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Background: Tuberculosis is a highly prevalent disease in India, while Histoplasmosis, an emerging disease, is often underreported due to limited resources in developing countries. Coinfection with both these organisms is rarely documented in immunocompetent host. Due to overlapping symptoms, it can be easily missed and treatment delays are not uncommon., Case Presentation: Here, we report a case of a 62-year-old male with a chronic history of intermittent fever and dry cough, splenomegaly, lymphadenopathy, and persistent pancytopenia. He was diagnosed with tuberculosis with cartridge-based nucleic acid amplification test (CBNAAT) positivity from a paratracheal lymph node biopsy. Simultaneously, a bone marrow biopsy revealed Histoplasmosis and the patient was started on dual treatment (Itraconazole and antitubercular drugs). After an initial response, the patient developed new space-occupying cerebral lesions. CSF histoplasma antigen was also positive. The reason for treatment failure was likely to be drug interaction (suboptimal levels of itraconazole due to rifampicin). The patient received liposomal amphotericin and subsequently put on a modified antitubercular treatment regimen to avoid interaction with itraconazole. At 2-month follow-up, the patient's condition significantly improved with a substantial resolution in CNS lesions., Conclusions: Histoplasmosis and tuberculosis have overlapping symptoms, diagnosing one does not preclude the possibility of other, even in non-HIV patients. Clinicians should also be vigilant about potential drug interactions., Competing Interests: Declarations Ethics approval and consent to participate This study did not require ethical approval. Consent for publication Written informed consent was obtained from the patient included in this report. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Histoplasma is a fungal pathogen found in many parts of the world. In North America, its distribution is traditionally thought to be endemic to the Ohio and Mississippi River valleys. Development of histoplasmosis after Histoplasma exposure is related to degree of inoculum exposure and susceptibility, for example, immunocompromised status. Most exposed, healthy individuals are asymptomatic and few develop pulmonary symptoms. A limited number of infectious etiologies (that is, Histoplasma, Coccidioides, and Mycobacterium tuberculosis) can cause miliary pattern on chest imaging, and thus, histoplasmosis should be considered whenever a patient presents with pulmonary symptoms and these unique radiographic findings., Case Presentation: A previously healthy 13-year-old Hispanic male presented as a transfer from an outside hospital with fever and hypoxia in the setting of a progressive, subacute gastrointestinal illness. Given hypoxia, the concern for sepsis, and unclear etiology of his illness, broad-spectrum antimicrobial therapy and noninvasive ventilation were started. Initial evaluation demonstrated miliary pulmonary infiltrates, and travel history raised suspicion for coccidioidomycosis or tuberculosis. After a complete evaluation, lab studies confirmed a diagnosis of histoplasmosis, and the patient made a full recovery after the initiation and completion of antifungal therapy., Conclusion: Herein, we present a patient who acquired histoplasmosis from an area of Mexico not currently acknowledged as endemic and review recently published data emphasizing new areas of Histoplasma endemicity in North America, particularly the southwest USA and most states of Mexico. Though limited surveillance data exist, mounting case reports/series and local epidemiologic studies illustrate the expanding worldwide endemicity of Histoplasma and underscore histoplasmosis as a growing global health concern., (© 2024. The Author(s).)

Histoplasmosis is a systemic infection caused by an endemic dimorphic fungus, Histoplasma capsulatum. Though prevalent in the eastern United States of America, near the Ohio and Mississippi River Valleys, the evidence underlying the global prevalence of histoplasmosis, especially in immunocompromised populations, is underappreciated. This article highlights the global epidemiology, risk factors, microbiology and pathophysiological characteristics, pulmonary and extrapulmonary manifestations, prevention measures, radiographic patterns, diagnostic techniques, and antifungal treatment approaches for Histoplasma capsulatum., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest in relation to the main objectives of this work., (Copyright © 2024. Published by Elsevier Inc.)

Competing Interests: Potential conflicts of interest. J. W. B. reports payments from Up-to-Date for serving as an author or editor for sections on histoplasmosis. P. G. P. reports institutional support from Cidara, Amplyx, Pfizer, F2G, Mayne Pharmaceuticals, Merck & Co., Inc, and Astellas and personal payments for participation on a Data Safety Monitoring Board or Advisory Board from F2G, Matinas, and Cidara. G. R. T. III reports support (grants or contracts) from Cidara, Amplyx, Pfizer, F2G, Mayne Pharmaceuticals, and Merck & Co., Inc. L. A. T. reports grants from BMS and Novartis for a skin cancer health equity project in farmworker communities. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Histoplasma capsulatum is a thermally dimorphic fungal pathogen endemic to the Mississippi and Ohio River Valley regions of North America and much of Central and South America. As an opportunistic pathogen, H. capsulatum can assume a latent infection that can be reactivated by immunocompromised states or immunosuppressive therapy. We report a case of a 72-year-old man who lived in rural regions of Panama, Honduras, and Nicaragua while serving in the U.S. military from 1987 to 1991. Three decades after his initial exposure, the patient presented for evaluation of a painful tongue ulcer that originated when he began taking adalimumab to manage his psoriatic arthritis 2 years earlier. Tissue scraping of the tongue ulcer grew a whitish to cream-colored, fluffy-textured mold that was morphologically identified as Histoplasma. Molecular analysis of the fungus confirmed H. capsulatum var. Latin American group A, known as Histoplasma suramericanum. Further testing showed a positive H. capsulatum antibody mycelial complement fixation, and a 1-cm calcified nodule in the lower lobe of the left lung on computed tomography. Here, we highlight the importance of recognizing disseminated histoplasmosis in patients with exposure to endemic regions before initiating immunosuppressive therapy.

Histoplasmosis is caused by the fungus Histoplasma capsulatum and is often fatal for individuals with acquired immunodeficiency syndrome (AIDS). Delayed diagnosis is a major factor in worsening coinfection, as it can be mistaken for other diseases. Thus, rapid identification of Histoplasma in immunocompromised patients is essential. Molecular techniques, particularly polymerase chain reaction (PCR), were used in this study to identify H. capsulatum in patients coinfected with histoplasmosis and AIDS. Blood samples from 14 individuals with AIDS and disseminated histoplasmosis were collected and analyzed. The PCR method successfully amplified the fungal region in whole blood samples, while PCR-RFLP analysis confirmed a consistent profile in the samples. Genetic sequencing further confirmed the fungal species. Compared to clinical tests such as fungal culture and urinary antigen detection, molecular analysis proved faster, more sensitive, and cost-effective. These molecular markers can potentially be incorporated into routine diagnostics in the future. Further studies are needed to expand and enhance this diagnostic approach, particularly in patients with nonprogressive clinical forms of histoplasmosis.

Background: Paracoccidioidomycosis (PCM) and histoplasmosis are endemic fungal diseases in South America. Both can lead to lung involvement with fungal dissemination progressing to systemic and severe clinical manifestations, especially in immunosuppressed hosts. As the population of immunosuppressed individuals has been rising, a higher occurrence of fungal infections is predicted in this setting. This poses challenges regarding the differential diagnosis due to overlapping clinical and laboratorial findings, hampering the management of cases., Objectives: In this study, the authors discuss the occurrence of a false-positive Histoplasma urinary antigen detection in a kidney transplant recipient with acute PCM. Given the scarce information about this subject, a review on literature data is provided., Methods: A comprehensive literature search was conducted to investigate previous studies that found cross-reactivity between Histoplasma urinary antigen assays in human patients with confirmed diagnosis of PCM. Additionally, an update of PCM in transplant recipients is provided., Findings: The included studies reported 120 samples from patients with PCM tested for Histoplasma antigen, presenting an overall cross-reactivity of 51.67% and 17 cases of PCM in transplant recipients. CONCLUSIONS: The galactomannan urinary antigen developed to diagnose histoplasmosis can cross react with PCM, which may represent a concern in countries where both mycoses overlap., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Oliveira Bastos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Histoplasmosis capsulatum is a dimorphic fungus, recognised for its endemic presence in multiple global regions. It may cause severe opportunistic disseminated infection in immunocompromised individuals. This is a case report of a 33-year-old man from Thailand who was admitted at a Danish hospital with fever, weight loss, cough, nosebleeds, and newly diagnosed HIV. The clinical condition rapidly deteriorated with lung and kidney failure. The patient was diagnosed with H. capsulatum fungaemia first detected on blood smear. He was treated with intravenous amphotericin B followed by oral itraconazole as well as antiretroviral therapy., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Histoplasmosis is a fungal disease associated with substantial mortality rates among persons with advanced HIV disease. Our systematic review synthesized data on the global prevalence of Histoplasma--caused antigenuria in persons with HIV. We searched PubMed/Medline, Embase, and Scopus databases on January 3, 2023, to identify cross-sectional and cohort studies evaluating Histoplasma antigenuria prevalence among adults with HIV infection. We calculated point estimates and 95% CIs to summarize prevalence. Of 1,294 studies screened, we included 15. We found Histoplasma antigenuria among 581/5,096 (11%; 95% CI 11%-12%) persons with HIV and 483/3,789 persons with advanced HIV disease (13%; 95% CI 12%-14%). Among persons with HIV and symptoms consistent with histoplasmosis, Histoplasma antigenuria prevalence was 14% (95% CI 13%-15%; 502/3,631 participants). We determined that persons with advanced HIV disease, inpatients, and symptomatic persons might benefit from a systematic approach to early detection of histoplasmosis using urine antigen testing.

Antigen testing is an important diagnostic tool for histoplasmosis but has limited availability globally. We evaluated the OIDx urine lateral flow antigen assay among 204 persons suspected to have histoplasmosis. Among patients with proven histoplasmosis, sensitivity was 33.3% (3/9, 95% CI 7.5%-70.1%) and specificity 80.5% (157/195, 95% CI 74.3%-85.8%). The MiraVista urine antigen test had better specificity (96.9%) and equal sensitivity. The OIDx test demonstrated 33.3% (3/9) positive agreement and 84.0% (163/194) negative agreement with the MiraVista test. These results should be considered in the context of our low HIV prevalence population with a mixture of pulmonary and disseminated disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Histoplasmosis is a frequent cause of infections in people living with HIV/AIDS (PLWHA). This study introduces the application of a Histoplasma capsulatum urine antigen lateral flow assay (LFA) for diagnosing disseminated histoplasmosis in PLWHA in Suriname. The LFA's diagnostic accuracy was compared with the current diagnostic approach, aiming to assess whether this test resulted in improved early detection and management. Additionally, the prevalence of histoplasmosis among advanced stage HIV patients without clinical suspicion of infection was evaluated using the same LFA. In total, 98 patients were included in the study, of which 58 were classified as "possible disseminated histoplasmosis (DH)" based on clinical criteria and 40 as "controls". Of these possible DH cases, only 19 (32.7%) had a positive LFA. During the study, decisions for treatment were made without the treating physician being aware of the LFA result. Only 55% of the patients who started treatment for histoplasmosis based on clinical criteria had a positive LFA, and 21% of untreated patients had a positive LFA. This study shows that combining clinical signs with LFA results enhances diagnostic accuracy and is cost effective, resulting in better treatment decisions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Woittiez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Histoplasmosis is a mycosis due to a dimorphic fungus Histoplasma capsulatum. This study aimed at providing an overview of histoplasmosis epidemiological, clinical, diagnostic, and therapeutic aspects from the last 30 years. This review was carried out using a systematic literature search on histoplasmosis from 1992 to 2021. We describe the clinical features, diagnostic methods and treatment. Empirical searches were conducted via the databases PubMed, Google Scholar and Science Direct. Between 1992 and 2021, 190 manuscripts were published and reported 212 cases of histoplasmosis. These publications included 115 and 97 cases of American and African histoplasmosis respectively. The number of publications increased over the last ten years with a maximum in 2020 (12.34 % of the cases reported). The disseminated forms of histoplasmosis were the most frequently reported cases as compared to the localized forms. This was the case with the American histoplasmosis (75.65 %) as well as with the African histoplasmosis (55.67 %). Itraconazole (31.17 %) and Amphotericin B (26.62 %) were the most used drugs in the management of these cases. American histoplasmosis is distributed worldwide whereas African histoplasmosis is mainly present in intertropical Africa. There is a critical need for setting up a global surveillance system, towards a better understanding of the disease., Competing Interests: Declaration of competing interest We hereby declare no conflict of interest related to this work., (Copyright © 2024. Published by Elsevier Masson SAS.)

Objectives: The aim of the present study was to evaluate minimally invasive diagnostic techniques, such as the semi-quantitative indirect IgG antibody enzyme immunoassay (EIA) using blood serum and the urinary lateral flow assay (LFA), for the detection of Histoplasma capsulatum in cats with histoplasmosis., Methods: Eight client-owned domestic cats diagnosed with histoplasmosis were selected based on cytological, histopathological, mycological, molecular or antigenic techniques. The blood serum of these animals was tested in a semi-quantitative indirect IgG antibody EIA for the detection of H capsulatum . Urine samples were tested for H capsulatum antigen using LFA., Results: Five cats were seropositive on IgG EIA (5/8, with diagnostic sensitivity equal to 62.5%; 95% confidence interval [CI] 24.5-91.5) and five cats were positive on H capsulatum antigen LFA (5/7, with diagnostic sensitivity equal to 71.4%; 95% CI 29.0-96.3). The combined diagnostic sensitivity when interpreted in parallel was 87.5% (7/8, 95% CI 47.3-99.7). The specificity for the anti- Histoplasma IgG EIA was 100% (95% CI 71.5-100) and for the H capsulatum antigen LFA it was also 100% (95% CI 71.5-100)., Conclusions and Relevance: The semi-quantitative indirect IgG antibody EIA for the detection of H capsulatum in blood serum and the urinary LFA for the detection of the same agent emerge as new minimally invasive diagnostic techniques that can assist in the approach to disseminated and pulmonary feline histoplasmosis, especially when both techniques are considered together., Competing Interests: Conflict of interestAndrew Hanzlicek is employed by MiraVista Diagnostics, which offers commercially the diagnostic tests for histoplasmosis used in this study. The other authors reported no potential conflict of interest.

Histoplasmosis is an expected endemic mycosis in solid organ transplant recipients and occurs as a primary infection, reactivation, or, rarely, acquired from an infected allograft. Reactivation is favored by maintenance immunosuppression or anti-rejection therapy, which facilitates the appearance of disseminated forms as well as unusual presentations. We present the case of a 66-year-old woman with isolated tenosynovitis due to Histoplasma capsulatum 25 years after a kidney transplant., (© 2024 Wiley Periodicals LLC.)

Background: Despite recognition of histoplasmosis as a disease of national public health concern in Kenya, the burden of Histoplasma capsulatum in the general population remains unknown. This study examined the human seroprevalence of anti-Histoplasma antibody and explored associations between seropositivity and demographic and environmental variables, in Busia county, western Kenya., Methodology: Biobanked serum samples and associated data, from a previous cross-sectional survey, were examined. Latex agglutination tests to detect the presence of anti-Histoplasma antibody were performed on serum samples from 670 survey respondents, representing 178 households within 102 sub-locations. Potential epidemiologic risk factors for H. capsulatum exposure were explored using multi-level multivariable logistic regression analysis with household and sub-location included as random effects., Principal Findings: The apparent sample seroprevalence of anti-Histoplasma antibody was 15.5% (n = 104/670, 95% Confidence Interval (CI) 12.9-18.5%). A multivariable logistic regression model identified increased odds of H. capsulatum seropositivity in respondents reporting rats within the household within the previous 12 months (OR = 2.99 90% CI 1.04-8.55, p = 0.04). Compared to respondents aged 25-34 years, the odds of seropositivity were higher in respondents aged 15-24 years (OR = 2.70 90% CI 1.04-6.97, p = 0.04)., Conclusions: The seroprevalence result provides a baseline for sample size approximations for future epidemiologic studies of the burden of H. capsulatum exposure in Busia county. The final model explored theoretically plausible risk factors for H. capsulatum exposure in the region. A number of factors may contribute to the complex epidemiological picture impacting H. capsulatum exposure status at the human-animal-environment interface in western Kenya. Focussed H. capsulatum research is warranted to determine the contextual significance of identified associations, and in representative sample populations., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Cornell et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: In the United States, the true geographic distribution of the environmental fungus Histoplasma capsulatum remains poorly understood but appears to have changed since it was first characterized. Histoplasmosis is caused by inhalation of the fungus and can range in severity from asymptomatic to life threatening. Due to limited public health surveillance and under detection of infections, it is challenging to directly use reported case data to characterize spatial risk., Methods: Using monthly and yearly county-level public health surveillance data and various environmental and socioeconomic characteristics, we use a spatio-temporal occupancy model to estimate latent, or unobserved, presence of H. capsulatum , accounting for imperfect detection of histoplasmosis cases., Results: We estimate areas with higher probabilities of the presence of H. capsulatum in the East North Central states around the Great Lakes, reflecting a shift of the endemic region to the north from previous estimates. The presence of H. capsulatum was strongly associated with higher soil nitrogen levels., Conclusions: In this investigation, we were able to mitigate challenges related to reporting and illustrate a shift in the endemic region from historical estimates. This work aims to help inform future surveillance needs, clinical awareness, and testing decisions for histoplasmosis., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

A sandwich enzyme immunoassay (EIA) for the detection of Histoplasma antigens (Ag) in urine, developed by Optimum Imaging Diagnostics (OIDx) was evaluated. A verification using a standardized reference panel of urine samples found sensitivity of 92%, specificity of 32% and accuracy of 51%. In this study, the OIDx Histoplasma urinary Ag EIA displayed high sensitivity, however, in non-histoplasmosis cases this EIA displayed false-positive results in 68% of specimens tested., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Histoplasma antigen detection in urine is a rapid diagnostic method for disseminated histoplasmosis, although cross-reactivity has been reported in specimens from patients with other thermally dimorphic fungal infections. We tested urine specimens, from persons with suspected invasive fungal infections, using a commercial monoclonal antibody Histoplasma enzyme immunoassay (EIA) at a South African national mycology reference laboratory from August 2014 through December 2018. Corresponding fungal culture and histopathology results were obtained from an electronic laboratory information system. In some cases, cultured fungal isolates were sent with the urine specimen for species-level identification by phenotypic and molecular methods. Cross-reactivity was confirmed using culture filtrates of several fungal pathogens. Of 212 referred cases, 41 (19%) were excluded since they had no recorded clinical history (n = 1), alternative diagnoses were confirmed (n = 2), or no fungal culture or histopathology results (n = 38). Eighty-seven of 212 (41%) had laboratory evidence of an invasive fungal disease, while 84 (40%) did not. Of the 87 cases, 37 (43%) were culture-confirmed mycoses: emergomycosis (n = 18), histoplasmosis (n = 8), sporotrichosis (n = 6), cryptococcosis (n = 2), talaromycosis (n = 1), and other fungi isolated (n = 2). The sensitivity and specificity of the EIA were calculated for two groups: culture-confirmed (n = 37) and histology-confirmed invasive fungal disease (n = 50). The sensitivity and specificity of the EIA for diagnosis of histoplasmosis compared to culture were 88% (7/8, 95%CI 47-100%) and 72% (21/29, 95%CI 53-87%), respectively, and for diagnosis of emergomycosis/histoplasmosis compared to histology was 83% (29/35, 95%CI 66-93%) and 93% (14/15, 95%CI 68-100%), respectively. Cross-reactions occurred in urine specimens of patients with Emergomyces africanus infection and in culture filtrates of E. africanus, T. marneffei and Blastomyces species. A commercial Histoplasma EIA had satisfactory accuracy for diagnosis of culture-confirmed histoplasmosis, but cross-reacted in urine specimens from patients with invasive disease caused by the closely-related pathogen, E. africanus and in culture filtrates of E. africanus and other related fungi., Lay Summary: Emergomyces africanus and Histoplasma capsulatum are fungi that cause a multi-system disease among HIV-seropositive persons with a low CD4 cell count. Handling live cultures of these fungi to confirm a diagnosis requires specialized laboratory equipment and infrastructure which is infrequently accessible in low-resource settings. The features of the two diseases (i.e., disseminated histoplasmosis and emergomycosis) may be indistinguishable when infected tissue is prepared, stained, and examined under a microscope. Enzyme immunoassays (EIA) have been developed as rapid diagnostic tools for the detection of a cell wall component of H. capsulatum in urine specimens, although cross-reactions have been reported in specimens from patients with other fungal infections. We evaluated the accuracy of a commercial Histoplasma EIA to diagnose histoplasmosis and to assess cross-reactions in urine specimens from persons with emergomycosis and in cultures of E. africanus and related fungi. We report a sensitivity and specificity of 88% (95%CI 47-100%) and 72% (95%CI 53-87%) for diagnosis of histoplasmosis compared to culture and 83% (95%CI 66-93%) and 93% (95%CI 68-100%) for diagnosis of either histoplasmosis/emergomycosis compared to a diagnosis made by microscopic examination of infected tissue. The assay cross-reacted in urine specimens from patients with emergomycosis and in culture filtrates of related fungi. Although the EIA cross-reacted with other related fungi, this test can decrease the time to diagnosis and facilitate early treatment of emergomycosis and histoplasmosis in South Africa., (© The Author(s) 2020. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Histoplasmosis is one of the commonest endemic mycoses in the Americas yet is often underdiagnosed and neglected as a public health priority. This review outlines the evolving understanding of its epidemiology and the clinical syndromes of histoplasmosis, in addition to up-to-date diagnostic and treatment guidelines. A focus on histoplasmosis in advanced HIV is included. The challenges pertinent to histoplasmosis management in Latin America, with recommendations made through international expert consensus are discussed., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The Republic of Congo (RoC) is one of the African countries with the most histoplasmosis cases reported. This review summarizes the current status regarding epidemiology, diagnostic tools, and treatment of histoplasmosis in the RoC. A computerized search was performed from online databases Medline, PubMed, HINARI, and Google Scholar to collect literature on histoplasmosis in the RoC. We found 57 cases of histoplasmosis diagnosed between 1954 and 2019, corresponding to an incidence rate of 1-3 cases each year without significant impact of the AIDS epidemic in the country. Of the 57 cases, 54 (94.7%) were cases of Histoplasma capsulatum var. duboisii (Hcd) infection, African histoplasmosis. Three cases (5.3%) of Histoplasma capsulatum var. capsulatum infection were recorded, but all were acquired outside in the RoC. The patients' ages ranged between 13 months to 60 years. An equal number of cases were observed in adults in the third or fourth decades (n = 14; 24.6%) and in children aged ≤15 years. Skin lesions (46.3%), lymph nodes (37%), and bone lesions (26%) were the most frequent clinical presentations. Most diagnoses were based on histopathology and distinctive large yeast forms seen in tissue. Amphotericin B (AmB) was first line therapy in 65% of the cases and itraconazole (25%) for maintenance therapy. The occurrence of African histoplasmosis in apparently normal children raises the possibility that African histoplasmosis is linked to environmental fungal exposure., Competing Interests: The authors have declared that no competing interests exist.

Histoplasma capsulatum, the fungus causing histoplasmosis, has a strong impact on public health. Histoplasmosis is one of the most prevalent systemic mycoses in the Americas and occurs in several mammalian species. Bats are important in the epidemiological cycle of histoplasmosis because they disseminate the fungus throughout the environment. The aim of the present study was to investigate natural H. capsulatum infection in bats located in forested areas, which have undergone anthropogenic perturbations, as well as in the urban areas of the state of Pará. Twenty-two species of bats were captured in 18 municipalities of Pará; the samples obtained from these animals were subjected to nested PCR for amplification of H. capsulatum DNA. The HCI/HCII and HCIII/HCIV primers were used, and the final 210-pb fragment was amplified. Of the 100 bats analysed, two were confirmed to be positive for H. capsulatum. Samples amplified by nested PCR were sequenced and found to share identity and have 100% match with H. capsulatum DNA. H. capsulatum was detected in the area of study: the state of Pará has a wide diversity of bat species, and the region under investigation is situated in the north of the state, which suffers the most severe environmental and climatic changes. Therefore, it is essential to elucidate the distribution of H. capsulatum hosts in this region to facilitate the implementation of effective disease surveillance., (© 2020 Blackwell Verlag GmbH.)

Background: Granulomas caused by infectious lung diseases can present as indeterminate pulmonary nodules (IPN). This study aims to validate an enzyme immunoassay (EIA) for Histoplasma immunoglobulin G (IgG) and immunoglobulin M (IgM) for diagnosing benign IPN in areas with endemic histoplasmosis., Methods: Prospectively collected serum samples from patients at Vanderbilt University Medical Center (VUMC [n = 204]), University of Pittsburgh Medical Center (n = 71), and University of Cincinnati (n = 51) with IPN measuring 6 to 30 mm were analyzed for Histoplasma IgG and IgM with EIA. Diagnostic test characteristics were compared with results from the VUMC pilot cohort (n = 127). A multivariable logistic regression model was developed to predict granuloma in IPN., Results: Cancer prevalence varied by cohort: VUMC pilot 60%, VUMC validation 65%, University of Pittsburgh Medical Center 35%, and University of Cincinnati 75%. Across all cohorts, 19% of patients had positive IgG titers, 5% had positive IgM, and 3% had positive both IgG and IgM. Of patients with benign disease, 33% were positive for at least one antibody. All patients positive for both IgG and IgM antibodies at acute infection levels had benign disease (n = 13), with a positive predictive value of 100%. The prediction model for granuloma in IPN demonstrated an area under the receiver-operating characteristics curve of 0.84 and Brier score of 0.10., Conclusions: This study confirmed that Histoplasma EIA testing can be useful for diagnosing benign IPN in areas with endemic histoplasmosis in a population at high risk for lung cancer. Integrating Histoplasma EIA testing into the current diagnostic algorithm where histoplasmosis is endemic could improve management of IPN and potentially decrease unnecessary invasive biopsies., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Histoplasma capsulatum is an endemic fungus in especially tropical areas. While mostly asymptomatic, histoplasmosis can be life-threatening in immunocompromised patients., Case Description: A 60-year-old woman of Suriname origin, with a history of renal transplantation and use of mycophenolate mofetil and prednisone, presented with abdominal pain and diarrhea. Colonoscopy revealed ulcerative ileocolitis and biopsy showed active granulomatous inflammation. Morbus Crohn was considered the most plausible diagnosis after ruling out several infectious and pharmacological causes. Despite prednisone treatment, symptoms persisted and infliximab was initiated. The patient developed constitutional symptoms and radiological examination revealed disseminated granulomatous disease. Liver biopsy and re-evaluation of previous intestinal histopathology confirmed suspected histoplasmosis., Conclusion: Histoplasmosis should be considered in immunocompromised patients with ileocolitis who have been in endemic regions (South America). Physicians need to assess the risk of previous exposure to histoplasmosis before starting anti-TNF-α therapy.

One adult leopard ( Panthera pardus ) and five adult tigers ( Panthera tigris ) presented with a range of nonspecific clinical signs, including lethargy (6/6), mobility deficits (4/6), and hyporexia (3/6). Hematology and biochemistry revealed a hyperproteinemia characterized by hyperglobulinemia (4/6), hepatocellular enzyme activity increases (3/6), azotemia (3/6), leukocytosis (2/6), hyperbilirubinemia (2/6), or a combination of conditions. Further diagnostics and management varied with the presenting signs and clinicopathological findings, including supportive care, diagnostic imaging, and blastomyces urine antigen analyses. Two animals died, and four were euthanatized. Postmortem findings included granulomatous pneumonia (6/6), fibrinous pleural effusion (3/ 6), pericardial effusion (2/6), and diffuse icterus (1/6). Histopathology revealed round to oval structures with a thin clear wall and purple inclusions within cells of the mononuclear phagocyte system, consistent with Histoplasma capsulatum , in each animal. Disseminated histoplasmosis was found in five cases, with organisms present in the lung (5/5), liver (3/5), lymph nodes (3/5), spleen (2/5), bone marrow (2/5), thyroid (1/5), tongue (1/ 5), kidney (1/5), or a combination of organs. One tiger was found to have pulmonary histoplasmosis without evidence of disseminated infection. On the basis of clinical and pathological findings, histoplasmosis was diagnosed. This case series illustrates the difficulties in antemortem diagnosis of histoplasmosis on the basis of complete blood count, serum biochemistry profile, and antigen testing and underscores that histoplasmosis should be considered a differential diagnosis in any felid presenting with nonspecific clinical signs in endemic areas.

Limited information is available concerning the coexistence of COVID-19 and opportunistic infections in people living with HIV. The possible association of COVID-19 with AIDS-related respiratory diseases should be considered, particularly in patients with advance immunosuppression. We report the case of a male patient with AIDS-related disseminated histoplasmosis associated with COVID-19.

Background: Fungal peritonitis (FP) is a rare complication of peritoneal dialysis. We herein describe the second case in Asia of Histoplasma capsulatum peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD)., Case Presentation: An 85-year-old woman with end-stage renal disease (ESRD) who had been on CAPD for 3 years and who had a history of 3 prior episodes of peritonitis presented with intermittent abdominal pain for 2 weeks and high-grade fever for 3 days. Elevated white blood cell (WBC) count and rare small oval budding yeasts were found in her peritoneal dialysis (PD) fluid. From this fluid, a white mold colony was observed macroscopically after 7 days of incubation, and numerous large, round with rough-walled tuberculate macroconidia along with small smooth-walled microconidia were observed microscopically upon tease slide preparation, which is consistent with H. capsulatum. The peritoneal dialysis (PD) catheter was then removed, and it also grew H. capsulatum after 20 days of incubation. The patient was switched from CAPD to hemodialysis. The patient was successfully treated with intravenous amphotericin B deoxycholate (AmBD) for 2 weeks, followed by oral itraconazole for 6 months with satisfactory result. The patient remains on hemodialysis and continues to be clinically stable., Conclusion: H. capsulatum peritonitis is an extremely rare condition that is associated with high morbidity and mortality. Demonstration of small yeasts upon staining of PD fluid, and isolation of slow growing mold in the culture of clinical specimen should provide important clues for diagnosis of H. capsulatum peritonitis. Prompt removal of the PD catheter and empirical treatment with amphotericin B or itraconazole is recommended until the culture results are known.

We describe a case of haemophagocytic lymphohistiocytosis (HLH) secondary to disseminated histoplasmosis, which was treated with chemotherapy in addition to standard antifungal therapy. While HLH in the setting of infections is very well described, its treatment in this setting is controversial, with some physicians treating only the underlying infection, whereas others using immune suppression in addition to antimicrobials. To the best of our knowledge, this is the first report documenting the successful treatment of an adult patient with HLH due to disseminated histoplasmosis using etoposide chemotherapy after initial antifungal therapy failed to show improvement., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

The diagnosis of histoplasmosis depends on various approaches: direct clinical examination, fungus isolation from cultures of clinical samples, histopathological evaluation, and serological testing. In serodiagnostic assays, the Histoplasma capsulatum H and M antigenic glycoproteins have been extensively used. However, both antigens showed limitations attributed mainly to their cross-reactivity with glycoproteins from other pathogenic fungi, which compromises specificity, and generates false positives, misdiagnosis, and therapeutic failure. In this work, we deglycosylated extracellular released antigens from the Venezuelan 7090 H. capsulatum clinical isolate, using chemical and enzymatic methods and evaluated their effectiveness by indirect enzyme-linked immunosorbent assay (ELISA) with sera from patients with either histoplasmosis or PCM. Prior to deglycosylation, the extracellular released antigen showed 62% of sensitivity 66% of specificity and 68% of cross-reactivity with paracoccidioidomicosis sera. The chemically deglycosylated extracellular released antigen, for 8 or 18  h showed 72 and 52% sensitivity with 98% and 92% specificity, respectively. Moreover, cross-reactivity with Paracoccidioides decreased to 4 and 16%, following deglycosylation for 8 or 18 h, respectively. The enzymatically treated antigen showed 52% of sensitivity, 92% of specificity and 8% cross-reactivity against Paracoccidioides. Deglycosylation of the H. capsulatum antigen improves its specificity and decreases its cross-reactivity against Paracoccidioides when using indirect ELISA for serodiagnosis. Therefore, it is recommended to deglycosylate the fungal extracellular released antigen for clinical serodiagnosis, and to monitor humoral immune responses during therapy of patients with the different clinical forms of histoplasmosis., Competing Interests: Declaration of Competing Interest The authors declare no potential conflict of interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Histoplasmosis is usually clinically suspected only in people who reside in, are migrants from or are travelling to endemic areas such as North America. Immunocompetent patients with a low level of exposure typically have either subclinical or mild and self-limiting infection. The most common risk for the development of progressive disseminated form is HIV infection. We recently managed two patients with disseminated histoplasmosis, presenting with prolonged fever, significant weight loss, pallor and hepatosplenomegaly. Both were HIV-negative and lived in Himachal Pradesh (India), a region that was considered " Histoplasma -free" until recently.

The goal of the present work was to develop a novel reagent with potential for histoplasmosis diagnosis. For this purpose, the genetic sequence of the 100 kDa protein of Histoplasma capsulatum (Hcp100) was cloned and expressed as a secretory protein in Pichia pastoris. After optimizing the culture conditions and purifying by immobilized metal ion affinity chromatography, the highest yield of Hcp100 reached approximately 1.3 mg/l with > 90% purity in shake flasks using basal salt medium supplemented with casamino acids after 72 h of methanol induction. To investigate its potential for diagnosis, its detection in urine samples using specific polyclonal antibodies as reagent was evaluated by dot blot in 6 patients with progressive disseminated histoplasmosis (PDH), of whom all had AIDS. Antigen was detected in urine from all 6 (100%) PDH patients. Urine samples from a pool of 20 healthy individuals did not react with the anti-Hcp100 antibodies. The dot blot assay performed in this study provides preliminary data of a simple technology that can be performed in medical institutions with limited resources to facilitate the rapid diagnosis of histoplasmosis, particularly the disseminated forms. Hence, use of these assays may provide a rapid diagnostic tool of PDH in endemic areas for histoplasmosis where PDH-related mortality is high, hastening treatment and improving patient survival. Finally, this novel antigen and its specific antibodies may provide an alternative diagnostic reagent to the largely unknown and poorly characterized polysaccharide antigens (HPA, galactomannan, histoplasmin) frequently used in the diagnostic tests. KEY POINTS: Few antigens are used as laboratory tools for the immunodiagnosis of histoplasmosis. P. pastoris was an excellent system for recombinant Hcp100 expression. Maximum expression levels of rHcp100 were achieved in BSM with 1% casamino acids. Dot blot assays with anti-rHcp100 antisera can be successfully used for diagnosing PHD.

A 50-year-old woman with a history of kidney transplant presented with 2 days of abdominal pain after 6 months of recurrent streptococcal pharyngitis, fevers, weight loss and a new rash on her chest and back. Her examination was notable for a unilateral tonsillar exudate and 2-3 mm pink papules with a fine scale over her chest and back. CT of the abdomen and chest demonstrated several large lymph nodes, and laboratory investigation revealed new cytopenias and elevated transaminases. Urine antigen testing for Histoplasma capsulatum was negative, but a fungal complement fixation panel was reactive for Histoplasma antibodies. Skin biopsy revealed intracellular organisms consistent with H. capsulatum She underwent treatment with liposomal amphotericin B but due to nephrotoxicity, drug interactions and worsening transaminitis, therapy was changed to itraconazole. The diagnosis and management of disseminated histoplasmosis presents multiple challenges, which are of particular importance in patients with a history of renal transplantation., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Central nervous system (CNS) infection by Histoplasma capsulatum is a rare disease in immunocompromised individuals in endemic areas. About one quarter of cases result from hematogenous dissemination. A 23-year-old upholsterer with chronic occipital headache had developed intracranial hypertension and dizziness, incoordination with ataxic gait, and acute confusion 5 months prior to admission. Laboratory examinations and chest roentgenogram were normal. Postcontrast T1-weighted MRI of the brain revealed a multiple ring-enhancing cerebellar, brain stem and parietal lobe lesions, and meningeal contrast enhancement. Cerebrospinal fluid culture was positive for H. capsulatum species complex, which was confirmed by phylogenetic analysis. Thirteen years after the diagnosis and treatment, there was no H. capsulatum recurrence; sequels related to complications due to the ventriculoperitoneal shunt. This case shows a primary neurological presentation of cerebral histoplasmosis, without meningitis or disseminated disease in nonimmune-compromised patient. The authors propose a categorization of the diagnosis of CNS histoplasmosis. Routine diagnostics of sibling species within the H. capsulatum complex proved to be difficult.

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.

Gingival lesions as the sole manifestation of African histoplasmosis (Histoplasma capsulatum var. duboisii) have never been reported in baboons. Grossly, lesions can be indistinguishable from bacterial ulcerative gingivitis or gingival hyperplasia. Clinical outcomes of primary gingival histoplasmosis in baboons are unknown and may complicate colony management decisions., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose : Histoplasmosis is a fungal infection acquired through inhalation of Histoplasma capsulatum microconidia, mostly present in the Americas. Both immunocompetent and immunocompromised patients can present a wide spectrum of signs/symptoms, ranging from mild disease to a severe, disseminated infection. The aim of this observational study is to describe histoplasmosis cases diagnosed in travelers and their clinical/radiological and therapeutic pattern. Methods : Retrospective study at the Department of Infectious - Tropical Diseases and Microbiology (DITM) of Negrar, Verona, Italy, between January 2005 and December 2015. Results : Twenty-three cases of acute histoplasmosis were diagnosed, 17 of which belong to the same cluster. Seven of the 23 patients (30.4%) were admitted to hospital, four of whom underwent invasive diagnostic procedures. Thirteen patients (56.5%) received oral itraconazole. All patients recovered, although nine (39.1%) had radiological persisting lung nodules at 12 month follow up. Conclusions : Clinical, laboratory and radiological features of histoplasmosis can mimic other conditions, resulting in unnecessary invasive diagnostic procedures. However, a history of travel to endemic areas and of exposure to risk factors (such as visits to caves and presence of bats) should trigger the clinical suspicion of histoplasmosis. Treatment may be indicated in severe or prolonged disease.

Background: Progressive disseminated histoplasmosis (PDH) is an important cause of mortality in persons living with HIV (PLHIV), especially in countries where patients have limited access to antiretroviral therapies and diagnostic testing., Objective: A lateral flow assay (LFA) to detect Histoplasma capsulatum antigen in serum developed by MiraVista ® was evaluated., Methods: We tested 75 serum samples: 24 from PLHIV and culture-proven PDH and 51 from PLHIV with other fungal and bacterial infections as well as people without HIV. LFA devices were read manually (read by eye) and by an automated reader., Results: When the LFA was read manually, sensitivity was 96% and specificity was 90%. When an automated reader was used, sensitivity was 92% and specificity was 94%. The Kappa index comparing manual and automated reader was 0.90. Cross-reactions were observed principally in samples from patients with proven diagnosis of paracoccidioidomycosis., Conclusions: The MiraVista ® Diagnostics Histoplasma antigen LFA had high analytical performance and good agreement between manual and automated reader. This LFA allows Histoplasma antigen testing with minimal laboratory equipment and infrastructure requirements., (© 2019 Blackwell Verlag GmbH.)

Background: Disseminated Kaposi sarcoma (DKS) is present in patients with advanced HIV infection in whom co-infection with other opportunistic pathogens can occur. Bone marrow (BM) aspirate and biopsy comprise a robust diagnostic tool in patients with fever, cytopenias, and abnormal liver tests. However, the yield in patients with DKS has not been determined., Objective: The aim of this study was to evaluate the utility of BM aspirate and biopsy in patients with DKS., Methods: We included 40 male patients with a recent diagnosis of DKS. BM aspirate and biopsy was performed as part of the workup to rule out co-infections., Results: In four patients, Mycobacterium avium complex (MAC) was recovered from culture. In other four patients, intracellular yeasts were observed in the Grocott stain, diagnosed as Histoplasma. The yield of BM was calculated in 20%. Only 12 patients (30%) had fever and 11 (27.5%) had pancytopenia. Alkaline phosphatase (ALP) above normal values and C-reactive protein (CRP) were higher in patients with positive results for BM than in those with negative results (63% vs. 21.9%, and 3.0 vs. 1.2 mg/L; p = 0.03 in both comparisons). No differences were found when complete blood-count abnormalities were compared., Conclusion: We recommend performing a BM aspirate for stains, culture, and biopsy in all HIV patients with DKS, as this will permit the early diagnosis of co-infections and prevent further complications in those who receive chemotherapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Histoplasmosis is one of the invasive fungal infections and presents with symptoms mainly in the lungs. Disseminated histoplasmosis (DH) is rare and its lesions in the gastrointestinal tract are even uncommon. The concomitant involvement of the upper and lower gastrointestinal tract has never been described in the immunocompetent individuals., Case Presentation: A 44-year-old immunocompetent Chinese man presented with fever, hepatosplenomegaly, fungal esophagitis and protuberant lesions with central depression and erosion along the mucous membrane of the colon. The patient was diagnosed as disseminated histoplasmosis by gastrointestinal endoscopy., Conclusions: Histoplasmosis should be taken caution in patients with fever and hepatosplenomegaly. Actions should be taken to avoid its disseminated infection associated high mortality.