Parasite Population Dynamics Shape pfhrp2 and pfhrp3 Deletion Patterns in the Peruvian Amazon

Area of Science:

• Genomics and Parasitology
• Evolutionary Biology
• Malaria Diagnostics

Background:

• Increasing prevalence of Plasmodium falciparum parasites with deletions in pfhrp2 and pfhrp3 genes in the Peruvian Amazon since 2012.
• These gene deletions are linked to rapid diagnostic test (RDT) failure.
• Unclear evolutionary drivers for this phenomenon, as HRP2-based RDTs were not widely used in the region.

Purpose of the Study:

• To characterize the P. falciparum population in Peru from 2006-2018.
• To identify genomic regions exhibiting evidence of recent positive selection.
• To understand the evolutionary factors driving the predominance of parasites with pfhrp2/3 deletions.

Main Methods:

• PCR genotyping of 159 P. falciparum samples from the Loreto region.
• Whole genome sequencing (WGS) of 42 PCR-genotyped samples, integrated with 60 existing genome data.
• Analysis of population structure complexity and identification of positive selection signals.

Main Results:

• 60% of samples showed double pfhrp2/3 deletions, 22% had no deletions, and 16% had single pfhrp2 deletion.
• Significant reduction in parasite population structure complexity from 2006-2011 to 2012-2018, suggesting a bottleneck event.
• No evidence of positive selection on pfhrp2/3 genes; observed expansion attributed to genetic drift.

Conclusions:

• The spread of pfhrp2/3 deletions is likely driven by genetic drift and a population bottleneck, not positive selection.
• The observed phenotype (RDT evasion) evolved differently than anticipated by positive selection forces.
• Advocates for continuous surveillance using untargeted genomic approaches like WGS to monitor adaptations affecting malaria control.