Following widespread
chloroquine (CQ) resistance,
sulfadoxine plus
pyrimethamine (SP) is now the first line
antimalarial drug in a number of African countries including Tanzania. Unlike CQ, SP has no
antipyretic effects, a feature that might delay
fever clearance, and by acting on late stage parasites, SP could theoretical be slow in parasite clearance. We therefore assessed the
antipyretic effects of CQ in therapeutic combination with SP, and the speed of parasite clearance by SP in an open-labelled, randomized trial of CQ alone (n=39), SP alone (n=39), SP plus CQ (n=37) and SP plus
paracetamol (PCM) (n=38) in children with uncomplicated
malaria. Over 72 h, there were eight (20.5%) treatment failures in the CQ group but none in the other groups. Although not significant (P > 0.1), irrespective of resistance CQ alone had a shorter median survival time to
fever clearance than SP alone (54 vs. 60 h). SP plus CQ had a highly significantly shorter median survival time to
fever clearance than SP alone (48 vs. 60 h) (P < 0.001). Although borderline (P=0.038), the median survival time to parasite clearance was significantly longer in SP plus PCM (72 h) than SP alone (48 h). Irrespective of resistance, CQ alone had a median survival time to parasite clearance equal to that of SP alone (48 h). Parasite clearance by SP was rapid and at the end of 72 h, most (77.3%, 95% confidence interval: 69.6, 85.0) of the children on SP (as a group) had become aparasitaemic. The findings rule out concerns on possible delayed parasitological and clinical responses to SP that could result from its action on late stage parasites. Despite its diminishing
antimalarial activity, CQ has beneficial in vivo
antipyretic effects in therapeutic combination with SP.