Misdiagnosis of imported <i>falciparum</i> malaria from African areas due to an increased prevalence of <i>pfhrp2/pfhrp3</i> gene deletion: the Djibouti case

Abstract

Following the diagnosis of a <i>falciparum</i> malaria case imported from Djibouti and not detected by a pfHRP2-based rapid diagnostic test (RDT), we investigated the prevalence of the <i>pfhrp2/pfhrp3</i>-deleted parasites in Djibouti using 378 blood samples collected between January and May 2019, from Djiboutian patients with suspected malaria. Malaria diagnosis by quantitative PCR confirmed the presence of <i>Plasmodium falciparum</i> for 20.9% (79/378) samples while RDTs did not detect HRP2 antigen in 83.5% (66/79) of these samples. Quantitative PCRs targeting the <i>pfhrp2/pfhrp3</i> genes confirmed the absence of both genes for 86.5% of <i>P. falciparum</i> strains. The very large number (86.5%) of f<i>alciparum</i> parasites lacking the <i>pfhrp2/pfhrp3</i> genes observed in this study, now justifies the use of non-HRP2 alternative RDTs in Djibouti. In this area and in most countries where HRP2-based RDTs constitute the main arsenal for <i>falciparum</i> malaria diagnosis, it is important to implement a systematic surveillance and to inform biologists and clinicians about the risk of malaria misdiagnosis. Further investigations are needed to better understand the mechanism of selection and diffusion of the <i>pfhrp2/pfhrp3</i>-deleted parasites.