Sulfadoxine-Pyrimethamine–Based Combinations for Malaria: A Randomised Blinded Trial to Compare Efficacy, Safety and Selection of Resistance in Malawi

摘要: Background: In Malawi, there has been a return of Plasmodium falciparum sensitivity to chloroquine (CQ) since sulfadoxinepyrimethamine (SP) replaced CQ as first line treatment for uncomplicated malaria. When used prophylaxis, Amodiaquine (AQ) was associated with agranulocytosis but is considered safe and increasingly being in Africa. Here we compare the efficacy, safety selection resistance using SP or CQ+SP artesunate (ART)+SP AQ+SP the treatment malaria. Methodology Findings: 455 children aged 1–5 years were recruited into double-blinded randomised trial comparing SP three combination therapies. Using intention treat analysis missing outcomes treated successes, and without adjustment distinguish recrudescence from new infections, day 28 adequate clinical parasitological response (ACPR) rate 25%, inferior each therapies (p,0.001). had an ACPR rate 97%, higher than (81%) ART+SP (70%), p,0.001. Nineteen developed neutropenia of #0.56103 cells/ml by 14, more commonly after (p = 0.03). The mutation pfcrt 76T, resistance, was detected none pre-treatment post-treatment parasites. prevalence pfmdr1 86Y was higher SP, p 0.002. Conclusions: highly efficacious, despite low efficacy alone; however, we found evidence that AQ may exert selective pressure mutations many weeks treatment. This study confirms Malawi importantly, shows no evidence re-emergence 76T after treatment AQ. Given record when our observations marked falls in neutrophil counts group requires further scrutiny.