Malaria chemotherapy trial at a minimal effective dose of mefloquine/sulfadoxine/pyrimethamine compared with equivalent doses of sulfadoxine/pyrimethamine or mefloquine alone.
In murine malaria the addition of mefloquine to sulfadoxine/pyrimethamine has been shown to exert an additive effect and to significantly slow the emergence of resistance to the individual components. In a pilot study carried out in Gabon, a reduced dosage of the triple combination with a mean of 1 mg/kg of mefloquine/2 mg/kg of sulfadoxine/0.1 mg/kg of pyrimethamine (Fansimef; Roche, Basel, Switzerland) had previously been shown to achieve high cure rates in Plasmodium falciparum malaria. To evaluate the additive effect, a randomized, double-blind trial in school children with mild P. falciparum malaria was performed in Gabon. Two hundred thirty-one patients evaluated received a single dose of either the triple combination with a mean of 1.07 mg/kg of mefloquine/2.14 mg/kg of sulfadoxine/0.11 mg/kg of pyrimethamine (group MSP), or 1.07 mg/kg of mefloquine alone (group M), or 2.14 mg/kg of sulfadoxine/0.11 mg/kg of pyrimethamine alone (group SP). In the MSP group and the SP group, 67% and 69% of the patients were parasitologically cured, respectively, compared with only 13% in the M group (P < 0.001). A significantly higher parasitemia was found in the M group compared with the MSP group or the SP group on days 2 and 3 after the start of treatment. The high efficacy of the low dose sulfadoxine/pyrimethamine regimen was the most surprising finding of this study.
Lell
B
B
Laboratoire de Recherches, Hopital Albert Schweitzer, Lambarene, Gabon.
Lehman
L G
LG
Schmidt-Ott
J R
JR
Sturchler
D
D
Handschin
J
J
Kremsner
P G
PG
D000293:Adolescent; D000962:Antimalarials / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D015767:Mefloquine / Q000008:administration & dosage / Q000627:therapeutic use; D011739:Pyrimethamine / Q000008:administration & dosage / Q000627:therapeutic use; D013413:Sulfadoxine / Q000008:administration & dosage / Q000627:therapeutic use
D000962:Antimalarials; D013413:Sulfadoxine; D015767:Mefloquine; D011739:Pyrimethamine