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Histoplasmosis is the most common endemic mycosis in the Americas. Currently, there is no laboratory test capable to detect subclinical or latent infections by Histoplasma capsulatum (Hc), which might develop as severe infections in immunocompromised individuals. For the first time to our knowledge, we explore the suitability of an interferon gamma release assay (IGRA) to detect latent Hc infection in asymptomatic individuals. A cohort of 126 volunteers was enrolled in the study, 13 of which underwent a Hc infection in the past, and 93 of them showing risk factors for this infection. The remaining 20 participants did not refer any risk factors of Hc infection, but eight of them showed evidences of infection with Mycobacterium tuberculosis. All participants were recruited in Medellin, Colombia, between January 2014 and December 2017. Whole blood samples were cultured with four different Hc crude antigens and phytohemaglutinin as positive control. The interferon (IFN)-γ released by T lymphocytes upon antigen stimulation was quantified by ELISA. A defined cutoff value of 20 pg/ml for the IFN-γ concentration allowed us to distinguish between the group with documented past infections and the group of noninfected individuals with high sensitivity (70-92%) and specificity (85-95%), for the four tested antigens. Positive 82-95% and negative 77-92% predictive values were also very high, comparable to those reported for commercially available IGRAs. The new test constitutes a promising screening method to detect individuals with latent Hc infection, even decades after the primary infection, as evidenced in this study., (© The Author(s) 2018. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Severe pulmonary or disseminated histoplasmosis often necessitates presumptive antifungal treatment while awaiting definitive diagnosis. Histoplasma antigen assays have improved sensitivity but results may lag up to 7 days. In order to increase diagnostic certainty, "soft clues" may be looked for in laboratory and radiologic data, such as elevated alkaline phosphatase or ferritin levels and findings of mediastinal adenopathy or hepatosplenomegaly. To determine if elevated aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio is specific to histoplasmosis or a non-specific marker for disseminated fungal infection or sepsis in general, we retrospectively examined records of all patients diagnosed with an endemic fungal infection (EFI) at Rush University Medical Center from January of 1997 to October of 2012, and a cohort of septic patients with elevated liver enzymes. We identified 90 cases of EFIs during the study period that met all inclusion criteria (Histoplasma 21, Blastomyces 56, Coccidioides 12, Paracoccidioides 1). We also evaluated 10 control patients with bacterial sepsis. The mean ratio of AST to ALT in patients with disseminated histoplasmosis was 2.69 (95% CI:1.22, 4.16) while for other EFIs, the mean ratio ranged from 0.38 to 1.14 with disseminated coccidioidomycosis and blastomycosis respectively (P < 0.0001). The ratio in patients with bacterial sepsis was 0.84. We propose the use of the AST/ALT ratio as a clinical "soft clue" suggestive of disseminated histoplasmosis in the appropriate host, and to possibly distinguish cross reactivity of the Histoplasma antigen assay with other EFIs., (© The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Ocular histoplasmosis syndrome (OHS) is a significant cause of vision loss in young and middle-aged adults. We report here a case of an immunocompetent 37-year-old man who presented fever, malaise, headache, and anterior cervical lymphadenopathy for one week, after which he started to experience a sudden loss in visual acuity of his right eye. Fluorescent angiography and an optical coherent tomography demonstrated the presence of a type II choroidal neo-vascular membrane in the right eye, suggesting a diagnosis of OHS. A peripheral blood sample was tested by nested PCR to detect Histoplasma capsulatum using a set of primers known to amplify a DNA sequence coding for a specific 100-kDa protein of this fungus (Hc100-PCR). The blood sample was Hc100-PCR-positive and sequence analysis showed an identity of 97% with the reference sequence. The patient received intravitreal bevacizumab injection and itraconazol therapy, leading to an improvement in media vision acuity. In this case, the molecular test provided evidence linking the ocular lesions with an earlier infection by H. capsulatum and demonstrated that the Hc100-nested PCR assay is a valuable tool in the diagnosis of histoplasmosis.

We evaluated the Fungitell beta-glucan (BG) test with specimens from patients with presumed histoplasmosis. The sensitivity of the test was 87% in histoplasmosis cases and had a specificity of 68% with controls. Histoplasmosis should be considered as a possible cause for a positive BG test, but such results may be found with many other conditions that are clinically similar to this fungal disease. Therefore, there is a need to conduct confirmatory tests for histoplasmosis in the appropriate clinical setting.