Modelling the drivers of the spread of <i>Plasmodium falciparum hrp2</i> gene deletions in sub-Saharan Africa.

Abstract

Rapid diagnostic tests (RDTs) have transformed malaria diagnosis. The most prevalent <i>P. falciparum</i> RDTs detect histidine-rich protein 2 (PfHRP2). However, <i>pfhrp2</i> gene deletions yielding false-negative RDTs, first reported in South America in 2010, have been confirmed in Africa and Asia. We developed a mathematical model to explore the potential for RDT-led diagnosis to drive selection of <i>pfhrp2</i>-deleted parasites. Low malaria prevalence and high frequencies of people seeking treatment resulted in the greatest selection pressure. Calibrating our model against confirmed <i>pfhrp2</i>-deletions in the Democratic Republic of Congo, we estimate a starting frequency of 6% <i>pfhrp2</i>-deletion prior to RDT introduction. Furthermore, the patterns observed necessitate a degree of selection driven by the introduction of PfHRP2-based RDT-guided treatment. Combining this with parasite prevalence and treatment coverage estimates, we map the model-predicted spread of <i>pfhrp2</i>-deletion, and identify the geographic regions in which surveillance for <i>pfhrp2</i>-deletion should be prioritised.