Plasmodium falciparum Histidine-Rich Protein 2 and 3 Gene Deletions in Strains from Nigeria, Sudan, and South Sudan

Abstract

Deletion of histidine-rich protein genes pfhrp2/3 in Plasmodium falciparum causes infections to go undetected by HRP2-based malaria rapid diagnostic tests. We analyzed P. falciparum malaria cases imported to Australia (n = 210, collected 2010–2018) for their pfhrp2/3 status. We detected gene deletions in patients from 12 of 25 countries. We found >10% pfhrp2- deletion levels in those from Nigeria (13.3%, n = 30), Sudan (11.2%, n = 39), and South Sudan (17.7%, n = 17) and low levels of pfhrp3 deletion from Sudan (3.6%) and South Sudan (5.9%). No parasites with pfhrp2/3 double deletions were detected. Microsatellite typing of parasites from Nigeria, Sudan, and South Sudan revealed low relatedness among gene-deleted parasites, indicating independent emergences. The gene deletion proportions signify a risk of false-negative HRP2-RDT results. This study’s findings warrant surveillance to determine whether the prevalence of gene-deleted parasites justifies switching malaria rapid diagnostic tests in Nigeria, Sudan, and South Sudan.

Epidemiology of mutant Plasmodium falciparum parasites lacking histidine-rich protein 2/3 genes in Eritrea 2 years after switching from HRP2-based RDTs

“…The prevalence estimates of hrp2 and hrp3 deletions determined for Gash Barka zone in the current survey, 6.4% and 37.9%, was also lower than the corresponding prevalence of 10.8% and 47.7% reported for the same zone in a set of samples collected in 2013–2014 7 . Furthermore, the current prevalence estimates of hrp2 -deleted parasites in Eritrea (9.4%) appears to be lower than that recently reported from areas in neighbouring countries of Ethiopia (50%, 100%) 8 , 9 , Djibouti (86.5%) 10 , and amongst samples tested in returning travellers from Sudan (11.2%) and South Sudan (17.7%) 11 . This reduction in prevalence may reflect a genuine downward trend following the removal of HRP2-based RDTs for case management in Eritrea, but may also result from different sampling, different levels of genetic diversity and different laboratory methods used.…”

High-throughput Plasmodium falciparum hrp2 and hrp3 gene deletion typing by digital PCR to monitor malaria rapid diagnostic test efficacy

“…A single hrp2 deletion was found in southwestern Ethiopia. This is in stark contrast to very high levels of deletion in western Ethiopia ( Alemayehu et al, 2021 ), Eritrea ( Berhane et al, 2018 ), and Sudan ( Prosser et al, 2021 ). The results corroborate the need for studies assessing hrp2 deletion and selection of diagnostic tools at subnational level.…”

Plasmodium falciparum pfhrp2 and pfhrp3 Gene Deletions in Malaria-Hyperendemic Region, South Sudan

“…Malaria is a leading cause of illness and death in South Sudan ( 3 ), where insufficient malaria prevention activities and a lack of access to healthcare combine dangerously. Despite the geographic and strategic importance of South Sudan in East and Central Africa, the only evidence of pfhrp2 and pfhrp3 deletions from the country come from a single report confirming their presence in 3 travelers to Australia ( 4 ). Accurate estimates of deletions could help responders delineate factors associated with deletions, predict future RDT needs, and clarify dynamics of false negativity rates in South Sudan overall.…”