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Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Plasmodium knowlesi<\/jats:italic>\n                      causes zoonotic malaria across Southeast Asia. First-line diagnostic microscopy cannot reliably differentiate\n                      <jats:italic>P. knowlesi<\/jats:italic>\n                      from other human malaria species. Rapid diagnostic tests (RDTs) designed for\n                      <jats:italic>P. falciparum<\/jats:italic>\n                      and\n                      <jats:italic>P. vivax<\/jats:italic>\n                      are used routinely in\n                      <jats:italic>P. knowlesi<\/jats:italic>\n                      co-endemic areas despite potential cross-reactivity for species-specific antibody targets.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Ten RDTs were evaluated: nine to detect clinical\n                      <jats:italic>P. knowlesi<\/jats:italic>\n                      infections from Malaysia, and nine assessing limit of detection (LoD) for\n                      <jats:italic>P. knowlesi (PkA1-H.1)<\/jats:italic>\n                      and\n                      <jats:italic>P. falciparum<\/jats:italic>\n                      (\n                      <jats:italic>Pf3D7<\/jats:italic>\n                      ) cultures. Targets included\n                      <jats:italic>Plasmodium<\/jats:italic>\n                      -genus parasite lactate dehydrogenase (pan-pLDH) and\n                      <jats:italic>P. vivax<\/jats:italic>\n                      (\n                      <jats:italic>Pv<\/jats:italic>\n                      )-pLDH.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Samples were collected prior to antimalarial treatment from 127 patients with microscopy-positive PCR-confirmed\n                      <jats:italic>P. knowlesi<\/jats:italic>\n                      mono-infections. Median parasitaemia was 788\/\u00b5L (IQR 247-5,565\/\u00b5L). Pan-pLDH sensitivities ranged from 50.6% (95% CI 39.6\u201361.5) (SD BIOLINE) to 87.0% (95% CI 75.1\u201394.6) (First Response\n                      <jats:sup>\u00ae<\/jats:sup>\n                      and CareStart\u2122 PAN) compared to reference PCR.\n                      <jats:italic>Pv<\/jats:italic>\n                      -pLDH RDTs detected\n                      <jats:italic>P. knowlesi<\/jats:italic>\n                      with up to 92.0% (95% CI 84.3-96.7%) sensitivity (Biocredit\u2122). For parasite counts \u2265200\/\u00b5L, pan-pLDH (Standard Q) and\n                      <jats:italic>Pv<\/jats:italic>\n                      -pLDH RDTs exceeded 95% sensitivity. Specificity of RDTs against 26 PCR-confirmed negative controls was 100%. Sensitivity of six highest performing RDTs were not significantly different when comparing samples taken before and after (median 3 hours) antimalarial treatment. Parasite ring stages were present in 30% of pre-treatment samples, with ring stage proportions (mean 1.9%) demonstrating inverse correlation with test positivity of Biocredit\u2122 and two CareStart\u2122 RDTs.\n                    <\/jats:p>\n                    <jats:p>\n                      For cultured\n                      <jats:italic>P. knowlesi<\/jats:italic>\n                      , CareStart\u2122 PAN demonstrated the lowest LoD at 25 parasites\/\u00b5L; LoDs of other pan-pLDH ranged from 98 to &amp;gt;2000 parasites\/\u00b5L.\n                      <jats:italic>Pv<\/jats:italic>\n                      -pLDH LoD for\n                      <jats:italic>P. knowlesi<\/jats:italic>\n                      was 49 parasites\/\u00b5L. No false-positive results were observed in either\n                      <jats:italic>P. falciparum<\/jats:italic>\n                      -pLDH or histidine-rich-protein-2 channels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Selected RDTs demonstrate sufficient performance for detection of major human malaria species including\n                      <jats:italic>P. knowlesi<\/jats:italic>\n                      in co-endemic areas where microscopy is not available, particularly for higher parasite counts, although cannot reliably differentiate among\n                      <jats:italic>non-falciparum<\/jats:italic>\n                      malaria.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2022.1023219","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T01:42:32Z","timestamp":1665970952000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":27,"title":["Diagnostic accuracy and limit of detection of ten malaria parasite lactate dehydrogenase-based rapid tests for Plasmodium knowlesi and P. falciparum"],"prefix":"10.3389","volume":"12","author":[{"given":"Angelica F.","family":"Tan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sitti Saimah binti","family":"Sakam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giri\u00a0S.","family":"Rajahram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"William","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad\u00a0Faruq","family":"Abd Rachman Isnadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Daim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridget\u00a0E.","family":"Barber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Kho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin J.","family":"Sutherland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas M.","family":"Anstey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seda","family":"Yerlikaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donelly A.","family":"van Schalkwyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Grigg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,17]]},"reference":[{"key":"B1","first-page":"1465","article-title":"Rapid diagnostic tests for diagnosing uncomplicated non-falciparum or Plasmodium vivax malaria in endemic countries","author":"Abba","year":"2014","journal-title":"Cochrane Database Systematic Rev."},{"key":"B2","first-page":"22","article-title":"Outcomes from the evidence review group on Plasmodium knowlesi","volume":"1","author":"Abeysinghe","year":"2017","journal-title":"Present. 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