Molecular detection of Histoplasma capsulatum in organ samples from bats randomly captured in urban areas of Araraquara, São Paulo state, Brazil.

The mycosis histoplasmosis is also considered a zoonosis that affects humans and other mammalian species worldwide. Among the wild mammals predisposed to be infected with the etiologic agent of histoplasmosis, bats are relevant because they are reservoir of Histoplasma species, and they play a fundamental role in maintaining and spreading fungal propagules in the environments since the infective mycelial phase of Histoplasma grows in their accumulated guano. In this study, we detected the fungal presence in organ samples of bats randomly captured in urban areas of Araraquara City, São Paulo, Brazil. Fungal detection was performed using a nested polymerase chain reaction to amplify a molecular marker (Hcp100) unique to H. capsulatum, which revealed the pathogen presence in organ samples from 15 out of 37 captured bats, indicating 40.5% of infection. Out of 22 Hcp100-amplicons generated, 41% corresponded to lung and trachea samples and 59% to spleen, liver, and kidney samples. Data from these last three organs suggest that bats develop disseminated infections. Considering that infected bats create environments with a high risk of infection, it is important to register the percentage of infected bats living in urban areas to avoid risks of infection to humans, domestic animals, and wildlife.

Case Report: Primary Cutaneous Histoplasmosis in an Immunocompetent Patient After Cosmetic Injection of Platelet-Rich Plasma Treated with Trimethoprim-Sulfamethoxazole.

BACKGROUND Histoplasmosis is typically associated with immunocompromised individuals, but cases in immunocompetent patients are rare. Primary cutaneous histoplasmosis (PCH) is a challenging diagnosis due to its clinical polymorphism and can mimic other infectious and non-infectious diseases. Previous cases of PCH have been reported in immunocompetent patients with underlying medical conditions or trauma history. So far there have been no reports of PCH after platelet-rich plasma (PRP) application due to inadequate hygiene measures in an immunocompetent host. CASE REPORT This case report presents a rare occurrence of PCH following a cosmetic procedure (PRP injection) in an immunocompetent patient. The patient developed nodule-like lesions at the application sites, which progressed to ulceration with purulent discharge. Initially, atypical mycobacterial infection was suspected, and empirical antibiotic therapy was initiated. Complementary tests were performed, ruling out immunosuppression and systemic pathogens. The patient showed complete resolution of the lesions after one month of atypical treatment with trimethoprim-sulfamethoxazole (TMP/SMX). Pathological examination confirmed the diagnosis of PCH with intracytoplasmic inclusions of Histoplasma sp. CONCLUSIONS This case highlights the importance of considering histoplasmosis as a diagnostic possibility, especially in hyperendemic areas like Venezuela. Direct inoculation of Histoplasma sp. after aesthetic procedures without proper hygiene measures can lead to pathological lesions, even in immunocompetent individuals. TMP/SMX can be considered as an alternative treatment option in the absence of the first-line medication. Further exploration of this treatment approach may benefit patients with similar clinical conditions or when ideal treatment options are unavailable.

Survival Against the Odds-Hemophagocytic Lymphohistiocytosis Amidst the Shadows of Disseminated Histoplasmosis: A Case Report and Literature Review.

Hemophagocytic lymphohistiocytosis (HLH) secondary to Histoplasma capsulatum is rare, impacting <1% globally, with a mortality rate of up to 31%. Herein, we present a rare case of HLH secondary to H capsulatum, affecting a 57-year-old female with rheumatoid arthritis. Extensive investigations were unrevealing and despite broad-spectrum antibiotics, her condition worsened, leading to respiratory failure requiring extracorporeal membrane oxygenation (ECMO) support, shock requiring multiple vasopressors, and acute kidney injury (AKI) requiring hemodialysis. Diagnosis confirmed disseminated histoplasmosis (DHP), prompting Amphotericin B and methylprednisolone treatment, resulting in significant improvement and discharge with posaconazole therapy. Secondary HLH, primarily arising from severe infections like DHP, is discussed. Limited research exists on this condition in human immunodeficiency virus (HIV)-seronegative individuals. Diagnosis involves HLH-2004 and HScore criteria. Managing histoplasmosis-associated HLH remains challenging due to multiorgan failure risks and treatment complexities and needs further research.

A Case Report of Pulmonary Vein Stenosis Within the Labyrinth of Fibrosing Mediastinitis.

This case centers on a 76-year-old male experiencing exertional dyspnea and hemoptysis, with a medical history marked by recurrent pulmonary embolism and chronic obstructive pulmonary disease (COPD). Notably, he resides in a histoplasmosis-endemic area. A computed tomography (CT) pulmonary embolism scan revealed notable findings, including an enlarged right lower pulmonary artery, vascular congestion, atelectasis, and a mass exerting pressure on the right lower pulmonary vein. Biopsy results identified the mass as fibrosing mediastinitis, likely attributed to histoplasmosis. A transthoracic echocardiogram indicated right ventricular dilatation, impaired function, and a right ventricular systolic pressure of 63 mm Hg. During right heart catheterization, the patient displayed disparate pulmonary artery wedge pressures (PAWPs) between the right and left sides. This discrepancy was linked to a blunted back wave from the left atrium to the catheter, induced by pulmonary vein compression. Although an infrequent phenomenon, the recorded asymmetry in PAWPs played a crucial role in guiding accurate patient management. The absence of subsequent evaluation of PAWP on the left side could have altered the treatment plan, potentially delaying appropriate patient care. This case emphasizes the necessity of thorough exploration with right heart catheterization when clinical symptoms warrant, highlighting the importance of standardized practices in such procedures.

Implementation of a rapid diagnostic assay package for cryptococcosis, histoplasmosis and tuberculosis in people living with HIV in Paraguay.

BACKGROUND: Opportunistic infections (OIs) are common causes of mortality among people living with HIV (PLHIV). We determined prevalence and 30-day mortality due to histoplasmosis, cryptococcosis, and TB in PLHIV with advanced HIV disease (AHD). METHODS: PLHIV 18 years and older, with a CD4 + T-cell count of less than 350 cells/mm3 newly diagnosed with HIV infection or re-engaged in care after being without ART for more than 90 days (Group A). The second group included symptomatic PLHIV regardless of ART status or CD4 + T-cell count (Group B); all followed for 30 days. Detection of Histoplasma Ag (HisAg) in urine was done by enzyme immunoassay (EIA), Cryptococcus antigen (CrAg) was detected in serum and cerebrospinal fluid (CSF) specimens by lateral flow assay (LFA), and lipoarabinomannan (LAM) detection in urine was by LFA (TB LAM) and in sputum by GeneXpert for diagnosis of Mycobacterium infections. RESULTS: From August 2021 to June 2022, 491 PLHIV were enrolled; 482 (98%) had a CD4 + T-cell result, and 381 patients (79%) were classified with AHD according to CD4 + T-cell count (< 200 CD4/mm3). Frequency of an OI was 38% (n = 145/381). Antigen test positivity rate was 16% (72/467) for TB-LAM, 9% (43/464) for HisAg, and 11% (51/484) for CrAg. Twenty-one of 34 (62%) patients receiving CSF CrAg tests were positive, confirming meningitis. Significant differences in 30-day mortality were observed in patients with an OI (16%) vs. no OI (7%) (p = 0.002). Mortality was highest in patients with histoplasmosis (25%), co-infection (22%), cryptococcosis (18% overall; 19% for cryptococcal meningitis), and TB (10%). CONCLUSIONS: TB and fungal OIs, including co-infection, were common in PLHIV in Paraguay and had high associated mortality. Laboratories and health facilities need access to CD4 + T-cell testing and rapid diagnostic assays.

Presentación atípica de histoplasmosis diseminada / Atypical presentation of disseminated histoplasmosis

La histoplasmosis es una micosis sistémica producida por una variedad de hongo dimorfo perteneciente al complejo Histoplasma capsulatum. Es una enfermedad prevalente en nuestro medio y sobre todo en pacientes viviendo con HIV con recuento de <200 linfocitos CD4/ml y con cargas virales mayores a 100.000 copias/ml. La presentación de la forma diseminada raramente suele afectar al aparato reproductor; siendo la forma más frecuente pulmonar

Tracing histoplasmosis genomic epidemiology and species occurrence across the USA.

ABSTRACTHistoplasmosis is an endemic mycosis in North America frequently reported along the Ohio and Mississippi River Valleys, although autochthonous cases occur in non-endemic areas. In the United States, the disease is provoked by two genetically distinct clades of Histoplasma capsulatum sensu lato, Histoplasma mississippiense (Nam1) and H. ohiense (Nam2). To bridge the molecular epidemiological gap, we genotyped 93 Histoplasma isolates (62 novel genomes) including clinical, environmental, and veterinarian samples from a broader geographical range by whole-genome sequencing, followed by evolutionary and species niche modelling analyses. We show that histoplasmosis is caused by two major lineages, H. ohiense and H. mississippiense; with sporadic cases caused by H. suramericanum in California and Texas. While H. ohiense is prevalent in eastern states, H. mississipiense was found to be prevalent in the central and western portions of the United States, but also geographically overlapping in some areas suggesting that these species might co-occur. Species Niche Modelling revealed that H. ohiense thrives in places with warmer and drier conditions, while H. mississippiense is endemic to areas with cooler temperatures and more precipitation. In addition, we predicted multiple areas of secondary contact zones where the two species co-occur, potentially facilitating gene exchange and hybridization. This study provides the most comprehensive understanding of the genomic epidemiology of histoplasmosis in the USA and lays a blueprint for the study of invasive fungal diseases.

Pulmonary histoplasmosis on the Chinese mainland: two case reports and literature review.

INTRODUCTION: Pulmonary histoplasmosis is a fungal disease that is endemic in North and Central America. It is relatively rare in China and commonly misdiagnosed as tuberculosis or cancer due to nonspecific clinical and radiographic manifestations. Rapid and accurate pathogen tests are critical for the diagnosis of pulmonary histoplasmosis. METHODOLOGY: We report two cases of pulmonary histoplasmosis. We collected all the relevant case reports on the Chinese mainland (from 1990 to 2022) to analyze features of this disease among Chinese patients. RESULTS: A total of 42 articles reporting 101 cases were identified, and the two cases reported in this article were also included for analysis. Sixty-three (61.2%) patients had respiratory symptoms and 35 (34.0%) patients were asymptomatic. The most common radiographic findings were pulmonary nodules or masses (81.6%). Twenty-two (21.4%) patients were misdiagnosed as tuberculosis, and 37 (35.9%) were misdiagnosed as lung tumors before pathological findings. Metagenomic next­generation sequencing (mNGS) testing provided a rapid diagnostic and therapeutic basis for three patients. CONCLUSIONS: Clinical features and imaging findings of pulmonary histoplasmosis are not specific. Relevant epidemiological history and timely pathogen detection are important for diagnosis. mNGS can shorten the time required for diagnosis and allow earlier initiation of targeted antibiotic therapy.

Surveillance for Coccidioidomycosis, Histoplasmosis, and Blastomycosis During the COVID-19 Pandemic - United States, 2019-2021.

Coccidioidomycosis, histoplasmosis, and blastomycosis are lower respiratory tract fungal infections whose signs and symptoms can resemble those of other respiratory illnesses, including pneumonia caused by bacterial or viral etiologies; this overlap in clinical presentation might lead to missed or delayed diagnoses. The causative fungi live in the environment, often in soil or plant matter. To describe the epidemiologic characteristics of cases of coccidioidomycosis, histoplasmosis, and blastomycosis during the COVID-19 pandemic, CDC analyzed case surveillance data for 2019-2021. During this period, a total of 59,655 coccidioidomycosis cases, 3,595 histoplasmosis cases, and 719 blastomycosis cases were reported to CDC. In 2020, fewer cases of each disease occurred in spring compared with other seasons, and most cases occurred in fall; national seasonality is not typically observed, and cases were seasonally distributed more evenly in 2019 and 2021. Fewer cases coinciding with the start of the COVID-19 pandemic, along with an unusually high blastomycosis case fatality rate in 2021 (17% compared with more typical rates of 8%-10%), suggest that the pandemic might have affected patients' health care-seeking behavior, public health reporting practices, or clinical management of these diseases. Increased awareness and education are needed to encourage health care providers to consider fungal diseases and to identify pneumonia of fungal etiology. Standardized diagnostic guidance and informational resources for fungal testing could be incorporated into broader respiratory disease awareness and preparedness efforts to improve early diagnosis of coccidioidomycosis, histoplasmosis, and blastomycosis.

Gastrointestinal histoplasmosis with small intestinal perforation: 20-year experience.

Postmortem studies show gastrointestinal tract involvement in as many as 70% of patients affected by disseminated histoplasmosis. Although gastrointestinal involvement is common in disseminated disease, the presentation of small intestinal perforation is exceedingly rare with few reported cases in the literature. Herein we present our institutional case series. The aim of the study is to describe small intestinal perforation in gastrointestinal histoplasmosis with attention to management and outcomes. This is a retrospective single-institution review of patients ≥ 18 years of age treated for small intestinal perforation due to gastrointestinal histoplasmosis. A prospectively maintained institutional database was searched from 2002 to 2022. Data obtained included demographics, comorbidities, treatment course, and outcomes. Five patients with a mean age of 54 years (range 25-72) were identified. Pertinent underlying comorbid conditions included Crohn's disease, psoriatic arthritis, rheumatoid arthritis, and solid organ transplantation. All patients were on chronic immunosuppressive medication(s) with the most common being tumor necrosis factors alpha inhibitors and corticosteroids. Four had a clinical diagnosis of perforation based on physical examination and imaging. All patients underwent segmental resection(s) of the small intestine and received medical treatment with intravenous amphotericin B and eventual transition to an oral antifungal. No patients experienced complications related to surgery. The limitations of the study include nonrandomized retrospective review, single-institution experience, and small patient sample size. Although rare, histoplasmosis should be considered in the differential of patients on chronic immunosuppressive therapy who present with gastrointestinal symptoms concerning perforation, especially from endemic areas. Small intestinal perforation due to gastrointestinal histoplasmosis can be successfully treated with resection and antifungal therapy.

Histoplasma antigens as novel players for the development of new enzyme immunoassays for the serodiagnosis of histoplasmosis: A comparative study of their analytical performance.

Definitive diagnosis of histoplasmosis relies on culture and/or cytology/histopathology; however, these procedures have limited sensitivity and cultures are time-consuming. Antibodies detection by immunodiffusion has low sensitivity in immunocompromised individuals and uses histoplasmin (HMN), a crude antigenic extract, as reagent. Novel protein antigen candidates have been recently identified and produced by DNA-recombinant techniques to obtain standardized and specific reagents for diagnosing histoplasmosis. To compare the analytical performance of novel enzyme-linked immunosorbent assays (ELISAs) for antibodies testing for diagnosing histoplasmosis using different Histoplasma capsulatum antigens as reagents. The H. capsulatum 100 kDa protein (Hcp100), the M antigen and its immunoreactive fragment F1 were produced by DNA-recombinant techniques. Galactomannan was purified from both the yeast and mycelial cell walls (yGM and mGM, respectively). The analytical performance of the ELISA tests for the serological detection of antibodies against these antigens was evaluated and compared with those obtained using HMN as reagent. Antibodies detection by the Hcp100 ELISA demonstrated 90.0% sensitivity and 92.0% specificity, versus 43.3% sensitivity and 95.0% specificity of the M ELISA, 33.3% sensitivity and 84.0% specificity of the F1 ELISA, 96.7% sensitivity and 94.0% specificity of the yGM ELISA, 83.3% sensitivity and 88.0% specificity of the mGM ELISA, and 70.0% sensitivity and 86.0% specificity for the HMN ELISA. In summary, Hcp100 is proposed as the most promising candidate for the serodiagnosis of histoplasmosis. The primary immunoreactive element in HMN proved to be GM rather than the M antigen. Nevertheless, a higher incidence of cross-reactions was noted with GM compared to M.

Hcp100 is a promising serodiagnostic candidate for histoplasmosis, boasting high sensitivity and specificity. Notably, GM, rather than M antigen, emerged as the primary immunoreactive element in HMN, despite a higher incidence of cross-reactions with GM compared to M.

Epidemiological, clinical, diagnostic, and therapeutic features of histoplasmosis: A systematic review.

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.

A diverse spectrum of mycoses histologically diagnosed in Ghana: Insights from a 10-year retrospective study.

In Ghana, most laboratory diagnoses of severe mycoses are based on histopathology findings due to inadequate availability of serology, culture, and molecular tests. The aim of this study was to evaluate the spectrum of mycoses diagnosed in Ghana. We retrospectively reviewed reports from 2012 to 2021 from three major pathology laboratories in Ghana to identify reports indicating the presence of fungal elements and diagnosis of a mycosis, then extracted demographic, clinical history, site of infection, stain(s), used and diagnosed mycosis details. Over the 10-year period, 107 cases were found. No apparent increasing and decreasing trend in the number of cases per year or in a period was observed. The age range of affected patients was from 4 to 86 years. Special stains for fungi were only used in 22 of 107 (20.6%) of cases. The most frequently affected site was the sino-nasal area (34%). Mycosis type was determined for 58 (54.2%) cases, comprising aspergillosis (21), candidiasis (14), dermatophytosis (6), mucormycosis (3), two cases each of chromoblastomycosis, histoplasmosis, eumycetoma, entomophthoromycosis, sporotrichosis, and Malassezia infection and a single case each of cryptococcosis and deep onychomycosis. Of the 53 (49.5%) cases with presumptive diagnosis data, only seven (13.2%) had a pre-biopsy suspicion of mycosis. There is a wide spectrum of mycoses in Ghana, including endemic mycoses not previously reported. Improving the use of special fungal stains could increase yield and mycoses identification. Laboratory diagnostic capacity needs enhancement to complement histopathology investigations with serology, culture, and molecular methods.

In Ghana, diagnosis of mycoses is mainly based on histopathology findings. To appreciate the varied mycoses diagnosed, we reviewed the reports of major laboratories from 2012 to 2021 and found 107 cases including endemic, rare, and previously unreported cases with fungal stains unusually used.

Validation of a real-time polymerase chain reaction for the detection and quantification of the nucleic acid of Histoplasma from equine clinical samples.

Histoplasma capsulatum var. farciminosum (HCF) is a dimorphic fungus that causes epizootic lymphangitis in equids. Current diagnostic approaches, including culture, microscopy, and clinical presentation, lack speed, sensitivity, and specificity when diagnosing clinical cases. In this study, equine blood and pus samples on Whatman FTA cards from Senegal (n = 3), The Gambia (n = 19), Ethiopia (n = 16), and Mali (n = 13) were tested using a real-time PCR (qPCR) protocol. The assay was optimized and tested for its suitability to detect and quantify HCF in blood and pus loaded onto Whatman FTA cards at sampling. Whatman FTA cards were tested for their suitability for use with qPCR and were found to recover DNA more efficiently than from direct extraction. Using TaqMan fluorescent probes and specific primers, the assay demonstrated 100% analytical specificity when detecting multiple strains of Histoplasma and no false positives with off-target organisms. The assay's diagnostic performance was measured against an existing nested internal transcribed spacer PCR protocol using a receiver operating characteristic curve. The test was found to have a diagnostic specificity and sensitivity of 100% and 71.4%, respectively, when analyzing pus samples using a cycle threshold (Ct) cutoff determined by Youden's index (27.75). Blood sample cutoff Ct value was proposed at 34.55. Further optimization is required to improve the performance of the protocol when applied to blood samples. This study has, for the first time, demonstrated the ability to detect and quantify the DNA of Histoplasma spp. in equine blood and pus samples with a high degree of accuracy, providing a platform to further investigate the pathogenesis and epidemiology of this disease. IMPORTANCE: Histoplasmosis is a neglected yet major cause of morbidity and mortality in both equids and people in resource-scarce settings. One of the major hindrances to the control of histoplasmosis is a lack of readily available diagnostic tests. Tests are needed to support clinical decision-making and to be applied in population-based research to further understand this disease in situ. This paper reports, for the first time, the validation and application of a qPCR to detect Histoplasma directly from equine clinical samples, bypassing the need to culture this notoriously difficult organism. We report and comment on the performance of the qPCR in comparison with our previously developed nested PCR.

Prevalence and risk factors for epizootic lymphangitis among equids in ethiopia during 2002-2023: A systematic review and meta-analysis.

In Sub-Saharan Africa (SSA), particularly in Ethiopia, Epizootic Lymphangitis (EL) is the most prevalent fungal disease of equids, which causes significant economic losses as well as a decrease in equid populations. Therefore, this systematic review and meta-analysis were designed to pool the results of individual studies and estimate the prevalence of EL among equids in Ethiopia. A systematic search of research articles on the prevalence and risk factors of EL among equids in Ethiopia was conducted in registers, databases, and other sources. Cochrane's Q, inverse variance (I2), sensitivity analysis, funnel plot, Begg's, and Egger's regression tests were used to check heterogeneity and publication bias. A random-effects model was used to calculate the pooled burden of EL among equids. For this meta-analysis, a total of 7217 equids were included in the 14 eligible studies. The overall pooled prevalence of EL among equids in Ethiopia was 20.24% (95% CI: 16.27, 24.21). According to the subgroup analysis, the highest prevalence was observed in cart horses (20.98%), the Amhara region (21.46%), and studies conducted using sample sizes of 384 equids or greater (24.67%) and from 2002 to 2018 (25.52%) study periods. Harness-inflicted wounds, sharing stables or yards with harnesses, and the presence of preexisting wounds were identified as factors significantly associated with EL magnitude. Early diagnosis and proper medication, as well as implementing appropriate prevention and control measures, are necessary for the management of EL in equids.