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Differential Effect of Regional Drug Pressure on Dihydrofolate Reductase and Dihydropteroate Synthetase Mutations in Southern Mozambique

Jaishree RamanMalaria Lead Programme, Medical Research Council, Durban, South Africa; London School of Hygiene and Tropical Medicine, London, England; Maputo Province Directorate of Health, Matola, Maputo Province, Mozambique; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa

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Brian SharpMalaria Lead Programme, Medical Research Council, Durban, South Africa; London School of Hygiene and Tropical Medicine, London, England; Maputo Province Directorate of Health, Matola, Maputo Province, Mozambique; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa

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Immo KleinschmidtMalaria Lead Programme, Medical Research Council, Durban, South Africa; London School of Hygiene and Tropical Medicine, London, England; Maputo Province Directorate of Health, Matola, Maputo Province, Mozambique; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa

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Cally RoperMalaria Lead Programme, Medical Research Council, Durban, South Africa; London School of Hygiene and Tropical Medicine, London, England; Maputo Province Directorate of Health, Matola, Maputo Province, Mozambique; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa

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Elizabeth StreatMalaria Lead Programme, Medical Research Council, Durban, South Africa; London School of Hygiene and Tropical Medicine, London, England; Maputo Province Directorate of Health, Matola, Maputo Province, Mozambique; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa

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Val KellyMalaria Lead Programme, Medical Research Council, Durban, South Africa; London School of Hygiene and Tropical Medicine, London, England; Maputo Province Directorate of Health, Matola, Maputo Province, Mozambique; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa

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Karen I. BarnesMalaria Lead Programme, Medical Research Council, Durban, South Africa; London School of Hygiene and Tropical Medicine, London, England; Maputo Province Directorate of Health, Matola, Maputo Province, Mozambique; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa

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The prevalence and frequency of the dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) mutations associated with sulfadoxine–pyrimethamine (SP) resistance at 13 sentinel surveillance sites in southern Mozambique were examined regularly between 1999 and 2004. Frequency of the dhfr triple mutation increased from 0.26 in 1999 to 0.96 in 2003, remaining high in 2004. The dhps double mutation frequency peaked in 2001 (0.22) but declined to baseline levels (0.07) by 2004. Similarly, parasites with both dhfr triple and dhps double mutations had increased in 2001 (0.18) but decreased by 2004 (0.05). The peaking of SP resistance markers in 2001 coincided with a SP–resistant malaria epidemic in neighboring KwaZulu-Natal, South Africa. The decline in dhps (but not dhfr) mutations corresponded with replacement of SP with artemether–lumefantrine as malaria treatment policy in KwaZulu-Natal. Our results show that drug pressure can exert its influence at a regional level rather than merely at a national level.

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