A pair of industry-funded multicenter studies has contributed to the growing call for infant vaccination against severe rotavirus gastroenteritis in the developing world.
The findings come more than a year after the World Health Organization's Strategic Advisory Group of Experts declared that rotavirus vaccines should be included in national immunization programs all over the world – particularly in countries with high diarrheal fatalities (Lancet 2010 Aug. 6 [doi:10.1016/S0140-6736(10)60755-6]).
Previous trials conducted in industrialized nations demonstrated rotavirus vaccine to be both safe and effective. However, far less clinical research has been conducted in low-income populations in Africa and Asia, where an estimated 85% of rotavirus fatalities occur (J. Infect. Dis. 2009;200:S1–8).
The two new studies explored African and Asian infant populations in double-blind, placebo-controlled, multicenter randomized trials.
A comment accompanying the two studies called for long-term subsidies from wealthier countries to ensure effective use of the vaccination in places with the greatest need (Lancet 2010 Aug. 6 [doi:10.1016/S0140-6736(10)60896-3]).
“It is likely that diarrhea deaths in the poorest countries could be reduced by 25%, which will greatly help these [countries] achieve the target of Millennium Development Goal 4,” coauthor Dr. E. Anthony S. Nelson, of the pediatrics department at the Chinese University of Hong Kong, said in an interview.
In the first of the two studies, an international team led by K. Zaman, Ph.D., of the International Centre for Diarrhoeal Disease Research in Bangladesh, carried out its trials in rural Matlab, Bangladesh, and neighborhoods in and around the seaside city of Nha Trang, Vietnam.
A total of 2,036 infants aged 4–12 weeks were randomly assigned three 2-mL oral doses of Merck's pentavalent rotavirus vaccine or placebo. There were no enrollment restrictions based on HIV status. The investigators said the infants showed no signs of preexisting gastrointestinal disorders when they began administering the dosages at roughly 6, 10, and 14 weeks of age.
Over the course of the next 2 years, Dr. Zaman and colleagues noted 38 cases of severe rotavirus gastroenteritis in the vaccinated group, compared with 71 in the placebo group. The investigators calculated the overall vaccine efficacy at 48%, which is lower than efficiencies observed in industrialized countries in Europe and the Americas.
Adverse events were relatively few. A total of 2.5% of the vaccinated subjects and 2.0% in the placebo group had at least one adverse event, and the investigators did not attribute any of those effects to the vaccine.
The second study, led by George E. Armah, Ph.D., of the University of Ghana, Accra, was conducted in Africa, where diarrheal disease remains the second biggest culprit in the continent's 800,000 annual child deaths (Lancet 2007;369:91–2).
Dr. Armah and colleagues employed the same methodology on a larger population − 5,468 infants. HIV-positive cases were not excluded.
They conducted the multicenter trial in clinics located in rural Ghana and Kenya, as well as an urban center in Mali. During the 2-year follow-up, Dr. Armah and colleagues recorded 79 cases of severe rotavirus gastroenteritis in the vaccinated group, compared with 129 in the placebo group. Severe adverse events occurred in 1.5% of those vaccinated and 1.7% of those who received placebos.
The overall vaccine efficacy was calculated at 39.3%. “This protection was especially high through the first year of life (64.2% vaccine efficacy), when the disease burden, including mortality, is highest,” the investigators wrote (Lancet 2010 Aug. 6 [doi:10.1016/S0140-6736(10)60889-6]).
The authors of both studies endorsed the WHO's call for the expansion of rotavirus vaccination.
Both teams, as well as a comment coauthor, stated some financial conflicts. Merck, the manufacturer of the oral vaccine used for both trials, helped design and oversee the studies with substantial input from the international nonprofit group PATH (Program for Appropriate Technology in Health). Merck employees and shareholders participated in the research process and helped fund the projects. Grant funding from GAVI (Global Alliance for Vaccines and Immunization) was contributed to the effort via PATH. Dr. Nelson has funding and other research relationships with Merck, Baxter, Intercell, GlaxoSmithKline, MedImmune, and Wyeth, including a phase III Rotarix vaccine study.