{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T15:04:53Z","timestamp":1768921493792,"version":"3.49.0"},"reference-count":26,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,15]]},"abstract":"<jats:title>ABSTRACT.<\/jats:title>\n<jats:p>Reports of increasing false-negative HRP2-based rapid diagnostic test results across Africa require constant monitoring of factors associated with these false-negative outcomes, as failure of this diagnostic tool will have severe consequences on malaria treatment and control programs. This study characterized the extent of genetic diversity in the <jats:italic>Plasmodium falciparum<\/jats:italic> histidine-rich protein 2 (<jats:italic>Pfhrp<\/jats:italic>2) gene in <jats:italic>P. falciparum<\/jats:italic> isolates from symptomatic malaria patients across the regions of Ghana. Exon 2 of <jats:italic>Pfhrp2<\/jats:italic> was amplified from gDNA using polymerase chain reaction. All <jats:italic>Pfhrp<\/jats:italic>2-negative samples were subjected to Pf<jats:italic>18S rRNA<\/jats:italic> and <jats:italic>Pfmsp<\/jats:italic>2 gene amplifications. The amplified <jats:italic>Pfhrp<\/jats:italic>2 exon 2 fragments from clonal samples were sent for commercial Sanger sequencing. The type and number of <jats:italic>Pf<\/jats:italic>HRP2 repeats, classified based on repeat types previously reported, were estimated from the sequence data and compared among geographical regions. About 81% (2,333\/2,890) of the original microscopy positive dried blood spot (DBS) samples were available and used in this study. The <jats:italic>Pfhrp<\/jats:italic>2 exon 2 amplification was successful in 98.5% (2,297\/2,333) of the tested samples, with band size ranging from 400 bp to 1,050 bp. A total of 13 out of the 24 previously reported repeat types were identified among the samples, with three samples lacking both type 2 and type 7 repeat motifs. This study suggested that the genetic diversity of <jats:italic>Pfhrp<\/jats:italic>2 exon 2 identified in <jats:italic>P. falciparum<\/jats:italic> circulating in symptomatic malaria patients in Ghana is unlikely to influence the sensitivity and specificity of HRP2 RDT-based diagnosis.<\/jats:p>","DOI":"10.4269\/ajtmh.21-1342","type":"journal-article","created":{"date-parts":[[2022,5,2]],"date-time":"2022-05-02T13:09:54Z","timestamp":1651496994000},"page":"1660-1666","source":"Crossref","is-referenced-by-count":10,"title":["Nationwide Surveillance of Pfhrp2 Exon 2 Diversity in Plasmodium falciparum Circulating in Symptomatic Malaria Patients Living in Ghana"],"prefix":"10.4269","volume":"106","author":[{"given":"Dorcas G.","family":"Bredu","sequence":"first","affiliation":[{"name":"Department of Immunology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George K.","family":"Ahadzi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medical Sciences, College of Health and Allied Sciences, University of Cape Coast, Cape Coast, Ghana;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dickson","family":"Donu","sequence":"additional","affiliation":[{"name":"Department of Immunology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nana Y.","family":"Peprah","sequence":"additional","affiliation":[{"name":"National Malaria Control Program, Ghana Health Services, Accra, Ghana;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Asamoah","sequence":"additional","affiliation":[{"name":"National Malaria Control Program, Ghana Health Services, Accra, Ghana;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George A.","family":"Asumah","sequence":"additional","affiliation":[{"name":"National Malaria Control Program, Ghana Health Services, Accra, Ghana;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Abuaku","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwame K.","family":"Asare","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, School of Allied Health Sciences, College of Allied Health Sciences, University of Cape Coast, Cape Coast, Ghana;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorcas","family":"Obiri-Yeboah","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medical Sciences, College of Health and Allied Sciences, University of Cape Coast, Cape Coast, Ghana;"},{"name":"Directorate of Research, Innovation and Consultancy, University of Cape Coast, Cape Coast, Ghana;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colby T.","family":"Ford","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, University of North Carolina, Charlotte, North Carolina;"},{"name":"School of Data Science, University of North Carolina, Charlotte, North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugenia","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Genomics, University of North Carolina, Charlotte, North Carolina;"},{"name":"School of Data Science, University of North Carolina, Charlotte, North Carolina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keziah L.","family":"Malm","sequence":"additional","affiliation":[{"name":"National Malaria Control Program, Ghana Health Services, Accra, Ghana;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda E.","family":"Amoah","sequence":"additional","affiliation":[{"name":"Department of Immunology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2795","reference":[{"key":"b1","year":"2019"},{"key":"b2","series-title":"Malar J","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/s12936-019-2639-8","article-title":"Molecular monitoring of the diversity of human pathogenic malaria species in blood donations on Bioko Island, Equatorial Guinea","volume":"18:","year":"2019"},{"key":"b3","series-title":"Malar J","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1186\/s12936-018-2588-7","article-title":"Molecular identification of Plasmodium species responsible for malaria reveals Plasmodium vivax isolates in Duffy negative individuals from southwestern Nigeria","volume":"17:","year":"2018"},{"key":"b4","series-title":"Malar J","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1186\/1475-2875-9-129","article-title":"Global sequence variation in the histidine-rich proteins 2 and 3 of Plasmodium falciparum: implications for the performance of malaria rapid diagnostic tests","volume":"9:","year":"2010"},{"key":"b5","series-title":"Malar J","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/1475-2875-13-34","article-title":"Analysis of pfhrp2 genetic diversity in Senegal and implications for use of rapid diagnostic tests","volume":"13:","year":"2014"},{"key":"b6","series-title":"Malar J","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1186\/s12936-020-03328-z","article-title":"Plasmodium falciparum histidine-rich protein 2 diversity in Ghana","volume":"19:","year":"2020"},{"key":"b7","series-title":"J Clin Microbiol","doi-asserted-by":"publisher","first-page":"2773","DOI":"10.1128\/JCM.02557-05","article-title":"Effect of sequence variation in Plasmodium falciparum histidine-rich protein 2 on binding of specific monoclonal antibodies: implications for rapid diagnostic tests for malaria","volume":"44:","year":"2006"},{"key":"b8","series-title":"Trop Med Int Health","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1111\/tmi.13223","article-title":"Genetic diversity and population structure of Plasmodium falciparum in Kenyan\u2013Ugandan border areas","volume":"24:","year":"2019"},{"key":"b9","series-title":"PLoS One","doi-asserted-by":"publisher","first-page":"e0238749","DOI":"10.1371\/journal.pone.0238749","article-title":"Contribution of P. falciparum parasites with Pfhrp 2 gene deletions to false negative PfHRP 2 based malaria RDT results in Ghana: a nationwide study of symptomatic malaria patients","volume":"15:","year":"2020"},{"key":"b10","doi-asserted-by":"publisher","year":"2015","DOI":"10.1186\/1475-2875-6-124"},{"key":"b11","series-title":"Malar J","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1186\/s12936-020-03178-9","article-title":"Comparison of three molecular methods for the detection and speciation of Plasmodium vivax and Plasmodium falciparum.","volume":"6:","year":"2007"},{"key":"b12","series-title":"Malar J","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1186\/s12879-018-3350-z","article-title":"First evidence of the deletion in the pfhrp2 and pfhrp3 genes in Plasmodium falciparum from Equatorial Guinea","volume":"19:","year":"2020"},{"key":"b13","series-title":"BMC Infect Dis","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1186\/s12936-016-1640-8","article-title":"Seasonal variations in Plasmodium falciparum genetic diversity and multiplicity of infection in asymptomatic children living in southern Ghana","volume":"18:","year":"2018"},{"key":"b14","series-title":"Malar J","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1093\/nar\/gkf436","article-title":"Plasmodium falciparum genotype and gametocyte prevalence in children with uncomplicated malaria in coastal Ghana","volume":"15:","year":"2016"},{"key":"b15","series-title":"Nucleic Acids Res","first-page":"3059","article-title":"MAFFT: a novel method for rapid multiple sequence alignment based on fast Fourier transform","volume":"30:","year":"2002"},{"key":"b16","series-title":"Genes (Basel)","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s12936-021-03928-3","article-title":"The diversity, multiplicity of infection and population structure of P. falciparum parasites circulating in asymptomatic carriers living in high and low malaria transmission settings of Ghana","volume":"2019:","year":"2019"},{"key":"b17","series-title":"Malar J","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1038\/s41598-018-38175-1","article-title":"Genetic variation of Plasmodium falciparum histidine-rich protein 2 and 3 in Assosa zone, Ethiopia: its impact on the performance of malaria rapid diagnostic tests","volume":"20:","year":"2021"},{"key":"b18","doi-asserted-by":"publisher","author":"Nderu","year":"2019","DOI":"10.1186\/1475-2875-13-34"},{"key":"b19","series-title":"Malar J","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.cmi.2018.09.009","article-title":"Analysis of pfhrp2 genetic diversity in Senegal and implications for use of rapid diagnostic tests","volume":"13:","year":"2014"},{"key":"b20","series-title":"Clin Microbiol Infect","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1016\/j.actatropica.2015.08.003","article-title":"Genetic diversity and deletion of Plasmodium falciparum histidine-rich protein 2 and 3: a threat to diagnosis of P. falciparum malaria","volume":"25:","year":"2019"},{"key":"b21","series-title":"Acta Trop","doi-asserted-by":"publisher","first-page":"26","DOI":"10.4269\/ajtmh.18-0137","article-title":"Genetic diversity of Plasmodium falciparum histidine-rich protein 2 in the China-Myanmar border area","volume":"152:","year":"2015"},{"key":"b22","series-title":"Am J Trop Med Hyg","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1371\/journal.pone.0241807","article-title":"Plasmodium falciparum histidine-rich protein 2 gene variation in a malaria-endemic area of Papua New Guinea","volume":"99:","year":"2018"},{"key":"b23","series-title":"PLoS One","doi-asserted-by":"publisher","first-page":"e0241807","DOI":"10.1186\/s13071-015-1008-x","article-title":"High prevalence and extended deletions in Plasmodium falciparum hrp2\/3 genomic loci in Ethiopia","volume":"15:","year":"2020"},{"key":"b24","series-title":"Parasit Vectors","doi-asserted-by":"publisher","first-page":"388","DOI":"10.4103\/0255-0857.103790","article-title":"Genetic variation of pfhrp2 in Plasmodium falciparum isolates from Yemen and the performance of HRP2-based malaria rapid diagnostic test","volume":"8:","year":"2015"},{"key":"b25","series-title":"Indian J Med Microbiol","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1093\/infdis\/jiz335","article-title":"Fragment size polymorphism in Plasmodium falciparum histidine rich proteins among Indian population is a cause for concern in rapid diagnosis of malaria","volume":"30:","year":"2012"},{"key":"b26","series-title":"J Infect Dis","first-page":"1444","article-title":"pfhrp2 and pfhrp3 gene deletions that affect malaria rapid diagnostic tests for Plasmodium falciparum: analysis of archived blood samples from 3 African countries","volume":"220:","year":"2019"}],"container-title":["The American Journal of Tropical Medicine and Hygiene"],"original-title":[],"link":[{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/106\/6\/article-p1660.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/106\/6\/article-p1660.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/www.ajtmh.org\/downloadpdf\/journals\/tpmd\/106\/6\/article-p1660.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T19:40:48Z","timestamp":1658259648000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ajtmh.org\/view\/journals\/tpmd\/106\/6\/article-p1660.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,15]]},"references-count":26,"journal-issue":{"issue":"6"},"URL":"https:\/\/doi.org\/10.4269\/ajtmh.21-1342","relation":{},"ISSN":["0002-9637","1476-1645"],"issn-type":[{"value":"0002-9637","type":"print"},{"value":"1476-1645","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,15]]}}}