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

The emergence and spread of drug- and diagnostic-resistant Plasmodium falciparum are 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 by P. falciparum carrying the candidate artemisinin partial-resistance K13 622I mutation, which occurred less commonly in diagnostic-resistant pfhrp2/3- 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 both pfhrp2/3 deletion 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.