RANDOMIZED TRIAL OF EFFICACY OF SPF66 VACCINE AGAINST PLASMODIUM-FALCIPARUM MALARIA IN CHILDREN IN SOUTHERN TANZANIA

Effective, safe antimalarial vaccines have proved elusive. The synthet ic polypeptide SPf66 vaccine is based on preerythrocytic acid asexual blood-stage proteins of Plasmodium falciparum. We report here a random ised double-blind placebo-controlled trial of the efficacy of the SPf6 6 vaccine against clinical P falciparum malaria in Idete, southern Tan zania, an area of intense perennial malaria transmission. 586 children aged 1-5 years received three doses of vaccine (n=274) or placebo (n= 312). The incidence and density of parasitaemia were assessed through repeated cross-sectional surveys on subgroups of children. Morbidity w as monitored over a 1 year period through passive case detection in al l children plus active case detection in a subgroup of 191. An episode of clinical malaria was defined as measured fever (greater than or eq ual to 37.5 degrees C) and parasite density >20 000/mu L. No severe si de-effects were seen and the frequency of mild side-effects after the third dose was less than 6%. The vaccine was highly immunogenic and af ter three doses all vaccine recipients had detectable anti-SPf66 antib odies: the geometric mean index of response was 8.3 in the vaccine gro up and 0.7 in the placebo group. The incidence of parasitaemia was sim ilar in both groups. 123 children had at feast one episode of clinical malaria during the follow-up period after the third dose and annual i ncidence rates were 0.25 in the vaccine group and 0.35 in the placebo group. Estimated vaccine efficacy was 31% (95% confidence interval 0-5 2%; p=0.046). After the third dose there were 6 deaths among the study cohort (1 vaccine, 5 placebo). This study confirms that SPf66 is safe , immunogenic and reduces the risk of clinical malaria among children exposed to intense P falciparum transmission.