Primary Central Nervous System Infection by Histoplasma in an Immunocompetent Adult: A Case Report

Histoplasma capsulatum infection is endemic in many regions around the world, including Latin America [1]. However, cerebral presentation occurs in less than 25% of patients with disseminated histoplasmosis and even rarer as a stand-alone presentation. Three forms are described: meningeal, miliary granulomatous and parenchymal with formation of “histoplasmoma” [2]. Due to the rarity of the case and unusual clinical presentation and topography we describe the case below.

A Simple Predictive Score to Distinguish between Disseminated Histoplasmosis and Tuberculosis in Patients with HIV

Disseminated histoplasmosis is a common differential diagnosis of tuberculosis in disease-endemic areas. We aimed to find a predictive score to orient clinicians towards disseminated histoplasmosis or tuberculosis when facing a non-specific infectious syndrome in patients with advanced HIV disease. We reanalyzed data from a retrospective study in Cayenne Hospital between January 1997–December 2008 comparing disseminated histoplasmosis and tuberculosis: 100 confirmed disseminated histoplasmosis cases and 88 confirmed tuberculosis cases were included. A simple logit regression model was constructed to predict whether a case was tuberculosis or disseminated histoplasmosis. From this model, a score may be obtained, where the natural logarithm of the probability of disseminated histoplasmosis/tuberculosis = +3.917962 × WHO performance score (1 if >2, 0 if ≤2) −1.624642 × Pulmonary presentation (1 yes, 0 no) +2.245819 × Adenopathies > 2 cm (1 yes, 0 no) −0.015898 × CD4 count − 0.001851 × ASAT − 0.000871 × Neutrophil count − 0.000018 × Platelet count + 6.053793. The area under the curve was 98.55%. The sensitivity of the model to distinguish between disseminated histoplasmosis and tuberculosis was 95% (95% CI = 88.7–98.3%), and the specificity was 93% (95% CI = 85.7.3–97.4%). In conclusion, we here present a clinical-biological predictive score, using simple variables available on admission, that seemed to perform very well to discriminate disseminated histoplasmosis from tuberculosis in French Guiana in well characterized patients.

721. Diagnosis of Histoplasmosis Using the MVista Histoplasma Galactomannan Antigen Qualitative Lateral Flow-Based Immunoassay; A Multicenter Study

Background 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. Table 1. Statistical characteristics of the LFA test for histoplasmosis in different categories. PPV: Positive Predictive Value. NPV: Negative Predictive Value. EIA: Enzyme Immunoassay. The LFA test for histoplasmosis is more accurate in patients with high burden of infection. 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. Disclosures Melissa Minderman, Bachelor's Degree, Molecular Biology, MiraVista Diagnostics (Employee) Suphansa Gunn, Bachelor's Degree, psychology, MiraVista Diagnostics (Employee) Lawrence J. Wheat, MD, MiraVista Diagnostics (Employee)

A Case Of Disseminated Histoplasmosis In A Patient With Sarcoidosis

Introduction/Objective Sarcoidosis is a syndrome of unknown cause that may manifest with clinical, radiographic and pathological findings similar to those seen with histoplasmosis. We present a case of disseminated histoplasmosis in an immunocompetent patient previously diagnosed with sarcoidosis. Methods/Case Report A 69-year-old obese male with a history of hypertension, diabetes mellitus and long-standing sarcoidosis was admitted to the hospital for several months of intermittent fevers and pancytopenia. His sarcoidosis was diagnosed 21 years prior, initially involving the lungs and eventually showing cardiac involvement, requiring a pacemaker. He had been treated with methotrexate and prednisone. His recent medical history was also significant for COVID-19 infection, diagnosed 3 months before admission. His fevers were initially attributed to sarcoidosis and his pancytopenia to methotrexate. However, his symptoms continued despite discontinuation of his medications, and further workup was initiated. Computed tomography showed hepatomegaly, splenomegaly, and lymphadenopathy, concerning for a lymphoproliferative disorder. The patient underwent a bone marrow biopsy that showed noncaseating granulomas and microorganisms consistent with histoplasmosis on fungal stain. Bone marrow cultures were not possible as the marrow was inaspirable. The patient subsequently underwent a lymph node biopsy with both morphology and culture identifying histoplasmosis. Urine and serum histoplasma antigen also returned positive. The patient’s overall clinical picture was consistent with disseminated histoplasmosis and he was administered intravenous Amphotericin B for 3 weeks followed by oral itraconazole for 1 year. One month follow-up after discharge showed significant improvement in the patient’s condition. Results (if a Case Study enter NA) N/A Conclusion Sarcoidosis reduces T-cell activity, and treatment with steroids causes further immunosuppression and vulnerability for development of a disseminated infection. COVID-19 also presumably increases the predisposition to acquire bacterial or fungal co-infections. Clinicians and pathologists should be aware of the overlap in clinical, radiologic and pathological presentations of sarcoidosis and histoplasmosis to make the correct diagnosis and administer the appropriate treatment.