Browsing by Subject "Histoplasmosis"
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Item 721. Diagnosis of Histoplasmosis Using the MVista Histoplasma Galactomannan Antigen Qualitative Lateral Flow-Based Immunoassay; A Multicenter Study(Oxford University Press, 2021) Abdallah, Wassim; Myint, Thein; LaRue, Richard W.; Minderman, Melissa; Gunn, Suphansa; Wheat, Lawrence J.; Hage, Chadi A.; Medicine, School of MedicineBackground: Accurate and timely methods for the diagnosis of histoplasmosis in endemic resource-limited settings are largely lacking. Histoplasma galactomannan antigen detection by enzyme immunoassay (EIA) is the most widely used method for the diagnosis of acute pulmonary and disseminated histoplasmosis in the United States (USA). EIA methods have constraints in resource-limited settings including cost, turnaround time, and the need for large reference laboratories, leading to missed or delayed diagnoses and poor outcomes. Lateral flow assays (LFA) are practical methods that can be used in this setting for Histoplasma antigen detection. Methods: Frozen urine specimens were submitted to MiraVista (MVista) for Histoplasma antigen EIA testing from three academic medical centers in highly endemic areas of the USA. They were also blinded and tested for the MVista Histoplasma LFA by skilled MVista technologists. Medical records were reviewed for clinical information. Patients were classified as controls or cases of histoplasmosis. Cases were divided into proven or probable, pulmonary, or disseminated, immune competent or immune suppressed, and mild, moderate, or severe. Results: 352 subjects were enrolled, including 66 cases of histoplasmosis (44 proven, 22 probable) and 286 controls. Most of the cases were immunocompromised (68%). 76% had disseminated histoplasmosis. 6% were mild, 66% moderate, and 28% severe. A high degree of concordance was found between LFA and EIA results (kappa 0.837, OR 372.7, LR 204, p< 0.001). Overall, the sensitivity and specificity of the LFA were 78.8% and 99.3% respectively (kappa 0.84, p< 0.001). The sensitivity was higher in proven cases (93.2%), in patient with disseminated (94.7%), moderate (80%) and severe disease (94%), and those with galactomannan levels ≥ 2 ng/mL (97.7%). Specificity was 99.3% in proven cases, 99.3% in patient with moderate and severe disease, and 96.4% in those with galactomannan levels ≥ 2 ng/mL. Conclusion: The MVista Histoplasma galactomannan LFA may meet the need for accurate rapid diagnosis of histoplasmosis in resource-limited settings, especially in patients with relatively high disease burden, potentially reducing morbidity and mortality.Item Bilateral Adrenal Nodules in the Setting of Disseminated Fungal Infection: An Important Consideration for Appropriate Management of Adrenal Pathology(Elsevier, 2024-12-16) Johnson, Bailey N.; Braafladt, Signe; Lavik, John-Paul; Walton, Lillian; McDow, Alexandria D.; Surgery, School of MedicineBackground/objective: Increased utilization of cross-sectional imaging has led to a rise in diagnosis of incidental adrenal lesions. Physicians in many clinical settings are increasingly faced with addressing these incidental lesions by initiating the correct workup, diagnosis, and long-term follow-up plan. Our objective was to demonstrate the importance of maintaining a broad differential and completing a thorough workup in determining the correct treatment plan for patients with bilateral adrenal lesions. Case report: We present 2 patients who recently completed chemotherapy for lymphoma, found to have new bilateral adrenal lesions on postchemotherapy imaging. Urine antigen and/or adrenal biopsy was performed to confirm the diagnosis of disseminated fungal infection. This diagnosis has major implications on the treatment plan, which includes antifungal therapy instead of surgical management or additional chemotherapy. Cross-sectional imaging after initiation of antifungal treatment demonstrated decreasing size of nodules. Discussion: A broad differential is critical when working up and developing treatment plans for adrenal nodules, specifically considering a fungal etiology in the setting of immunosuppression or primary extra-adrenal malignancy. Conclusion: Incidentally found adrenal lesions are becoming more common, and in turn, the obligation for appropriate management of adrenal pathology not only falls to medical and surgical endocrinologists but also to general practitioners. It is prudent to consider atypical etiologies including disseminated fungal infection prior to surgical excision or initiation of chemotherapy as those treatment strategies would not benefit select patients.Item Cutaneous presentation of progressive disseminated histoplasmosis nine years after renal transplantation(Wiley, 2013) Rosado-Odom, Vera M.; Daoud, Jacques; Johnson, Raymond; Allen, Stephen D.; Lockhart, Shawn R.; Iqbal, Naureen; Shieh, Wun-Ju; Zaki, Sherif; Sharfuddin, Asif; Medicine, School of MedicineInitial presentation of invasive fungal infections such as histoplasmosis can include non-specific clinical manifestations, especially in immunocompromised patients. A high index of suspicion is required to identify atypical manifestations of these diseases, which carry a high risk of mortality, if the diagnosis is delayed or missed. We describe a case of a kidney transplant recipient with cutaneous lesions as initial manifestation of progressive disseminated histoplasmosis where a skin biopsy was crucial to an early diagnosis.Item Diagnosis of Histoplasmosis Using the MVista Histoplasma Galactomannan Antigen Qualitative Lateral Flow–Based Immunoassay: A Multicenter Study(Oxford University Press, 2021-08-31) Abdallah, Wassim; Myint, Thein; LaRue, Richard; Minderman, Melissa; Gunn, Suphansa; Wheat, L. Joseph; Hage, Chadi A.; Medicine, School of MedicineBackground: Accurate and timely methods for the diagnosis of histoplasmosis in resource-limited countries are lacking. Histoplasma antigen detection by enzyme immunoassay (EIA) is widely used in the United States (US) but not in resource-limited countries, leading to missed or delayed diagnoses and poor outcomes. Lateral flow assays (LFAs) can be used in this setting. Methods: Frozen urine specimens were submitted to MiraVista diagnostics for antigen testing from 3 medical centers in endemic areas of the US. They were blinded and tested for the MVista Histoplasma LFA. Patients were classified as controls or cases of histoplasmosis. Cases were divided into proven or probable; pulmonary or disseminated; immunocompetent or immunosuppressed; and mild, moderate, or severe. Results: Three hundred fifty-two subjects were enrolled, including 66 cases (44 proven, 22 probable) and 286 controls. Most of the cases were immunocompromised (71%), and 46 had disseminated and 20 had pulmonary histoplasmosis. Four cases were mild, 42 moderate, and 20 severe. LFA and EIA were highly concordant (κ = 0.84). Sensitivity and specificity of the LFA were 78.8% and 99.3%, respectively. LFA sensitivity was higher in proven cases (93.2%), patients with disseminated (91.3%), moderate (78.6%), and severe disease (80%), and those with galactomannan levels >1.8 ng/mL (97.8%). Specificity was 99.3% in proven cases, 99.3% in patients with moderate or severe disease, and 96.8% in those with galactomannan levels >1.8 ng/mL. Cross-reactivity was noted with other endemic mycoses. Conclusions: The MVista Histoplasma LFA meets the need for accurate rapid diagnosis of histoplasmosis in resource-limited countries, especially in patients with high disease burden, potentially reducing morbidity and mortality.Item Histoplasmosis complicating tumor necrosis factor-α blocker therapy: a retrospective analysis of 98 cases(Oxford University Press, 2015-08-01) Vergidis, Paschalis; Avery, Robin K.; Wheat, L. Joseph; Dotson, Jennifer L.; Assi, Maha A.; Antoun, Smyrna A.; Hamoud, Kassem A.; Burdette, Steven D.; Freifeld, Alison G.; McKinsey, David; Money, Mary E.; Myint, Thein; Andes, David R.; Hoey, Cynthia A.; Kaul, Daniel A.; Dickter, Jana K.; Liebers, David E.; Miller, Rachel A.; Muth, William E.; Prakash, Vidhya; Steiner, Frederick T.; Walker, Randall C.; Hage, Chadi A.; Department of Medicine, IU School of MedicineBACKGROUND: 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.Item Histoplasmosis in Solid Organ Transplantation(MDPI, 2024-02-02) Barros, Nicolas; Wheat, L. Joseph; Medicine, School of MedicineHistoplasma capsulatum, the etiological agent for histoplasmosis, is a dimorphic fungus that grows as a mold in the environment and as a yeast in human tissues. It has a broad global distribution with shifting epidemiology during recent decades. While in immunocompetent individuals infection is usually self-resolving, solid organ transplant recipients are at increased risk of symptomatic disease with dissemination to extrapulmonary tissue. Diagnosis of histoplasmosis relies on direct observation of the pathogen (histopathology, cytopathology, and culture) or detection of antigens, antibodies, or nucleic acids. All transplant recipients with histoplasmosis warrant therapy, though the agent of choice and duration of therapy depends on the severity of disease. In the present article, we describe the pathogenesis, epidemiology, clinical manifestations and management of histoplasmosis in solid organ transplant recipients.Item Pulmonary Histoplasmosis: A Clinical Update(MDPI, 2023-02-10) Barros, Nicolas; Wheat, Joseph L.; Hage, Chadi; Medicine, School of MedicineHistoplasma capsulatum, the etiological agent for histoplasmosis, is a dimorphic fungus that grows as a mold in the environment and as a yeast in human tissues. The areas of highest endemicity lie within the Mississippi and Ohio River Valleys of North America and parts of Central and South America. The most common clinical presentations include pulmonary histoplasmosis, which can resemble community-acquired pneumonia, tuberculosis, sarcoidosis, or malignancy; however, certain patients can develop mediastinal involvement or progression to disseminated disease. Understanding the epidemiology, pathology, clinical presentation, and diagnostic testing performance is pivotal for a successful diagnosis. While most immunocompetent patients with mild acute or subacute pulmonary histoplasmosis should receive therapy, all immunocompromised patients and those with chronic pulmonary disease or progressive disseminated disease should also receive therapy. Liposomal amphotericin B is the agent of choice for severe or disseminated disease, and itraconazole is recommended in milder cases or as "step-down" therapy after initial improvement with amphotericin B. In this review, we discuss the current epidemiology, pathology, diagnosis, clinical presentations, and management of pulmonary histoplasmosis.Item The leukotriene B₄/BLT₁ axis is a key determinant in susceptibility and resistance to histoplasmosis(Public Library of Science, 2014-01-21) Secatto, Adriana; Soares, Elyara Maria; Locachevic, Gisele Aparecida; Assis, Patricia Aparecida; Paula-Silva, Francisco Wanderlei Garcia; Serezani, Carlos Henrique; de Medeiros, Alexandra Ivo; Faccioli, Lúcia Helena; Microbiology and Immunology, School of MedicineThe bioactive lipid mediator leukotriene B4 (LTB4) greatly enhances phagocyte antimicrobial functions against a myriad of pathogens. In murine histoplasmosis, inhibition of the LT-generating enzyme 5-lypoxigenase (5-LO) increases the susceptibility of the host to infection. In this study, we investigated whether murine resistance or susceptibility to Histoplasma capsulatum infection is associated with leukotriene production and an enhancement of in vivo and/or in vitro antimicrobial effector function. We show that susceptible C57BL/6 mice exhibit a higher fungal burden in the lung and spleen, increased mortality, lower expression levels of 5-LO and leukotriene B4 receptor 1 (BLT1) and decreased LTB4 production compared to the resistant 129/Sv mice. Moreover, we demonstrate that endogenous and exogenous LTs are required for the optimal phagocytosis of H. capsulatum by macrophages from both murine strains, although C57BL/6 macrophages are more sensitive to the effects of LTB4 than 129/Sv macrophages. Therefore, our results provide novel evidence that LTB4 production and BLT1 signaling are required for a histoplasmosis-resistant phenotype.