Molecular surveillance of pfhrp2 and pfhrp3 deletions in Plasmodium falciparum isolates from Mozambique

Abstract

BackgroundMalaria programmes use Plasmodium falciparum histidine-rich protein-2 (PfHRP2) based rapid diagnostic tests (RDTs) for malaria diagnosis. The deletion of this target antigen could potentially lead to misdiagnosis, delayed treatment and continuation of active transmission.Methods Plasmodium falciparum isolates (n = 1162) collected in Southern Mozambique were assessed by RDTs, microscopy and/or 18SrRNA qPCR. pfhrp2 and pfhrp3 deletions were investigated in isolates from individuals who were negative by RDT but positive by microscopy and/or qPCR (n = 69) using gene-specific PCRs, with kelch13 PCR as the parasite DNA control.ResultsLack of pfhrp2 PCR amplification was observed in one of the 69 isolates subjected to molecular analysis [1.45% (95% CI 0.3–7.8%)].ConclusionsThe low prevalence of pfhrp2 deletions suggests that RDTs will detect the vast majority of the P. falciparum infections. Nevertheless, active surveillance for changing deletion frequencies is required.

Global analysis of Plasmodium falciparum histidine-rich protein-2 (pfhrp2) and pfhrp3 gene deletions using whole-genome sequencing data and meta-analysis

“…Of these, six studies were excluded from the analysis, because they did not evaluate pfhrp2 and pfhrp3 deletions in the field (Ramutton et al, 2012;Mendoza et al, 2013;Das et al, 2018;Parr et al, 2018) or referred to case studies (Houzé et al, 2011;Johora et al, 2017). Other six studies determined the combined genotypes of pfhrp2 and pfhrp3 status only on a subset of samples with negative RDT result (Kumar et al, 2013;Wurtz et al, 2013;Li et al, 2015;Bharti et al, 2016;Parr et al, 2016;Gupta et al, 2017). These studies were discarded from the analysis, because the respective data were intrinsically incomplete and biased by study design.…”

Prevalence of Plasmodium falciparum field isolates with deletions in histidine-rich protein 2 and 3 genes in context with sub-Saharan Africa and India: a systematic review and meta-analysis

“…4). Regarding pfhrp3 deletion prevalence in Africa, highest and lowest values were 82 and 1%, respectively [30,35]. Pooled prevalence of parasites with deletions in pfhrp3 gene was 16% (95% CI 10-23%) and 4% (95% CI 1-7%) in Africa and India, respectively (Fig.…”

“…Eight studies were excluded from the analysis on the proportion of P. falciparum isolates with deletions in pfhrp2/3 genes among false negative PfHRP2-based RDT results because of small sample size and the topic not being addressed. Sixteen and 10 studies were included in the meta-analysis to determine the prevalence of deletions in pfhrp2/3 genes and their proportion among false negative PfHRP2-based RDT results, respectively [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] (Fig. 1, Additional file 2).…”

“…The 16 studies from 13 SSA countries: Mali, Senegal, Ghana, Kenya, Mozambique, Rwanda, Zambia, Eritrea, Eswatini (Swaziland), Nigeria, Sudan, Madagascar and Democratic Republic of Congo, were conducted locally with one exception which was conducted at national level ( Table 1) [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44]. Three studies found deletions in pfhrp2 in Uganda, Gambia and Tanzania [45][46][47], but these were excluded from the systematic review (Additional file 5).…”

Extensive Deletion and Sequence Variation of Plasmodium Falciparum Histidine Rich Protein 2/3 (pfhrp2/3) Genes in Ethiopia: Implication for RDT-based Malaria Diagnosis and Control

“…Similarly, a study on P. falciparum outbreak on the northern Paci c coast of Peru (2010-2012) using 54 samples showed all 100% samples lacked the pfhrp2 gene [11]. Following this, several countries have reported occurrence of pfhrp2 and pfhrp3 gene deletions [9,[12][13][14][15][16][17][18][19][20][21]. For highly malaria endemic Africa, the prevalence of the deletion from recent report have generally been low or absent.…”