1004 Rotavirus vaccine studied in Africa

Making headlines in recent weeks is a study, first-authored by Madhi of Witwatersrand University, giving results of a multi-centre vaccine trial carried out in South Africa and Malawi with input and support from the UK, WHO and the vaccine manufacturer. Given that rotaviral infection is deemed to be responsible for >500 000 deaths per annum around the world, with some 40% occurring in sub-Saharan Africa, it was not only timely but also essential for a study such as this to be undertaken. The study was randomized and placebo-controlled (because vaccine was not licensed or available in the two countries at the time: 2005-7) and involved the enrolment of 4939 healthy 5-10 week-old infants. 1647 were assigned to a 2-dose regimen (10 and 14 weeks), 1651 to 3 doses (6, 10 and 14 weeks) and 1641 to placebo (identical composition except for the virus). 3166 were studied in South Africa and 1773 in Malawi during appropriate months using Rotarix (Glaxo-SmithKline). Participants were followed up until one year of age with recording of gastroenteritis episodes, assessment of severity (using 20-point Vesikari scale), stool culture when necessary and serology testing for immunogenicity. 4417 infants were included in the final, overall per-protocol analysis: severe rotavirus gastroenteritis occurred in 4.9% of placebo infants vs 1.9% in the pooled vaccine group (vaccine efficacy 61.2%; 95% CI 44.0-73.2). There was no difference in efficacy between the 2- and 3-dose groups. At country level, vaccine efficacy was 49.9% in Malawi vs 76.9% in South Africa, but a greater number of severe episodes of rotavirus gastroenteritis were prevented in Malawi (6.7 per 100 infants vaccinated per year vs 4.2). Efficacy against gastroenteritis went beyond rotavirus, and efficacy against all-cause severe gastroenteritis was 30.2%. The rates of adverse events (including death) were similar in vaccinated and placebo groups (around 10%). Seroconversion rates one month after the last dose were between ~47% and 57% in the 2- and 3-dose groups in Malawi, and between ~57% and 67% in South Africa. (Note: South African health authorities introduced rotavirus vaccine into national schedules in 2008).

Read more:
N Engl J Med 2010; 362: 289-98 358-60 299-305
N Engl J Med 2006; 354: 23-33
Vaccine 2003; 21: 354-60