Sulfadoxine/pyrimethamine alone or with amodiaquine or artesunate for treatment of uncomplicated malaria: a longitudinal randomised trial.
BACKGROUND
New antimalarial treatments are urgently needed in sub-Saharan Africa. Improved therapies should decrease failure rates in the short term, but their effect on incidence of subsequent episodes of malaria is little studied. We aimed to compare the short-term and long-term effectiveness of three antimalarial regimens in children from Kampala, Uganda.


METHODS
We randomly allocated healthy children aged 6 months to 5 years to receive 25 mg/kg sulfadoxine and 1.25 mg/kg pyrimethamine plus either placebo, 25 mg/kg amodiaquine, or 12 mg/kg artesunate. Participants were followed up for 1 year and received the same preassigned treatment for every new episode of uncomplicated malaria diagnosed during follow-up. Recrudescent and new infections were distinguished by comparison of polymorphisms in merozoite surface protein 2 (MSP2). Our primary endpoint was the total number of treatments for malaria per time at risk. Analyses were done per protocol.


RESULTS
183 (61%) of 316 participants were diagnosed with at least one episode of uncomplicated malaria. A total of 577 episodes of uncomplicated Plasmodium falciparum malaria were treated with study drugs; all regimens were safe and well tolerated. Clinical treatment failure after 14 days was significantly more frequent in the sulfadoxine/pyrimethamine group (38 of 215, 18%) compared with either the sulfadoxine/pyrimethamine plus amodiaquine group (two of 164, 1%; p<0.0001) or sulfadoxine/pyrimethamine plus artesunate group (one of 198, 1%; p<0.0001). After 28 and 42 days, patients in the sulfadoxine/pyrimethamine plus amodiaquine group were significantly less likely to develop malaria than were those in the other groups. Overall, sulfadoxine/pyrimethamine plus amodiaquine reduced the rate of subsequent treatments for malaria by 54% (95% CI 36-66, p<0.0001) compared with sulfadoxine/ pyrimethamine alone and by 37% (12-54, p=0.007) compared with sulfadoxine/pyrimethamine plus artesunate.


CONCLUSIONS
Sulfadoxine/pyrimethamine plus amodiaquine could be used as an inexpensive regimen to decrease the rate of subsequent episodes of malaria.
Dorsey
Grant
G
Department of Medicine, San Francisco General Hospital, University of California, 94110, USA. grantd@itsa.ucsf.edu
Njama
Denise
D
Kamya
Moses R
MR
Cattamanchi
Adithya
A
Kyabayinze
Daniel
D
Staedke
Sarah G
SG
Gasasira
Anne
A
Rosenthal
Philip J
PJ
D000655:Amodiaquine / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000627:therapeutic use*; D037621:Artemisinins / Q000008:administration & dosage / Q000627:therapeutic use*; D000077332:Artesunate; D002675:Child, Preschool; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000517:prevention & control*; D008297:Male; D010963:Plasmodium falciparum / Q000187:drug effects; D011739:Pyrimethamine / Q000008:administration & dosage / Q000627:therapeutic use*; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000008:administration & dosage / Q000627:therapeutic use*; D017211:Treatment Failure; D014454:Uganda
D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D012717:Sesquiterpenes; D000655:Amodiaquine; C001205:fanasil, pyrimethamine drug combination; D000077332:Artesunate; D013413:Sulfadoxine; D011739:Pyrimethamine