Project Details

Early Career

Status: Funded - Closed

Evolution and spread of pfhrp2-deleted Plasmodium falciparum in the Democratic Republic of the Congo

Jonathan Parr, MD, MPH

Summary

BACKGROUND: Malaria killed over 300,000 children under 5 years of age in 2015, with 97% of these deaths occurring in sub-Saharan Africa. One of the cornerstones of modern malaria programs is the use of rapid diagnostic tests (RDTs) instead of traditional microscopy for diagnosis. Recently, false-negative RDT results have been reported in individuals infected with Plasmodium falciparum parasites harboring a deletion of the the pfhrp2 gene.

GAP: It is unknown whether this mutation is evolving and spreading within communities in sub-Saharan Africa.

HYPOTHESIS: Use of RDTs as indicators for treatment is exerting evolutionary pressure favoring the spread of “stealth” parasites, resistant to detection by currently used RDTs.

METHODS: We genotyped parasites using PCR and attempted whole-genome sequencing on parasites identified among subjects in the Democratic Republic of the Congo (DRC).

RESULTS: Initial attempts to whole-genome sequence parasites were successful using dried blood spot (DBS) samples from symptomatic subjects with high parasite densities but failed in DBS samples collected from asymptomatic subjects with lower parasite densities. False-negative RDT results due to parasites with deletions of the pfhrp2 and pfhrp3 genes were not identified in a 2017-18 survey of subjects presenting to DRC government health facilities with symptomatic malaria.

IMPACT: The absence of parasites with these gene deletions among people with symptomatic malaria in this survey supports the continued use of PfHRP2-based RDTs in the DRC. However, reports of pfhrp2/3 gene deletions in the region emphasize the need for ongoing surveillance.

Publications:

Parr JB, Anderson O, Juliano JJ, Meshnick SR. Streamlined, PCR-based testing for pfhrp2- and pfhrp3-negative Plasmodium falciparum. Malar J. 2018 Apr 2;17(1):137. doi: 10.1186/s12936-018-2287-4.