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Sulfadoxine-Pyrimethamine in Treatment of Malaria in Western Kenya: Increasing Resistance and Underdosing

Dianne J. Terlouw,^1,2,3 Bernard L. Nahlen,^1,2,4 Jeanne M. Courval,^1, Simon K. Kariuki,² Oren S. Rosenberg,^1, Aggrey J. Oloo,^2,|| Margarette S. Kolczak,¹ William A. Hawley,^1,2 Altaf A. Lal,¹ and Feiko O. ter Kuile^1,2,3*

Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia,¹ Kenya Medical Research Institute, Center for Vector Biology and Control Research, Kisumu, Kenya,² Unit of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands,³ Roll Back Malaria, World Health Organization, Geneva, Switzerland⁴

Received 20 February 2003/ Returned for modification 24 March 2003/ Accepted 10 June 2003

Between 1993 and 1999, we monitored the efficacy of sulfadoxine-pyrimethamine in 1,175 children aged <24 months receiving 2,789 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.

Asembo Bay Cohort Project manuscript XIX.

Present address: Division of Tuberculosis Elimination, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30333.

Present address: Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510.

^|| Present address: Department of Epidemiology and Preventive Medicine, Moi University, Eldoret, Kenya.

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