Molecular surveillance of pfhrp2 and pfhrp3 genes deletion in Plasmodium falciparum isolates and the implications for rapid diagnostic tests in Nigeria.

Autor: Funwei R; Department of Pharmacology and Therapeutics, University of Ibadan, Ibadan, Nigeria; Department of Pharmacy Technician Studies, Bayelsa State College of Health Technology, Nigeria., Nderu D; Institute of Tropical Medicine, University of Tübingen, Germany., Nguetse CN; Department of Pediatrics, Stanford University School of Medicine, Stanford, USA., Thomas BN; Department of Biomedical Sciences, College of Health Sciences and Technology, Rochester Institute of Technology, Rochester, NY, USA., Falade CO; Department of Pharmacology and Therapeutics, University of Ibadan, Ibadan, Nigeria; Institute for Advanced Medical Research and Training, University College Hospital Ibadan, Nigeria., Velavan TP; Institute of Tropical Medicine, University of Tübingen, Germany; Faculty of Medicine. Duy Tan University, Da Nang, Vietnam., Ojurongbe O; Department of Medical Microbiology and Parasitology, Ladoke Akintola University of Technology, Osogbo, Nigeria. Electronic address: oojurongbe@lautech.edu.ng.
Jazyk: angličtina
Zdroj: Acta tropica [Acta Trop] 2019 Aug; Vol. 196, pp. 121-125. Date of Electronic Publication: 2019 May 16.
DOI: 10.1016/j.actatropica.2019.05.016
Abstrakt: Prompt diagnosis and appropriate treatment of malaria remain the hallmark for reducing malaria-related mortality in high transmission areas. Plasmodium falciparum histidine-rich protein2 (PfHRP2) based rapid diagnostic tests (RDT) play a vital role in prompt and accurate malaria diagnosis. However, pfhrp2 gene deletion threatens the RDT test sensitivity. This study reports the presence of pfhrp2 and pfhrp3 genes deletion among parasite isolates in Nigeria. Febrile children were screened using histidine-rich protein (HRP2) specific RDT (SD-Bioline RDT) and microscopy for P. falciparum infections. All RDT negative samples were re-evaluated by polymerase chain reaction (PCR). The presence of parasite in RDT false negative cases and randomly selected RDT positive cases were validated using PCRs targeting glutamate-rich protein (glurp) and merozoite surface proteins (msp-1 and msp-2). Thereafter, exon 2 of pfhrp2 and pfhrp3 were amplified, and Sanger sequenced. A total of 511 febrile children were enrolled out of which 309 (61%) were positive by RDT. The presence of pfhrp2 and pfhrp3 genes were analyzed in 66 PCR positive samples comprising of 31 RDT false negative and 35 RDT true positive randomly selected samples. The pfhrp2 and pfhrp3 genes failed to amplify in 17% (11/66) and 6% (4/66) samples, respectively. Seven of the eleven samples had only pfhrp2 deletion while four had both pfhrp2 and pfhrp3 deletions. The absence of the pfhrp2 gene may be responsible for the seven RDT false negative cases observed. Three RDT positive cases lacked pfhrp2 whereas pfhrp3 was absent in only four RDT false negative cases. The pfhrp2 and pfhrp3 amino acid repeat sequences were highly diverse. The P. falciparum isolates lacking pfhrp2 and pfhrp3 genes may be circulating and contributing to RDT false negativity in Nigeria. More studies in larger population and seasonally defined cases will be needed to determine the extent of pfhrp2/3 genes deletion in different geographical areas of Nigeria.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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