Community-based surveys for Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions in selected regions of mainland Tanzania

Malaria Journal

Steven G. Nyanjom¹  Caleb K. Kibet¹  Catherine Bakari²  Venkatachalam Udhayakumar³  Eric Rogier³  Douglas P. Nace³  Camelia Herman⁴  Gireesh Subramaniam⁵  Sophie Jones⁶  Susan Rumisha⁷  Deus S. Ishengoma⁸  Mercy G. Chiduo⁹  Celine I. Mandara^1,10  Renata Mandike^1,11  Sigsbert Mkude^1,11  Ally Mohamed^1,11  Frank Chacky^1,11  Fabrizio Molteni^1,11  Ritha Njau^1,12 

[1] Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya;Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya;National Institute for Medical Research, Tanga Research Centre, Tanga, Tanzania;Malaria Branch, Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, GA, USA;Malaria Branch, Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, GA, USA;CDC Foundation (CDCF), Atlanta, GA, USA;Malaria Branch, Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, GA, USA;Oak Ridge Institute for Science and Education, Atlanta, GA, USA;Malaria Branch, Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, GA, USA;Williams Consulting, Baltimore, MD, USA;National Institute for Medical Research, Dar es Salaam, Tanzania;National Institute for Medical Research, Dar es Salaam, Tanzania;Faculty of Pharmaceutical Sciences, Monash University, Melbourne, Australia;Harvard T.H Chan School of Public Health, Boston, MA, USA;National Institute for Medical Research, Tanga Research Centre, Tanga, Tanzania;National Institute for Medical Research, Tanga Research Centre, Tanga, Tanzania;Kilimanjaro Christian Medical University College, Moshi, Tanzania;National Malaria Control Programme (NMCP), Dodoma, Tanzania;World Health Organization (WHO) Country Office, Dar es Salaam, Tanzania;

关键词: Tanzania;    Malaria;    Rapid diagnostic tests;    Histidine-rich protein 2/3;    Lactate dehydrogenase;    Aldolase;    Plasmodium falciparum;   

DOI  :  10.1186/s12936-020-03459-3

来源: Springer

【 摘 要 】

BackgroundHistidine-rich protein 2 (HRP2)-based malaria rapid diagnostic tests (RDTs) are effective and widely used for the detection of wild-type Plasmodium falciparum infections. Although recent studies have reported false negative HRP2 RDT results due to pfhrp2 and pfhrp3 gene deletions in different countries, there is a paucity of data on the deletions of these genes in Tanzania.MethodsA community-based cross-sectional survey was conducted between July and November 2017 in four regions: Geita, Kigoma, Mtwara and Ruvuma. All participants had microscopy and RDT performed in the field and provided a blood sample for laboratory multiplex antigen detection (for Plasmodium lactate dehydrogenase, aldolase, and P. falciparum HRP2). Samples showing RDT false negativity or aberrant relationship of HRP2 to pan-Plasmodium antigens were genotyped to detect the presence/absence of pfhrp2/3 genes.ResultsOf all samples screened by the multiplex antigen assay (n = 7543), 2417 (32.0%) were positive for any Plasmodium antigens while 5126 (68.0%) were negative for all antigens. The vast majority of the antigen positive samples contained HRP2 (2411, 99.8%), but 6 (0.2%) had only pLDH and/or aldolase without HRP2. Overall, 13 samples had an atypical relationship between a pan-Plasmodium antigen and HRP2, but were positive by PCR. An additional 16 samples with negative HRP2 RDT results but P. falciparum positive by microscopy were also chosen for pfhrp2/3 genotyping. The summation of false negative RDT results and laboratory antigen results provided 35 total samples with confirmed P. falciparum DNA for pfhrp2/3 genotyping. Of the 35 samples, 4 (11.4%) failed to consistently amplify positive control genes; pfmsp1 and pfmsp2 and were excluded from the analysis. The pfhrp2 and pfhrp3 genes were successfully amplified in the remaining 31 (88.6%) samples, confirming an absence of deletions in these genes.ConclusionsThis study provides evidence that P. falciparum parasites in the study area have no deletions of both pfhrp2 and pfhrp3 genes. Although single gene deletions could have been missed by the multiplex antigen assay, the findings support the continued use of HRP2-based RDTs in Tanzania for routine malaria diagnosis. There is a need for the surveillance to monitor the status of pfhrp2 and/or pfhrp3 deletions in the future.

【 授权许可】

CC BY