Plasmodium falciparum isolate with histidine-rich protein 2 gene deletion from Nyala City, Western Sudan

Abstract

In remote areas of malaria-endemic countries, rapid diagnostic tests (RDTs) have dramatically improved parasitological confirmation of suspected malaria cases, especially when skilled microscopists are not available. This study was designed to determine the frequency of Plasmodium falciparum isolates with histidine-rich protein 2 ( pfhrp2 ) gene deletion as one of the possible factors contributing to the failure of PfHRP2-based RDTs in detecting malaria. A total of 300 blood samples were collected from several health centres in Nyala City, Western Sudan. The performance of PfHRP2-based RDTs in relation to microscopy was examined and the PCR-confirmed samples were investigated for the presence of pfhrp2 gene. A total of 113 out of 300 patients were P. falciparum positive by microscopy. Among them, 93.81% (106 out of 113) were positives by the PfHRP2 RDTs. Seven isolates were identified as false negative on the basis of the RDTs results. Only one isolate (0.9%; 1/113) potentially has pfhrp2 gene deletion. The sensitivity and specificity of PfHRP2-based RDTs were 93.81% and 100%, respectively. The results provide insights into the pfhrp2 gene deletion amongst P. falciparum population from Sudan. However, further studies with a large and systematic collection from different geographical settings across the country are needed.

Failure of rapid diagnostic tests in Plasmodium falciparum malaria cases among travelers to the UK and Ireland: Identification and characterisation of the parasites

“…For the present study, a multiplex qPCR assay — recently validated as a one-step genotyping method ( Grignard et al, 2020 ) — was used to demonstrate that false-negative RDT results were caused by the deletion of pfhrp2 / 3 in three patients. Our results confirmed that pfhrp2 / 3 -deleted parasites are in circulation in Ethiopia and Sudan, as previously reported ( Boush et al, 2020 , Girma et al, 2019 , Golassa et al, 2020 , Mussa et al, 2019 ). Interestingly, a mathematical modelling exercise ( Watson et al, 2017 ) predicted the insurgence of such parasites in African countries with low endemicity, such as Sudan, Somalia, or Ethiopia, which were the travel origins of the patients we analysed.…”

Plasmodium falciparum is evolving to escape malaria rapid diagnostic tests in Ethiopia

“…Eritrea's alarming reports of false-negative RDTs due to pfhrp2/3-deleted parasites prompted an immediate change in national diagnostic testing policy in 2016 14,38 . Recent evidence from Sudan, Djibouti and Somalia suggests that the Horn of Africa may already be heavily affected by pfhrp2/3-deleted parasites 39,40 , although results from ongoing surveillance efforts are not yet publicly available. Within affected regions in Ethiopia, we observed spatial heterogeneity in P. falciparum RDT profiles by district, with prevalence of the discordant HRP2−, Pf-LDH+ RDT profile ranging from 1 to 30% (Supplementary Table 2).…”

Emergence and evolution of Plasmodium falciparum histidine-rich protein 2 and 3 deletion mutant parasites in Ethiopia

“…Eritrea’s alarming reports of false-negative RDTs due to pfhrp2/3- deleted parasites prompted an immediate change in national diagnostic testing policy in 2016 15,36 . Recent evidence from Sudan, Djbouti, and Somalia suggests that the Horn of Africa may already be heavily affected by pfhrp2/3- deleted parasites 37,38 , though results from ongoing surveillance efforts are not yet publicly available. Within affected regions in Ethiopia, we observed spatial heterogeneity in P. falciparum RDT profiles by district, with prevalence of the discordant HRP2-, PfLDH+ RDT profile ranging from 0.9 to 30% ( Supplementary Table 2 ).…”