Rotavirus Vaccine
Of the nearly 11 million deaths that occur annually among children under five years of age, diarrheal disease is the second leading cause. The most common cause of severe gastroenteritis worldwide, rotavirus accounts for 29 to 45 percent of nearly 2 million deaths attributed to diarrheal disease.1,2 An estimated 600,000 children die from rotavirus each year, and more than 2 million are hospitalized due to the severe dehydration caused by rotavirus infection.2,3
The disease burden of rotavirus falls starkly and disproportionately on children in developing countries, where adequate and timely medical care is often out of reach: more than 80 percent of rotavirus deaths occur in south Asia and sub-Saharan Africa.2
The Promise of a Vaccine
The world health community believes that vaccines offer the best hope for protection against rotavirus. Why?
- Naturally acquired rotavirus infections provide protection against disease; a vaccine could also stimulate immunity.4
- Rotavirus transmission rates seem unaffected by improvements in sanitation and hygiene, one of the principal public health approaches to controlling other types of diarrheal disease.
- Life-saving intravenous treatment to rehydrate children with severe rotavirus diarrhea is unavailable to many children in the developing world.
- For many countries of both the developed and developing world, a vaccine will be the most cost-effective way to stop rotavirus.
New Rotavirus Vaccines
Two live, oral, attenuated vaccines against rotavirus infection (Rotarix®, manufactured by GlaxoSmithKline; and RotaTeq®, manufactured by Merck & Co., Inc.) were licensed by the European Medicines Agency and the US Food and Drug Administration, respectively, in 2006. Clinical trials in Europe, Latin America, and the US have demonstrated that these vaccines are safe and highly efficacious at preventing rotavirus-associated severe gastroenteritis. A number of countries, including some developing countries, have licensed these vaccines, and they are beginning to be introduced in routine immunization programs in some settings.
To date, both vaccines have been primarily studied in middle- and high-income countries. But historically, oral vaccines have been shown to perform differently in different regions of the world. The global health community recognizes the need to carry out additional studies of the safety and efficacy of these vaccines in developing countries of Africa and Asia, where the burden of disease is very high.5 PATH is designing and conducting such clinical trials in collaboration with the vaccine manufacturers.
The table below provides further details about Rotarix® and RotaTeq®.
| Rotarix® (GSK) | RotaTeq® (Merck) | |
|---|---|---|
| Origin | Human monovalent | Bovine pentavalent |
| Strain | G1, P(8) | G1, G2, G3, G4, P(8) |
| Dosage | 2 doses (with DTP1, DTP2) | 3 doses (with DTP1, DTP2, DTP3) |
| Presentation | Lyophilized; reconstituted | Liquid |
| Administration | Oral; applicator | Oral; squeeze tube |
| Co-administration | OPV, IPV, DTaP, DTwP HepB, Hib, PCV-7 |
IPV, DTaP, DTwP HepB, Hib, PCV-7 |
| Phase II & III safety & efficacy trials6,7 | n=63,225 healthy infants USA, Canada, Latin America (11), Taiwan, Singapore, Hong Kong, Belgium, Germany, Finland, South Africa, Bangladesh, Sweden |
n=70,301 healthy infants USA, Mexico, Costa Rica, Jamaica, Guatemala, Puerto Rico, Taiwan, Belgium, Finland, Germany, Italy |
| Efficacy vs. rotavirus gastroenteritis 6,7 | 85% vs. severe rotavirus gastroenteritis and 100% vs. more severe episodes | 98% vs. severe G1-G4 rotavirus gastroenteritis |
| Efficacy vs. gastroenteritis of any cause6,7 | 40% vs. severe gastroenteritis of any cause; 42% vs. hospitalization for severe gastroenteritis | 59% vs. hospitalization for diarrhea of any cause in first year of life. |
| Association with intussusception6,7 | None | None |
History of Rotavirus Vaccine Development
In 1998, prior to the development and licensure of Rotarix® and RotaTeq®, the world's first rotavirus vaccine, Rotashield™, was licensed for use in the United States. Clinical trials in the United States, Finland, and Venezuela had found it to be 80 to 100% effective at preventing severe rotavirus diarrhea, and researchers had detected no statistically significant serious adverse effects.4
The manufacturer of Rotashield™, however, withdrew it from the market in 1999, after it was discovered that the vaccine may have contributed to an increased risk for intussusception, or bowel obstruction, in one of every 12,000 vaccinated infants.4
The experience provoked intense debate among public health officials, scientists, vaccine manufacturers, and others about the relative risks and benefits of a rotavirus vaccine. As the debate continued, so did deaths, disease, and hospitalizations caused by rotavirus.
Today's vaccines against rotavirus were rigorously studied to determine any association with an increased risk of intussusception. In the studies conducted to date, both vaccines were found to have no association with the disorder.6,7
This fact sheet from the US Centers for Disease Control and Prevention provides additional information about Rotashield™.
Challenges for Vaccine Introduction
Experience shows that, even once a vaccine is available, years may pass before the people who need it most receive it.
For instance, 15 to 18 years elapsed between the introduction of vaccines for hepatitis B and influenza in wealthy nations and their widespread use in the developing world. Uncertain demand, insufficient supply, and high prices formed a vicious cycle that limited vaccine availability.8 In some countries, these problems resulted from a lack of information on the burden and extent of disease. Without such knowledge, health officials underestimated the vaccines’ potential value.
The Rotavirus Vaccine Program is working with all possible partners to avoid a similar situation and to dramatically reduce the lag time between vaccine development and availability in developing countries.
References
1 Bryce J, Boschi-Pinto C, Shibuya K, Black R. WHO estimates of the causes of death in children. Lancet. 2005;365(9465):1147-1152.
2 Parashar U, Gibson, C, Bresee, J, Glass, R. Rotavirus and severe childhood diarrhea. Emerging Infectious Diseases. 2006;12(2).
3 Parashar UD, Hummelman EG, Bresee JS, Miller MA, Glass RI. Global illness and deaths caused by rotavirus disease in children. Emerging Infectious Diseases. 2003;9(5):565-5.
4 Cunliffe, NA, Bresee, JS, Hart, CA. Rotavirus vaccines: development, current issues and future prospects. Journal of Infection. 45: 1-9. The British Infection Society. 2002.
5 World Health Organization. Rotavirus vaccines. Weekly Epidemiological Record. 2006; 81(1):8.
6 Ruiz-Palacios G, Pérez-Schael I, Velázquez, F, et al. Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. New England Journal of Medicine. 2006;354(1):11–22.
7 Vesikari, T, Matson D, Dennehy P, et al. Safety and efficacy of a pentavalent human–bovine (WC3) reassortant rotavirus vaccine. New England Journal of Medicine. 2006;354(1):23–33.
8 Accelerated development and introduction of priority new vaccines: The case of pneumococcal and rotavirus vaccines. McKinsey & Company. 2002.
Top photo by Richard Lord.