High prevalence of pfhrp2 and pfhrp3 gene deletions and major threat to malaria control programs in Ethiopia

Background Rapiddiagnostictests (RDTs) targeting pf histidine rich protein2 ( pf HRP2) are widely used for diagnosis of Plasmodium falciparum infections in resource-limited malaria endemic countries. However, test results are affected by deletions of the pfhrp2 , pfhrp3 and flanking genes and associated negative results from rapid diagnostic devices were previously reported. Therefore, the aim of this study was to reveal the existing genetic profile of Pfhrp 2 and pfhrp 3 genes of P. falciparum infected patients in northwestern Ethiopia. Methods A total number of 302 blood samples were collected from children at Aykel, Negade Bahir, and Sanja health centers in northwestern Ethiopia. Thirty-three (10.9%) samples tested positive for P. falciparum malaria. The pfhrp2 , pfhrp3 and flanking genes (MAL7P1_228 and MAL7P1_230 for pfhrp2 , and MAL13P1_475 and MAL13P1_485 for pfhrp3 ) were amplified using standard nested-PCR. Results Pfhrp2 and both of its flanking genes were found to be present in 12 (36.4%) out of the 33 samples. Twenty-one (63.6%) samples tested negative for the pfhrp2 gene and 19 samples (57.6%) tested positive for at least one of the flanking genes. Five (15.2%) samples gave positive results for the pfhrp3 gene and both of its flanking genes, whereas 16 (48.5%) tested negative for all three. Conclusions Our study provides widespread deletions in the pfhrp2 and pfhrp3 genes in Ethiopia thereby confirming anecdotal reports of diagnostic failure with HRP2-based rapid diagnostic tests in the region. The implications of our finding for the current diagnostic paradigm, which relies on the detection of P. falciparum by HRP2-based rapid diagnostic tests in remote areas, may need rethinking.