{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T00:08:31Z","timestamp":1783728511405,"version":"3.55.0"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T00:00:00Z","timestamp":1646352000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T00:00:00Z","timestamp":1646352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000200","name":"United States Agency for International Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000200","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Malar J"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Rapid diagnostic tests (RDTs) are widely used for malaria diagnosis of both symptomatic and asymptomatic infections. Although RDTs are a reliable and practical diagnostic tool, the sensitivity of histidine-rich protein 2 (HRP2)-based RDTs can be reduced if <jats:italic>pfhrp2<\/jats:italic> or <jats:italic>pfhrp3<\/jats:italic> (<jats:italic>pfhrp2\/3<\/jats:italic>) gene deletions exist in the <jats:italic>Plasmodium falciparum<\/jats:italic> parasite population. This study evaluated dried blood spot (DBS) samples collected from a national household survey to investigate the presence of <jats:italic>pfhrp2\/3<\/jats:italic> deletions and the performance of the RDT used in the cross-sectional survey in a low transmission setting.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The 2015 Ethiopia Malaria Indicator Survey tested household members by RDT and collected DBS samples. DBS (n\u2009=\u20092648) from three regions in northern Ethiopia were tested by multiplex bead-based antigen detection assay after completion of the survey. The multiplex assay detected pan-<jats:italic>Plasmodium<\/jats:italic> lactate dehydrogenase (LDH), pAldolase, and HRP2 antigens in samples. Samples suspected for <jats:italic>pfhrp2\/3<\/jats:italic> gene deletions (pLDH and\/or pAldolase positive but low or absent HRP2) were further investigated by molecular assays for gene deletions. Antigen results were also compared to each individual\u2019s RDT results. Dose\u2013response logistic regression models were fit to estimate RDT level of detection (LOD) antigen concentrations at which 50, 75, 90, and 95% of the RDTs returned a positive result during this survey.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Out of 2,648 samples assayed, 29 were positive for pLDH or pAldolase antigens but low or absent for HRP2 signal, and 15 of these samples (51.7%) were successfully genotyped for <jats:italic>pfhrp2\/3<\/jats:italic>. Of these 15 <jats:italic>P. falciparum<\/jats:italic> infections, eight showed single deletions in <jats:italic>pfhrp3,<\/jats:italic> one showed a single <jats:italic>pfhrp2<\/jats:italic> deletion, and six were <jats:italic>pfhrp2\/3<\/jats:italic> double-deletions. Six <jats:italic>pfhrp2<\/jats:italic> deletions were observed in Tigray and one in Amhara. Twenty-five were positive for HRP2 by the survey RDT while the more sensitive bead assay detected 30 HRP2-positive samples. A lower concentration of HRP2 antigen generated a positive test result by RDT compared to pLDH (95% LOD: 16.9\u00a0ng\/mL vs. 319.2\u00a0ng\/mL, respectively).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>There is evidence of dual <jats:italic>pfhrp2\/3<\/jats:italic> gene deletions in the Tigray and Amhara regions of Ethiopia in 2015. As the prevalence of malaria was very low (&lt;\u20092%), it is difficult to make strong conclusions on RDT performance, but these results challenge the utility of biomarkers in household surveys in very low transmission settings.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12936-022-04097-7","type":"journal-article","created":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T06:02:49Z","timestamp":1646373769000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Investigation of Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions and performance of a rapid diagnostic test for identifying asymptomatic malaria infection in northern Ethiopia, 2015"],"prefix":"10.1186","volume":"21","author":[{"given":"Colleen M.","family":"Leonard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashenafi","family":"Assefa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica N.","family":"McCaffery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camelia","family":"Herman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateusz","family":"Plucinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heven","family":"Sime","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hussein","family":"Mohammed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amha","family":"Kebede","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiwot","family":"Solomon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mebrahtom","family":"Haile","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimee","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7375-8304","authenticated-orcid":false,"given":"Eric","family":"Rogier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,4]]},"reference":[{"key":"4097_CR1","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1128\/CMR.15.1.66-78.2002","volume":"15","author":"A Moody","year":"2002","unstructured":"Moody A. 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The informed consent form was read to each participant in the appropriate local language and verbal informed consent was obtained. For children, parent\u2019s consent was obtained before any blood sample was collected.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors approved of this manuscript for publication.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no conflicts of interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"70"}}