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Prevalence of Plasmodium falciparum lacking histidine-rich proteins 2 and 3: a systematic review.

ABSTRACT: Objective:To calculate prevalence estimates and evaluate the quality of studies reporting Plasmodium falciparum lacking histidine-rich proteins 2 and 3, to inform an international response plan. Methods:We searched five online databases, without language restriction, for articles reporting original data on Plasmodium falciparum-infected patients with deletions of the pfhrp2 and/or pfhrp3 genes (pfhrp2/3). We calculated prevalence estimates of pfhrp2/3 deletions and mapped the data by country. The denominator was all P. falciparum-positive samples testing positive by microscopy and confirmed positive by species-specific polymerase chain reaction testing (PCR). If microscopy was not performed, we used the number of samples based on a different diagnostic method or PCR alone. We scored studies for risk of bias and the quality of laboratory methods using a standardized scoring system. Findings:A total of 38 articles reporting 55 studies from 32 countries and one territory worldwide were included in the review. We found considerable heterogeneity in the populations studied, methods used and estimated prevalence of P. falciparum parasites with pfhrp2/3 deletions. The derived prevalence of pfhrp2 deletions ranged from 0% to 100%, including focal areas in South America and Africa. Only three studies (5%) fulfilled all seven criteria for study quality. Conclusion:The lack of representative surveys or consistency in study design impairs evaluations of the risk of false-negative results in malaria diagnosis due to pfhrp2/3 deletions. Accurate mapping and strengthened monitoring of the prevalence of pfhrp2/3 deletions is needed, along with harmonized methods that facilitate comparisons across studies.

SUBMITTER: Thomson R

PROVIDER: S-EPMC7411324 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Prevalence of <i>Plasmodium falciparum</i> lacking histidine-rich proteins 2 and 3: a systematic review.

Thomson Rebecca R Parr Jonathan B JB Cheng Qin Q Chenet Stella S Perkins Mark M Cunningham Jane J

Bulletin of the World Health Organization 20200619 8

<h4>Objective</h4>To calculate prevalence estimates and evaluate the quality of studies reporting <i>Plasmodium falciparum</i> lacking histidine-rich proteins 2 and 3, to inform an international response plan.<h4>Methods</h4>We searched five online databases, without language restriction, for articles reporting original data on <i>Plasmodium falciparum</i>-infected patients with deletions of the <i>pfhrp2</i> and/or <i>pfhrp3</i> genes (<i>pfhrp2/3</i>). We calculated prevalence estimates of <i> ...[more]

PMID: 32773901

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Project description:BackgroundMalaria rapid diagnostic tests (RDTs) are precious tools to diagnose malaria. Most RDTs used currently are based on the detection of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) in a patient's blood. However, concern has been raised in recent years that deletion of pfhrp2 in the parasite could affect the accuracy of PfHRP2-based RDTs. In addition, genetic variation in pfhrp2 might influence the accuracy and sensitivity of RDTs. In this study, the genetic variation in pfhrp2 and pfhrp3 in Myanmar P. falciparum isolates was analysed.MethodsBlood samples were collected from malaria patients who were infected with P. falciparum in Mandalay, Naung Cho, Tha Beik Kyin, and Pyin Oo Lwin, Upper Myanmar between 2013 and 2015. The pfhrp2 and pfhrp3 were amplified by nested polymerase chain reaction (PCR), cloned and sequenced. Genetic variation in Myanmar pfhrp2 and pfhrp3 was analysed using the DNASTAR program. Comparative analysis of Myanmar and global pfhrp2 and pfhrp3 isolates was also performed.ResultsOne-hundred and two pfhrp2 and 89 pfhrp3 were amplified from 105 blood samples, of which 84 pfhrp2 and 56 pfhrp3 sequences were obtained successfully. Myanmar pfhrp2 and pfhrp3 showed high levels of genetic variation with different arrangements of distinct repeat types, which further classified Myanmar pfhrp2 and pfhrp3 into 76 and 47 haplotypes, respectively. Novel amino acid changes were also found in Myanmar pfhrp2 and pfhrp3, but their frequencies were very low. Similar structural organization was shared by Myanmar and global pfhrp2 and pfhrp3, and differences in frequencies of repeat types and lengths were also observed between and among global isolates.ConclusionLength polymorphisms and amino acid substitutions generated extensive genetic variation in Myanmar pfhrp2 and pfhrp3. Comparative analysis revealed that global pfhrp2 and pfhrp3 share similar structural features, as well as extensive length polymorphisms and distinct organizations of repeat types. These results provide a better understanding of the genetic structure of pfhrp2 and pfhrp3 in global P. falciparum populations and suggest useful information to develop RDTs with improved quality.

Dataset Information

Prevalence of Plasmodium falciparum lacking histidine-rich proteins 2 and 3: a systematic review.

Publications

Prevalence of <i>Plasmodium falciparum</i> lacking histidine-rich proteins 2 and 3: a systematic review.

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