Prevalence of pfhrp2 and pfhrp3 gene deletions in Puerto Lempira, Honduras

Abdallah, Joseph F.; Okoth, Sheila; Fontecha, Gustavo; Torres, Rosa Elena Mejía; Banegas, Engels; Matute, María Luisa; Bucheli, Sandra Tamara Mancero; Goldman, Ira F.; Oliveira, Alexandre Macedo de; Barnwell, John W.; Udhayakumar, Venkatachalam

doi:10.1186/s12936-014-0537-7

Cited by 76 publications

(116 citation statements)

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“…When comparing the results of this study with those reported previously [18], it is noteworthy that the 4 flanking regions, both of pfhrp2 and pfhrp3 now reveal a high number of deletions, which would support the hypothesis of the rapid appearance of deletions in these genetic regions. Nevertheless, one of the most interesting results of this study is the finding of 26 (20.3%) isolates with a double deletion ( pfhrp2 / pfhrp3 negative for exon 1–2).…”

Section: Discussionsupporting

confidence: 86%

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

Fontecha

Mejía²,

Banegas³

et al. 2018

Malar J

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BackgroundMalaria remains a public health problem in some countries of Central America. Rapid diagnostic tests (RDTs) are one of the most useful tools to assist in the diagnosis of malaria in remote areas. Since its introduction, a wide variety of RDTs have been developed for the detection of different parasite antigens. PfHRP2 is the most targeted antigen for the detection of Plasmodium falciparum infections. Genetic mutations and gene deletions are important factors influencing or affecting the performance of rapid diagnostic tests.MethodsIn order to demonstrate the presence or absence of the pfhrp2 and pfhrp3 genes and their flanking regions, a total of 128 blood samples from patients with P. falciparum infection from three Central American countries were analysed through nested or semi-nested PCR approaches.ResultsIn total, 25.8 and 91.4% of the isolates lacked the region located between exon 1 and exon 2 of pfhrp2 and pfhrp3 genes, respectively. Parasites from the three countries showed deletions of one or both genes. The highest proportion of pfhrp2 deletions was found in Nicaragua while the isolates from Guatemala revealed the lowest number of pfhrp2 deletions. Parasites collected from Honduras showed the highest proportion of phfrp3 absence (96.2%). Twenty-one percent of isolates were double negative mutants for the exon 1–2 segment of both genes, and 6.3% of isolates lacked the full-length coding region of both genes.ConclusionsThis study provides molecular evidence of the existence of P. falciparum isolates lacking the pfhrp2 and pfhrp3 genes, and their flanking regions, in Honduras, Guatemala and Nicaragua. This finding could hinder progress in the control and elimination of malaria in Central America. Continuous evaluation of RDTs and molecular surveillance would be recommended.

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Section: Discussionsupporting

confidence: 86%

“…2 [18]. Primers’ list, sequences, annealing temperatures, and amplicon sizes are detailed in Table 1.…”

Section: Methodsmentioning

confidence: 99%

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

Fontecha

Mejía²,

Banegas³

et al. 2018

Malar J

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“…However, this approach may be compromised by the emergence of P. falciparum parasites with deleted pfhrp2. South America was the first region to report the occurrence of false negative RDT results due to this gene deletion (Gamboa et al, 2010;Akinyi et al, 2013;Abdallah et al, 2015;Akinyi Okoth et al, 2015;Murillo Solano et al, 2015;Rachid Viana et al, 2017). Similar evidence was followed by more recent studies from Africa (Dolo et al, 2012;Wurtz et al, 2013;Parr et al, 2016;Beshir et al, 2017) and Asia (Kumar et al, 2013;Li et al, 2015;Bharti et al, 2016).…”

Section: Introductionmentioning

confidence: 65%

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

Sepúlveda

Phelan

Benavente

et al. 2018

Infection, Genetics and Evolution

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Many rapid diagnostic tests (RDT) used on suspected malaria cases are based on the detection of the protein encoded by the Plasmodium falciparum histidine-rich protein-2 (pfhrp2) gene, which shares a high sequence homology with pfhrp3 in the 3D7 reference genome. Parasite isolates showing pfhrp2 and pfhrp3 gene deletions have been emerging over the years, but a comprehensive genetic analysis of these variants is still lacking. With this purpose, genomic data from experimental P. falciparum genetic crosses between different laboratory lines (3D7, HB3, DD2, 7G8 and GB4) were first analysed (n = 98). The frequency of pfhrp2 deletions was consistent with a Mendelian prediction in HB3 × DD2 (56.7%; 95%CI = (39.5%-72.9%)). Moreover, the pfhrp2 and pfhrp3 deletions segregated independently of each other in the same genetic cross. Analysis of 3D7 × HB3 and 7G8 × GB4 estimated the probability of spontaneously generating a pfhrp2 deletion during sexual recombination to be up to 6.2%. Next, whole genome sequence data from 1970 P. falciparum isolates collected globally were analysed. Nine samples displayed depth of coverage consistent with pfhrp2 deletions (0.5%), but the corresponding split-read analysis could not confirm deletions in seven of these samples. Twenty-eight isolates had evidence of pfhrp3 deletions (1.4%), which are widespread in Southeast Asia. Finally, a meta-analysis of published data revealed a positive mean association between the frequencies of pfhrp2 and pfhrp3 deletions in Africa and South America. This result suggested a shared selective pressure acting on these genetic variants. In conclusion, evidence of genetic selection on both pfhrp2 and pfhrp3 deletions was presented, but experimental crosses do not provide evidence of a fitness cost of these variants. Further work is urgently needed to accurately determine the prevalence and the degree of association between these genetic variants, and the respective impact on diagnostic accuracy of many in-use RDT.

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“…The presence of Pfhrp2 and Pfhrp3 genes was evaluated by PCR amplification. Pfhrp2 and Pfhrp3 genes were amplified using a nested PCR approach as previously reported 33,70 . Briefly, thirty randomly selected 18S PCR amplification positive samples were amplified using primers spanning fragments of exons 1 and 2 and intervening intron for Pfhrp2 and 3.…”

Section: Active Malaria Case Detection: Asymptomatic Malaria At Bothmentioning

confidence: 99%

Spatio-temporal dynamics of Plasmodium falciparum transmission within a spatial unit on the Colombian Pacific Coast

Knudson

González-Casabianca

Feged-Rivadeneira

et al. 2020

Sci Rep

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As malaria control programmes concentrate their efforts towards malaria elimination a better understanding of malaria transmission patterns at fine spatial resolution units becomes necessary. Defining spatial units that consider transmission heterogeneity, human movement and migration will help to set up achievable malaria elimination milestones and guide the creation of efficient operational administrative control units. Using a combination of genetic and epidemiological data we defined a malaria transmission unit as the area contributing 95% of malaria cases diagnosed at the catchment facility located in the town of Guapi in the South Pacific Coast of Colombia. We provide data showing that P. falciparum malaria transmission is heterogeneous in time and space and analysed, using topological data analysis, the spatial connectivity, at the micro epidemiological level, between parasite populations circulating within the unit. To illustrate the necessity to evaluate the efficacy of malaria control measures within the transmission unit in order to increase the efficiency of the malaria control effort, we provide information on the size of the asymptomatic reservoir, the nature of parasite genotypes associated with drug resistance as well as the frequency of the Pfhrp2/3 deletion associated with false negatives when using Rapid Diagnostic tests.Sustained global malaria control and elimination initiatives, driven by local and international funding agencies, regional malaria control programmes, and the World Health Organisation (WHO), have led to a dramatic decrease in malaria mortality and case incidence in the last 15 years. Worldwide, there has been a reduction in case incidence of 18% and reduction in mortality of 48%, with significant impact in Africa 1 . Although the 2019 WHO Malaria Report suggests that progress may be slowing, malaria elimination is still an active target for many Colombia, represents relatively high gametocytemia 39,40 . More than 96% of malaria cases diagnosed at the Guapi malaria health facility originated within a 25 km radius of the town of Guapi. We therefore define the Guapi malaria transmission unit as the area where the catchment facility captures 95% of cases ( Fig. S1 4). Scientific RepoRtS |(2020) 10:3756 | https://doi.

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Prevalence of pfhrp2 and pfhrp3 gene deletions in Puerto Lempira, Honduras

Cited by 76 publications

References 24 publications

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

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

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

Spatio-temporal dynamics of Plasmodium falciparum transmission within a spatial unit on the Colombian Pacific Coast

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