Sulfadoxine-pyrimethamine monotherapy in Tanzanian children gives rapid parasite clearance but slow fever clearance that is improved by chloroquine in combination therapy

TY - JOUR

T1 - Sulfadoxine-pyrimethamine monotherapy in Tanzanian children gives rapid parasite clearance but slow fever clearance that is improved by chloroquine in combination therapy

AU - Tarimo, D S

AU - Minjas, J N

AU - Bygbjerg, I C

N1 - Keywords: Acetaminophen; Antimalarials; Child, Preschool; Chloroquine; Drug Combinations; Drug Resistance; Drug Therapy, Combination; Female; Fever; Humans; Infant; Malaria, Falciparum; Male; Parasitemia; Prospective Studies; Pyrimethamine; Recurrence; Sulfadoxine; Tanzania; Treatment Failure; Treatment Outcome

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

M3 - Journal article

C2 - 12100442

SN - 1360-2276

VL - 7

SP - 592

EP - 598

JO - Tropical Medicine & International Health

JF - Tropical Medicine & International Health

IS - 7

ER -