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Coccidioidomycosis and HistoplasmosisThe authors discuss the endemic fungal infections coccidioidomycosis and histoplasmosis, including ecologic niches, signs and symptoms, the course of illness, complications, diagnosis, and treatment.

The rapid diagnosis of opportunistic infections (OIs) is critical for improving the health outcomes of people living with HIV/AIDS (PLWHA). This study aimed to describe the feasibility of implementing a package for the rapid diagnosis of tuberculosis, histoplasmosis, and cryptococcosis in patients with advanced HIV/AIDS disease in Porto Alegre, Brazil. The research involved two focus groups with health professionals, four in-depth interviews with healthcare managers, and twelve interviews with PLWHA. The corpus was analyzed using Descending Hierarchical Classification (DHC). The study found that the rapid test diagnosis intervention was generally well-received by patients and health professionals, improving diagnosis and treatment outcomes. However, it also identified several areas for improvement, including the need for expanded psychosocial support and enhanced coordination between health services. The findings have important implications for the development and implementation of policies and programs aimed at enhancing the diagnosis and treatment of OIs among PLWHA with advanced diseases. Further research should explore social determinants of HIV/AIDS mortality to offer valuable insights into improving prevention and treatment strategies. By prioritizing patient-centered care and improving coordination between health services, policymakers and health professionals can improve the health outcomes of PLWHA with advanced disease in Porto Alegre and other similar settings.

Background. Histoplasmosis may complicate tumor necrosis factor (TNF)–α blocker therapy. Published case series provide limited guidance on disease management. We sought to determine the need for long-term antifungal therapy and the safety of resuming TNF-α blocker therapy after successful treatment of histoplasmosis. Methods. We conducted a multicenter retrospective review of 98 patients diagnosed with histoplasmosis between January 2000 and June 2011. Multivariate logistic regression was used to evaluate risk factors for severe disease. Results. The most commonly used biologic agent was infliximab (67.3%). Concomitant corticosteroid use (odds ratio [OR], 3.94 [95% confidence interval {CI}, 1.06–14.60]) and higher urine Histoplasma antigen levels (OR, 1.14 [95% CI, 1.03–1.25]) were found to be independent predictors of severe disease. Forty-six (47.4%) patients were initially treated with an amphotericin B formulation for a median duration of 2 weeks. Azole treatment was given for a median of 12 months. TNF-α blocker therapy was initially discontinued in 95 of 98 (96.9%) patients and later resumed in 25 of 74 (33.8%) patients at a median of 12 months (range, 1–69 months). The recurrence rate was 3.2% at a median follow-up period of 32 months. Of the 3 patients with recurrence, 2 had restarted TNF-α blocker therapy, 1 of whom died. Mortality rate was 3.2%. Conclusions. In this study, disease outcomes were generally favorable. Discontinuation of antifungal treatment after clinical response and an appropriate duration of therapy, probably at least 12 months, appears safe if pharmacologic immunosuppression has been held. Resumption of TNF-α blocker therapy also appears safe, assuming that the initial antifungal therapy was administered for 12 months.

Evidence-based guidelines for the management of patients with histoplasmosis were prepared by an Expert Panel of the Infectious Diseases Society of America. These updated guidelines replace the previous treatment guidelines published in 2000 (Clin Infect Dis 2000; 30:688–95). The guidelines are intended for use by health care providers who care for patients who either have these infections or may be at risk for them. Since 2000, several new antifungal agents have become available, and clinical trials and case series have increased our understanding of the management of histoplasmosis. Advances in immunosuppressive treatment for inflammatory disorders have created new questions about the approach to prevention and treatment of histoplasmosis. New information, based on publications from the period 1999–2006, are incorporated into this guideline document. In addition, the panel added recommendations for management of histoplasmosis in children for those aspects that differ from aspects in adults.

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.

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. 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. 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. 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.

Adrenal Involvement in Disseminated HistoplasmosisAn 82-year-old man presented with a 3-year history of progressive generalized weakness. PET-CT showed a metabolically active adrenal mass on each side.

Disseminated histoplasmosis (DH) is a rare but serious systemic fungal infection that can trigger secondary hemophagocytic lymphohistiocytosis (HLH), a hyperinflammatory syndrome with high mortality. However, the immunopathogenesis of DH-associated HLH remains poorly defined due to the lack of high-resolution immune profiling data. The dynamics of immunological and metabolic analysis was performed in a 14-year-old female patient with DH-HLH using mass cytometry (CyTOF) and multiplex cytokine profiling. Peripheral blood mononuclear cells and plasma were collected at three timepoints: before antifungal treatment, and at 1, and 2 weeks post-treatment, respectively. Immune subsets, functional markers, and cytokine/chemokine levels were evaluated. Mass cytometry identified 13 distinct immune cell subsets, including NK cells, double-negative T (DNT) cells, memory CD8 + T cells, and M2 macrophages. Longitudinal analysis demonstrated a progressive decline in proinflammatory cytokines (such as IL-6, TNF-α, and IP-10) accompanied by an expansion of reparative subsets, particularly M2 macrophages. Concurrent immune-metabolic profiling revealed a metabolic shift from glycolysis to lipid oxidation, characterized by decreased expression of GLUT1 and CPT1A and increased expression of CD36. This transition from a glycolysis-driven inflammatory state to an oxidative, immunoregulatory phenotype correlated with clinical recovery and attenuation of the cytokine storm. This case demonstrates the utility of mass cytometry for dynamic immune monitoring in infection-triggered HLH. The findings highlight metabolic reprogramming and immune restoration as key features of disease resolution and suggest potential immunometabolic targets for future diagnostic and therapeutic strategies.

Disseminated histoplasmosis is one the main AIDS-defining opportunistic infections in HIV-infected patients, notably in Latin America. The non-specific and proteiform clinical presentation leads to diagnostic delays that may lead to fatal outcomes. This retrospective multicentric study aimed to describe the frequency and manifestations of gastrointestinal histoplasmosis in French Guiana, and to compare patients with disseminated histoplasmosis with or without gastrointestinal involvement. Between January 1, 1981 and October 1, 2014 co-infections with HIV and histoplasmosis were enrolled. Inclusion criteria were: age >18 years, confirmed HIV infection; first proven episode of histoplasmosis. Among 349 cases of disseminated histoplasmosis, 245 (70%) had a gastrointestinal presentation. Half of patients with gastrointestinal signs had abdominal pain or diarrhea, mostly watery. Half of patients with abdominal pain had diarrhea (63/124) and half of those with diarrhea (63/123) had abdominal pain. A significant proportion of patients also had hepatomegaly and, to a lesser degree, splenomegaly. After adjusting for potential confounding, the presence of lymphadenopathies >2cm (AOR = 0.2, IC95 = 0.04–0.7, P = 0.01), Haitian origin (AOR = 0.04, IC95 = 0.004–0.4, P = 0.006) were associated with a lower prevalence of gastrointestinal signs and positive gastrointestinal presence of H . capsulatum . Persons with a gastrointestinal H . capsulatum were more likely to have a decreased prothrombin time, lower ferritin, lower liver enzymes, and lower concentrations of LDH than those without gastrointestinal signs and symptoms. They also had a shorter interval between symptoms onset and diagnosis. Patients with a positive gastrointestinal identification of H . capsulatum were less likely to die at 1 month than those without a gastrointestinal presentation (respectively, 4.6% vs 18.5%, P = 0.01). Subacute or chronic gastrointestinal presentations are very frequent during disseminated histoplasmosis, they seem less severe, and should lead to suspect the diagnosis in endemic areas. There were populational or geographic differences in the frequency of gastrointestinal manifestations that could not be explained.

Musculoskeletal manifestations of Histoplasma capsulatum infection are uncommon but can mimic inflammatory arthritis. Early diagnosis of this complication is of critical importance in the era of potent immunosuppression for rheumatologic diseases. We conducted a retrospective chart review for patients with histoplasmosis and tenosynovitis, synovitis, or arthritis, diagnosed and treated at our institution between January 1, 2000, and December 31, 2019. We also reviewed the relevant literature. Four patients with biopsy-proven, culture-proven histoplasma tenosynovitis were identified at our institution. All four patients had wrist or hand involvement in an asymmetric pattern, and one patient had lower extremity involvement as well. Two patients were not immunocompromised at baseline. One patient underwent a lengthy evaluation and received immunosuppression for 4 years without improvement prior to the diagnosis of histoplasmosis. Histoplasma serologic tests varied among patients with localized infection. Pathologic findings revealed non-caseating granulomatous inflammation. Three patients recovered after 6–12 months of antifungal treatment. One patient still had recurrent infection despite 20 months of treatment. Histoplasma tenosynovitis and synovitis are rare causes of inflammatory arthritis. Infectious causes should be considered and carefully evaluated when patients present with asymmetric oligoarthritis. Early recognition is crucial for successful treatment, especially in patients with concomitant rheumatologic diseases receiving immunosuppressive treatment.