Five Years of Large-Scale dhfr and dhps Mutation Surveillance Following the Phased Implementation of Artesunate Plus Sulfadoxine-Pyrimethamine in Maputo Province, Southern Mozambique


Raman, J; Little, F; Roper, C; Kleinschmidt, I; Cassam, Y; Maharaj, R; Barnes, KI; (2010) Five Years of Large-Scale dhfr and dhps Mutation Surveillance Following the Phased Implementation of Artesunate Plus Sulfadoxine-Pyrimethamine in Maputo Province, Southern Mozambique. The American journal of tropical medicine and hygiene, 82 (5). pp. 788-794. ISSN 0002-9637 DOI: 10.4269/ajtmh.2010.09-0401

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Abstract

Accumulation of mutations in dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) is strongly associated with sulfadoxine-pyrimethamine (SP) treatment failure. Routine surveillance for these resistance markers was conducted annually at 26 sentinel sites in Maputo Province, Mozambique, before and after the phased deployment of artesunate plus SP (AS-SP), with 15,758 children sampled between 2004 and 2008. Mean asexual parasite prevalence, polymerase chain reaction (PCR) corrected, decreased from 44.2% in 2004 to 3.8% in 2008 (P < 0.0001). Among the 2,012 PCR-confirmed falciparum samples, the dhfr triple mutation remained close to fixation, whereas both dhps double and dhfr/dhps "quintuple." mutations increased from 11.0% in 2004, to 75.0% by 2008 (I) < 0.0001). Adding artesunate to SP did not retard the spread of SP-resistant parasites. The high "quintuple" mutation prevalence suggests a limited useful therapeutic lifespan of AS-SP for treating uncomplicated malaria, and may curb efficacy of SP-monotherapy for intermittent preventive treatment in Mozambique.

Item Type: Article
Keywords: plasmodium-falciparum malaria, 1st line treatment, dihydrofolate-reductase, molecular surveillance, mefloquine resistance, drug-resistance, high prevalence, efficacy, trial, amodiaquine
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Research Centre: Antimicrobial Resistance Centre (AMR)
Malaria Centre
Tropical Epidemiology Group
PubMed ID: 20439956
Web of Science ID: 277406500008
URI: http://researchonline.lshtm.ac.uk/id/eprint/3699

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