{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T05:01:40Z","timestamp":1792904500913,"version":"4.5.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,11,4]],"date-time":"2020-11-04T00:00:00Z","timestamp":1604448000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,11,4]],"date-time":"2020-11-04T00:00:00Z","timestamp":1604448000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UNITAID"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Malar J"],"published-print":{"date-parts":[[2020,12]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n Malaria rapid diagnostic tests (RDTs) have greatly improved access to diagnosis in endemic countries. Most RDTs detect\n Plasmodium falciparum<\/jats:italic>\n histidine-rich protein 2 (HRP2), but their sensitivity is seriously threatened by the emergence of\n pfhrp2<\/jats:italic>\n -deleted parasites. RDTs detecting\n P. falciparum<\/jats:italic>\n or pan-lactate dehydrogenase (Pf- or pan-LDH) provide alternatives. The objective of this study was to systematically assess the performance of malaria RDTs against well-characterized\n pfhrp2<\/jats:italic>\n -deleted\n P. falciparum<\/jats:italic>\n parasites.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Thirty-two RDTs were tested against 100 wild-type clinical isolates (200 parasites\/\u00b5L), and 40 samples from 10 culture-adapted and clinical isolates of\n pfhrp2<\/jats:italic>\n -deleted parasites. Wild-type and\n pfhrp2<\/jats:italic>\n -deleted parasites had comparable Pf-LDH concentrations. Pf-LDH-detecting RDTs were also tested against 18 clinical isolates at higher density (2,000 parasites\/\u00b5L) lacking both\n pfhrp2<\/jats:italic>\n and\n pfhrp3.<\/jats:italic>\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n RDT positivity against\n pfhrp2<\/jats:italic>\n -deleted parasites was highest (>\u200994%) for the two pan-LDH-only RDTs. The positivity rate for the nine Pf-LDH-detecting RDTs varied widely, with similar median positivity between double-deleted (\n pfhrp2\/3<\/jats:italic>\n negative; 63.9%) and single-deleted (\n pfhrp2<\/jats:italic>\n -negative\/\n pfhrp3<\/jats:italic>\n -positive; 59.1%) parasites, both lower than against wild-type\n P. falciparum<\/jats:italic>\n (93.8%). Median positivity for HRP2-detecting RDTs against 22 single-deleted parasites was 69.9 and 35.2% for HRP2-only and HRP2-combination RDTs, respectively, compared to 96.0 and 92.5% for wild-type parasites. Eight of nine Pf-LDH RDTs detected all clinical, double-deleted samples at 2,000 parasites\/\u00b5L.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n The pan-LDH-only RDTs evaluated performed well. Performance of Pf-LDH-detecting RDTs against wild-type\n P. falciparum<\/jats:italic>\n does not necessarily predict performance against\n pfhrp2<\/jats:italic>\n -deleted parasites. Furthermore, many, but not all HRP2-based RDTs, detect\n pfhrp2<\/jats:italic>\n -negative\/\n pfhrp3<\/jats:italic>\n -positive samples, with implications for the HRP2-based RDT screening approach for detection and surveillance of HRP2-negative parasites.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1186\/s12936-020-03460-w","type":"journal-article","created":{"date-parts":[[2020,11,4]],"date-time":"2020-11-04T07:46:02Z","timestamp":1604475962000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Impact of Plasmodium falciparum gene deletions on malaria rapid diagnostic test performance"],"prefix":"10.1186","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1188-609X","authenticated-orcid":false,"given":"Michelle L.","family":"Gatton","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisha","family":"Chaudhry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Glenn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Ah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalynn L.","family":"Ord","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxanne R.","family":"Rees-Channer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Chiodini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Incardona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Aidoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Cunningham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,11,4]]},"reference":[{"key":"3460_CR1","unstructured":"WHO. 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PLoS One. 2017;12:e0171150.","DOI":"10.1371\/journal.pone.0171150"},{"key":"3460_CR11","doi-asserted-by":"publisher","first-page":"2694","DOI":"10.1128\/JCM.00281-11","volume":"49","author":"S Houze","year":"2011","unstructured":"Houze S, Hubert V, Le Pessec G, Le Bras J, Clain J. Combined deletions of pfhrp2 and pfhrp3 genes result in Plasmodium falciparum malaria false-negative rapid diagnostic test. J Clin Microbiol. 2011;49:2694\u20136.","journal-title":"J Clin Microbiol"},{"key":"3460_CR12","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1186\/s12936-018-2470-7","volume":"17","author":"G Fontecha","year":"2018","unstructured":"Fontecha G, Mejia RE, Banegas E, Ade MP, Mendoza L, Ortiz B, et al. Deletions of pfhrp2 and pfhrp3 genes of Plasmodium falciparum from Honduras Guatemala and Nicaragua. 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Pfhrp2-deleted Plasmodium falciparum parasites in the Democratic Republic of Congo: a national cross-sectional survey J Infect Dis. 2017;216:36-44.","DOI":"10.1093\/infdis\/jiw538"},{"key":"3460_CR20","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1186\/s12936-017-1768-1","volume":"16","author":"CT Kozycki","year":"2017","unstructured":"Kozycki CT, Umulisa N, Rulisa S, Mwikarago EI, Musabyimana JP, Habimana JP, et al. False-negative malaria rapid diagnostic tests in Rwanda: impact of Plasmodium falciparum isolates lacking hrp2 and declining malaria transmission. Malar J. 2017;16:123.","journal-title":"Malar J"},{"key":"3460_CR21","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s12936-015-0544-3","volume":"14","author":"NM Laban","year":"2015","unstructured":"Laban NM, Kobayashi T, Hamapumbu H, Sullivan D, Mharakurwa S, Thuma PE, et al. Comparison of a PfHRP2-based rapid diagnostic test and PCR for malaria in a low prevalence setting in rural southern Zambia: implications for elimination. Malar J. 2015;14:25.","journal-title":"Malar J"},{"key":"3460_CR22","doi-asserted-by":"publisher","first-page":"14718","DOI":"10.1038\/s41598-017-15031-2","volume":"7","author":"KB Beshir","year":"2017","unstructured":"Beshir KB, Sepulveda N, Bharmal J, Robinson A, Mwanguzi J, Busula AO, et al. Plasmodium falciparum parasites with histidine-rich protein 2 (pfhrp2) and pfhrp3 gene deletions in two endemic regions of Kenya. Sci Rep. 2017;7:14718.","journal-title":"Sci Rep"},{"key":"3460_CR23","doi-asserted-by":"publisher","first-page":"462","DOI":"10.3201\/eid2403.171723","volume":"24","author":"A Berhane","year":"2018","unstructured":"Berhane A, Anderson K, Mihreteab S, Gresty K, Rogier E, Mohamed S, et al. Major Threat to malaria control programs by Plasmodium falciparum lacking Histidine-Rich Protein 2 Eritrea. 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Pan-Plasmodium band sensitivity for Plasmodium falciparum detection in combination malaria rapid diagnostic tests and implications for clinical management. Malar J. 2015;14:115.","journal-title":"Malar J"}],"container-title":["Malaria Journal"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12936-020-03460-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12936-020-03460-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12936-020-03460-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T22:03:07Z","timestamp":1604613787000},"score":1,"resource":{"primary":{"URL":"https:\/\/malariajournal.biomedcentral.com\/articles\/10.1186\/s12936-020-03460-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,4]]},"references-count":32,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["3460"],"URL":"https:\/\/doi.org\/10.1186\/s12936-020-03460-w","relation":{},"ISSN":["1475-2875"],"issn-type":[{"value":"1475-2875","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,4]]},"assertion":[{"value":"27 May 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 October 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 November 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Each collection site for the clinical isolates obtained approval from a WHO research ethics review committee and\/or a local institutional review board for specimen collection, transport and archiving of blood samples for the purpose of RDT product testing, lot testing and quality assurance.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"MLG, RRR, AC, JG, SW and YA report grants from Foundation for Innovative New Diagnostics during the conduct of the study; MLG also reports personal fees from World Health Organization; QC, SI, RLO, PC, MA, JC and AK have nothing to disclose.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"392"}}