Abstract
Because ≈90% of malaria cases occur in Africa, emergence of artemisinin-resistant Plasmodium falciparum in Africa poses a serious public health threat. To assess emergence of artemisinin-resistant parasites in Uganda during 2014–2016, we used the recently developed ex vivo ring-stage survival assay, which estimates ring-stage–specific P. falciparum susceptibility to artemisinin. We conducted 4 cross-sectional surveys to assess artemisinin sensitivity in Gulu, Uganda. Among 194 isolates, survival rates (ratio of viable drug-exposed parasites to drug-nonexposed controls) were high (>10%) for 4 isolates. Similar rates have been closely associated with delayed parasite clearance after drug treatment and are considered to be a proxy for the artemisinin-resistant phenotype. Of these, the PfKelch13 mutation was observed in only 1 isolate, A675V. Population genetics analysis suggested that these possibly artemisinin-resistant isolates originated in Africa. Large-scale surveillance of possibly artemisinin-resistant parasites in Africa would provide useful information about treatment outcomes and help regional malaria control.
Highlights
Because ≈90% of malaria cases occur in Africa, emergence of artemisinin-resistant Plasmodium falciparum in Africa poses a serious public health threat
We found no significant differences for patient background characteristics or parasitemia in all enrolled and ex vivo ring-stage survival assay (RSA)–successful patients (Table 1; online Technical Appendix Table 2)
The recently developed ex vivo RSA found that 4 (2.1%) isolates from Uganda showed high (>10%) survival rates, levels of which are reported to be closely associated with slow-clearing P. falciparum infections [12]
Summary
Because ≈90% of malaria cases occur in Africa, emergence of artemisinin-resistant Plasmodium falciparum in Africa poses a serious public health threat. To assess emergence of artemisinin-resistant parasites in Uganda during 2014–2016, we used the recently developed ex vivo ring-stage survival assay, which estimates ring-stage–specific P. falciparum susceptibility to artemisinin. The recently developed ring-stage survival assay (RSA) can evaluate ring-stage–specific reduction of artemisinin susceptibility [12]. In this assay, ring-stage parasites are exposed to 700 nmol/L of dihydroartemisinin for 6 h and cultured for 66 h in the absence of the drug. Levels of artemisinin susceptibility are estimated according to the survival rate (i.e., the ratio of viable parasites exposed to 700 nmol/L dihydroartemisinin to parasites cultured simultaneously in drug-free medium). In a study of isolates from 31 persons in Cambodia, all isolates classified as artemisinin resistant by ex vivo conventional assay (having parasite clearance half-lives >5 h after artemisinin treatment [4,13]) had an ex vivo survival rate >10% by RSA [12]
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