711. A Unique Breath Secondary Metabolite Volatile Signature for the Diagnosis of Histoplasmosis

Abstract Background Histoplasmosis is a common endemic fungal infection in the Americas, causing significant morbidity and mortality, particularly in immunocompromised patients. Existing diagnostic methods are limited in their sensitivity (especially in pulmonary histoplasmosis) and turnaround time. Methods We examined prospectively collected breath samples from 84 patients with suspected histoplasmosis 3/2019 - 2/2020 at Hospital Roosevelt (HR; Guatemala City, Guatemala, n = 56) and suspected invasive fungal disease 1/2018 - 10/2019 at Brigham and Women’s Hospital (BWH; Boston, MA, USA, n = 28) using thermal desorption gas chromatography-tandem mass spectrometry (TDU-GC-MS/MS). Patients were evaluated for histoplasmosis and other infections according to the local standard of care – of note, 18/56 patients at HR did not have Histoplasma urine antigen testing. Results Median age was 44 years, 60 (71%) were male, 23 (27%) had HIV, 15 (18%) had hematologic malignancy. 7 patients were diagnosed with histoplasmosis over the study period (4 at HR, 5 at BWH), with a clinical syndrome + positive Histoplasma urine or serum antigen test, with some patients also having yeast forms on tissue biopsy. 3 patients had disseminated and 4 pulmonary histoplasmosis. 4 patients with histoplasmosis had co-infections – 2 tuberculosis (TB), 1 influenza, and 1 Pneumocystis jirovecii (PJP) pneumonia. 4 patients were receiving antifungal therapy active against Histoplasma at the time of their first breath sample. We found 3 sesquiterpenes: (A) cyperene, (B) 1R,4aR,8aR)-2,5,5,8a-Tetramethyl-4,5,6,7,8,8a-hexahydro-1H-1,4a-methanonaphthalene, and (C) viridiflorol in patients with histoplasmosis, that distinguished these patients from those with other pneumonia (TB, coccidioidomycosis, invasive aspergillosis, mucormycosis, PJP, bacterial pneumonia) with 100% sensitivity and 70% (95% CI 59, 80) specificity. Figure 1. TDU GC-MS/MS spectral comparison in histoplasmosis vs. the other invasive mycoses aspergillosis or mucormycosis. A: Cyperene; B: (1R,4aR,8aR)-2,5,5,8a Tetramethyl-4,5,6,7,8,8a-hexahydro-1H-1,4a-methanonaphthalene; C: viridiflorol; D: 1H-Indene, 2,3,3a,4-tetrahydro-3,3a,6-trimethyl-1-(1-methylethyl)-; E: β-funebrene; F: trans-α-bergamotene; G: eremophilene; H: spathulenol; I: cedrene; J: cedranoxide, 8,14- Conclusion Conclusion: Patients with histoplasmosis have a unique secondary metabolite breath signature that can be used for the noninvasive diagnosis of pulmonary and disseminated histoplasmosis. Many patients in this cohort did not undergo urine antigen testing or other diagnostic workup for histoplasmosis, which may have affected our specificity estimates. Disclosures Francisco M. Marty, MD, SCYNEXIS, Inc. (Scientific Research Study Investigator)


Comparison of Initial CXR to CT in Patients (pts) with Hematologic
Background. There is a spectrum of pulmonary disease burden in pts with HEM and PM. There have not been any data comparing the sensitivity and findings of initial Chest X-Ray (CXR) and chest CT in these pts.
Methods. We compared the findings of the initial CXR and CT in all pts with proven or probable PM via EORTC/MSG criteria. We included only pts who had pulmonary symptoms and who had both CXR and CT within 5 days of each other and within seven days of symptom onset or date of culture at MD Anderson Cancer Center from April 2000 and April 2020. We collected data regarding demographics, status of HEM, clinical presentation, frequency and findings of BAL and imaging findings, mold-active prophylaxis and treatment regimens, and mortality. CXR findings were classified as normal or abnormal, and if abnormal sub-classified as mass-like/consolidative, nodular, cavitary or heterogenous/non-specific. CT findings were classified in a similar manner.
Results. We Identified such 39 pts with PM who had both CXR and CT within 5 d. All pts had positive CT. Five pts (13%) had a negative CXR. The majority of pts 28 (72%) were neutropenic (neutrophil count < 500). The most common CXR findings were consolidation or mass-like lesions (56%), followed by patchy, heterogenous or non-specific findings (33%) and nodules (13%). Only 3% had cavitary lesions. Similarly, consolidation or mass-like lesions were the most common finding on CT (69%), followed by nodular lesions with or without ground glass halos (56%). Cavitary lesions and/or reverse halo sign (RHS) were common (31%) on CT. Patients with normal CXR vs those with abnormal CXR were comparable in all clinical parameters we collected. The median survival from time of symptoms onset for all pts was 45 days. There was a trend for lower 42 day mortality in pts with normal CXR (20% vs 47%, P=.253).

Conclusion.
A negative CXR does not preclude PM, especially in neutropenic pts. A CT is recommended for better sensitivity and although there was concordance in CXR with CT findings in some chest abnormalities (mass, consolidation), CT more commonly revealed nodules and signs highly suggestive of PM such as RHS. Although small numbers precluded a robust comparison, it is possible that HEM pts with PM and negative initial CXR have better prognosis, perhaps reflecting a lower burden of pulmonary involvement Disclosures Background. Histoplasmosis is a common endemic fungal infection in the Americas, causing significant morbidity and mortality, particularly in immunocompromised patients. Existing diagnostic methods are limited in their sensitivity (especially in pulmonary histoplasmosis) and turnaround time.
Methods. We examined prospectively collected breath samples from 84 patients with suspected histoplasmosis 3/2019 -2/2020 at Hospital Roosevelt (HR; Guatemala City, Guatemala, n = 56) and suspected invasive fungal disease 1/2018 -10/2019 at Brigham and Women's Hospital (BWH; Boston, MA, USA, n = 28) using thermal desorption gas chromatography-tandem mass spectrometry (TDU-GC-MS/MS). Patients were evaluated for histoplasmosis and other infections according to the local standard of care -of note, 18/56 patients at HR did not have Histoplasma urine antigen testing.

Conclusion. Conclusion:
Patients with histoplasmosis have a unique secondary metabolite breath signature that can be used for the noninvasive diagnosis of pulmonary and disseminated histoplasmosis. Many patients in this cohort did not undergo urine antigen testing or other diagnostic workup for histoplasmosis, which may have affected our specificity estimates.
Disclosures Background. Neurocysticercosis (NCC) is a parasitic infection that results from the ingestion of eggs from the adult tapeworm Taenia solium that develops when cysticercoids migrate into the central nervous system. In addition, this infection has been found to affect over 50 million individuals worldwide. In the United States, NCC mainly affects immigrants from Latin America, where the disease is endemic with seroprevalence rates ranging from 5% to 11%. Most data regarding NCC in the United States comes from hospital reports from California and Texas. We are undertaking this study to determine the differences seen in a higher Latin American and Haitian population compared to a previously seen predominantly Mexican population. In this retrospective review, we characterized the population diagnosed with NCC at one large tertiary medical center in South Florida, University of Miami Hospital.
Methods. This retrospective chart review included adult patients from January 2009 to December 2019 with the admission or discharge diagnosis of neurocysticercosis (ICD 10 Code B 69.0 Neurocysticercosis and CPT code 86682 Cysticercosis). We extracted data on demographics, clinical symptoms, recurrence, treatment, resolution and follow up.
Results. Forty-seven patients were analyzed to completion. Most of the cases were seen in Hispanics 72.3 % and from Central America 40.4%. The most common symptom was headache 53.2% followed by seizures 42.6%. Normal physical exam was noted in 93.6% of the cases. Most of the cases have 1-10 lesions (98%), located in the brain parenchyma (75%). Serum serology, CSF antibody or stool studies were not obtained in around 90% of the cases. Treatment was indicated in 70.2% of cases and recurrence was low at 17.0%. Refer to Tables 1-5 for full results.