Artemisinin-Resistant and HRP-Negative Malaria Parasites in Africa

This NEJM Perspective outlines emerging threats to malaria control in sub-Saharan Africa, particularly artemisinin-resistant Plasmodium falciparum and hrp2/hrp3 gene deletions that compromise rapid diagnostic test (RDT) sensitivity. Data from Eritrea highlight co-occurrence of resistance-linked Pfkelch13 R622I mutation and HRP-negative strains. Artemisinin resistance manifested as delayed parasite clearance (2.4% parasitemia on day 3), rising from 0.4% in 2016 to 4.2% in 2019. R622I mutation prevalence doubled in 3 years (8.6% → 21.0%), with a strong association between R622I and hrp2 deletion (69.2% vs. 22.5%). Genomic evidence suggests independent African emergence. These dual mutations risk both treatment failure and missed diagnosis, especially in regions reliant on HRP-based RDTs. Eritrea’s shift to LDH-based RDTs exemplifies adaptive response, but wider deployment is hindered by cost and supply limitations. The author calls for enhanced mutation surveillance, RDT reassessment, and development of next-generation antimalarials to preempt widespread therapeutic collapse.

This NEJM Perspective outlines emerging threats to malaria control in sub-Saharan Africa, particularly artemisinin-resistant Plasmodium falciparum and hrp2/hrp3 gene deletions that compromise rapid diagnostic test (RDT) sensitivity. Data from Eritrea highlight co-occurrence of resistance-linked Pfkelch13 R622I mutation and HRP-negative strains. Artemisinin resistance manifested as delayed parasite clearance (2.4% parasitemia on day 3), rising from 0.4% in 2016 to 4.2% in 2019. R622I mutation prevalence doubled in 3 years (8.6% → 21.0%), with a strong association between R622I and hrp2 deletion (69.2% vs. 22.5%). Genomic evidence suggests independent African emergence. These dual mutations risk both treatment failure and missed diagnosis, especially in regions reliant on HRP-based RDTs. Eritrea’s shift to LDH-based RDTs exemplifies adaptive response, but wider deployment is hindered by cost and supply limitations. The author calls for enhanced mutation surveillance, RDT reassessment, and development of next-generation antimalarials to preempt widespread therapeutic collapse.