Abstract
Histoplasmosis occurs in 5–10% of HIV-infected patients in endemic areas and evolves to severe and disseminated infection with mortality rates over 50% in some regions. This report presents epidemiological, clinical and outcome data from HIV-infected patients with histoplasmosis confirmed by culture and/or at necropsy who were admitted to a Brazilian teaching hospital. Data from 65 patients were obtained from their respective medical and necropsy records. From 2005 to 2018, 36 HIV-infected patients were diagnosed with histoplasmosis confirmed by culture. At admission, most of these patients presented disseminated fungal infection, whereas 15 (41.7%) were simultaneously diagnosed with both HIV infection and histoplasmosis. Fever, weight loss, hepatosplenomegaly, respiratory and digestive symptoms were present in 86.2%, 50%, 44.4% and 41.7% of the patients, respectively. At admission, 24 patients had low CD4 T-cell count and high viral load values. Among the 30 patients who received antifungals, 16 (53.3%) were cured, 13 (43.3%) died, and one was lost to follow-up. Six patients died prior to therapy. From 1990 to 2018, 63 necropsies of patients with Histoplasma capsulatum infection were performed. Of these patients, 29 (46.0%) were HIV-infected individuals, including 21 (72.4%) who presented disseminated histoplasmosis and 21 (72.4%) who were diagnosed with histoplasmosis at necropsy. The epidemiological, clinical and outcome profiles presented herein are similar to those described elsewhere and reinforce the difficulties that are still present in limited-resource settings where advanced immunodeficiency, combined with severe fungal infection and late patient admissions, is related to poor outcomes.
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References
Hajjeh RA. Disseminated histoplasmosis in persons infected with human immunodeficiency virus. Clin Infect Dis. 1995;21(Suppl 1):S108–10.
McKinsey DS, Spiegel RA, Hutwagner L, et al. Prospective study of histoplasmosis in patients infected with human immunodeficiency virus: incidence, risk factors, and pathophysiology. Clin Infect Dis. 1997;24:1195–203.
Wheat LJ, Slama TG, Zeckel ML. Histoplasmosis in the acquired immune deficiency syndrome. Am J Med. 1985;78:203–10.
Couppié P, Sobesky M, Aznar C, et al. Histoplasmosis and acquired immunodeficiency syndrome: a study of prognostic factors. Clin Infect Dis. 2004;38:134–8.
Wheat LJ, Connolly-Stringfield P, Baker RL, et al. Disseminated histoplasmosis in the acquired immune deficiency syndrome: clinical findings, diagnosis and treatment, and review of the literature. Med (Baltimore). 1990;69:361–74.
Huber F, Nacher M, Aznar C, et al. AIDS-related Histoplasma capsulatum var. capsulatum infection: 25 years experience of French Guiana. AIDS. 2008;22(9):1047–53.
Adenis A, Nacher M, Hanf M, et al. HIV-associated histoplasmosis early mortality and incidence trends: from neglect to priority. PLoS Negl Trop Dis. 2014;8(8):e3100.
Nacher M, Adenis A, Mc Donald S, et al. Disseminated histoplasmosis in HIV-infected patients in South America: a neglected killer continues on its rampage. PLoS Negl Trop Dis. 2013;7:e2319.
Cano-Torres JO, Olmedo-Reneaum A, Esquivel-Sánchez JM, et al. Progressive disseminated histoplasmosis in Latin America and the Caribbean in people receiving highly active antiretroviral therapy for HIV infection: a systematic review. Med Mycol. 2019;57(7):791–9.
Prado M, Silva MB, Laurenti R, et al. Mortality due to systemic mycoses as a primary cause of death or in association with AIDS in Brazil: a review from 1996 to 2006. Mem Inst Oswaldo Cruz. 2009;104(3):513–21.
Teixeira TRA, Gracie RM, Monica SB, Francisco I. Social geography of AIDS in Brazil: identifying patterns of regional inequalities. Cadernos de Saúde Pública. 2014;30(2):259–71.
Brazil. Health Ministry. Adherence to antiretroviral treatment in Brazil: a collection of studies from the ATAR project. Brasília, DF; 2010. (in Portuguese).
Damasceno LS, Ramos AN, Alencar CH, et al. Disseminated histoplasmosis in HIV-infected patients: determinants of relapse and mortality in a northeastern area of Brazil. Mycoses. 2014;57:406–13.
De Oliveira RB, Atobe JH, Souza SA, de Castro Lima Santos DW. Epidemiology of invasive fungal infections in patients with acquired immunodeficiency syndrome at a reference hospital for infectious diseases in Brazil. Mycopathologia. 2014;178:71–8.
Brilhante RSN, Fechine MAB, Mesquita JRL, et al. Histoplasmosis in HIV positive patients in Ceará, Brazil: clinical-laboratory aspects and in vitro antifungal susceptibility of Histoplasma capsulatum isolates. Trans R Soc Trop Med Hyg. 2012;106:484–8.
Mora DJ, dos Santos CT, Silva-Vergara ML. Disseminated histoplasmosis in acquired immunodeficiency syndrome patients in Uberaba, MG Brazil. Mycoses. 2008;51:136–40.
Daher EF, Silva GB Jr, Barros FAS, Takeda CFV, Mota RMS, Arau MHA. Clinical and laboratory features of disseminated histoplasmosis in HIV patients from Brazil. Trop Med Int Health. 2007;12:1108–15.
Borges AS, Ferreira MS, Silvestre MTA, Nishioka SA, Rocha A. Histoplasmose em pacientes imunossuprimidos: estudo de 18 casos Observados em Uberlândia, MG. Rev Soc Bras Med Trop. 1997;30(2):119–24.
Hui AN, Koss MN, Meyer PR. Necropsy findings in acquired immunodeficiency syndrome: a comparison of premortem diagnoses with postmortem diagnoses with postmortem findings. Hum Pathol. 1984;15:670–6.
Eza D, Cerrillo G, Moore DA, et al. Postmortem findings and opportunistic infections in HIV-positive patients from a public hospital in Peru. Pathol Res Pract. 2006;202(11):767–75.
Antinori S, Nebuloni M, Magni C, et al. Trends in the postmortem diagnosis of opportunistic invasive fungal infections in patients with AIDS: a retrospective study of 1,630 autopsies performed between 1984 and 2002. Am J Clin Pathol. 2009;132(2):221–7.
Centers for Disease Control (CDC). Revision of the case definition of acquired immunodeficiency syndrome for national reporting-United States. MMWR Morb Mortal Wkly Rep. 1985; 34: 373–75.
Nacher M, Adenis A, Adriouch L, et al. What is AIDS in the Amazon and the Guianas? Establishing the burden of disseminated histoplasmosis. Am J Trop Med Hyg. 2011;84:239–40.
Samayoa B, Roy M, Ahlquist Cleveland A, et al. High mortality and coinfection in a prospective cohort of human immunodeficiency virus/acquired immune deficiency syndrome patients with histoplasmosis in Guatemala. Am J Trop Med Hyg. 2017;97:42–8.
Gutierrez ME, Canton A, Sosa N, Puga E, Talavera L. Disseminated histoplasmosis in patients with AIDS in Panama: a review of 104 cases. Clin Infect Dis. 2005;40:1199–202.
Caceres DH, Adenis A, de Souza JVB, et al. The manaus declaration: current situation of histoplasmosis in the Americas, report of the II regional meeting of the international histoplasmosis advocacy group. Curr Fungal Infect Rep. 2019;13:244–9.
Pontes LB, Leitão TD, Lima GG, Gerhard ES, Fernandes TA. Características clínico-evolutivas de 134 pacientes com histoplasmose disseminada associada a SIDA no Estado do Ceará. Rev Soc Bras Med Trop. 2010;43(1):27–31.
Baddley JW, Sankara IR, Rodriquez JM, Pappas PG, Many WJ Jr. Histoplasmosis in HIV- infected patients in a southern regional medical center: poor prognosis in the era of highly active antiretroviral therapy. Diagn Microbiol Infect Dis. 2008;62:151–6.
Tobon AM, Agudelo CA, Rosero DS, et al. Disseminated histoplasmosis: a comparative study between patients with acquired immunodeficiency syndrome and nonhuman immunodeficiency virus-infected individuals. AmJ Trop Med Hyg. 2005;73:576–82.
Karimi K, Wheat LJ, Connolly P, et al. Differences in histoplasmosis in patients with acquired immunodeficiency syndrome in the United States and Brazil. J Infect Dis. 2002;186(11):1655–60.
Hajjeh RA, Pappas PG, Henderson H, et al. Multicenter case-control study of risk factors for histoplasmosis in human immunodeficiency virus-infected persons. Clin Infect Dis. 2001;32:1215–20.
Wheat LJ, Chetchotisakd P, Williams B, Connolly P, Shutt K, Hajjeh R. Factors associated with severe manifestations of histoplasmosis in AIDS. Clin Infect Dis. 2000;30:877–81.
Souza SL, Feitoza PV, Araújo JR, Andrade RV, Ferreira LC. Causes of death among patients with acquired immunodeficiency syndrome autopsied at the Tropical Medicine Foundation of Amazonas. Rev Soc Bras Med Trop. 2008;41:247–51.
Cury PM, Pulido CF, Furtado VM, da Palma FM. Autopsy findings in AIDS patients from a reference hospital in Brazil: analysis of 92 cases. Pathol Res Pract. 2003;199(12):811–4.
Falci DR, Pasqualotto AC. Clinical mycology in Latin America and the Caribbean: a snapshot of diagnostic and therapeutic capabilities. Mycoses. 2019;62(4):368–73.
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Damasceno-Escoura, A.H., Mora, D.J., Cardeal, A.C. et al. Histoplasmosis in HIV-Infected Patients: Epidemiological, Clinical and Necropsy Data from a Brazilian Teaching Hospital. Mycopathologia 185, 339–346 (2020). https://doi.org/10.1007/s11046-020-00435-y
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DOI: https://doi.org/10.1007/s11046-020-00435-y