{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T19:33:05Z","timestamp":1792611185296,"version":"4.5.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2019,5,31]],"date-time":"2019-05-31T00:00:00Z","timestamp":1559260800000},"content-version":"vor","delay-in-days":150,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,6,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Little is known about clinical characteristics and management of severe yellow fever as previous yellow fever epidemics often occurred in times or areas with little access to intensive care units (ICU). We aim to describe the clinical characteristics of severe yellow fever cases requiring admission to the ICU during the 2018 yellow fever outbreak in S\u00e3o Paulo, Brazil. Furthermore, we report on preliminary lessons learnt regarding clinical management of severe yellow fever.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Retrospective descriptive cohort study. Demographic data, laboratory test results on admission, clinical follow-up, and clinical outcomes were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>From 10 January to 11 March 2018, 79 patients with laboratory confirmed yellow fever were admitted to the ICU in a tertiary hospital in Sao Paolo because of rapid clinical deterioration. On admission, the median AST was 7,000 IU\/L, ALT 3,936 IU\/L, total bilirubin 5.3 ml\/dL, platelet 74\u00a0\u00d7\u00a0103\/mm3, INR 2.24 and factor V 37%. Seizures occurred in 24% of patients, even without substantial intracranial hypertension. The high frequency of pancreatitis and rapidly progressive severe metabolic acidosis were notable findings. 73% of patients required renal replacement therapy. The in-hospital fatality rate was 67%. Patients with diabetes mellitus had a higher case fatality rate (CFR) of 80%, while patients without diabetes had a CFR of 65%. Leading causes of death were severe gastrointestinal bleeding, epileptic status, severe metabolic acidosis, necrohemorrhagic pancreatitis, and multi-organ failure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Severe yellow fever is associated with a high CFR. The following management lessons were learnt: Anticonvulsant drugs in patients with any symptoms of hepatic encephalopathy or arterial ammonia levels &gt;70\u00a0\u03bcmol\/L was commenced which reduced the frequency of seizures from 28% to 17%. Other new therapy strategies included early institution of plasma exchange. Due to the high frequency of gastric bleeding, therapeutic doses of intravenous proton pump inhibitors should be administered.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jtm\/taz040","type":"journal-article","created":{"date-parts":[[2019,5,30]],"date-time":"2019-05-30T07:07:48Z","timestamp":1559200068000},"source":"Crossref","is-referenced-by-count":83,"title":["Severe yellow fever in Brazil: clinical characteristics and management"],"prefix":"10.1093","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8719-2508","authenticated-orcid":false,"given":"Yeh-Li","family":"Ho","sequence":"first","affiliation":[{"name":"Departamento e Divis\u00e3o de Mol\u00e9stias Infecciosas e Parasit\u00e1rias, Hospital das Cl\u00ednicas, Faculdade de Medicina USP (HCFMUSP), Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Joelsons","sequence":"additional","affiliation":[{"name":"Departamento e Divis\u00e3o de Mol\u00e9stias Infecciosas e Parasit\u00e1rias, Hospital das Cl\u00ednicas, Faculdade de Medicina USP (HCFMUSP), Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel F C","family":"Leite","sequence":"additional","affiliation":[{"name":"Departamento e Divis\u00e3o de Mol\u00e9stias Infecciosas e Parasit\u00e1rias, Hospital das Cl\u00ednicas, Faculdade de Medicina USP (HCFMUSP), Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz M S","family":"Malbouisson","sequence":"additional","affiliation":[{"name":"Departamento de Gastroenterologia, HCFMUSP, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice T W","family":"Song","sequence":"additional","affiliation":[{"name":"Disciplina de Transplantes de \u00d3rg\u00e3os do Aparelho Digestivo do Departamento de Gastroenterologia, HCFMUSP, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Perondi","sequence":"additional","affiliation":[{"name":"Diretoria Cl\u00ednica, HCFMUSP, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia C","family":"Andrade","sequence":"additional","affiliation":[{"name":"Departamento de Nefrologia, FMUSP, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e9cio F","family":"Pinto","sequence":"additional","affiliation":[{"name":"Divis\u00e3o de Cl\u00ednica Neurol\u00f3gica, HCFMUSP, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz A C","family":"D\u2019Albuquerque","sequence":"additional","affiliation":[{"name":"Disciplina de Transplantes de \u00d3rg\u00e3os do Aparelho Digestivo do Departamento de Gastroenterologia, HCFMUSP, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aluisio A C","family":"Segurado","sequence":"additional","affiliation":[{"name":"Departamento e Divis\u00e3o de Mol\u00e9stias Infecciosas e Parasit\u00e1rias, Hospital das Cl\u00ednicas, Faculdade de Medicina USP (HCFMUSP), Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Hospital das Cl\u00ednicas Yellow Fever Assistance Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,5,31]]},"reference":[{"key":"2019091012145845800_ref1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.5123\/S2176-62232011000100002","article-title":"Evolu\u00e7\u00e3o hist\u00f3rica da vigil\u00e2ncia epidemiol\u00f3gica e do controle da febre amarela no Brasil","volume":"2","author":"Costa","year":"2011","journal-title":"Rev Pan-Amaz Saude"},{"key":"2019091012145845800_ref2","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1002\/jmv.2078","article-title":"Epidemic of jungle yellow fever in Brazil, 2000: implications of climatic alterations in disease spread","volume":"65","author":"Vasconcelos","year":"2001","journal-title":"J Med Virol"},{"key":"2019091012145845800_ref3","doi-asserted-by":"crossref","first-page":"e17","DOI":"10.1590\/s1678-9946201759017","article-title":"What to expect from the 2017 yellow fever outbreak in Brazil?","volume":"59","author":"Rossetto","year":"2017","journal-title":"Rev Inst Med Trop Sao Paulo"},{"key":"2019091012145845800_ref4","doi-asserted-by":"crossref","first-page":"7385","DOI":"10.1038\/s41598-017-07873-7","article-title":"Phylodynamics of yellow fever virus in the Americas: new insights into the origin of the 2017 Brazilian outbreak","volume":"7","author":"Mir","year":"2017","journal-title":"Sci Rep"},{"key":"2019091012145845800_ref5","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1126\/science.aat7115","article-title":"Genomic and epidemiological monitoring of yellow fever virus transmission potential","volume":"361","author":"Faria","year":"2018","journal-title":"Science"},{"key":"2019091012145845800_ref6","volume-title":"Atualiza\u00e7\u00e3o: Situa\u00e7\u00e3o epidemiol\u00f3gica da febre amarela silvestre em Minas Gerais, 2017. In: Superintend\u00eacia de vigil\u00e2ncia Epidemiologica. Atualiza\u00e7\u00e3o 21\/08\/2017","author":"Secretaria da Sa\u00fade Minas Gerais","year":"2017"},{"key":"2019091012145845800_ref7","volume-title":"Vigilancia Epidemiologica da Sa\u00fade","author":"Minist\u00e9rio da Sa\u00fade","year":"2017"},{"key":"2019091012145845800_ref8","volume-title":"Centro de Vigilancia Epidemiologica professo Alexandre Vranjac, ed. Vol 26\/03\/2018","author":"Secretaria de Estado da Sa\u00fade S\u00e3o Paulo","year":"2018"},{"key":"2019091012145845800_ref9","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/s41426-018-0128-8","article-title":"Yellow fever in the diagnostics laboratory","volume":"7","author":"Domingo","year":"2018","journal-title":"Emerg Microbes Infect"},{"key":"2019091012145845800_ref10","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.ajem.2016.02.012","article-title":"Bedside sonographic measurement of optic nerve sheath diameter as a predictor of intracranial pressure in ED","volume":"34","author":"Komut","year":"2016","journal-title":"Am J Emerg Med"},{"key":"2019091012145845800_ref11","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.trstmh.2006.04.001","article-title":"Clinical and epidemiological characteristics of yellow fever in Brazil: analysis of reported cases 1998-2002","volume":"101","author":"Tuboi","year":"2007","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"2019091012145845800_ref12","first-page":"11","article-title":"Epidemiological characteristics of yellow fever in Brazil, 2000\u20132012","volume":"25","author":"Cavalcante","year":"2016","journal-title":"Epidemiol Serv Saude"},{"key":"2019091012145845800_ref13","doi-asserted-by":"crossref","first-page":"340","DOI":"10.15585\/mmwr.mm6711e1","article-title":"Fatal yellow fever in travelers to Brazil, 2018","volume":"67","author":"Hamer","year":"2018","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"2019091012145845800_ref14","doi-asserted-by":"crossref","DOI":"10.1093\/jtm\/tax008","article-title":"Importation of yellow fever into China: assessing travel patterns","volume":"24","author":"Wilder-Smith","year":"2017","journal-title":"J Travel Med"},{"key":"2019091012145845800_ref15","article-title":"Vaccination and associated factors among health workers","volume":"35","author":"Araujo","year":"2019","journal-title":"Cad Sa\u00fade Publica"},{"key":"2019091012145845800_ref16","volume-title":"Vigilancia epidemiologica em Sa\u00fade","author":"Minist\u00e9rio da Saude"},{"key":"2019091012145845800_ref17","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.4269\/ajtmh.1999.60.1045","article-title":"Comparison of the immunogenicity and safety of two 17D yellow fever vaccines","volume":"60","author":"Lang","year":"1999","journal-title":"Am J Trop Med Hyg"},{"key":"2019091012145845800_ref18","doi-asserted-by":"crossref","first-page":"e536","DOI":"10.1016\/j.ijid.2012.03.004","article-title":"Epidemiological and laboratory characterization of a yellow fever outbreak in northern Uganda, October 2010\u2013January 2011","volume":"16","author":"Wamala","year":"2012","journal-title":"Int J Infect Dis"},{"key":"2019091012145845800_ref19","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1055\/s-0032-1301733","article-title":"Acute liver failure","volume":"33","author":"Lee","year":"2012","journal-title":"Semin Respir Crit Care Med"},{"key":"2019091012145845800_ref20","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1002\/rmv.1752","article-title":"Immunity and immune response, pathology and pathologic changes: progress and challenges in the immunopathology of yellow fever","volume":"23","author":"Quaresma","year":"2013","journal-title":"Rev Med Virol"},{"key":"2019091012145845800_ref21","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/S0065-3527(03)60009-6","article-title":"Pathogenesis and pathophysiology of yellow fever","volume":"60","author":"Monath","year":"2003","journal-title":"Adv Virus Res"},{"key":"2019091012145845800_ref22","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1136\/gut.2004.061754","article-title":"Predictive value of arterial ammonia for complications and outcome in acute liver failure","volume":"55","author":"Bhatia","year":"2006","journal-title":"Gut"},{"key":"2019091012145845800_ref23","article-title":"Ultrasonographic optic nerve sheath diameter to detect increased intracranial pressure in adults: a meta-analysis","author":"Kim","year":"2018","journal-title":"Acta Radiol"},{"key":"2019091012145845800_ref24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2147\/HMER.S118964","article-title":"Hepatic encephalopathy: current challenges and future prospects","volume":"10","author":"Swaminathan","year":"2018","journal-title":"Hepat Med"},{"key":"2019091012145845800_ref25","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.12688\/f1000research.11938.1","article-title":"Recent advances in hepatic encephalopathy","volume":"6","author":"Liere","year":"2017","journal-title":"F1000Res"},{"key":"2019091012145845800_ref26","doi-asserted-by":"crossref","first-page":"e69","DOI":"10.1038\/emi.2016.89","article-title":"A fatal yellow fever virus infection in China: description and lessons","volume":"5","author":"Chen","year":"2016","journal-title":"Emerg Microbes Infect"},{"key":"2019091012145845800_ref27","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.pan.2017.02.008","article-title":"Frequency and prognosis of acute pancreatitis associated with fulminant or non-fulminant acute hepatitis a: a systematic review","volume":"17","author":"Haffar","year":"2017","journal-title":"Pancreatology"},{"key":"2019091012145845800_ref28","first-page":"1","article-title":"Extra-hepatic manifestations associated with hepatitis E virus infection: a comprehensive review of the literature","volume":"4","author":"Bazerbachi","year":"2016","journal-title":"Gastroenterol Rep (Oxf)"},{"key":"2019091012145845800_ref29","first-page":"104","article-title":"Pancreatitis developing in the context of acute hepatitis: a literature review","volume":"16","author":"Khedmat","year":"2015","journal-title":"JOP"},{"key":"2019091012145845800_ref30","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0344-0338(11)81176-3","article-title":"Human fatal yellow fever. Immunohistochemical detection of viral antigens in the liver, kidney and heart","volume":"188","author":"De Brito","year":"1992","journal-title":"Pathol Res Pract"},{"key":"2019091012145845800_ref31","first-page":"143","article-title":"Estudo da coagula\u00e7\u00e3o sanguinea na febre amarela","volume":"2","author":"Borges","year":"1973","journal-title":"J Trop Pathol"},{"key":"2019091012145845800_ref32","article-title":"Coagula\u00e7\u00e3o intravascular disseminada aguda na febre amarela: dosagem dos factores da coagulac\u00e3o","volume":"9","author":"Santos","year":"1973","journal-title":"Brasilia Med"},{"key":"2019091012145845800_ref33","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S1473-3099(01)00016-0","article-title":"Yellow fever: an update","volume":"1","author":"Monath","year":"2001","journal-title":"Lancet Infect Dis"},{"key":"2019091012145845800_ref34","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.jhep.2015.09.010","article-title":"High volume plasma exchange in acute liver failure: dampening the inflammatory cascade?","volume":"64","author":"Karvellas","year":"2016","journal-title":"J Hepatol"},{"key":"2019091012145845800_ref35","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s11011-013-9403-5","article-title":"Efficacy of liver assisting in patients with hepatic encephalopathy with special focus on plasma exchange","volume":"28","author":"Stenbog","year":"2013","journal-title":"Metab Brain Dis"},{"key":"2019091012145845800_ref36","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1111\/j.1572-0241.2001.03706.x","article-title":"Effects of high-volume plasmapheresis on ammonia, urea, and amino acids in patients with acute liver failure","volume":"96","author":"Clemmesen","year":"2001","journal-title":"Am J Gastroenterol"},{"key":"2019091012145845800_ref37","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.jhep.2015.08.018","article-title":"High-volume plasma exchange in patients with acute liver failure: an open randomised controlled trial","volume":"64","author":"Larsen","year":"2016","journal-title":"J Hepatol"},{"key":"2019091012145845800_ref38","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/j.jhep.2016.12.003","article-title":"EASL clinical practical guidelines on the management of acute (fulminant) liver failure","volume":"66","author":"Wendon","year":"2017","journal-title":"J Hepatol"},{"key":"2019091012145845800_ref39","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.amjcard.2018.11.032","article-title":"Cardiac involvement by yellow fever (from the PROVAR+ study)","volume":"123","author":"Paixao","year":"2019","journal-title":"Am J Cardiol"},{"key":"2019091012145845800_ref40","doi-asserted-by":"crossref","DOI":"10.1016\/S1473-3099(19)30125-2","article-title":"Predictors of mortality in patients with yellow fever: an observational cohort study","author":"Kallas","year":"2019","journal-title":"Lancet Infect Dis"},{"key":"2019091012145845800_ref41","doi-asserted-by":"crossref","DOI":"10.1093\/jtm\/tay016","article-title":"Recommendations for travellers during the yellow fever outbreaks in Brazil\u20142018","volume":"25","author":"Fujita","year":"2018","journal-title":"J Travel Med"},{"key":"2019091012145845800_ref42","doi-asserted-by":"crossref","DOI":"10.1093\/jtm\/tay097","article-title":"Pandemic yellow fever: a potential threat to global health via travelers","volume":"25","author":"Gubler","year":"2018","journal-title":"J Travel Med"},{"key":"2019091012145845800_ref43","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1016\/S1473-3099(17)30494-2","article-title":"Yellow fever vaccination: estimating coverage","volume":"17","author":"Wilder-Smith","year":"2017","journal-title":"Lancet Infect Dis"},{"key":"2019091012145845800_ref44","doi-asserted-by":"crossref","first-page":"e101","DOI":"10.1016\/S1473-3099(16)30518-7","article-title":"Epidemic arboviral diseases: priorities for research and public health","volume":"17","author":"Wilder-Smith","year":"2017","journal-title":"Lancet Infect Dis"}],"container-title":["Journal of Travel Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jtm\/advance-article-pdf\/doi\/10.1093\/jtm\/taz040\/28915053\/taz040.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jtm\/article-pdf\/26\/5\/taz040\/28926826\/taz040.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,10]],"date-time":"2019-09-10T13:11:40Z","timestamp":1568121100000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jtm\/article\/doi\/10.1093\/jtm\/taz040\/5509466"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019]]},"references-count":44,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2019,5,31]]},"published-print":{"date-parts":[[2019,6,11]]}},"URL":"https:\/\/doi.org\/10.1093\/jtm\/taz040","relation":{},"ISSN":["1708-8305"],"issn-type":[{"value":"1708-8305","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019]]},"published":{"date-parts":[[2019]]},"article-number":"taz040"}}