Deletions of pfhrp2 and pfhrp3 genes of Plasmodium falciparum from Honduras, Guatemala and Nicaragua

Fontecha, Gustavo; Mejía, Rosa Elena; Banegas, Engels; Adé, Maria Paz; Mendoza, L; Ortiz, Bryan; Sabillón, Isaac; Alvarado, Gerardo Rodríguez; Matamoros, Gabriela; Pinto, Alejandra

doi:10.1186/s12936-018-2470-7

Cited by 27 publications

(26 citation statements)

References 44 publications

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“…Although earlier studies in Honduras only reported pfhrp3 and not pfhrp2 deletions, recent reports have documented extensive deletions of both genes [ 39 , 54 ]. The frequency of parasites lacking pfhrp2 and pfhrp3 in South and Central Americas has increased over time, and there is a need to evaluate the selective pressures that favor the survival of parasites that lack these genes [ 41 ].…”

Section: Resultsmentioning

confidence: 99%

Plasmodium falciparum Histidine-Rich Protein 2 and 3 Gene Deletions and Their Implications in Malaria Control

et al. 2020

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Malaria remains the biggest threat to public health, especially among pregnant women and young children in sub-Saharan Africa. Prompt and accurate diagnosis is critical for effective case management and detection of drug resistance. Conventionally, microscopy and rapid diagnostic tests (RDTs) are the tools of choice for malaria diagnosis. RDTs are simple to use and have been extensively used in the diagnosis of malaria among travelers to malaria-endemic regions, routine case management, and surveillance studies. Most RDTs target the histidine-rich protein (PfHRP) which is exclusively found in Plasmodium falciparum and a metabolic enzyme Plasmodium lactate dehydrogenase (pLDH) which is common among all Plasmodium species. Other RDTs incorporate the enzyme aldolase that is produced by all Plasmodium species. Recently, studies have reported false-negative RDTs primarily due to the deletion of the histidine-rich protein (pfhrp2 and pfhrp3) genes in field isolates of P. falciparum. Herein, we review published literature to establish pfhrp2/pfhrp3 deletions, the extent of these deletions in different geographical regions, and the implication in malaria control. We searched for publications on pfhrp2/pfhrp3 deletions and retrieved all publications that reported on this subject. Overall, 20 publications reported on pfhrp2/pfhrp3 deletions, and most of these studies were done in Central and South America, with very few in Asia and Africa. The few studies in Africa that reported on the occurrence of pfhrp2/pfhrp3 deletions rarely evaluated deletions on the flanking genes. More studies are required to evaluate the existence and extent of these gene deletions, whose presence may lead to delayed or missed treatment. This information will guide appropriate diagnostic approaches in the respective areas.

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Section: Resultsmentioning

confidence: 99%

Plasmodium falciparum Histidine-Rich Protein 2 and 3 Gene Deletions and Their Implications in Malaria Control

et al. 2020

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“…There was a statistically signi cant difference in pfhrp2 gene deletion prevalence in Bandundu health zone compared to Kikwit-Nord and Kikwit-Sud health zones (p = 0.012). Variations in pfhrp2 gene deletion status within regions and countries have been previously reported and depend on several factors including level of transmission and magnitude of PfHRP2-RDT use (10,12,20,52). Further analysis of population genetics may clarify this nding.…”

Section: Discussionmentioning

confidence: 88%

Prevalence of Plasmodium falciparum Isolates Lacking the Histidine Rich Protein 2 Gene Among Symptomatic Malaria Patients in Kwilu Province, DR. Congo.

Munyeku¹,

Musaka²,

Ernest³

et al. 2020

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BackgroundMalaria rapid diagnostic tests have become a primary and critical tool for malaria diagnosis in malaria-endemic countries where PfHRP2-based RDTs are widely used. However, in the last decade, the accuracy of PfHRP2-based RDTs has been challenged by the emergence of P. falciparum strains harbouring deletions of the pfhrp2 gene, resulting in false-negative results. In DR. Congo, little is known about the prevalence of the pfhrp2 gene deletion among P. falciparum isolates infecting symptomatic patients, especially in low to moderate transmission areas where pfhrp2 deletion parasites are assumed to emerge and spread. Here we determine the local prevalence and factors associated with pfhrp2 gene deletions among symptomatic malaria patients in the Kwilu province of the Democratic Republic of Congo, a low to moderate malaria transmission area.MethodsWe used secondary data from a prospective health facility-based cross-sectional study conducted on 684 individuals of all ages, seeking healthcare with symptoms suggestive of malaria from October to December 2018 in 34 randomly selected health facilities. Sociodemographic, malaria prevention and treatment practices, and clinical variables were collected using a pre-tested structured questionnaire. Patients’ medical records were used to collect additional clinical data. Blood was collected for microscopy, PfHRP2-RDT, and spotted onto Whatman filter paper for downstream genetic analysis. Genomic DNA was extracted and used to perform PCR assays for the detection and confirmation of pfhrp2 gene deletions. Data were entered and analysed using STATA15. Fischer’s exact and the Kruskal-Wallis tests were applied to look for associations between exposures and the pfhrp2 gene deletion with a level of statistical significance set at p < 0.05. ResultsThe overall prevalence of the pfhrp2 gene deletion was 9.2% (95% CI 6.7% – 12.1%). The deletion of the pfhrp2 gene was associated with health zone of origin (p=0.012) and age (p=0.019). Among false-negative PfHRP2-RDT results, only 9.9% were due to pfhrp2 gene deletion.ConclusionP. falciparum isolates with pfhrp2 gene deletions are relatively common among symptomatic patients in Kwilu province. Further investigations are needed to provide enough evidence for policy change. Meanwhile, the use of RDTs targeting PfHRP2 and pLDH antigens could limit the spread of deleted isolates.

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“…Other possible reasons for the variation in the number of amplicons obtained after exon 2 and exon 1-2 PCR is the possibility of polymorphisms in the 3' end(s) of the primer binding sites of exon 2 which are absent in the exon 1-2 region as well as partial degradation of the DNA template as has been previously suggested [37,38]. Despite the possibility of false negative Pfhrp 2 exon 2 PCR results, some studies have identified samples with higher frequencies of deletions in Pfhrp 2 exon 1-2 than Pfhrp 2 exon 2 [39]. Parasites with intact Pfhrp 3 genes have been found to compensate for the absence of Pfhrp 2 exon 2 in a parasite, especially at high parasite densities and result in a positive PfHRP 2 based malaria RDT test due to the cross-reactivity of PfHRP 3 antigen with the PfHRP 2 antibodies on the RDT kits [9,40].…”

Section: Plos Onementioning

confidence: 99%

Contribution of P. falciparum parasites with Pfhrp 2 gene deletions to false negative PfHRP 2 based malaria RDT results in Ghana: A nationwide study of symptomatic malaria patients

et al. 2020

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Introduction False-negative malaria rapid diagnostic test (RDT) results amongst symptomatic malaria patients are detrimental as they could lead to ineffective malaria case management. This study determined the nationwide contribution of parasites with Pfhrp2 and Pfhrp 3 gene deletions to false negative malaria RDT results in Ghana. Methods This was a cross sectional study where whole blood (~2 ml) was collected from patients presenting with malaria symptoms at 100 health facilities in all the regions in Ghana from May to August 2018. An aliquot of the blood was used to prepare thin and thick blood smears, filter paper blood spots (DBS) and spot a PfHRP 2 RDT kit. The remaining blood was separated into plasma and blood cells and stored at-20˚C. Plasmodium parasite density and species identity was estimated from the blood smears. Plasmodium falciparum specific 18S rRNA PCR, merozoite surface protein (msp 1) and glutamate rich protein (glurp) gene PCR were used to identify P. falciparum positive samples, which were subjected to Pfhrp 2/3 exon1-2 and exon2 genotyping. Results Of the 2,860 microscopically P. falciparum positive patients analyzed, 134 (4.69%) had false negative P. falciparum specific RDT results. Samples for PCR analysis was available for 127 of the false negative patients, and the analysis identified 116 (91.3%) as positive for

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Deletions of pfhrp2 and pfhrp3 genes of Plasmodium falciparum from Honduras, Guatemala and Nicaragua

Cited by 27 publications

References 44 publications

Plasmodium falciparum Histidine-Rich Protein 2 and 3 Gene Deletions and Their Implications in Malaria Control

Plasmodium falciparum Histidine-Rich Protein 2 and 3 Gene Deletions and Their Implications in Malaria Control

Prevalence of Plasmodium falciparum Isolates Lacking the Histidine Rich Protein 2 Gene Among Symptomatic Malaria Patients in Kwilu Province, DR. Congo.

Contribution of P. falciparum parasites with Pfhrp 2 gene deletions to false negative PfHRP 2 based malaria RDT results in Ghana: A nationwide study of symptomatic malaria patients

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