Prevalence of Plasmodium falciparum lacking histidine-rich proteins 2 and 3: a systematic review

To calculate prevalence estimates and evaluate the quality of studies reporting Plasmodium falciparum lacking histidine-rich proteins 2 and 3, to inform an international response plan.

We searched five online databases, without language restriction, for articles reporting original data on Plasmodium falciparum-infected patients with deletions of the pfhrp2 and/or pfhrp3 genes (pfhrp2/3). We calculated prevalence estimates of pfhrp2/3 deletions and mapped the data by country. The denominator was all P. falciparum-positive samples testing positive by microscopy and confirmed positive by species-specific polymerase chain reaction testing (PCR). If microscopy was not performed, we used the number of samples based on a different diagnostic method or PCR alone. We scored studies for risk of bias and the quality of laboratory methods using a standardized scoring system.

A total of 38 articles reporting 55 studies from 32 countries and one territory worldwide were included in the review. We found considerable heterogeneity in the populations studied, methods used and estimated prevalence of P. falciparum parasites with pfhrp2/3 deletions. The derived prevalence of pfhrp2 deletions ranged from 0% to 100%, including focal areas in South America and Africa. Only three studies (5%) fulfilled all seven criteria for study quality.

The lack of representative surveys or consistency in study design impairs evaluations of the risk of false-negative results in malaria diagnosis due to pfhrp2/3 deletions. Accurate mapping and strengthened monitoring of the prevalence of pfhrp2/3 deletions is needed, along with harmonized methods that facilitate comparisons across studies.