Background: Histoplasmosis is a systemic disease caused by the dimorphic fungus Histoplasma capsulatum. Diagnosis is often delayed, or it is misdiagnosed as tuberculosis. In Brazil, the infection is common and cases of histoplasmosis have been described in all regions of the country; however, the real problem is underestimated since notification of histoplasmosis is not mandatory. Methods: Human histoplasmosis cases diagnosed in Brazil and published up to December 2018 were identified through a search conducted in the PubMed/MEDLINE, SciELO, and Web of Science databases. Moreover, the isolation of H. capsulatum from animals or environmental sources in Brazil was also evaluated. Results: A total of 207 articles fulfilled the inclusion criteria and were evaluated, involving a total of 3530 patients with a diagnosis of histoplasmosis during the period studied. Of these patients, 78.3% were male, giving a male-to-female ratio of approximately 4:1. Histoplasmosis presented a higher frequency in individuals between the fourth and fifth decades of life. Disseminated disease was the most common form of histoplasmosis. Isolation of H. capsulatum on culture media and histopathology using staining methods were the diagnostic methods with the best efficiency. The best results in the identification of the H. capsulatum were achieved for samples from mononuclear phagocyte system components, skin and mucosa, and hematological samples. Regarding predisposing factors for histoplasmosis, HIV infection was the most common underlying condition. The overall mortality rate was 33.1%. Conclusions: This study represents the first available systematic review demonstrating Brazilian cases of histoplasmosis in the literature and highlights that the disease is more widespread in the Brazilian territory than has previously been thought.

The acute form of histoplasmosis usually occurs after the exposition of more than one individual to a common environmental source harboring Histoplasma capsulatum. Here, we present two cases of acute pulmonary histoplasmosis seen within two weeks at a reference center for infectious diseases at Rio de Janeiro, Brazil. The patients did not present a common epidemiologic history for histoplasmosis, however both presented COVID-19 before the onset of histoplasmosis symptoms. Due to the difficulties in the diagnosis of acute histoplasmosis, novel laboratory methods such as Western Blot and PCR were included in the investigation of these cases. Both patients presented negative cultures for H. capsulatum and negative urinary galactomannan. However, they presented H and M bands in the Western blot as well as a positive H. capsulatum DNA detection in sputum. These results were available approximately 36 h after sample collection, fastening the beginning of treatment of one patient. Both patients progressed well with itraconazole treatment. These cases suggest that COVID-19 may facilitate the development of acute pulmonary histoplasmosis and, therefore, clinicians must be aware of this differential diagnosis in patients from endemic areas with fever and coughing after recovery from COVID-19.

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antigenic targets: the M antigen, previously demonstrated in the diagnosis of histoplasmosis, and the catalase P and YPS-3 proteins, characterized as virulence factors of H. capsulatum, with antigenic properties still unclear. The other two proteins were fragments of the YPS-3 and M antigen. Overlapping results obtained from the two aforementioned bioinformatic tools, 16 regions from these three proteins are proposed as putative B-cell epitopes exclusive to H. capsulatum. These data reveal a new role for these proteins on H. capsulatum interactions with the immune system and indicate their possible use in new methods for the diagnosis of histoplasmosis.

BackgroundHistoplasmosis is worldwide systemic mycoses caused by the dimorphic fungus Histoplasma capsulatum. The isolation and identification of H. capsulatum in culture is the reference test for histoplasmosis diagnosis confirmation. However, in the absence of it, serology has been used as a presumptive diagnosis through antibody and antigen detection. The purpose of the present study was to validate an immunoassay method (western blot) for antibodies detection in the diagnosis of histoplasmosis.MethodsTo validate the western blot (WB) a study was conducted using 118 serum samples from patients with histoplasmosis and 118 serum controls collected from January 2000 to December 2013 in residents of the Rio de Janeiro State, Brazil. Diagnostic validation parameters were calculated based on the categorization of results obtained in a 2 × 2 table and subjected to statistical analysis. In addition, the viability of deglycosylated histoplasmin antigen (ptHMIN) onto nitrocellulose membranes previously sensitized was evaluated during the same period.ResultsThe WB test showed sensitivity of 94.9 %, specificity of 94.1 %, positive predictive value of 94.1 %, negative predictive value of 94.9 %, accuracy of 94.5 %, and almost perfect precision. Besides, the strips have proved to be viable for using at least 5 years after ptHMIN antigen sensitization.ConclusionWestern blot test using ptHMIN provides sensitive, specific, and faster results. Therefore, could be considered a useful tool in the diagnosis of histoplasmosis being used by public health system, even in situations where laboratory facilities are relatively limited.

Diagnosis of invasive fungal diseases remains problematic, especially in undeveloped countries. We have developed an enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies to Histoplasma capsulatum using metaperiodate treated purified histoplasmin (ptHMIN). Our ELISA was validated comparing sera from patients with histoplasmosis, related mycoses, and healthy individuals. The overall test specificity was 96%, with sensitivities of 100% (8/8) in acute disease, 90% (9/10) in chronic disease, 89% (8/9) in disseminated infection in individuals without HIV infection, 86% (12/14) in disseminated disease in the setting of HIV infection and 100% (3/3) in mediastinal histoplasmosis. These parameters are superior to the use of untreated histoplasmin in diagnostic ELISAs. The high specificities, sensitivities, and simplicity of our ELISA support further development of a deglycosylated HMIN ELISA for clinical use and for monitoring the humoral immune response during therapy in patients with chronic and disseminated histoplasmosis.

Summary Background Histoplasmosis is a frequent fungal infection in HIV/AIDS patients, with high morbimortality rates when diagnosis and treatment are delayed. Antibody detection, which is faster than the gold standard culture test, hastens the laboratory investigation. Objectives To evaluate the role of WB for antibody detection in the diagnosis of histoplasmosis among HIV/AIDS patients. Patients and Methods Fifty patients with proven or probable histoplasmosis were included. Clinical, epidemiological and laboratory data were described in the same population after a review of their medical records. WB was performed using deglycosylated histoplasmin. Results About 82% of patients were adult males and the mean age was 39.3 years. CD4+ T lymphocyte count less than 150 cells/mm3 was observed in 62% patients. Antibodies against Histoplasma capsulatum M antigen were detected in 62% of patients, and against both M and H antigens in 28% of individuals. Sera from 10% of patients were nonreactive. Histoplasmosis was the first opportunistic infection in 38% of the cases. Disseminated and pulmonary histoplasmosis occurred in 84% and 16% of patients, respectively. The overall mortality was 16%. Conclusion WB could be useful for the histoplasmosis diagnosis in HIV/AIDS patients because of its easefulness and good sensitivity in a population where antibody production is hampered.

Histoplasmosis is a worldwide-distributed deep mycosis that affects healthy and immunocompromised hosts. Severe and disseminated disease is especially common in HIV-infected patients. At least 11 phylogenetic species are recognized and the majority of diversity is found in Latin America. The northeastern region of Brazil has one of the highest HIV/AIDS prevalence in Latin America and Ceará State has one of the highest death rates due to histoplasmosis in the world, where the mortality rate varies between 33–42%. The phylogenetic distribution and population genetic structure of 51 clinical isolates from Northeast Brazil was studied. For that morphological characteristics, exoantigens profile, and fungal mating types were evaluated. The genotypes were deduced by a MSLT in order to define local population structure of this fungal pathogen. In addition, the relationships of H . capsulatum genotypes with clinically relevant phenotypes and clinical aspects were investigated. The results suggest two cryptic species, herein named population Northeast BR1 and population Northeast BR2. These populations are recombining, exhibit a high level of haplotype diversity, and contain different ratios of mating types MAT1-1 and MAT1-2 . However, differences in phenotypes or clinical aspects were not observed within these new cryptic species. A HIV patient can be co-infected by two or more genotypes from Northeast BR1 and/or Northeast BR2, which may have significant impact on disease progression due to the impaired immune response. We hypothesize that co-infections could be the result of multiple exposure events and may indicate higher risk of disseminated histoplasmosis, especially in HIV infected patients.