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Temporal evaluation of diagnostic resistance (pfhrp2/3 gene deletions) in Ethiopia: 2007 - 2021 (2023)

Undergraduate: Halle Evans


Faculty Advisor: Jonathan Parr
Department: Institute for Global Health and Infectious Diseases


Malaria is a major cause of morbidity and mortality worldwide. In Ethiopia alone, 68% of the population is still at risk of contracting the disease. Plasmodium falciparum is the most common malaria parasite. Ethiopia’s National Malaria Control Program (NMCP) has taken direct action to actively reduce malaria infections and has set goals to reach country-wide elimination by 2030. Drug-resistant infections and the failure of widely used rapid diagnostic testing (RDTs) may be a challenge for malaria elimination efforts.
RDTs have been a primary intervention used by malaria prevention programs. These tests function by targeting the histidine-rich proteins in Plasmodium falciparum parasites (pfhrp2/pfhrp3). However, increasing evidence demonstrates that some Plasmodium falciparum parasites no longer express histidine-rich protein 2 (HRP2) and histidine-rich protein 3 (HRP3), due to deletions in the pfhrp2 and/ or pfhrp3 genes. These deletions are detrimental as they lead to false-negative results. This study aimed to determine the prevalence of pfhrp2/3 deletions at ten sites across Ethiopia which was part of a larger Therapeutic Efficacy Study. The results were further analyzed across two decades and various demographics (i.e. age and sex). We concluded that there was a notable expansion of pfhrp2-/3- and pfhrp2+/pfhrp3- gene deletions across North Central Ethiopia between pre-2019 and post-2019 dates. Across all sites, deletion rates increased from 2.7% pfhrp2-/3- and 28.6% pfhrp2+/3- in pre-2019 sites to 8.44% pfhrp2-/3- and 37% pfhrp2+/3- in post-2019 sites. The data supports recommendations for changing pfhrp2/3-based rapid diagnostic methods that are used by the NMCP.

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