Clonal spread ofPlasmodium falciparumcandidate artemisinin partial resistanceKelch13622I mutation and co-occurrence withpfhrp2/3deletions in Ethiopia

Abstract

AbstractThe emergence and spread of drug- and diagnostic-resistantPlasmodium falciparumare major impediments to malaria control and elimination. We deep sequenced known drug resistance mutations and other informative loci across the genome of 609 samples collected during a study across three regions of Ethiopia. We found that 8.0% (95% CI 7.0-9.0) of malaria cases were caused byP. falciparumcarrying the candidate artemisinin partial-resistanceK13622I mutation, which occurred less commonly in diagnostic-resistantpfhrp2/3-deleted than normal non-deleted parasites (p=0.03). Identity-by-descent analysis showed that 622I parasites were significantly more related than wild-type (p<0.001), consistent with recent expansion and spread.Pfhrp2/3-deleted parasites were also highly related, with evidence of clonal transmissions at the district level. Parasites carrying bothpfhrp2/3deletion and 622I mutation were observed in some sites. These findings raise concern for future spread of combined drug- and diagnostic-resistant parasites and warrant close monitoring.