Abstract
Sulfadoxine-resistant Plasmodium falciparum undermines malaria prevention with sulfadoxine/pyrimethamine. Parasites with a highly resistant mutant dihydropteroate synthase (dhps) haplotype have recently emerged in eastern Africa; they negated preventive benefits of sulfadoxine/pyrimethamine, and might exacerbate placental malaria. We explored emerging lineages of dhps mutant haplotypes in Malawi, the Democratic Republic of the Congo, and Tanzania by using analyses of genetic microsatellites flanking the dhps locus. In Malawi, a triple-mutant dhps SGEG (mutant amino acids are underlined) haplotype emerged in 2010 that was closely related to pre-existing double-mutant SGEA haplotypes, suggesting local origination in Malawi. When we compared mutant strains with parasites from the Democratic Republic of the Congo and Tanzania by multiple independent analyses, we found that SGEG parasites were partitioned into separate lineages by country. These findings support a model of local origination of SGEG dhps haplotypes, rather than geographic diffusion, and have implications for investigations of emergence and effects of parasite drug resistance.
Highlights
Malaria remains a leading cause of ill health, causing an estimated 243 million cases of clinical malaria and 863 thousand deaths[1]
More than 85% of malaria cases and 90% of malaria deaths occur in Africa, south of Sahara
Key interventions currently recommended by WHO for the control of malaria are the use of insecticidal treated nets (ITNs) or indoor residual spraying (IRS) for vector control, and prompt access to diagnosis and treatment of clinical malaria
Summary
Malaria remains a leading cause of ill health, causing an estimated 243 million cases of clinical malaria and 863 thousand deaths[1]. More than 85% of malaria cases and 90% of malaria deaths occur in Africa, south of Sahara. An additional intervention which is recommended for pregnant women – a high risk group in areas of high malaria transmission – is Intermittent Preventive Treatment in pregnancy (IPTp), which involves the administration of at least 2 doses of sulphadoxine-pyrimethamine (SP) during the second and third trimesters of pregnancy. WHO is recommending a new intervention against Plasmodium falciparum malaria: Intermittent Preventive Treatment for infants (IPTi). Intermittent Preventive Treatment in infancy with SP (SP-IPTi) is the administration of a full therapeutic course of SP delivered through the Expanded Program on Immunization (EPI) at defined intervals corresponding to routine vaccination schedules – usually at 10 weeks, 14 weeks, and ∼9 months of age – to infants at risk of malaria
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