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

Abstract

Background Histoplasmosis is highly endemic in the American continent. This condition is associated with a high mortality, particularly in people living with HIV/AIDS (PLWHA). Diagnosis of histoplasmosis is usually late in South America, as Histoplasma antigen detection is rarely available. Here we determined the prevalence, risk factors, and outcome of histoplasmosis in PLWHA in Brazilian hospitals. Methods This was a prospective cohort study (2016–2018) involving 14 tertiary medical centers in Brazil. We included hospitalized PLWHA presenting with fever and additional clinical findings. Patients were investigated at each participant center with classical mycology methods. Also, Histoplasma antigen detection was performed in urine samples (IMMY). Probable/proven histoplasmosis was defined according to European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group/National Institute of Allergy and Infectious Diseases Mycoses Study Group criteria. Results From 616 eligible patients, 570 were included. Histoplasmosis was identified in 21.6% (123/570) of patients. Urine antigen testing increased the diagnostic yield in 53.8%, in comparison with standard mycology methods. Variables independently associated with histoplasmosis were CD4+ count <50 cells/mm 3 , use of an antiretroviral (protective effect), and sample collection in the Northeast region of Brazil. Dyspnea at presentation was independently associated with death. Histoplasmosis was more frequent than tuberculosis in patients with low CD4+ counts. Overall 30-day mortality was 22.1%, decreasing to 14.3% in patients with antigen-based diagnosis. Conclusions Histoplasmosis is a very frequent condition affecting PLWHA in Brazil, particularly when CD4+ counts are lower than 50 cells/mm 3 . Antigen detection may detect earlier disease, with a probable impact on outcomes. Access to this diagnostic tool is needed to improve clinical management of PLWHA in endemic countries.

The occurrence of histoplasmosis in Brazil: A systematic review

“…Brazil, histoplasmosis was identified in 21.6% of the patients. In this study, the overall mortality was 22.1% in 30 days, decreasing to 14.3% in patients with a Histoplasma antigen test diagnosis (Falci et al, 2019).…”

<p>HIV-Associated Histoplasmosis: Current Perspectives</p>

“…74 The second study was prospective and reported sensitivity of 56.4% (44 of 78) in culture-proven cases using the IMMY ASR. 75 Although there were 447 controls in that study, they did not report specificity. The authors suggested that the sensitivity may have been reduced because of treatment with antifungal medications for at least 7 days before testing in 39.7% (35 of the 74) of cases.…”

“…A Brazilian study reported 19.6% (8 of 41) of patients had detected antibodies against H. capsulatum. 75 Another Brazilian study reported testing Western blot using deglycosylated histoplasmin antigen with sensitivity of 90%, specificity of 90.9% and accuracy of 90.3%. 80…”

COVID-19 associated histoplasmosis in an AIDS patient

“…On the other hand, histoplasmosis, an emergent systemic fungal infection in HIV patients in Brazil and other Latin American countries [9,10], has not yet been described in the context of Covid-19. Therefore, here we report the case of a Covid-19 patient who was later diagnosed with histoplasmosis in Southern Brazil.…”