Clonal spread of Plasmodium falciparum candidate artemisinin partial resistance Kelch13 622I mutation and co-occurrence with pfhrp2/3 deletions in Ethiopia
Fola, A. A.; Feleke, S. M.; Mohammed, H.; Brhane, B. G.; Hennelly, C. M.; Bahita, A. A.; Crudale, R.; Reichert, E. N.; Juliano, J. J.; Cunningham, J.; Mamo, H.; Solomon, H.; Tasew, G.; Petros, B.; Parr, J. B.; Bailey, J. A.
Show abstract
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.
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