Abstract

BackgroundMalaria rapid diagnostic tests based on histidine-rich protein-2 have played a vital role in improving malaria case management and surveillance particularly in Africa, where Plasmodium falciparum is predominant. However, their usefulness has been threatened by the emergence of gene deletion on P. falciparum histidine rich protein 2 (pfhrp2) and P. falciparum histidine rich protein 3 (pfhrp3). Use of standard and recommended methods is key for accurate investigation, confirmation and reporting of pfhrp2 and pfhrp3 gene deletion.MethodsA systematic review was conducted to assess the status, methods and approaches that have been used for investigation, confirmation and reporting of pfhrp2 and pfhrp3 gene deletion in Africa. An online search was done using PubMed and MEDLINE Google Scholar for all articles published in English on pfhrp2/3 gene deletion in Africa. Relevant articles that met the inclusion criteria were summarized and assessed based on the protocol recommended by the World Health Organization for confirmation and reporting of pfhrp2/3 gene deletion.ResultsThe search identified a total of 18 articles out of which 14 (77.7%) fulfilled the criteria for inclusion and were retained for review. The articles were distributed across 12 countries where the pfhrp2 and pfhrp3 gene deletion studies were conducted and reported. The level of pfhrp2/3 gene deletion across selected studies in Africa ranged from the highest 62% to the lowest 0.4%. There was wide variation in methods and approaches including study designs, size and sampling and whether both pfhrp2 and pfhrp3 double deletions or pfhrp2 single deletion were investigated, with a wide variation in laboratory methods.ConclusionBased on the review, there is evidence of the presence of pfhrp2/3 gene-deleted P. falciparum parasites in Africa. The approaches and methods used for investigation, confirmation and reporting of pfhrp2/3 deleted parasites have varied between studies and across countries. Countries that are considering plans to investigate, confirm and report pfhrp2/3 deletion should use recommended standard and harmonized methods to prevent unnecessary recommendations for costly switch of RDTs in Africa.

Highlights

  • Malaria rapid diagnostic tests based on histidine-rich protein-2 have played a vital role in improving malaria case management and surveillance in Africa, where Plasmodium falciparum is predominant

  • The occurrence of P. falciparum with missing pfhrp2/3 genes pose a public health threat as a large number of malaria infected patients will go undetected by the histidine rich protein 2 (HRP2) rapid diagnostic tests (RDTs) and, remain untreated leading to increased risk of malaria morbidity and mortality, and continued malaria transmission [3, 5, 6]

  • This review aims to assess the current status of pfhrp2 gene deletion and the methods and approaches being used for its estimation, confirmation and reporting in Africa

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Summary

Introduction

Malaria rapid diagnostic tests based on histidine-rich protein-2 have played a vital role in improving malaria case management and surveillance in Africa, where Plasmodium falciparum is predominant. Their usefulness has been threatened by the emergence of gene deletion on P. falciparum histidine rich protein 2 (pfhrp2) and P. falciparum histidine rich protein 3 (pfhrp). Plasmodium falciparum parasites lacking the pfhrp2/3 gene do not express HRP2 protein antigen threatening the usefulness of HRP2 RDTs in malaria diagnosis [3, 4, 6]. The occurrence of P. falciparum with missing pfhrp2/3 genes pose a public health threat as a large number of malaria infected patients will go undetected by the HRP2 RDTs and, remain untreated leading to increased risk of malaria morbidity and mortality, and continued malaria transmission [3, 5, 6]

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