{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:27:04Z","timestamp":1787009224738,"version":"build-2736575974"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T00:00:00Z","timestamp":1620345600000},"content-version":"vor","delay-in-days":0,"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":[[2021,9,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>Disseminated histoplasmosis (DH) is endemic in Latin America and the Caribbean where diagnostic tools are restricted. We carried-out a 1-year prospective cohort study at a referral hospital in S\u00e3o Paulo, Brazil. Participants had\u00a0&amp;gt;\u00a0or\u00a0=18 years old, were hospitalized due to any indication and had CD4+ &amp;lt; 200 cells\/\u00b5l. A urine commercial monoclonal Histoplasma galactomannan enzyme-linked immunosorbent assay (IMMY, Norman, OK, USA) and \u2018in house\u2019 Histoplasma blood nested PCR were performed in all cases. Probable\/proven DH cases were defined according to international guidelines. Conventional mycological methods were available in routine conditions to investigate suspected DH cases. Treatment of participants followed the institutional routine. One-hundred six participants were included. Median age (interquartile range [IQR]) was 39.5 years (30.0\u201347.3) and 80 individuals (75.5%) were males. Median (IQR) CD4 cell count was 26.5 (9.4\u201389.3) cells\/mm3. DH was diagnosed in 8\/106 patients (7.5%). Antigen assay and\/or PCR were positive in 4.7% (5\/106) of patients. The antigen assay and\/or PCR identified 37.5% (3\/8) of DH cases, which had not been diagnosed with conventional mycological methods, but had clinical manifestations compatible with HD. In conclusion, the use of Histoplasma urine antigen and Histoplasma blood PCR guided by CD4 status contributed to the diagnosis of DH in hospitalized individuals. These assays were complementary to conventional mycologic methods and are urgently needed in our setting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Lay Summary<\/jats:title>\n                    <jats:p>In this prospective cohort study carried-out in a referral center in S\u00e3o Paulo, Brazil, we found a high frequency of AIDS-related disseminated histoplasmosis (8\/106, 7.5%). We used urine antigen test and blood PCR assay to improve the diagnosis of this opportunistic disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/mmy\/myab022","type":"journal-article","created":{"date-parts":[[2021,4,13]],"date-time":"2021-04-13T18:17:14Z","timestamp":1618337834000},"page":"916-922","source":"Crossref","is-referenced-by-count":14,"title":["Combining urine antigen and blood polymerase chain reaction for the diagnosis of disseminated histoplasmosis in hospitalized patients with advanced HIV disease"],"prefix":"10.1093","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7830-8716","authenticated-orcid":false,"given":"Jos\u00e9 E","family":"Vidal","sequence":"first","affiliation":[{"name":"Departamento de Neurologia, Instituto de Infectologia Emilio Ribas, S\u00e3o Paulo 01246-900, Brazil"},{"name":"Divis\u00e3o de Cl\u00ednica de Mol\u00e9stias Infecciosas e Parasit\u00e1rias, Hospital das Cl\u00ednicas, Faculdade de Medicina da Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05403-000, Brazil"},{"name":"Laborat\u00f3rio de Investiga\u00e7\u00e3o M\u00e9dica, Unidade 49, Hospital das Clinicas, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 05403-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula Custodio","family":"Werlang","sequence":"additional","affiliation":[{"name":"Departamento de Infectologia, Instituto de Infectologia Emilio Ribas, S\u00e3o Paulo 01246-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno M","family":"Muniz","sequence":"additional","affiliation":[{"name":"Departamento de Infectologia, Instituto de Infectologia Emilio Ribas, S\u00e3o Paulo 01246-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline Martins","family":"Rego","sequence":"additional","affiliation":[{"name":"Departamento de Infectologia, Instituto de Infectologia Emilio Ribas, S\u00e3o Paulo 01246-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata Elisie","family":"Barbalho","sequence":"additional","affiliation":[{"name":"Departamento de Infectologia, Instituto de Infectologia Emilio Ribas, S\u00e3o Paulo 01246-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 Miranda","family":"Baptista","sequence":"additional","affiliation":[{"name":"Departamento de Infectologia, Instituto de Infectologia Emilio Ribas, S\u00e3o Paulo 01246-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joao Paulo","family":"Telles","sequence":"additional","affiliation":[{"name":"Departamento de Infectologia, Instituto de Infectologia Emilio Ribas, S\u00e3o Paulo 01246-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allecineia Bispo","family":"da Cruz","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular de Parasitas e Fungos, Instituto Adolfo Lutz, S\u00e3o Paulo 01246-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid de Siqueira","family":"Pereira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular de Parasitas e Fungos, Instituto Adolfo Lutz, S\u00e3o Paulo 01246-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Gava","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular de Parasitas e Fungos, Instituto Adolfo Lutz, S\u00e3o Paulo 01246-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Marcusso","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular de Parasitas e Fungos, Instituto Adolfo Lutz, S\u00e3o Paulo 01246-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro C","family":"Pasqualotto","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Doen\u00e7as Infecciosas, Universidade Federal de Ci\u00eancias da Sa\u00fade de Porto Alegre, Porto Alegre 90050-170, Brazil"},{"name":"Laborat\u00f3rio de Biologia Molecular, Santa Casa de Miseric\u00f3rdia de Porto Alegre, Porto Alegre 90035-075, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera Lucia","family":"Pereira-Chioccola","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Biologia Molecular de Parasitas e Fungos, Instituto Adolfo Lutz, S\u00e3o Paulo 01246-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,5,7]]},"reference":[{"key":"2021090300022017300_bib1","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.ijid.2019.07.009","article-title":"The occurrence of histoplasmosis in Brazil: a systematic review","volume":"86","author":"Almeida","year":"2019","journal-title":"Int J Infec Dis"},{"key":"2021090300022017300_bib2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1186\/s13104-020-05054-w","article-title":"HIV patients dying on anti-tuberculosis treatment: are undiagnosed infections still a problem in Frech Guiana?","volume":"13","author":"Nacher","year":"2020","journal-title":"BMC Res Notes"},{"key":"2021090300022017300_bib3","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1097\/QAD.0000000000000961","article-title":"Disseminated histoplasmosis in Central and South America, the invisible elephant: the lethal blind spot of international health organizations. The neglected histoplasmosis in Latin America Group","volume":"30","author":"Nacher","year":"2016","journal-title":"AIDS"},{"key":"2021090300022017300_bib4","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1111\/j.1365-3156.2007.01894.x","article-title":"Clinical and laboratory features of disseminated histoplasmosis in HIV patients from Brazil","volume":"12","author":"Daher","year":"2007","journal-title":"Trop Med Int Health"},{"key":"2021090300022017300_bib5","doi-asserted-by":"crossref","first-page":"ofz073","DOI":"10.1093\/ofid\/ofz073","article-title":"Histoplasmosis, an underdiagnosed disease affecting people living with HIV\/AIDS in Brazil: results of a multicenter prospective cohort study using both classical mycology tests and histoplasma urine antigen detection","volume":"6","author":"Falci","year":"2019","journal-title":"Open Forum Infect Dis"},{"key":"2021090300022017300_bib6","volume-title":"The Millennium Development Goals: a Latin America and Caribbean perspective","author":"Economic Commission for Latin America and the Caribbean (ECLAC)","year":"2005"},{"key":"2021090300022017300_bib7","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1128\/JCM.02430-16","article-title":"Laboratory diagnostics of histoplasmosis","volume":"55","author":"Azar","year":"2017","journal-title":"J Clin Microbiol"},{"key":"2021090300022017300_bib8","article-title":"Washington, DC: Pan American Health Organization and World Health Organization; 2020","author":"World Health Organization.","journal-title":"Diagnosing and Managing Disseminated Histoplasmosis among People Living with HIV"},{"key":"2021090300022017300_bib9","doi-asserted-by":"crossref","first-page":"e01487","DOI":"10.1128\/JCM.01487-19","article-title":"Updates in laboratory diagnostics for invasive fungal infections","volume":"58","author":"Terrero-Salcedo","year":"2020","journal-title":"J Clin Microbiol"},{"key":"2021090300022017300_bib10","volume-title":"Guidelines for Managing Advanced HIV Disease and Rapid Initiation of Antiretroviral Therapy","author":"World Health Organization","year":"2017"},{"key":"2021090300022017300_bib11","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1093\/cid\/ciz1008","article-title":"Revision and update of the consensus definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium","volume":"71","author":"Donnelly","year":"2020","journal-title":"Clin Infect Dis"},{"key":"2021090300022017300_bib12","doi-asserted-by":"crossref","first-page":"e01959","DOI":"10.1128\/JCM.01959-17","article-title":"Multicenter validation of commercial antigenuria reagents to diagnose progressive disseminated histoplasmosis in people living with HIV\/AIDS in two Latin American countries","volume":"56","author":"C\u00e1ceres","year":"2018","journal-title":"J Clin Microbiol"},{"key":"2021090300022017300_bib13","doi-asserted-by":"crossref","first-page":"5044","DOI":"10.1128\/JCM.43.10.5044-5047.2005","article-title":"Diagnosis of cerebral toxoplasmosis in AIDS patients in Brazil: importance of molecular and immunological methods using peripheral blood samples","volume":"43","author":"Colombo","year":"2005","journal-title":"J Clin Microbiol"},{"key":"2021090300022017300_bib14","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.bjid.2014.09.004","article-title":"Molecular diagnosis of cryptococcal meningitis in cerebrospinal fluid: comparison of primer sets for Cryptococcus neoformans and Cryptococcus gattii species complex","volume":"19","author":"Martins","year":"2015","journal-title":"Braz J Infect Dis"},{"key":"2021090300022017300_bib15","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1128\/JCM.40.5.1644-1647.2002","article-title":"Evaluation of two nested PCR assays for detection of Histoplasma capsulatum DNA in human tissue","volume":"40","author":"Bialek","year":"2002","journal-title":"J Clin Microbiol"},{"key":"2021090300022017300_bib16","doi-asserted-by":"crossref","first-page":"e0190408","DOI":"10.1371\/journal.pone.0190408","article-title":"Comparison of diagnostic methods to detect Histoplasma capsulatum in serum and plasma samples from AIDS patients","volume":"13","author":"Dantas","year":"2018","journal-title":"PLoS One"},{"key":"2021090300022017300_bib17","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.bjid.2017.07.003","article-title":"Molecular diagnosis of symptomatic toxoplasmosis: a 9-year retrospective and prospective study in a referral laboratory in S\u00e3o Paulo, Brazil","volume":"21","author":"Camilo","year":"2017","journal-title":"Braz J Infect Dis"},{"key":"2021090300022017300_bib18","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1590\/S0074-02762009000300019","article-title":"Mortality due to systemic mycoses as a primary cause of death or in association with AIDS in Brazil: a review from 1996 to 2006","volume":"104","author":"Prado","year":"2009","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"2021090300022017300_bib19","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1111\/myc.12427","article-title":"The burden of serious human fungal infections in Brazil","volume":"59","author":"Giacomazzi","year":"2016","journal-title":"Mycoses"},{"key":"2021090300022017300_bib20","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1590\/S0037-86822009000200020","article-title":"Histoplasmosis","volume":"42","author":"Ferreira","year":"2009","journal-title":"Rev Soc Bras Med Trop"},{"key":"2021090300022017300_bib21","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1016\/S1473-3099(18)30354-2","article-title":"Burden of HIV-associated histoplasmosis compared with tuberculosis in Latin America: a modelling study","volume":"18","author":"Adenis","year":"2018","journal-title":"Lancet Infect Dis"},{"key":"2021090300022017300_bib22","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1111\/myc.12890","article-title":"Clinical mycology in Latin America and the Caribbean: a snapshot of diagnostic and therapeutic capabilities","volume":"62","author":"Falci","year":"2019","journal-title":"Mycoses"},{"issue":"Suppl_1","key":"2021090300022017300_bib23","doi-asserted-by":"crossref","first-page":"S108","DOI":"10.1093\/clinids\/21.Supplement_1.S108","article-title":"Disseminated histoplasmosis in persons infected with human immunodeficiency virus","volume":"21","author":"Hajjeh","year":"1995","journal-title":"Clin Infect Dis"},{"key":"2021090300022017300_bib24","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1086\/513653","article-title":"Prospective study of histoplasmosis in patients infected with human immunodeficiency virus: incidence, risk factors, and pathophysiology","volume":"24","author":"McKinsey","year":"1997","journal-title":"Clin Infect Dis"},{"key":"2021090300022017300_bib25","doi-asserted-by":"crossref","first-page":"ofz534","DOI":"10.1093\/ofid\/ofz534","article-title":"The diagnostic laboratory hub: a new health care system reveals the incidence and mortality of tuberculosis, histoplasmosis, and cryptococcosis of PWH in Guatemala","volume":"7","author":"Samayoa","year":"2019","journal-title":"Open Forum Infect Dis"},{"key":"2021090300022017300_bib26","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1128\/CMR.00027-06","article-title":"Histoplasmosis: a clinical and laboratory update","volume":"20","author":"Kauffman","year":"2007","journal-title":"Clin Microbiol Rev"},{"key":"2021090300022017300_bib27","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1097\/QAD.0000000000002631","article-title":"Comparative performance of the laboratory assays used by a Diagnostic Laboratory Hub for opportunistic infections in people living with HIV","volume":"34","author":"Medina","year":"2020","journal-title":"AIDS"},{"key":"2021090300022017300_bib28","doi-asserted-by":"crossref","first-page":"e0006872","DOI":"10.1371\/journal.pntd.0006872","article-title":"Diagnostic accuracy cohort study and clinical value of the Histoplasma urine antigen (ALPHA Histoplasma EIA) for disseminated histoplasmosis among HIV infected patients: a multicenter study","volume":"12","author":"Torres-Gonz\u00e1lez","year":"2018","journal-title":"PLoS Negl Trop Dis"},{"key":"2021090300022017300_bib29","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1097\/MD.0000000000000016","article-title":"Histoplasmosis in patients with human immunodeficiency virus\/acquired immunodeficiency syndrome (HIV\/AIDS): multicenter study of outcomes and factors associated with relapse","volume":"93","author":"Myint","year":"2014","journal-title":"Medicine (Baltimore)"},{"key":"2021090300022017300_bib30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/jof6010001","article-title":"The role of molecular tests in the diagnosis of disseminated histoplasmosis","volume":"6","author":"Vasconcellos","year":"2019","journal-title":"J Fungi (Basel)"},{"key":"2021090300022017300_bib31","doi-asserted-by":"crossref","first-page":"76","DOI":"10.3390\/jof5030076","article-title":"Diagnosis of progressive disseminated histoplasmosis in advanced HIV: a meta-analysis of assay analytical performance","volume":"5","author":"Caceres","year":"2019","journal-title":"J Fungi (Basel)"}],"container-title":["Medical Mycology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/mmy\/article-pdf\/59\/9\/916\/39740659\/myab022.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/mmy\/article-pdf\/59\/9\/916\/39740659\/myab022.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T21:13:09Z","timestamp":1630617189000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/mmy\/article\/59\/9\/916\/6272072"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,7]]},"references-count":31,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,5,7]]},"published-print":{"date-parts":[[2021,9,3]]}},"URL":"https:\/\/doi.org\/10.1093\/mmy\/myab022","relation":{},"ISSN":["1369-3786","1460-2709"],"issn-type":[{"value":"1369-3786","type":"print"},{"value":"1460-2709","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,9]]},"published":{"date-parts":[[2021,5,7]]}}}