Artemisinin-Resistant HRP2-Negative Malaria in Eritrea. Reply
Résumé
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The authors reply:
When Bayih et al. reported the Pfkelch13 R622I variant in northwest Ethiopia,1 they did not validate this mutation as a molecular marker of partial resistance to artemisinin. In our clinical studies spanning 2016 through 2019, we documented such resistance in Eritrea. In line with the World Health Organization definition,2 we found delayed clearance in more than 5% of the patients with the Pfkelch13 R622I variant, as evidenced by persistent parasitemia detected by microscopy at 72 hours. We validated this variant as a marker of in vitro artemisinin partial resistance by showing substantial differences in the results on the 3-hour ring-stage survival assay between NF54R622I and Dd2 R622I parasite lines as compared with their isogenic wild-type lines.
We agree that the NF54R622I and Dd2 R622I parasites may not perfectly reflect the phenotype of Pfkelch13 R622I found in Eritrean field isolates. Regarding PCR-based detection of hrp2 or hrp3 deletions, we found that almost one fifth of the Pfkelch13 R622I variants lacked these deletions, as recently observed in Ethiopia.3,4 Regardless of the methodologic differences between standard and droplet digital PCR, the data from our study speak to the urgency of confronting infections with partial artemisinin resistance, including those with hrp2 or hrp3 deletions that can cause false negative results on rapid diagnostic testing.