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Molecular markers for failure of sulfadoxine-pyrimethamine and chlorproguanil-dapsone treatment of Plasmodium falciparum malaria

Kublin, J. G., Dzinjalamala, F. K., Kamwendo, D. D., Malkin, E. M., Cortese, J. F., Martino, L. M., Mukadam, R. A. G., Rogerson, S. J., Lescano, A. G., Molyneux, Malcolm E, Winstanley, P., Chimpeni, P., Taylor, T. E. and Plowe, C. V. (2002) 'Molecular markers for failure of sulfadoxine-pyrimethamine and chlorproguanil-dapsone treatment of Plasmodium falciparum malaria'. Journal of Infectious Disease, Vol 185, Issue 3, pp. 380-388.

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Abstract

Molecular assays for monitoring sulfadoxine-pyrimethamine-resistant Plasmodium falciparum have not been implemented because of the genetic and statistical complexity of the parasite mutations that confer resistance and their relation to treatment outcomes. This study analyzed pretreatment dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) genotypes and treatment outcomes in a double-blind, placebo-controlled trial of sulfadoxine-pyrimethamine and chlorproguanildapsone treatment for uncomplicated P. falciparum malaria. Multiple logistic regression was used to identify mutations that were predictive of treatment failure and to identify interactions and confounding factors. Infections caused by parasites with 3 DHFR mutations and 2 DHPS mutations (the "quintuple mutant") were associated with sulfadoxine-pyrimethamine treatment failure but not with chlorproguanil-dapsone treatment failure. The presence of a single DHFR mutation (Arg-59) with a single DHPS mutation (Glu-540) accurately predicted the presence of the quintuple mutant. If this model is validated in other populations, it will finally be possible to use molecular markers for surveillance of antifolate-resistant P. falciparum malaria in Africa.

Item Type: Article
Additional Information: Presented in part: American Society of Tropical Medicine and Hygiene 48th annual meeting, Washington, DC, December 1999 (abstract 454).
Subjects: QU Biochemistry > Cells and Genetics > QU 350 Cellular structures
QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 256 Antimalarials
QX Parasitology > Protozoa > QX 135 Plasmodia
WA Public Health > Preventive Medicine > WA 110 Prevention and control of communicable diseases. Transmission of infectious diseases
WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
Digital Object Identifer (DOI): https://doi.org/10.1086/338566
Depositing User: Lynn Roberts-Maloney
Date Deposited: 21 Nov 2013 13:12
Last Modified: 17 Jul 2020 10:57
URI: https://archive.lstmed.ac.uk/id/eprint/2954

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