{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T11:10:30Z","timestamp":1740136230838,"version":"3.37.3"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,4,22]],"date-time":"2023-04-22T00:00:00Z","timestamp":1682121600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,4,22]],"date-time":"2023-04-22T00:00:00Z","timestamp":1682121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005744","name":"Lastentautien Tutkimuss\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005744","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Helsinki including Helsinki University Central Hospital"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Malar J"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>In malaria-endemic areas, children presenting to hospitals with a decreased level of consciousness remain a diagnostic dilemma. The definition of cerebral malaria in a comatose child demands exclusion of other possible reasons, which requires in-depth investigations that are not easily available. The aim of this study was to investigate the frequency and clinical characteristics of PCR-confirmed malaria in a cohort of children with a decreased level of consciousness, look for potential features that would aid in differentiating children with malaria from those without, and assess the performance of traditional thick film microscopy against the cytb-qPCR-method.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A total of 345 children aged 30\u00a0days\u201315\u00a0years old, presenting to Hospital Pedi\u00e1trico David Bernardino in Luanda, Angola, with a decreased level of consciousness (Glasgow coma scale score\u2009&lt;\u200915) were prospectively enrolled during 2014\u20132017. Malaria was defined as a positive cytb-qPCR result on any occasion in hospital. The clinical course and laboratory parameters were compared between children with malaria and those without. The performance of thick film microscopy was analysed against the PCR method.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>161 of 345 children (46.7%) had a positive malaria PCR test result. All cases were <jats:italic>Plasmodium falciparum<\/jats:italic> species, and 82.6% (133\/161) fulfilled the WHO criteria for severe malaria. Overall, children with malaria presented to hospital with a shorter duration of symptoms and less convulsions pre-admission compared to those without malaria. The median GCS score on admission was 8, which did not differ between children with or without malaria. Clinical findings on admission were mostly similar across the whole cohort, but an infection focus outside the central nervous system was more common in malaria-negative children. Moreover, severe anaemia, thrombocytopenia, and high CRP levels occurred more frequently in children with malaria. The case fatality ratio was 28.5% (91\/319) and did not differ between parasitaemic children and those without malaria, although parasitaemic children died sooner after hospital admission. When neurological sequelae were also considered, a positive malaria test was associated with a better outcome. The performance of thick film microscopy against PCR yielded a sensitivity of 96.8% and a specificity of 82.7%.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>In this cohort of children with a decreased consciousness, the frequent presence of a malarial infection could not be judged from the clinical findings on admission, but the combination of profound aneamia, thrombocytopenia, and a high CRP level increased the odds of a positive malaria test result. Mortality remained high regardless of etiology, but malaria infection associated with fewer neurological deficits at discharge. Thick film microscopy performed well compared to the cytb-qPCR method.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12936-023-04556-9","type":"journal-article","created":{"date-parts":[[2023,4,22]],"date-time":"2023-04-22T18:02:05Z","timestamp":1682186525000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["PCR-confirmed malaria among children presenting with a decreased level of consciousness in Angola: a prospective, observational study"],"prefix":"10.1186","volume":"22","author":[{"given":"Okko","family":"Savonius","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cintia F.","family":"de Souza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cl\u00e1udia","family":"Fan\u00e7ony","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel Leite","family":"Cruzeiro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel","family":"Brito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tuula","family":"Pelkonen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,4,22]]},"reference":[{"key":"4556_CR1","volume-title":"World malaria report 2022","author":"WHO","year":"2022","unstructured":"WHO. World malaria report 2022. Geneva: World Health Organization; 2022."},{"key":"4556_CR2","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1093\/qjmed\/92.3.151","volume":"92","author":"JA Berkley","year":"1999","unstructured":"Berkley JA, Mwangi I, Mellington F, Mwarumba S, Marsh K. Cerebral malaria versus bacterial meningitis in children with impaired consciousness. QJM. 1999;92:151\u20137.","journal-title":"QJM"},{"key":"4556_CR3","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1056\/NEJM199505253322102","volume":"332","author":"K Marsh","year":"1995","unstructured":"Marsh K, Forster D, Waruiru C, Mwangi I, Winstanley M, Marsh V, et al. Indicators of life-threatening malaria in African children. N Engl J Med. 1995;332:1399\u2013404.","journal-title":"N Engl J Med"},{"key":"4556_CR4","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1016\/S1474-4422(05)70247-7","volume":"4","author":"R Idro","year":"2005","unstructured":"Idro R, Jenkins NE, Newton CRJC. Pathogenesis, clinical features, and neurological outcome of cerebral malaria. Lancet Neurol. 2005;4:827\u201340.","journal-title":"Lancet Neurol"},{"key":"4556_CR5","doi-asserted-by":"publisher","first-page":"104","DOI":"10.3389\/fcimb.2014.00104","volume":"4","author":"DA Milner Jr","year":"2014","unstructured":"Milner DA Jr, Whitten RO, Kamiza S, Carr R, Liomba G, Dzamalala C, et al. The systemic pathology of cerebral malaria in African children. Front Cell Infect Microbiol. 2014;4:104.","journal-title":"Front Cell Infect Microbiol"},{"key":"4556_CR6","doi-asserted-by":"publisher","first-page":"349","DOI":"10.2217\/fmb.11.3","volume":"6","author":"NAV Beare","year":"2011","unstructured":"Beare NAV, Lewallen S, Taylor TE, Molyneux ME. Redefining cerebral malaria by including malaria retinopathy. Future Microbiol. 2011;6:349\u201355.","journal-title":"Future Microbiol"},{"key":"4556_CR7","volume-title":"Guidelines for the treatment of malaria","author":"WHO","year":"2010","unstructured":"WHO. Guidelines for the treatment of malaria. 2nd ed. Geneva: World Health Organization; 2010.","edition":"2"},{"key":"4556_CR8","volume-title":"Parasitological confirmation of malaria diagnosis: report of a WHO technical consultation, 6\u20138 October 2009","author":"WHO","year":"2010","unstructured":"WHO. Parasitological confirmation of malaria diagnosis: report of a WHO technical consultation, 6\u20138 October 2009. Geneva: World Health Organization; 2010."},{"key":"4556_CR9","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1186\/1475-2875-10-332","volume":"10","author":"J Kahama-Maro","year":"2011","unstructured":"Kahama-Maro J, D\u2019Acremont V, Mtasiwa D, Genton B, Lengeler C. Low quality of routine microscopy for malaria at different levels of the health system in Dar es Salaam. Malar J. 2011;10:332.","journal-title":"Malar J"},{"key":"4556_CR10","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1186\/1475-2875-13-437","volume":"13","author":"S Moura","year":"2014","unstructured":"Moura S, Fan\u00e7ony C, Mirante C, Neves M, Bernardino L, Fortes F, et al. Impact of a training course on the quality of malaria diagnosis by microscopy in Angola. Malar J. 2014;13:437.","journal-title":"Malar J"},{"key":"4556_CR11","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1186\/1475-2875-12-284","volume":"12","author":"C Fan\u00e7ony","year":"2013","unstructured":"Fan\u00e7ony C, Sebasti\u00e3o YV, Pires JE, Gamboa D, Nery SV. Performance of microscopy and RDTs in the context of a malaria prevalence survey in Angola: a comparison using PCR as the gold standard. Malar J. 2013;12:284.","journal-title":"Malar J"},{"key":"4556_CR12","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1086\/644781","volume":"200","author":"LC Okell","year":"2009","unstructured":"Okell LC, Ghani AC, Lyons E, Drakeley CJ. Submicroscopic infection in Plasmodium falciparum-endemic populations: a systematic review and meta-analysis. J Infect Dis. 2009;200:1509\u201317.","journal-title":"J Infect Dis"},{"key":"4556_CR13","volume-title":"Management of severe malaria: a practical handbook","author":"WHO","year":"2012","unstructured":"WHO. Management of severe malaria: a practical handbook. 3rd ed. Geneva: World Health Organization; 2012.","edition":"3"},{"key":"4556_CR14","doi-asserted-by":"publisher","first-page":"e0120210","DOI":"10.1371\/journal.pone.0120210","volume":"10","author":"W Xu","year":"2015","unstructured":"Xu W, Morris U, Aydin-Schmidt B, Msellem MI, Shakely D, Petzold M, et al. SYBR Green real-time PCR-RFLP assay targeting the Plasmodium cytochrome B gene\u2013a highly sensitive molecular tool for malaria parasite detection and species determination. PLoS ONE. 2015;10:e0120210.","journal-title":"PLoS ONE"},{"issue":"Suppl 1","key":"4556_CR15","first-page":"7","volume":"19","author":"WHO","year":"2014","unstructured":"WHO. Severe malaria. Trop Med Int Health. 2014;19(Suppl 1):7\u2013131.","journal-title":"Trop Med Int Health"},{"key":"4556_CR16","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1046\/j.1365-2257.1999.00220.x","volume":"21","author":"T H\u00e4nscheid","year":"1999","unstructured":"H\u00e4nscheid T. Diagnosis of malaria: a review of alternatives to conventional microscopy. Clin Lab Haematol. 1999;21:235\u201345.","journal-title":"Clin Lab Haematol"},{"key":"4556_CR17","volume-title":"Standard operating procedures for surveillance of meningitis preparedness and response to epidemics in Africa","author":"WHO","year":"2019","unstructured":"WHO. Standard operating procedures for surveillance of meningitis preparedness and response to epidemics in Africa. Brazzaville: Regional Office for Africa World Health Organization; 2019."},{"key":"4556_CR18","unstructured":"MedCalc Software Ltd. MedCalc Software Ltd. Diagnostic test evaluation calculator (Version 20.006). 2021. https:\/\/www.medcalc.org\/calc\/diagnostic_test.php. Accessed 7 Jun 2021."},{"key":"4556_CR19","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1186\/s12916-017-0906-5","volume":"15","author":"P Sypniewska","year":"2017","unstructured":"Sypniewska P, Duda JF, Locatelli I, Althaus CR, Althaus F, Genton B. Clinical and laboratory predictors of death in African children with features of severe malaria: a systematic review and meta-analysis. BMC Med. 2017;15:147.","journal-title":"BMC Med"},{"key":"4556_CR20","doi-asserted-by":"publisher","first-page":"e000475","DOI":"10.1136\/bmjopen-2011-000475","volume":"2","author":"S Gwer","year":"2012","unstructured":"Gwer S, Thuo N, Idro R, Ndiritu M, Boga M, Newton C, et al. Changing trends in incidence and aetiology of childhood acute non-traumatic coma over a period of changing malaria transmission in rural coastal Kenya: a retrospective analysis. BMJ Open. 2012;2:e000475.","journal-title":"BMJ Open"},{"key":"4556_CR21","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1093\/trstmh\/trv046","volume":"109","author":"T Pelkonen","year":"2015","unstructured":"Pelkonen T, Albino A, Roine I, Bernardino L, Peltola H. C-reactive protein in children with malaria in Luanda, Angola: a prospective study. Trans R Soc Trop Med Hyg. 2015;109:535\u20137.","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"4556_CR22","first-page":"441","volume":"71","author":"ME Molyneux","year":"1989","unstructured":"Molyneux ME, Taylor TE, Wirima JJ, Borgstein A. Clinical features and prognostic indicators in paediatric cerebral malaria: a study of 131 comatose Malawian children. Q J Med. 1989;71:441\u201359.","journal-title":"Q J Med"},{"key":"4556_CR23","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1179\/027249304225013240","volume":"24","author":"R Idro","year":"2004","unstructured":"Idro R, Karamagi C, Tumwine J. Immediate outcome and prognostic factors for cerebral malaria among children admitted to Mulago hospital. Uganda Ann Trop Paediatr. 2004;24:17\u201324.","journal-title":"Uganda Ann Trop Paediatr"},{"key":"4556_CR24","doi-asserted-by":"publisher","first-page":"20","DOI":"10.4269\/ajtmh.1997.57.20","volume":"57","author":"S Jaffar","year":"1997","unstructured":"Jaffar S, Van Hensbroek MB, Palmer A, Schneider G, Greenwood B. Predictors of a fatal outcome following childhood cerebral malaria. Am J Trop Med Hyg. 1997;57:20\u20134.","journal-title":"Am J Trop Med Hyg"},{"key":"4556_CR25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0163-7258(98)00008-4","volume":"79","author":"CR Newton","year":"1998","unstructured":"Newton CR, Krishna S. Severe falciparum malaria in children: current understanding of pathophysiology and supportive treatment. Pharmacol Ther. 1998;79:1\u201353.","journal-title":"Pharmacol Ther"},{"key":"4556_CR26","doi-asserted-by":"publisher","first-page":"1738","DOI":"10.1093\/cid\/ciaa341","volume":"72","author":"O Savonius","year":"2021","unstructured":"Savonius O, Rugemalira E, Roine I, Cruzeiro ML, Peltola H, Pelkonen T. Extended continuous \u03b2-lactam infusion with oral acetaminophen in childhood bacterial meningitis: a randomized, double-blind clinical trial. Clin Infect Dis. 2021;72:1738\u201344.","journal-title":"Clin Infect Dis"},{"key":"4556_CR27","volume-title":"Guidelines for malaria","author":"WHO","year":"2021","unstructured":"WHO. Guidelines for malaria. Geneva: World Health Organization; 2021."},{"key":"4556_CR28","first-page":"CD005967","volume":"2012","author":"D Sinclair","year":"2012","unstructured":"Sinclair D, Donegan S, Isba R, Lalloo DG. Artesunate versus quinine for treating severe malaria. Cochrane Database Syst Rev. 2012;2012:CD005967.","journal-title":"Cochrane Database Syst Rev"},{"key":"4556_CR29","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1186\/s12936-019-2711-4","volume":"18","author":"KO Mfuh","year":"2019","unstructured":"Mfuh KO, Achonduh-Atijegbe OA, Bekindaka ON, Esemu LF, Mbakop CD, Gandhi K, et al. A comparison of thick-film microscopy, rapid diagnostic test, and polymerase chain reaction for accurate diagnosis of Plasmodium falciparum malaria. Malar J. 2019;18:73.","journal-title":"Malar J"},{"key":"4556_CR30","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1186\/s12936-020-03163-2","volume":"19","author":"TA Leski","year":"2020","unstructured":"Leski TA, Taitt CR, Swaray AG, Bangura U, Reynolds ND, Holtz A, et al. Use of real-time multiplex PCR, malaria rapid diagnostic test and microscopy to investigate the prevalence of Plasmodium species among febrile hospital patients in Sierra Leone. Malar J. 2020;19:84.","journal-title":"Malar J"}],"container-title":["Malaria Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12936-023-04556-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12936-023-04556-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12936-023-04556-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,22]],"date-time":"2023-04-22T18:02:18Z","timestamp":1682186538000},"score":1,"resource":{"primary":{"URL":"https:\/\/malariajournal.biomedcentral.com\/articles\/10.1186\/s12936-023-04556-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,22]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["4556"],"URL":"https:\/\/doi.org\/10.1186\/s12936-023-04556-9","relation":{},"ISSN":["1475-2875"],"issn-type":[{"type":"electronic","value":"1475-2875"}],"subject":[],"published":{"date-parts":[[2023,4,22]]},"assertion":[{"value":"13 January 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 April 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 April 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study protocol was approved by the Ethics Committee of the Paediatric Hospital of Luanda on April 15, 2014.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"130"}}