Spatial and genetic dynamics of Plasmodium falciparum histidine-rich protein2 in sub-Saharan Africa

Malaria rapid diagnosis tests (mRDTs) detecting Plasmodium falciparum histidine-rich protein 2 (Pfhrp2) are the most widely adopted diagnostic tool in malaria-endemic areas. However, extensive polymorphisms in Pfhrp2 could modify Pfhrp2 epitopes, rendering it undetectable by Pfhrp2-based mRDTs. This study investigates the spatial distribution and population dynamics of Pfhrp2 in sub-Saharan Africa (sSA).

Pfhrp2 sequences (215) were retrieved from public repositories and analysed with MAFFT v7, DnaSP, and various packages in R. We computed genetic diversity metrics, neutrality tests, differentiation, haplotype networks, and phylogenetic analyses.

Varying degrees of insertion-deletion with about 10 polymorphic repeat motif types that varied in frequencies were observed. Repeat types 2, 4 and 7 were the most prevalent types. Baker model prediction with mRDTs monoclonal antibodies indicated the prevalence of highly detected Pfhrp2 isolates in sSA. Significant diversity was recorded across the sSA region (Hd = 1; θw = 0.09585). The single most dominant haplotype was conserved across countries, and very low differentiation (FST: 0.00-0.04) suggested gene flow between countries.

Our findings imply that the dominant evolutionary pressure in sSA is promoting the parasite's biological fitness and the diversity of Pfhrp2.However, the impact of this genetic diversity on diagnostic performance was not assessed as we could not obtain relevant mRDT test data for each country.