{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T17:51:49Z","timestamp":1782237109676,"version":"3.54.5"},"reference-count":25,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001713","name":"European and Developing Countries Clinical Trials Partnership","doi-asserted-by":"publisher","award":["TMA2019CDF-2697"],"award-info":[{"award-number":["TMA2019CDF-2697"]}],"id":[{"id":"10.13039\/501100001713","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      <jats:bold>To e<\/jats:bold>\n                      valuate the field accuracy of a malaria diagnostic algorithm combining sequential interpretation of two-step malaria RDT detecting\n                      <jats:italic>Pf<\/jats:italic>\n                      HRP2 and\n                      <jats:italic>p<\/jats:italic>\n                      LDH with information on previous antimalarial treatments within the past four weeks for the diagnosis of malaria in febrile children under 5 years compared to standard diagnosis using a\n                      <jats:italic>Pf<\/jats:italic>\n                      HRP2 only based RDT.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Febrile children aged 6\u201359 months attending outpatient clinics were randomized to either the control group, which received the standard RDT (\n                      <jats:italic>Pf<\/jats:italic>\n                      HRP2 only), or the intervention groups (an e-algorithm or a decisional algorithm), which was subjected to the diagnostic algorithm combining an RDT detecting\n                      <jats:italic>Pf<\/jats:italic>\n                      HRP2 and\n                      <jats:italic>p<\/jats:italic>\n                      LDH with information on previous antimalarial treatment. Malaria diagnosis with\n                      <jats:italic>Pf<\/jats:italic>\n                      HRP2-based RDT was reported as positive or negative. The sequential interpretation was reported as (i) positive when the\n                      <jats:italic>p<\/jats:italic>\n                      LDH line appeared, regardless of the\n                      <jats:italic>Pf<\/jats:italic>\n                      HRP2 results, (ii) negative when both lines did not appear and (iii) undetermined when only the\n                      <jats:italic>Pf<\/jats:italic>\n                      HRP2 line appeared, and information on previous antimalarial treatment within the past 4 weeks was used as a decision-support tool to classify active malaria from past infection. Blood samples were also collected for expert microscopy as the gold standard, and for qPCR to further evaluate undeterminate results and potential false-positive RDT outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In total 1176 children were included, with 66.7% (784\/1176) assigned to the intervention arms and 33.3% (392\/1176) to the control arm. In patients assigned to the sequential algorithm, the number of undetermined cases was 12.7% (100\/784). Considering microscopy as the gold standard,\n                      <jats:italic>Pf<\/jats:italic>\n                      HRP2-based RDT reported a sensitivity of 96.5% and a of specificity 79.1%, with positive and negative predictive values of 78.3% and 96.7%, respectively. For the sequential algorithm, the sensitivity, specificity, positive and negative predictive values of the conclusive-only results (i.e.,\n                      <jats:italic>Pf<\/jats:italic>\n                      HRP2\u00b1\/\n                      <jats:italic>p<\/jats:italic>\n                      LDH+ and\n                      <jats:italic>Pf<\/jats:italic>\n                      HRP2-\/\n                      <jats:italic>p<\/jats:italic>\n                      LDH-) were 97.4%, 98.4%, 98.0% and 97.9%. However, when undetermined result were combined with conclusive results, the sensitivity, specificity, positive and negative predictive values were 89.7%, 96.8%, 95.6% and 92.4% respectively. Among recently antimalarial treated participants in sequential algorithm arm, 59.5% (50\/84) were qPCR-positive, compared to 68.7% (11\/16) qPCR-positivity in those without recent treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The sequential diagnostic approach improves the diagnosis of malaria in a real world setting, compared to the use of\n                      <jats:italic>Pf<\/jats:italic>\n                      HRP2-(only) based RDT. However, relying only on history of antimalarial treatment in undetermined cases may decrease algorithm\u2019s sensitivity, which could result in missing active or recurrent malaria infections.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0351990","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T17:35:58Z","timestamp":1782236158000},"page":"e0351990","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Improving the field accuracy of a malaria diagnostic algorithm combining sequential interpretation of rapid diagnostic test detecting PfHRP2 and pLDH in febrile children in a seasonal hyperendemic malaria transmission area in Burkina Faso"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8917-1176","authenticated-orcid":true,"given":"Diane Yirgnur","family":"Some","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8828-5749","authenticated-orcid":true,"given":"Francois","family":"Kiemde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berenger","family":"Kabore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Valia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toussaint","family":"Rouamba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seydou","family":"Sawadogo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanase M.","family":"Some","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Sorgho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Macaire","family":"Nana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yacouba","family":"Nombre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine A.","family":"Kone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adelaide","family":"Compaore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadima Yaya","family":"Bocoum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massa dit Achille","family":"Bonko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georges","family":"Some","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gautier","family":"Tougri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie Yeri","family":"Youl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konseibo","family":"Noellie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeri Esther","family":"Hien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aly","family":"Savadogo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fla","family":"Koueta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henk D. F. H.","family":"Schallig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halidou","family":"Tinto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"pone.0351990.ref001","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/1475-2875-13-43","article-title":"Use of a three-band HRP2\/pLDH combination rapid diagnostic test increases diagnostic specificity for falciparum malaria in Ugandan children","volume":"13","author":"M Hawkes","year":"2014","journal-title":"Malar J"},{"key":"pone.0351990.ref002","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11908-018-0655-4","article-title":"An Update on Malaria Rapid Diagnostic Tests","volume":"20","author":"AN Mukkala","year":"2018","journal-title":"Curr Infect Dis Rep"},{"key":"pone.0351990.ref003","first-page":"1","article-title":"How long do rapid diagnostic tests remain positive after anti \u2011 malarial treatment?","author":"U Dalrymple","year":"2018","journal-title":"Malar J"},{"issue":"1","key":"pone.0351990.ref004","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1186\/s12936-017-1941-6","article-title":"Accuracy of a Plasmodium falciparum specific histidine-rich protein 2 rapid diagnostic test in the context of the presence of non-malaria fevers, prior anti-malarial use and seasonal malaria transmission","volume":"16","author":"F Kiemde","year":"2017","journal-title":"Malar J"},{"issue":"2","key":"pone.0351990.ref005","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0211801","article-title":"Algorithms for sequential interpretation of a malaria rapid diagnostic test detecting two different targets of Plasmodium species to improve diagnostic accuracy in a rural setting (Nanoro, Burkina Faso)","volume":"14","author":"F Kiemde","year":"2019","journal-title":"PLoS One"},{"key":"pone.0351990.ref006","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/1475-2875-13-20","article-title":"Accuracy of PfHRP2 versus Pf-pLDH antigen detection by malaria rapid diagnostic tests in hospitalized children in a seasonal hyperendemic malaria transmission area in Burkina Faso","volume":"13","author":"J Maltha","year":"2014","journal-title":"Malar J"},{"issue":"1","key":"pone.0351990.ref007","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s12936-022-04043-7","article-title":"Analysis of nucleic acids extracted from rapid diagnostic tests reveals a significant proportion of false positive test results associated with recent malaria treatment","volume":"21","author":"S Hosch","year":"2022","journal-title":"Malar J"},{"key":"pone.0351990.ref008","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1186\/1475-2875-12-123","article-title":"Field evaluation of HRP2 and pan pLDH-based immunochromatographic assay in therapeutic monitoring of uncomplicated falciparum malaria in Myanmar","volume":"12","author":"MH Nyunt","year":"2013","journal-title":"Malar J"},{"key":"pone.0351990.ref009","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1186\/1475-2875-7-221","article-title":"Operational accuracy and comparative persistent antigenicity of HRP2 rapid diagnostic tests for Plasmodium falciparum malaria in a hyperendemic region of Uganda","volume":"7","author":"DJ Kyabayinze","year":"2008","journal-title":"Malar J"},{"issue":"1","key":"pone.0351990.ref010","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1186\/s13063-022-06717-8","article-title":"Development and evaluation of an electronic algorithm using a combination of a two-step malaria RDT and other rapid diagnostic tools for the management of febrile illness in children under 5 attending outpatient facilities in Burkina Faso","volume":"23","author":"F Kiemde","year":"2022","journal-title":"Trials"},{"issue":"1","key":"pone.0351990.ref011","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1186\/s12936-023-04796-9","article-title":"Assessing the histidine-rich protein 2\/3 gene deletion in Plasmodium falciparum isolates from Burkina Faso","volume":"22","author":"CW Tarama","year":"2023","journal-title":"Malar J"},{"issue":"6","key":"pone.0351990.ref012","first-page":"481","article-title":"Malaria diagnosis challenges and pfhrp2 and pfhrp3 gene deletions using pregnant women as sentinel population in Nanoro region, Burkina Faso","volume":"118","author":"I Molina-de la Fuente","year":"2024","journal-title":"Pathog Glob Health"},{"issue":"3","key":"pone.0351990.ref013","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1001788","article-title":"Ultra-sensitive detection of Plasmodium falciparum by amplification of multi-copy subtelomeric targets","volume":"12","author":"N Hofmann","year":"2015","journal-title":"PLoS Med"},{"issue":"3","key":"pone.0351990.ref014","doi-asserted-by":"crossref","first-page":"276","DOI":"10.11613\/BM.2012.031","article-title":"Lessons in biostatistics interrater reliability: the kappa statistic","volume":"22","author":"ML McHugh","year":"2012","journal-title":"Biochem Medica"},{"issue":"12","key":"pone.0351990.ref015","first-page":"440","article-title":"Diagnostic Performance of Plasmodium falciparum Histidine-Rich Protein-2 Antigen-Specific Rapid Diagnostic Test in Children at the Peripheral Health Care Level in Nanoro (Burkina Faso)","volume":"7","author":"MDA Bonko","year":"2022","journal-title":"Trop Med Infect Dis"},{"issue":"2","key":"pone.0351990.ref016","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1007\/s12639-023-01566-x","article-title":"Performance of PfHRP2-RDT for malaria diagnosis during the first year of life in a high malaria transmission area in Burkina Faso","volume":"47","author":"HM Natama","year":"2023","journal-title":"J Parasit Dis"},{"issue":"1","key":"pone.0351990.ref017","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1186\/s12936-018-2468-1","article-title":"Implementation of a malaria rapid diagnostic test in a rural setting of Nanoro, Burkina Faso: from expectation to reality","volume":"17","author":"F Kiemde","year":"2018","journal-title":"Malar J"},{"key":"pone.0351990.ref018","article-title":"Efficacy of artemether \u2011 lumefantrine, dihydroartemisinin \u2011 piperaquine, and artesunate \u2011 pyronaridine for the treatment of uncomplicated Plasmodium falciparum malaria in Burkina Faso, 2020 \u2013 2021","author":"A Gansane","year":"2026","journal-title":"Malar J"},{"issue":"1","key":"pone.0351990.ref019","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s12936-019-3089-z","article-title":"In vivo\/ex vivo efficacy of artemether-lumefantrine and artesunate-amodiaquine as first-line treatment for uncomplicated falciparum malaria in children: an open label randomized controlled trial in Burkina Faso","volume":"19","author":"M Lingani","year":"2020","journal-title":"Malar J"},{"key":"pone.0351990.ref020","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1186\/s12936-015-0629-z","article-title":"Pan-Plasmodium band sensitivity for Plasmodium falciparum detection in combination malaria rapid diagnostic tests and implications for clinical management","volume":"14","author":"ML Gatton","year":"2015","journal-title":"Malar J"},{"key":"pone.0351990.ref021","volume-title":"Disease surveillance for malaria elimination: an operational manual","author":"World Health Organization","year":"2013"},{"issue":"1","key":"pone.0351990.ref022","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s13071-018-2617-y","article-title":"Diagnostic tools in childhood malaria","volume":"11","author":"A Amir","year":"2018","journal-title":"Parasit Vectors"},{"issue":"12","key":"pone.0351990.ref023","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1093\/infdis\/jit431","article-title":"Residual Plasmodium falciparum parasitemia in Kenyan children after artemisinin-combination therapy is associated with increased transmission to mosquitoes and parasite recurrence","volume":"208","author":"KB Beshir","year":"2013","journal-title":"J Infect Dis"},{"issue":"7","key":"pone.0351990.ref024","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgph.0001879","article-title":"Diagnostic performance of PfHRP2\/pLDH malaria rapid diagnostic tests in elimination setting, northwest Ethiopia","volume":"3","author":"MT Zeleke","year":"2023","journal-title":"PLOS Glob Public Health"},{"issue":"320","key":"pone.0351990.ref025","first-page":"1","article-title":"Is there evidence of anti \u2011 malarial multidrug resistance in Burkina Faso?","volume":"20","author":"C Rasmussen","year":"2021","journal-title":"Malar J"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0351990","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T17:36:03Z","timestamp":1782236163000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0351990"}},"subtitle":[],"editor":[{"given":"Enoch","family":"Aninagyei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,6,23]]},"references-count":25,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6,23]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0351990","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,23]]}}}