Rotavirus gastroenteritis is the leading cause of diarrhea-associated hospitalizations and death in children younger than 5 years of age. Rotavirus illness is caused by a virus which enters the body by mouth and infects the intestines. It is a particularly hardy and contagious virus, capable of surviving on inanimate surfaces for long periods and spreading readily from child to child and also to adults. Large quantities of virus are shed in the stool both prior and following acute illness which is characterized by fever, vomiting, and watery diarrhea. Illness typically lasts 3-7 days; death may ensue due to severe dehydration. Since the infection is caused by a virus, antibiotics and antiparasitic drugs are ineffective, and care is primarily supportive. Prior to the development of effective vaccines, 80% of children in the U.S. would develop rotavirus gastroenteritis. Elsewhere in developing countries, the numbers were staggering with more than 500,000 deaths occurring annually in children under 5 years old.
The first rotavirus vaccine, RotaShield (Wyeth Laboratories) was licensed in the United States in 1998 but was withdrawn in 1999 due to a suspected association with intussusception, a type of bowel obstruction. In 2006, RotaTeq (GlaxoSmithKline) was FDA approved, followed by Rotarix (Merck) in 2008. Both are live, attenuated, oral vaccines requiring either a 3 dose or a 2 dose series and have shown significant efficacy in the range of 80-90% in middle and high income countries. Prior to 2006 when routine rotavirus vaccination was recommended, rotavirus gastroenteritis was estimated to result in 400,000 visits to physician’s offices, 200,000 visits to Emergency Rooms, 55,000 hospitalizations, and 20-60 deaths annually among children under 5 years of age in the U.S. for an estimated total cost close to $300 million. Since introduction of the vaccine, the impact has been striking; hospitalizations and rotavirus-related Emergency Room visits have decreased by 80%. In addition, by vaccinating infants, serious rotavirus infections among older children and adults have demonstrated similar declines, presumably through the so-called “herd effect” resulting from wide-spread immunization practice. In summary, clinical trials and experience of rotavirus vaccines in middle and high income countries have demonstrated high efficacy against serious rotavirus disease. Rotavirus vaccination works!
Despite the high efficacy rates of RotaTeq and Rotarix vaccines in middle and high income countries, clinical studies consistently demonstrate lower efficacy rates in the range of 37-61% with either vaccine in the lowest income nations where the burden of rotavirus infection is greatest. Such performance is typical of other live oral vaccines in similar populations. The reasons are not completely understood, but factors such as earlier onset of recurrent episodes of infectious diarrhea, different gut microbiome, the presence of neutralizing antibodies, poor nutritional status, and varying circulating rotavirus strains may play a role. Nevertheless, even a moderately effective vaccine can have a huge public health impact when introduced into a population where the burden of disease is great, especially when combined with the herd protection that occurs when most children in an area are vaccinated and immune.
In 2000, the Global Alliance for Vaccines and Immunization (Gavi) was founded as a public-private global health partnership with the intent to improve childhood immunization coverage in poor countries and increase access to new vaccines. By design, Gavi leverages not only financial resources but also expertise to make vaccines more available, affordable, and their provision more sustainable. The two current rotavirus vaccines obtained prequalification by the World Health Organization (WHO) in 2008 which followed with UNICEF procurement of the vaccines through the financial support of Gavi. These vaccines have been introduced in 42 Gavi-eligible countries and in 6 additional countries classified as low and middle income and have had a major impact on rotavirus-associated hospitalizations and deaths in all settings.
According to WHO estimates in 2013, approximately 215,000 children under 5 years of age die each year from vaccine-preventable rotavirus infections with almost half of them in 4 countries: India, Pakistan, Nigeria, and Democratic Republic of Congo. Ten countries account for almost 2/3 of all deaths. It is in this context that findings recently published in the New England Journal of Medicine related to a new vaccine against rotavirus are incredibly encouraging. The study reported by Isanaka et al. was conducted in Niger in Sub-Saharan Africa, a region with the highest rate of death associated with rotavirus disease and where the current cost of vaccines is probably unsustainable and where refrigeration and transportation are unreliable. The new vaccine, BRV-PV (Rotasil), is a live, oral rotavirus vaccine manufactured by Serum Institute of India and is lower in cost relative to existing vaccines and heat stable for as long as 6 months at 104 degrees F. and for 2 years at 98.6 degrees F. In a double-blind, placebo-controlled randomized trial including over 4000 healthy infants, the new vaccine was found to have a calculated efficacy rate of 67% with no apparent short term adverse events. Since existing vaccines are costly and require refrigeration, the new vaccine provides major advantages in resource-constrained countries where the burden of rotavirus is greatest. If further surveillance continues to yield good findings, the new vaccine promises to provide a giant step in the progress against rotavirus.