Am J Epidemiol 2002; 156:230-238.
Copyright © 2002 by the
Johns Hopkins Bloomberg School of Public Health
ORIGINAL CONTRIBUTIONS |
Determinants of Treatment Response to Sulfadoxine-Pyrimethamine and Subsequent Transmission Potential in Falciparum Malaria
1 Secretaría Departamental de Salud del Valle, Cali, Colombia.
2 Escuela de Salud Pública, Universidad del Valle, Cali, Colombia.
3 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
4 Departamento de Microbiología, Universidad del Valle, Cali, Colombia.
5 Fundación para la Educacion Superior, Cali, Colombia.
6 Instituto de Inmunología, Universidad del Valle, Cali, Colombia.
7 Malaria Section, Center for Vaccine Development, University of Maryland, Baltimore, MD.
Drug resistance is contributing to increasing mortality from malaria worldwide. For assessment of the role of resistance-conferring parasite mutations on treatment responses to sulfadoxine-pyrimethamine (SP) and transmission potential, 120 subjects with uncomplicated falciparum malaria from Buenaventura, Colombia, were treated with SP and followed for 21 days in the period February 1999 to May 2000. Exposures of interest were mutations in Plasmodium falciparum dihydrofolate reductase (DHFR) and dihydropteroate synthase that confer resistance to pyrimethamine and sulfadoxine, respectively. Although SP was highly efficacious (96.7%), the presence together of DHFR mutations at codons 108 and 51 was associated with longer parasite clearance time (relative hazard = 0.24, p = 0.019) more so than the 108 mutation alone (relative hazard = 0.45, p = 0.188). This association remained after controlling for potential confounders. Infections with these mutations were also associated with the presence of gametocytes, the sexual form of the parasite responsible for transmission, 14 and 21 days after treatment (p = 0.016 and p = 0.048, respectively). Higher gametocytemia is probably due to DHFR mutations prolonging parasite survival under drug pressure, resulting in longer parasite clearance time and allowing asexual parasites to differentiate into gametocytes. These results suggest that even when SP efficacy is high, DHFR mutations that are insufficient to cause therapeutic failure may nevertheless increase malaria transmission and promote the spread of drug resistance. Am J Epidemiol 2002;156:230–8.
dihydropteroate synthase; drug resistance; malaria; Plasmodium falciparum; pyrimethamine; sulfadoxine
Abbreviations: Abbreviations: DHFR, dihydrofolate reductase; DHPS, dihydropteroate synthase; PCT, parasite clearance time; SP, sulfadoxine-pyrimethamine; WHO, World Health Organization.
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