Intermittent treatment for malaria and anaemia control at time of routine vaccinations in Tanzanian infants: a randomised, placebo-controlled trial

Background Clinical malaria and severe anaemia are major causes of paediatr ic hospital admission and death in many malaria-endemic settings. In the ab sence of an effective and affordable vaccine, control programmes continue t o rely on case management while attempting the large-scale deployment of in secticide-treated nets. We did a randomised, placebo-controlled trial to as sess the efficacy and safety of intermittent sulphadoxine-pyrimethamine tre atment on the rate of malaria and severe anaemia in infants in a rural area of Tanzania. Methods We randomly assigned 701 children living in Ifakara, southern Tanza nia, sulphadoxine-pyrimethamine or placebo at 2, 3, and 9 months of age. Al l children received iron supplementation between 2 and 6 months of age. The intervention was given alongside routine Vaccinations delivered through WH O's Expanded Program on Immunisation (EPI). The primary outcome measures we re first or only episode of clinical malaria, and severe anaemia in the per iod from recruitment to 1 year of age. Morbidity monitoring through a hospi tal-based passive case-detection system was complemented by cross-sectional surveys at 12 and 18 months of age. Results were expressed in terms of pro tective efficacy (100 [1-hazard ratio] %) and analysis was by intention to treat. Findings 40 children dropped out (16 died, 11 migrated, 12 parents withdrew consent, and one for other reasons). Intermittent sulphadoxine-pyrimethami ne treatment was well tolerated and no drug-attributable adverse events wer e recorded. During the first year of life, the rate of clinical malaria (ev ents per person-year at risk) was 0.15 in the sulphadoxine-pyrimethamine gr oup versus 0.36 in the placebo group (protective efficacy 59% [95% CI 41-72 ]), and the rate of severe anaemia was 0.06 in the sulphadoxine-pyrimethami ne group versus 0.11 in the placebo group (50% [8-73]). Serological respons es to EPI vaccines were not affected by the intervention. Interpretation This new approach to malaria control reduced the rate of cli nical malaria and severe anaemia by delivering an available and affordable drug through the existing EPI system. Data are urgently needed to assess th e potential cost-effectiveness of intermittent treatment in areas with diff erent patterns of malaria endemicity.