The Question
Has widespread implementation of AS-SP (an ACT) as a malaria treatment slowed the evolution of antimalarial resistance in Maputo Province, Southern Mozambique over a five year period?
What We Found
Evidence suggests that deploying artesunate plus SP (AS-SP) in Maputo Province has not slowed the spread of resistance to SP. Several possible explanations are proposed. Resistance may be the result of pre-existing parasitic mutations in the region, the use of SP monotherapy for pregnant women, and the systematic underdosing of SP for children under five. The study suggests that the therapeutic lifespan for AS-SP is reduced by the trends in resistance.
Why It Matters
Deployment of ACTs has been heralded as a means to fight resistance to antimalarial drugs, however evidence suggests that the strategy is not always effective at slowing the spread of resistance. Employing effective antimalarials is essential to reduce disease mortality and morbidity and to support other malaria interventions.
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 ( P < 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.
Keywords
ACTs,
MFTs