837. Performance of Blood (1- >3)-β-D-Glucan in People with AIDS Presenting with Respiratory Symptoms

Background The gold standard for diagnosis of Pneumocystis jirovecii pneumonia (PCP) is direct visualization of the microorganism in respiratory samples, usually obtained via bronchoalveolar lavage (BAL). Blood β-D-glucan (BDG) is used as a non-invasive adjunctive diagnostic test for PCP, but specificity is only modest, in part because other opportunistic fungal infections cause high BDG. We previously showed BDG-positivity in 94% of people with AIDS (PWA), progressive disseminated histoplasmosis (PDH), and respiratory symptoms in our hospital. In this study, we aim to assess the performance of BDG as a diagnostic test for PCP in PWA who have respiratory symptoms. Methods We retrospectively identified PWA who had a BDG result between 2014 and 2019. AIDS was defined as past or current absolute CD4 count < 200 cells/µL, or a past or current AIDS-defining condition. Positive cytological or histological evidence of P. jirovecii in bronchoalveolar lavage (BAL) fluid or lung biopsy, or positive Pneumocystis PCR on sputum or BAL confirmed PCP. The Fungitell Assay (Associates of Cape Cod, East Falmouth, MA) determined BDG levels as follows: negative, < 60 pg/mL; indeterminate, 60-79 pg/mL, and positive, ≥ 80 pg/mL. Values < 31 pg/mL and those >500 pg/mL were censored at 30 pg/mL and 500 pg/mL, respectively. Respiratory symptoms were defined as cough, dyspnea, chest pain, or hypoxia. We compared BDG results for participants with proven PCP and participants without proven PCP. Results We identified 260 PWA with a BDG result, of whom 183 had at least one respiratory symptom. 84 (45.9%) of these participants had a positive BDG. BDG results among participants with and without PCP are shown in Table 1. Of the 44 participants with a positive BDG who did not have PCP, 29 (65.9%) had PDH. Other diagnoses included cryptococcosis and candidemia. The test performance of BDG for the diagnosis of PCP is shown in Table 2. Exclusion of participants with PDH increased the specificity of BDG for PCP to 86.4%. Table 1. Results of (1->3)-β-D-glucan Testing by Pneumocystis jirovecii Pneumonia Diagnosis Among Participants with AIDS and Respiratory Symptoms Table 2. Test Performance of (1->3)-β-D-glucan for the Diagnosis of Pneumocystis jirovecii Pneumonia* Conclusion At our center where histoplasmosis is endemic, a positive BDG should not be attributed to PCP among PWA with respiratory symptoms because of low specificity and low positive predictive value. However, a negative BDG can exclude PCP in this population. Disclosures All Authors: No reported disclosures

Progressive disseminated histoplasmosis in idiopathic CD4 lymphocytopenia an underdiagnosed combination - a case report

Progressive disseminated histoplasmosis (PDH) usually presents as fever, anemia, leukopenia, hepatosplenomegaly, lymphadenopathy and pulmonary symptoms. There are few reports showed the association of Idiopathic CD4 lymphocytopenia (ICL) with histoplasmosis. We describe a 65-year-old female presented with history of fever, papulo-nodular rash and significant weight loss and diagnosed as progressive disseminated histoplasmosis. All immunocompromised conditions were ruled out. In addition, her 2 consecutive CD4 counts were below 300. The patient was diagnosed with PDH associated with ICL. Patient showed significant improvement with liposomal amphotericin B and itraconazole. Absolute CD4 counts should be done in all cases of progressive disseminated histoplasmosis even in HIV negative individuals to rule out associated ICL.

Histoplasmosis Diagnosed in Europe and Israel: A Case Report and Systematic Review of the Literature from 2005 to 2020

Human histoplasmosis is a mycosis caused by two distinct varieties of a dimorphic fungus: Histoplasma capsulatum var. capsulatum and H. capsulatum var. duboisii. In Europe, it is usually imported by migrants and travellers, although there have been some autochthonous cases, especially in Italy; however, most European physicians are unfamiliar with its clinical and pathological picture, particularly among immunocompromised patients without HIV infection. This systematic review of all the cases of histoplasmosis reported in Europe and Israel between 2005 and 2020 identified 728 cases diagnosed in 17 European countries and Israel described in 133 articles. The vast majority were imported (mainly from Central and South America), but there were also seven autochthonous cases (six in Europe and one in Israel). The patients were prevalently males (60.4%), and their ages ranged from 2 to 86 years. The time between leaving an endemic region and the diagnosis of histoplasmosis varied from a few weeks to more than 40 years. Progressive disseminated histoplasmosis was the most frequent clinical picture among people living with HIV infection (89.5%) or a different immunocompromising condition (57.1%), but it was also recorded in 6.2% of immunocompetent patients. Twenty-eight cases were caused by Histoplasma duboisii. Immunocompromised patients without HIV infection had the worst outcomes, with a mortality rate of 32%.

Comparison of Blood (1->3)-β-D-Glucan Levels in AIDS-Related Pneumocystis jirovecii Pneumonia and AIDS-Related Progressive Disseminated Histoplasmosis

In this retrospective study, (1->3)-β-D-glucan (B-glucan) was an unreliable marker for AIDS-related Pneumocystis jirovecii pneumonia (PCP) because a high percentage of participants with progressive disseminated histoplasmosis and respiratory symptoms had a positive B-glucan result. Where histoplasmosis is common attributing B-glucan positivity to PCP without further testing risks misdiagnosis.

Diagnostic accuracy of antigen detection in urine and molecular assays testing in different clinical samples for the diagnosis of progressive disseminated histoplasmosis in patients living with HIV/AIDS: A prospective multicenter study in Mexico

Background The progressive disseminated histoplasmosis (PDH) has been associated with severe disease and high risk of death among people living with HIV (PLWHIV). Therefore, the purpose of this multicenter, prospective, double-blinded study done in ten Mexican hospitals was to determine the diagnostic accuracy of detecting Histoplasma capsulatum antigen in urine using the IMMY ALPHA Histoplasma EIA kit (IAHE), clarus Histoplasma GM Enzyme Immunoassay (cHGEI IMMY) and MiraVista Histoplasma Urine Antigen LFA (MVHUALFA); as well as the Hcp100 and 1281-1283220SCAR nested PCRs in blood, bone-marrow, tissue biopsies and urine. Methodology/Principal findings We included 415 PLWHIV older than 18 years of age with suspicion of PDH. Using as diagnostic standard recovery of H. capsulatum in blood, bone marrow or tissue cultures, or histopathological exam compatible, detected 108 patients (26%, [95%CI, 21.78–30.22]) with proven-PDH. We analyzed 391 urine samples by the IAHE, cHGEI IMMY and MVHUALFA; the sensitivity/specificity values obtained were 67.3% (95% CI, 57.4–76.2) / 96.2% (95% CI, 93.2–98.0) for IAHE, 91.3% (95% CI, 84.2–96.0) / 90.9% (95% CI, 87.0–94.0) for cHGEI IMMY and 90.4% (95% CI, 83.0–95.3) / 92.3% (95% CI, 88.6–95.1) for MVHUALFA. The Hcp100 nested PCR was performed on 393, 343, 75 and 297, blood, bone marrow, tissue and urine samples respectively; the sensitivity/specificity values obtained were 62.9% (95%CI, 53.3–72.5)/ 89.5% (95%CI, 86.0–93.0), 65.9% (95%CI, 56.0–75.8)/ 89.0% (95%CI, 85.2–92.9), 62.1% (95%CI, 44.4–79.7)/ 82.6% (95%CI, 71.7–93.6) and 34.9% (95%CI, 24.8–46.2)/ 67.3% (95%CI, 60.6–73.5) respectively; and 1281-1283220SCAR nested PCR was performed on 392, 344, 75 and 291, respectively; the sensitivity/specificity values obtained were 65.3% (95% CI, 55.9–74.7)/ 58.8% (95%CI, 53.2–64.5), 70.8% (95%CI, 61.3–80.2)/ 52.9% (95%CI, 46.8–59.1), 71.4% (95%CI, 54.7–88.2)/ 40.4% (95%CI, 26.4–54.5) and 18.1% (95%CI, 10.5–28.1)/ 90.4% (95%CI, 85.5–94.0), respectively. Conclusions/Significance The cHGEI IMMY and MVHUALFA tests showed excellent performance for the diagnosis of PDH in PLWHIV. The integration of these tests in clinical laboratories will certainly impact on early diagnosis and treatment.