title: Sulfadoxine-pyrimethamine in treatment of malaria in Western Kenya: increasing resistance and underdosing.
abstract: Between 1993 and 1999, we monitored the efficacy of sulfadoxine-pyrimethamine in 1175 children aged <24 months receiving 2789 treatments for falciparum malaria in western Kenya using a widely deployed age-based dose regimen: infants, 125 plus 6.25 mg (sulfadoxine plus pyrimethamine); children aged 12 to 23 months; 250 plus 12.5 mg. Cumulative treatment failure by day 7, defined as early clinical failure by day 3 or presence of parasitemia on day 7, increased from 18% in 1993 to 1994 to 22% in 1997 to 1998 (P-trend test = 0.20). Based on body weight, the median dose received was 20 plus 1.00 mg/kg, and 73% of the treatments were given at lower than the recommended target dose of 25 plus 1.25 mg/kg. Underdosing accounted for 26% of cumulative treatment failures. After the dose was increased in 1998 (median, 36 plus 1.8 mg/kg), only 4.2% of patients received less than 25 plus 1.25 mg/kg and there was no association with treatment failure. However, the proportion of cumulative treatment failure continued to increase to 27% by 1999 (P-trend test = 0.03). These results raise concern about the longevity of sulfadoxine-pyrimethamine in these settings. Underdosing may have contributed to the rate at which sulfadoxine-pyrimethamine resistance developed in this area. Treatment guidelines should ensure that adequate doses are given from the initial deployment of antimalarials onward.
authors.affiliation: Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. dianne.terlouw@student.uva.nl
authors.forename: Dianne J
authors.initials: DJ
authors.lastname: Terlouw
authors.forename: Bernard L
authors.initials: BL
authors.lastname: Nahlen
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Courval
authors.forename: Simon K
authors.initials: SK
authors.lastname: Kariuki
authors.forename: Oren S
authors.initials: OS
authors.lastname: Rosenberg
authors.forename: Aggrey J
authors.initials: AJ
authors.lastname: Oloo
authors.forename: Margarette S
authors.initials: MS
authors.lastname: Kolczak
authors.forename: William A
authors.initials: WA
authors.lastname: Hawley
authors.forename: Altaf A
authors.initials: AA
authors.lastname: Lal
authors.forename: Feiko O ter
authors.initials: FO
authors.lastname: Kuile
mesh_terms: D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000962:Antimalarials / Q000008:administration & dosage / Q000627:therapeutic use*; D001835:Body Weight; D004338:Drug Combinations; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007223:Infant; D007630:Kenya; D008288:Malaria / Q000188:drug therapy*; D008297:Male; D011446:Prospective Studies; D011739:Pyrimethamine / Q000008:administration & dosage / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000890:Anti-Infective Agents; D000962:Antimalarials; D004338:Drug Combinations; D013413:Sulfadoxine; D011739:Pyrimethamine