Plasmodium falciparum histidine-rich protein 2/3 gene deletions and repeat motifs in Chhattisgarh, India (2017-2018)

Abstract

Background: Rapid diagnostic tests (RDTs) are vital for malaria diagnosis, especially in resource-limited areas. RDTs targeting histidine-rich protein 2 (PfHRP2) and its structural homologue PfHRP3 are commonly used for detecting Plasmodium falciparum. However, genetic deletions in these proteins can affect test accuracy. This study aims to examine the gene deletions and sequence variation in the Pfhrp2 and Pfhrp3 genes in P. falciparum isolates from Chhattisgarh, India, and assess their correlation with RDT reactivity.

Methods: A total of 264 microscopically confirmed P. falciparumpositive samples from Chhattisgarh were analyzed for deletions in the Pfhrp2 and Pfhrp3 genes. Nucleotide sequences were obtained for the Pfhrp2 (n=101) and Pfhrp3 (n=95) genes. The sequence data were analyzed for repeat motifs and correlated with the RDT performance, especially at low parasite densities.

Results: The deletion rates for Pfhrp2 and Pfhrp3 were found to be 3.8% and 14%, respectively. The Pfhrp2 gene exhibited 15 distinct repeat motifs, while the Pfhrp3 gene showed 10 repeat motifs. No significant correlation was observed between variations in repeat types 2 and 7 of Pfhrp2 and the commercial RDT performance, particularly at low parasite densities.

Conclusions: The results indicate that the deletion rates and sequence diversity of Pfhrp2 and Pfhrp3 in Chhattisgarh are below the WHO threshold of 5% for a policy change regarding Pfhrp2 gene deletion. Sequence diversity does not appear to compromise the performance of current PfHRP2-based RDTs. However, a larger-scale study encompassing other endemic regions of India is recommended for a more comprehensive understanding of the impact on RDT efficacy over time.

Keywords: Pfhrp2; Pfhrp3; gene deletion; malaria; rapid diagnostic test.