Plasmodium falciparum Kelch13 Variants and Histidine-Rich Protein 2/3 Deletions in Central Ethiopia, 2023

Ethiopia faces an increase in Plasmodium falciparum resistant to rapid diagnostic test (RDT) detection based on histidine-rich proteins (HRPs) because of deletions of the encoding genes (pfhrp2/3). Simultaneously, P. falciparum Kelch13 (pfk13) artemisinin partial resistance markers, particularly R622I, are common in northern and western Ethiopia. We assessed pfhrp2/3, pfk13, and Plasmodium falciparum multidrug resistance 1 (pfmdr1) variants among 220 symptomatic malaria patients presenting at health facilities in central Ethiopia in 2023. Plasmodium falciparum infection was present in 86.4%, Plasmodium vivax infection was present in 12.3%, and Plasmodium ovale infection was present in 3.6% of collected isolates. Among P. falciparum infections, the validated artemisinin partial resistance marker pfk13 R622I occurred in 1.1% (n = 2/174), and candidate marker P441L occurred in 1.7% (n = 3/174). pfhrp2, pfhrp3, and dual deletions were seen in 24.0% (n = 36/150), 78.8% (n = 118/150), and 22.7% (n = 34/150), respectively. The pfmdr1 pattern indicated reduced lumefantrine sensitivity. These data suggest that high proportions of P. falciparum infections are being missed by HRP-based RDTs, whereas pfk13 mutations are relatively rare.