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.

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.

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.

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.

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.

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.

Gastrointestinal bleeding in a kidney transplant recipient.

Opportunistic infections are common in transplant recipients, but gastrointestinal bleed is rarely reported to be due to opportunistic fungal infections, and hence could present as a diagnostic challenge. We report a case of disseminated histoplasmosis in a kidney transplant recipient whose initial presentation was acute lower gastrointestinal bleeding with no other symptoms. The colonoscopy showed scattered punchout circular colonic ulcers with biopsy revealing budding yeasts consistent with a diagnosis of histoplasmosis. The patient was successfully treated with a prolonged course of intravenous amphotericin B followed by oral itraconazole.

Pulmonary Histoplasmosis Complicated by Nonvalvular Right Ventricular Wall Histoplasma capsulatum Endocarditis.

Histoplasmosis is commonly a self-limited fungal disease that primarily affects the lung and reticuloendothelial system. Cardiac involvement by histoplasmosis is uncommon. In this report, we provide a detailed description of severe pulmonary histoplasmosis complicated by the disease involvement of the free wall of the right ventricle. A 55-year-old female presented with cough, fevers, dyspnea, and 30-pound unintentional weight loss in 6 months. Her past medical history was significant for supraventricular tachycardia with permanent pacemaker implantation. Imaging studies revealed an intracardiac mass accompanied by mediastinal lymphadenopathy and bilateral lung nodules. Endobronchial ultrasound-guided transbronchial needle aspiration of station 4R lymph nodes revealed numerous yeast forms, morphologically consistent with Histoplasma capsulatum. The diagnosis was further corroborated by the elevated titers of serum antibodies against Histoplasma capsulatum. The right ventricular mass debulking with biopsy showed necrotizing granulomatous inflammation involving nonvalvular endocardium and myocardium of the free wall of the right ventricle. The report documents an unusual presentation of pulmonary histoplasmosis accompanied by nonvalvular endocarditis and suggests a possible association between the site of the cardiac infection and the presence of a permanent intravascular pacer device.

Painful Granulomatous Hashimoto Thyroiditis Uncovered Systemic Histoplasmosis.

Background. Granulomatous thyroiditis is usually viral and very rarely due to fungal infection. Fungal thyroiditis affects the severely immunocompromised and only rarely immunocompetent individuals. Case report. A 32-year-old man with known Hashimoto thyroiditis was consulted for a 1-week history of neck pain, dysphagia, cough, asthenia, loss of appetite, and night sweats. Imaging showed an enlarged right thyroid lobe. Laboratory studies confirmed hypothyroidism. He underwent a thyroid lobectomy. Microscopic examination showed granulomas in a background of Hashimoto thyroiditis. Silver stain revealed numerous yeasts consistent with Histoplasma. Subsequent serology was also positive. Further evaluations were negative for acquired or constitutional immunodeficiencies. He was started on oral itraconazole with resolution of all constitutional symptoms. Conclusions. We report a second case of concurrent Hashimoto and Histoplasma thyroiditis in an immunocompetent patient. Systemic manifestations of fungal infection are confounded by systemic symptoms of thyroid dysfunction. Fungal thyroiditis is a manifestation of systemic fungal infection requiring prolonged systemic therapy to prevent complications or fatal outcomes.

Histoplasma antigen detection in unconfirmed pulmonary tuberculosis and cross-reactivity with Aspergillus antigen in patients and in food in Jakarta, Indonesia.

PURPOSE: H. capsulatum is endemic in Indonesia, but the value of Histoplasma antigen detection has not been studied. PATIENTS AND METHODS: Histoplasma galactomannan (GM) ELISA was applied to sera of patients with unproven pulmonary tuberculosis (TB) and patients with a positive Aspergillus GM. Both Histoplasma and Aspergillus GM tests were performed to determine any possible cross-reaction with certain foods. RESULTS: Fourteen of 122 (11.5%) sera of patients with newly diagnosed clinical TB were positive for Histoplasma GM. The positivity rate in the serum of patients 5-6 and 12 months after TB diagnosis was 3.8% and 3.5%, respectively. Of 88 positive Aspergillus GM sera, 63 (71.6%) were also positive for Histoplasma GM. All tested foods were positive for Aspergillus GM, while 65% of foods were positive for Histoplasma GM. CONCLUSION: Galactomannan is widespread in sera and food in Jakarta, possibly related to food consumption. Histoplasma and Aspergillus antigen detection for the diagnosis will require additional means of confirming the diagnosis; negative tests may be more helpful for ruling out invasive histoplasmosis and aspergillosis.