Sulfadoxine-pyrimethamine in treatment of malaria in Western Kenya: increasing resistance and underdosing.
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.
Terlouw
Dianne J
DJ
Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. dianne.terlouw@student.uva.nl
Nahlen
Bernard L
BL
Courval
Jeanne M
JM
Kariuki
Simon K
SK
Rosenberg
Oren S
OS
Oloo
Aggrey J
AJ
Kolczak
Margarette S
MS
Hawley
William A
WA
Lal
Altaf A
AA
Kuile
Feiko O ter
FO
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*
D000890:Anti-Infective Agents; D000962:Antimalarials; D004338:Drug Combinations; D013413:Sulfadoxine; D011739:Pyrimethamine