title: Efficacy and tolerability of a low-dose mefloquine-sulfadoxine-pyrimethamine combination compared with chloroquine in the treatment of acute malaria infection in a population with multiple drug-resistant Plasmodium falciparum.
abstract: The efficacy and tolerability of single, low-dose mefloquine, sulfadoxine-pyrimethamine (MSP) combination was compared with chloroquine (CQ) for malaria treatment in a malaria-endemic area of Nigeria with multiple drug-resistant Plasmodium falciparum. The two drug regimens (MSP and CQ) were tested in a 12-month prospective population study. The patients were divided into two groups. Group 1 patients were treated presumptively, based on malaria symptoms. Group 2 patients were treated based on a parasitologic diagnosis using the World Health Organization seven-day in vivo test and extended to a 28-day follow-up period. Tolerability was assessed by the incidence and intensity of adverse events. One thousand nine hundred thirty-five patients visiting 10 health facilities, including the University of Calabar Teaching Hospital, were enrolled. The study showed that the low-dose MSP was efficacious, with day 7 response rates of 95% and 91% for (presumptive) Group 1 and (in vivo) Group 2, respectively, while CQ had day 7 response rates of 82% and 66% in Groups 1 and 2, respectively. The low-dose MSP was significantly (P < 0.0001) more efficacious, with faster fever and parasite clearance times than CQ in this area of CQ-resistant P. falciparum malaria. Eight patients treated with CQ, including seven severe cases (RII-RIII) were successfully re-treated with MSP. Adverse events were generally more common among those treated with MSP (29%) than those treated with CQ (17%). However, the adverse events caused by both drugs were mild to moderate and self-limited. The MSP combination appears to be a good substitute for CQ, in view of multiple drug resistance, especially in areas with severe (RII-RIII) malaria.
authors.affiliation: Department of Medicine, University of Calabar, Nigeria.
authors.forename: E N
authors.initials: EN
authors.lastname: Ezedinachi
authors.forename: O J
authors.initials: OJ
authors.lastname: Ekanem
authors.forename: C M
authors.initials: CM
authors.lastname: Chukwuani
authors.forename: M M
authors.initials: MM
authors.lastname: Meremikwu
authors.forename: E A
authors.initials: EA
authors.lastname: Ojar
authors.forename: A A
authors.initials: AA
authors.lastname: Alaribe
authors.forename: A B
authors.initials: AB
authors.lastname: Umotong
authors.forename: L
authors.initials: L
authors.lastname: Haller
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000009:adverse effects / Q000592:standards / Q000627:therapeutic use*; D001769:Blood / Q000469:parasitology; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000008:administration & dosage / Q000009:adverse effects / Q000592:standards / Q000627:therapeutic use*; D004338:Drug Combinations; D018432:Drug Resistance, Multiple; D005260:Female; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D015767:Mefloquine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000592:standards / Q000627:therapeutic use; D008875:Middle Aged; D009549:Nigeria; D010963:Plasmodium falciparum / Q000187:drug effects*; D011446:Prospective Studies; D011739:Pyrimethamine / Q000008:administration & dosage / Q000009:adverse effects / Q000592:standards / Q000627:therapeutic use*; D011897:Random Allocation; D013413:Sulfadoxine / Q000008:administration & dosage / Q000009:adverse effects / Q000592:standards / Q000627:therapeutic use*; D000096926:Benzenesulfonamides
chemical_list: D000962:Antimalarials; D002738:Chloroquine; D004338:Drug Combinations; D015767:Mefloquine; D011739:Pyrimethamine; D013413:Sulfadoxine; C046846:mefloquine-sulfadoxine-pyrimethamine; D000096926:Benzenesulfonamides