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. 2019 Apr 13;6(4):ofz073.
doi: 10.1093/ofid/ofz073. eCollection 2019 Apr.

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

Diego R Falci  1   2 , Alexandre A Monteiro  3 , Cassia Ferreira Braz Caurio  3   4 , Tulio C O Magalhães  1 , Melissa O Xavier  5 , Rossana P Basso  5 , Marineide Melo  6 , Alexandre V Schwarzbold  7 , Paulo Roberto Abrão Ferreira  8 , Jose Ernesto Vidal  9 , João Paulo Marochi  9 , Cassia Silva de Miranda Godoy  10 , Renata de Bastos Ascenco Soares  10 , Aurea Paste  11 , Monica B Bay  12 , Vera Lucia Pereira-Chiccola  13 , Lisandra Serra Damasceno  14 , Terezinha do Menino Jesus Silva Leitão  14 , Alessandro C Pasqualotto  3   4
Affiliations

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

Diego R Falci et al. Open Forum Infect Dis. .

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/mm3, 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/mm3. 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.

Keywords: diagnosis; HIV; epidemiology; histoplasmosis.

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Figures

Figure 1.
Figure 1.
Criteria for diagnosis of histoplasmosis in the 123 patients with probable/proven disease. From the original cohort of 570 patients, 447 were excluded due to negative results. Abbreviation: CM, classical methods (mycological and histopathological examination).
Figure 2.
Figure 2.
Comparative frequency of histoplasmosis and tuberculosis in a cohort of PLWHA in Brazil. Abbreviations: HISTO, histoplasmosis; PLWHA, people living with HIV/AIDS; TB, tuberculosis.
Figure 3.
Figure 3.
Prevalence of probable/proven histoplasmosis in people living with HIV/AIDS according to city of sample collection.
See this image and copyright information in PMC

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