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Antimicrobial Agents and Chemotherapy, September 2003, p. 2929-2932, Vol. 47, No. 9
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.9.2929-2932.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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

Dianne J. Terlouw,1,2,3 Bernard L. Nahlen,1,2,4 Jeanne M. Courval,1,{ddagger} 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 Kuile1,2,3*

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.

* Corresponding author. Mailing address: Department of infectious Diseases, Tropical Medicine & AIDS, Academic Medical Center, University of Amsterdam, Meibergdreef 9, F4-217 1105 AZ Amsterdam Zuid Oost, The Netherlands. Phone: 31 20 5664380. Fax: 31 20 6972286. E-mail: dianne.terlouw{at}student.uva.nl.

{dagger} Asembo Bay Cohort Project manuscript XIX.

{ddagger} 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.

Antimicrobial Agents and Chemotherapy, September 2003, p. 2929-2932, Vol. 47, No. 9
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.9.2929-2932.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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