income countries than in lower-middle income countries.
Patel says the reasons for this are not fully understood. It may be that malnutrition and co-infections in children in lower-income countries impair the immune response, he says.
What is known is that both rotavirus vaccines are less effective in countries with higher child death rates, making the Bolivian results even more encouraging considering the context in which the vaccine was used, write the study authors.
Patel adds: “This single-strain rotavirus vaccine provided effective protection against a broad range of strains that are different from the vaccine strain.”
The study’s authors write that both RV1 and RV5 should be used in low- and lower-middle income countries. They add that this type of study provides decision-makers with strong evidence to draw upon when faced with challenges — for example funding — that jeopardise vaccine programmes.
“Ongoing monitoring of impact, particularly in Asia and Africa, will be crucial for fully understanding the vaccines and identifying factors that would allow us to realise the full potential of the life-saving benefits of rotavirus vaccines [in these countries],” says Patel.
Another study published in The Journal of Infectious Diseases last month (18 June) showed that RRV-TV, a rotavirus vaccine targeting four strains, had an efficacy of around 60 per cent in Ghana. The next step is to test the vaccine in newborn babies.
This post first appeared on the Johns Hopkins Bloomberg School of Public Health International Vaccine Access Center (IVAC) blog.
The Integrated Global Action Plan for Pneumonia and Diarrhoea (GAPPD) was launched last month. Now this week we’ve learned that a new rotavirus vaccine from India, Bharat Biotech‘s ROTAVAC, looks promising, and The Lancet featured results from the Global Enteric Multi-Center Study or GEMS, which offers a comprehensive look at the causes of diarrhea in children, such as rotavirus. In light of this recent news and its impact on efforts to prevent and treat diarrheal disease, especially rotavirus, we sat down with Mathu Santosham, MD, MPH. Dr. Santosham co-chairs the ROTA Council and also chaired the Data Safety and Monitoring Board for the ROTAVAC trial established to protect the participating infants’ rights and needs during the trial.
Why is all of this recent news important for children?
|Mathu Santosham, MD, MPH|
We know that pneumonia and diarrhea are the leading killers of children under 5 worldwide, and we know that we need an integrated approach that uses all proven tools to tackle these two illnesses and prevent unnecessary suffering and death. GAPPD is important because it provides a framework, designed to inform global and national programs and policies, for integrating efforts against these two child killers. It sets ambitious but achievable goals including reducing under-five pneumonia and diarrhea deaths to 3 per 1,000 live births and 1 per 1,000 live births, respectively. A big part of the strategy for tackling both illnesses is vaccination.
For diarrhea, we know rotavirus – a pathogen for which there is a vaccine – is the leading cause of severe diarrhea among infants and children. In fact, the active surveillance results announced from the seven sites in GEMS reaffirmed this understanding, and offered important insights that will help better target interventions to the pathogens like rotavirus that are causing the most diarrhea. We also know that rotavirus contributes significantly to child mortality. According to the most recent estimates, more than 450,000 children died from rotavirus diarrhea in 2008. Rotavirus vaccine is critical to protecting children from rotavirus and preventing illness and death.
There are currently two licensed rotavirus vaccines, and they are saving lives and improving health today in the countries where they are in use. Having an additional vaccine from an Indian manufacturer will expand the market, which will offer more options to protect children in India and around the world. If licensed, Bharat has committed to offering the initial frozen formulation at $1 per dose, which will increase market competition for countries and organizations procuring vaccine. Also, it is especially encouraging to see India making so much progress toward a vaccine because nearly one-quarter of rotavirus deaths occur in India.
Why is rotavirus such a large concern?
Rotavirus is highly contagious and can last for long periods of times on hands and surfaces. It is not adequately prevented by proper hygiene or improvements in water and sanitation, like other pathogens that cause diarrhea. So even children in developed countries are susceptible to contracting rotavirus. In fact, nearly every child will be infected at least once by the age of 5. Once infected, a child often experiences symptoms that include fever, vomiting, and diarrhea. In developed countries where access to care is more reliable, children are unlikely to die from this infection, but in developing countries, children are less likely to have quick access to oral rehydration, making them at risk to suffer severe dehydration. This can lead to hospitalization and even death. In addition, children who suffer from malnutrition are more vulnerable to diarrhea, and diarrhea in turn worsens their malnutrition, resulting in a vicious cycle. For these reasons, rotavirus is a concern worldwide, but especially in developing countries.
What can we do about rotavirus?
Rotavirus cannot be treated with antibiotics or other drugs. However, its symptoms can be alleviated by prompt use of oral rehydration therapy (ORT), which includes home available fluids, oral rehydration salts (ORS), and, in cases of severe dehydration, IV fluids. ORT can effectively treat most rotavirus infections, but when the treatment is received too late, rotavirus can be deadly. In India, only about 4 in 10 children receive ORT when they have diarrhea. Vaccination, on the other hand, can actually prevent rotavirus diarrhea from happening in the first place. The two currently licensed vaccines, Rotarix and RotaTeq, have been demonstrated to be safe and effective and have been introduced in more than 45 countries. When combined with ORT, zinc supplementation, breastfeeding, and improvements in nutrition, hygiene, and water quality, vaccines contribute to the comprehensive approach required to effectively prevent severe illness and deaths caused by rotavirus diarrhea.
What is ROTA Council doing about this problem?
The ROTA Council, which I co-chair with Dr. Ciro de Quadros of Sabin Vaccine Institute, is a dedicated team of technical experts with the mission of saving children’s lives by accelerating the introduction of rotavirus vaccines. We work at the global and country level to ensure that policy makers have the latest evidence-based information to inform their decisions about introducing and scaling up rotavirus vaccines as part of broader diarrhea control efforts. At the same time, many of our Council members are on the frontlines of research, conducting the studies needed to demonstrate vaccine efficacy, safety, and impact. We are pleased to see that more than 45 countries have introduced rotavirus vaccines, but many more are still leaving their children unprotected, particularly in Asia, where countries have been slow to introduce the vaccine.
Why should India and other low- and middle-income countries introduce rotavirus vaccine?
Rotavirus diarrhea is a ubiquitous problem that can have some very serious consequences. In India, and other countries where access to care can be quite unequal, prevention becomes even more critical. If left untreated, rotavirus infection can lead to unnecessary illness, hospitalization, and even death, which is not only concerning from a health standpoint, but also takes a very serious toll from a social and economic standpoint. Hospitalization for one child with rotavirus costs nearly the entire amount of an average Indian household’s spending in a month. Diarrhea related healthcare needs are also costly for the country and stretch its already burdened state healthcare system. Beyond direct costs, vaccination could avoid productivity losses and help children grow into healthy, educated, productive adults.
The vaccine has the potential to make a big difference in the lives of families around the developing world. In India alone, we could prevent tens of thousands of deaths, not to mention nearly 300,000 hospitalizations and more than 300,000 doctor visits, which amounts to savings of over US$20 million in medical costs.
Based on your experiences, what is your hope for India and the rotavirus vaccination?
As a medical student in India in the 60s I saw children dying of diarrhea every day. Over the years, we were fortunate enough to develop powerful treatments like ORT, which helped to reduce the number of diarrheal deaths per year from 5 million in 1980 to less than a million now. However, more than 700,000 children continue to die from diarrhea annually because they don’t get the necessary treatment on time. Rotavirus is the leading cause of these diarrheal deaths, and it is a tragedy to see a child die from rotavirus when we have such a powerful weapon to combat this disease. It is my sincere hope that every child in India will soon have access to this life-saving vaccine.
Mathuram Santosham, MD, MPH, is Co-Chair of the ROTA Council and Professor of Pediatrics and International Health at Johns Hopkins University. He also serves as Director of the Center for American Indian Health, Director of the International Center for Maternal and Neonatal Health, and a Senior Advisor at IVAC.
The Global Enteric Multicenter Study (GEMS), the largest study on diarrheal disease in developing countries to date, confirmed rotavirus is the leading cause of diarrheal diseases among infants. The study involved more than 20,000 children from seven sites across Asia and Africa, and found that approximately one in five children under the age of two suffer from moderate-to-severe diarrhea each year, which greatly increased children’s risk of death and led to stunted growth.
Because more than 90 percent of rotavirus deaths occur in developing countries, where access to treatment for severe diarrhea is out of reach for many children, the GEMS findings highlight the critical role of rotavirus vaccines in preventing child sickness and death.
The Government of India’s Department of Biotechnology and Bharat Biotech announced today the positive results from a Phase III clinical trial of a rotavirus vaccine, ROTAVAC®, developed and manufactured in India. Data from the trial showed ROTAVAC® significantly reduced severe rotavirus diarrhea by more than half—56 percent during the first year of life, with protection continuing into the second year of life. The vaccine was also found to protect against severe diarrhea of any cause. This is comparable to the efficacy in low-resource settings of the two currently available rotavirus vaccines.
Once licensed, Bharat Biotech has promised to make the drug available for US$1.00 per dose (or approximately INR 54 per dose), making it a more affordable alternative to the rotavirus vaccines currently on the market.
The burden of rotavirus is higher in India than any other country–rotavirus kills nearly 100,000 Indian children under age five each year, and sickens hundreds of thousands more. An affordable, effective vaccine, if introduced into the nation’s immunization program, will have a tremendous impact improving child health and saving children’s lives.
Statement on ROTAVAC® from Dr. Mathuram Santosham, co-chair of the ROTA Council:
“As someone who has conducted several Phase III trials as well as serving on several Data Safety Monitoring Boards, I am very impressed with the quality of the 116E Phase III trial. This trial meets the highest standards for ethics and patient care and has been conducted in compliance with international standards for Good Clinical Practices. The trial design included a strong safety net to identify and treat illnesses, especially gastroenteritis, among study infants as quickly as possible. All of the infants enrolled in the trial have received high-quality medical and emergency care, and the surveillance system for collecting cases of diarrhea is meticulous.”
Dr. Mathuram Santosham, a professor in the Departments of International Health and Pediatrics at Johns Hopkins University, was the Acting Chair of the Data Safety Monitoring Board for the ROTAVAC® Phase III efficacy trial.
Professor Julie Bines has led a team to make a world breakthrough in reducing child mortality, with the development of a natural immunisation which can now be administered at birth. The World Health Organisation recommendation that all children be immunised to prevent severe rotavirus gastroenteritis, a deadly diarrhoeal disease, is more likely to become a reality with the announcement that the new vaccine for the disease has been developed specifically for newborns.
To read the full article, click here.
Mathuram Santosham co-authored an article that showed protection against pneumococcus, rotavirus, and human papillomavirus infections are highly inadequate in most of the countries in the Asia Pacific region. Promoting coverage of newly developed vaccines will benefit a great number of children in this area.
To read the rest of this article, please click here.
With the recent postlicensure identification of an increased risk of intussusception with rotavirus vaccine, the 14 Latin American countries currently using rotavirus vaccine must now weigh the health benefits versus risks to assess whether to continue vaccination. This research found that the health benefits of vaccination far outweigh the short-term risks and support continued rotavirus vaccination in Latin America.