Aspergillus Antigen Research Articles

Invasive Aspergillosis after Renal Transplantation.

Over 95,000 renal transplantation procedures were completed in 2021. Invasive aspergillosis (IA) affects about 1 in 250 to 1 in 43 renal transplant recipients. About 50% of cases occur in the first 6 months after transplantation; the median time of onset is nearly 3 years. Major risk factors for IA include old age, diabetes mellitus (especially if prior diabetic nephropathy), delayed graft function, acute graft rejection, chronic obstructive pulmonary disease, cytomegalovirus disease, and neutropenia. Hospital construction, demolition activities, and residential refurbishments also increase the risk. Parenchymal pulmonary infection is the most common (~75%), and bronchial, sinus, cerebral, and disseminated disease are less common. Typical pulmonary features of fever, dyspnea, cough, and hemoptysis are seen in most patients, but 20% have non-specific general features of illness. Non-specific infiltrates and pulmonary nodules are the commonest radiological features, with bilateral disease carrying a worse prognosis. Bronchoscopy for direct microscopy, fungal culture, and Aspergillus antigen are the fastest means of establishing the diagnosis; a positive serum Aspergillus antigen presages a worse outcome. Standard therapy includes voriconazole, isavuconazole, or posaconazole, with great attention necessary to assess likely drug-drug interactions. Liposomal amphotericin B and echinocandins are less effective. A reduction in or stopping immunosuppression needs careful consideration, given the overall mortality of IA in renal-transplanted patients; continuing corticosteroid after the diagnosis of IA increases mortality by 2.5 times. Surgical resection or the addition of a gamma interferon should also be considered.

A case-control study of the effects of Aspergillus clinical phenotypes on pulmonary functions in patients with cystic fibrosis.

There are no precise data about the effect of Aspergillus infection on lung function other than allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis (pwCF). Here, we aimed to determine clinical phenotypes caused by Aspergillus spp. using laboratory and immunologic parameters and to compare Aspergillus phenotypes in terms of pulmonary function tests (PFT) prospectively. Twenty-three pwCF who had Aspergillus isolation from respiratory cultures in the last year (case group) and 20 pwCF without Aspergillus isolation in sputum (control group) were included. Aspergillus immunoglobulin (Ig)-G, Aspergillus IgE, Aspergillus polymerase chain reaction(PCR), galactomannan, total IgE from blood samples, and Aspergillus PCR and galactomannan from sputum, and skin prick test reactivity to Aspergillus antigen were used to distinguish different Aspergillus phenotypes. Pulmonary functions and frequency of pulmonary exacerbations were evaluated during a 1-year follow-up. Of 23 pwCF, 11 (47.8%) had Aspergillus colonization, nine (39.1%) had Aspergillus bronchitis, and three (13%) had ABPA. Aspergillus infection was not associated with worse z-scores of forced expiratory volume in the first second (FEV1) (p = 0.612), forced vital capacity (p = 0.939), and the median FEV 1% decline (0.0%/year vs. -4.7%/year, p = 0.626). The frequency of pulmonary exacerbations in the Aspergillus infected and noninfected groups was similar. Although Aspergillus spp. Isolation in pwCF was not associated with decreased lung function, a further decline was seen in the ABPA subgroup, and frequent pulmonary exacerbations during the 1-year follow-up.

Comparison of Indirect Fungal Diagnostic Tests in Patients With Proven Histoplasmosis.

Histoplasmosis is a common cause of invasive fungal infection in endemic regions and accurate diagnosis is difficult without direct tissue culture or pathology. Indirect fungal antigen testing for various fungal pathogens are typically performed to assist with diagnostic workup, though cross-reaction can lead to difficulty in interpreting results. We aimed to compare indirect fungal diagnostic tests and evaluate prevalence of positive antigen testing for non-Histoplasma fungal pathogens in patients with proven histoplasmosis. We performed a single-center retrospective review of adult patients with proven histoplasmosis diagnosed by fungal culture and/or cytology from January 2010 to March 2018. Patient demographics, clinical characteristics, and results of fungal antigen testing for Histoplasma, Blastomyces, Aspergillus, Cryptococcus, and (1→3)-β-D-glucan were evaluated. Two different urine Histoplasma antigen assays were used during the study period. Fifty-seven of 182 (31.3%) patients reviewed had proven histoplasmosis and presented with acute pulmonary (n = 10), chronic pulmonary (n = 7), and disseminated (n = 40) disease. Forty-one (72%) of these patients were immunosuppressed. Urine Blastomyces antigen (93%) and serum (1→3)-β-D-glucan (88%) were commonly positive in patients with histoplasmosis, whereas Aspergillus antigen was detected in 50% of patients and Cryptococcus antigenemia was rare (5%). In patients with disseminated disease, the MiraVista urine Histoplasma antigen assay had higher sensitivity than the Viracor urine Histoplasma antigen assay (86% vs 50%, respectively; P = .019). Noninvasive fungal antigen assays are helpful diagnostic tools; however, given their low specificity, clinicians must be aware of the various clinical presentations of invasive fungal infections and be aware of the limitations of these tests.

Performance of the JF5-Based Galactomannoprotein EIA Compared to the Lateral Flow Device and the Galactomannan EIA in Serum and Bronchoalveolar Lavage Fluid.

Early diagnosis of invasive aspergillosis is an important factor to improve survival but remains challenging. The detection of Aspergillus antigens is included in the consensus case definitions of the European Organization for Research and Treatment of Cancer and the National Institute of Allergy and Infectious Diseases Mycoses Study Group as a criterion of "probable" invasive aspergillosis. JF5, a mouse IgG3 monoclonal antibody detecting an Aspergillus mannoprotein, has already been implemented as a lateral flow device (LFD). Now, also a JF5-based enzyme-linked immunosorbent assay (EIA) is commercialized (Aspergillus specific galactomannoprotein [GP] EIA, Euroimmun Medizinische Labordiagnostika AG). In this study, we analyzed the diagnostic performance of GP in 63 bronchoalveolar lavage fluid (BALf) samples and 224 serum samples and compared it to performance of the galactomannan (GM) (Platelia Aspergillus enzyme immunoassay (EIA) (Bio-Rad, Marnes-la-Coquette, France)) and the JF5-based LFD (AspLFD; OLM Diagnostics, Newcastle Upon Tyne, United Kingdom). The diagnostic performance of GP and GM correlated well with both having high specificity. With an optimized cutoff threshold for positivity of 0.4-deviating from the 0.5 threshold recommended by the manufacturer-sensitivity of GP in serum is not significantly different than that of GM. However, in BALf sensitivity of GP is significantly less than for GM.

PULMONARY ASPERGILLOSIS POST-TOCILIZUMAB TREATMENT IN A PATIENT WITH COVID-19 PNEUMONIA

PULMONARY ASPERGILLOSIS POST-TOCILIZUMAB TREATMENT IN A PATIENT WITH COVID-19 PNEUMONIA

AIRWAY OBSTRUCTION FROM INFECTION-RELATED TRACHEOBRONCHIAL PSEUDOMEMBRANES

AIRWAY OBSTRUCTION FROM INFECTION-RELATED TRACHEOBRONCHIAL PSEUDOMEMBRANES

S10.2d Fungal beta-glucans and mannan performances in HIV-associated histoplasmosis

S10.2 Fungal Infections in Transplant Patients, September 24, 2022, 10:30 AM - 12:00 PMObjectivesDiagnosis of histoplasmosis in people living with HIV (PLWHIV) remains challenging despite developments in Histoplasma antigen and molecular detection tools. Fungal markers such as Beta-(1,3)-D-glucan (BDG) and galactomannan Aspergillus antigen (GM) are widely available, but the experience is limited during PLWHIV workup for suspicion of histoplasmosis. Our objective was to evaluate and compare BDG and GM performances for the diagnosis of HIV-associated histoplasmosis.MethodsWe performed a diagnostic accuracy study using primary serum samples stored frozen in a certified biorepository (CRB Amazonie-DC-2021-4649). Samples consisted of consecutive hospitalized PLWHIV unexposed to oral antifungals during the previous month (EDIRAPHIS study-NCT01884779). All patients gave consent for biobanking and ancillary studies on fungal markers.Histoplasmosis cases, proven (EORTC/MSG criteria) and probable (polyclonal or monoclonal Histoplasma antigen detections in urines or serum), as well as negative controls, were randomly selected. Patients with a proven or suspected Pneumocystis jirovecii infection were excluded. Following manufacturers’ instructions, samples were blindly tested for BDG and GM using Fungitell® and PlateliaTM Aspergillus Ag assays, respectively.Gold standard definition used three scenarios: EORTC scenario (cases and controls defined according to the EORTC/MSG 2020 criteria for endemic mycoses); strict scenario with proven cases restricted to those positives to all three previous Histoplasma antigen detections, and controls conversely negatives for all methods; and a large scenario with proven or probable cases and controls negatives for all methods.ResultsWe included 121 samples, 92 HIV-associated histoplasmosis cases (34 proven and 58 probable), and 29 negative controls. Compared with controls, histoplasmosis cases were significantly younger and advanced in the course of HIV disease [median CD4 count level 33/mm3 (15-87) vs 116 (62-245)].BDG and GM median detection levels were significantly higher among histoplasmosis cases compared with controls across all scenarios [368 (176-441) pg/ml vs 142 (89-211) for BDG and 2.5 (1.3-4.8) vs 0.19 (0.14-0.36) for GM, in cases vs controls of the strict scenario, respectively].In the strict scenario, at 150 pg/ml and 0.5 for BDG and GM respectively, sensitivity, specificity, positive and negative likelihood ratios were respectively: 95% [95%confidence interval (CI), 85-100] vs 90% [77-100], 52% [34-70] vs 83% [69-97], 2 [1.4-3.0] vs 5.3 [2.4-12.0], and 0.1 [0.01-0.7] vs 0.12 [0.03-0.45]. ROC curves found AUCs of 0.82 [0.68-0.91] vs 0.92 [0.80-0.98], and optimal thresholds at 288 pg/ml and 1.29, for BDG and GM, respectively (Fig. 1). Post-test probabilities showed best performances at the lowest thresholds for negative testing of both BDG and GM, and at the 0.7 thresholds for a positive GM test (Fig. 2).ConclusionBDG and GM may not be used for the same objective when searching for HIV-associated histoplasmosis. Although a negative BDG test at the lowest thresholds should rule out histoplasmosis in a screening context, limitations of a positive BDG test, even at the highest thresholds, call for a consecutive positive GM test before starting patients on antifungal therapy targeting histoplasmosis. Still, when considering the highest costs of BDG testing, higher balanced diagnostic performances, and lower costs of GM testing alone, one may favor the use of GM, notably in resources-limited settings.

COVID-19-Associated Rhino-Mucormycosis and Pulmonary Aspergillosis Infection

In the current pandemic, the incidence of fungal infections-associated COVID-19 is surging. Diabetes mellitus, overzealous steroid, and antibiotic use for COVID-19 management may cause or exacerbate the fungal disease. In paranasal sinus (PNS), ethmoids followed by the maxillary sinus are commonly involved with the risk of intra-orbital or/and intracranial involvement is quite common. In lungs, COVID-19 infection has higher mortality rate, if there is an associated fungal infection. Aspergillus fumigates is the most common fungus that cause lung infection and present as discrete lesion different from COVID-19 manifestation. Two cases of COVID-associated fungal infections, i.e., rhino-mucormycosis and pulmonary aspergillosis are described here. In the first case, computed tomography (CT) of PNS was done for the complaints of mild right-sided facial swelling and mild restriction of the eye globe on day 27 of illness. CT showed hyperdense content involving the right-sided nasal sinus with the remodeling of bones with erosion and thinning of the inferior and medial orbital wall with the extension of soft tissue into the extraorbital space. The patient was treated with Amphotericin B and posaconazole oral suspension as the first-line antifungal monotherapy. In the second case, on complaints of cough with expectoration on the 20th day of illness, X-ray chest and CT chest were done which confirmed a thick-walled cavity in the right lung and other post COVID features. The tracheal aspirate culture was suggestive of Aspergillus fumigatus and Aspergillus antigen galactomannan was found positive in the fluid. The patient was treated for the same with antifungal therapy. Hence it is important to pay attention to the high probability of fungal infections in COVID-19 patients. The association of coronavirus with mucormycosis of the PNSs and aspergillosis of the lung must be given outmost consideration. Noncontrast CT of the PNSs is usually the first investigation of choice for PNS involvement, and CT chest help in the diagnosis of pulmonary fungal infection. Uncontrolled diabetes and use of steroids are two of the main factors for aggravating factors. Both early surgical intervention and anti-fungal treatment should be sought for the management.

PULMONARY ASPERGILLOSIS: A CLINICAL NOTE

Aspergillosis is a mycotic sickness ordinarily brought about by Aspergillus fumigatus, a saprophytic and universal airborne growth. Obtrusive aspiratory aspergillosis happens essentially in patients with serious immunodeficiency. The meaning of this contamination has decisively expanded with developing quantities of patients with impeded insusceptible state related with the administration of danger, organ transplantation, immune system and fiery circumstances; fundamentally sick patients and those with constant obstructive aspiratory infection seem, by all accounts, to be at an expanded gamble. Persistent pneumonic aspergillosis influences patients without clear resistant split the difference, yet with a fundamental lung condition like COPD or sarcoidosis, earlier or simultaneous TB or non-tuberculous mycobacterial illness. Aspergillus bronchitis might be liable for tenacious respiratory side effects in patients with Aspergillus identified more than once in sputum without proof of parenchymal Aspergillus sickness, particularly in patients with bronchiectasis and cystic fibrosis. Unfavorably susceptible bronchopulmonary aspergillosis influences patients with asthma and cystic fibrosis and is vital to perceive as long-lasting lung or aviation routes harm might accumulate if untreated. Aspergilloma is normally tracked down in patients with recently shaped cavities in the lung, though unfavorably susceptible bronchopulmonary aspergillosis, an extreme touchiness response to Aspergillus antigens, is, for the most part, found in patients with atopy, asthma or cystic fibrosis. This survey gives a report on advancing the study of disease transmission and hazard elements of the significant indications of Aspergillus lung sickness and the clinical appearances that ought to provoke the clinician to think about these circumstances. Current methodologies for the determination and the board of these disorders are examined.

Respiratory Viral Infections in Pediatric Acute Leukemia Patients Presenting with Febrile Neutropenia in a Tertiary Hospital in Ankara, Turkey

Background: The prevalence and roles of respiratory viral pathogens in pediatric acute leukemia patients with febrile neutropenia is not well understood and laboratory tests to detect viral agents are not a routine practice in the investigation of these patients.Patients and methods: The medical records of 50 neutropenic episodes in pediatric acute leukemia patients in the Hacettepe University Children’s hospital, Ankara-Turkey, were reviewed. Blood samples were obtained for blood culture, aspergillus antigen and other routine tests. Nasopharyngeal aspirate samples were collected and transferred to the laboratory in a viral transport medium. Therapy for febrile neutropenia was initiated according to our institution’s protocols.Results: Fifty (50) consecutive febrile neutropenic episodes in 44 pediatric ALL and AML patients were included in the study between 1st October 2009 and 31st August 2010. Microbiologically documented infections were found in 36% of the episodes, clinically documented infections in 16% of the episodes and 48% of the episodes were accepted as Fever of Unknown Origin. Twenty-two percent (22%) of the microbiologically documented infections were due to viral agents, 56 % were due to Gram positive bacteria, 21% were due to Gram negative bacteria (E. coli) and only one episode of fungemia was documented.Conclusions: Fever of Unknown Origin constituted nearly 50% of the febrile neutropenic episodes in this study despite the availability of advanced laboratory diagnostic methods. Among the episodes with microbiologically documented infections, bacterial pathogens were especially common. Presenting complaints like cough and rhinorrhea are not specific to a viral etiology and care should be taken not to miss potentially threatening bacterial pathogens in such episodes.

Risk Stratification of Acute Invasive Fungal Rhinosinusitis in Patients With Hematologic Pathology.

The purpose of this study is to identify objective perioperative diagnostic factors for acute invasive fungal rhinosinusitis (AIFS) to create a diagnostic scoring system using objective criteria. Retrospective case-control study performed at an academic, tertiary care center. Biopsy-proven cases of AIFS identified from pathology records (2015-2019) were compared to patients the otolaryngology service was consulted to "Rule out AIFS" in the year 2019, only including those with underlying hematologic malignancy. Eighteen patients with AIFS and 20 patients without were included. One and two tailed T-tests were used for p-values. Receiver operating characteristic curves were generated for the significant data, and Youden's J-statistic was used to create the ideal cutoff values for each. Likelihood ratios were used to give a power for the scoring system. Compared to patients with non-hematologic malignancy-related AIFS, patients with hematologic malignancy-related AIFS have significantly elevated C-reactive protein (CRP) and blood glucose; while albumin, hematocrit, platelet count, and absolute neutrophil count (ANC) were found to be significantly lower. In addition, Lund-Mackay score asymmetry, extra-sinus spread, aspergillus antigen, and pre-existing diabetes mellitus correlated with disease. A scoring system with three categories: AIFS Unlikely, Indeterminate/AIFS Suspicious, and AIFS Highly Likely was developed. Patients with hematologic malignancy-related AIFS have measurable differences in lab values and standard imaging that could be used in determining the diagnostic probability of AIFS including: CRP, albumin, hematocrit, platelets, ANC, blood glucose, aspergillus antigen, Lund-Mackay score asymmetry, extra-sinus spread, and pre-existing diabetes mellitus. A novel scoring system was proposed that will require prospective validation. 3 Laryngoscope, 133:1059-1064, 2023.

UNILATERAL LUNG COLLAPSE: A RARE CAUSE

TYPE: Late Breaking Abstract TOPIC: Allergy and Airway INTRODUCTION: Allergic bronchopulmonary aspergillosis (ABPA) an allergic reaction to fungal antigens resulting in characteristic clinical and radiological mfeatures and is seen in patients asthma or cystic fibrosis. ABPA is characterised by uncontrolled asthma, wheezing, elevated agglutinins against aspergillus antigens,bilateral fleeting opacities on chest x-ray and central bronchiectasis..Immune response to Aspergillus antigens causes intense eosinophilic and neutrophilic inflammation and tenacious mucus secretions which can lead to airway obstruction and if untreated, bronchiectasis and pulmonary fibrosis CASE PRESENTATION: We report a middle aged lady who presented with a history of significant weight loss, chronic cough and breathing difficulty and was found to have complete left lung collapse with abrupt cut off left main bronchus on imaging. She was provisionally diagnosed as left lung collapse secondary to an endobronchial obstruction by a probable neoplastic lesion.Subsequent diagnosis of ABPA and conservative medical treatment led to complete resolution of the collapse over a period of 6 months. Serial chest x rays over 6 months DISCUSSION: Patients with ABPA can have diverse radiological manifestations. Although ABPA is usually a bilateral disease it is possible to have unilateral involvement which can in extreme instances lead to lung collapse . CONCLUSIONS: ABPA can rarely lead to unilateral lung collapse .When diagnosis is made early and treatment with steroid is initiated, irreversible lung damage can be prevented. Based on our case and similar reports we feel ABPA should be considered as a differential diagnosis whenever encountering a patient with total lung collapse and history of asthma. DISCLOSURE: I have been a member of the advisory board of M/s Cipla, M/s Glenmark pharmaceuticals, M/s Zydus cadila and am a member of the speakers bureau of M/s Astra Zeneca pharmaceuticals ( all of the above mentioned are pharmaceutical companies ) I hold shares o KEYWORD: ABPA

Donor-derived T cells specific for tumor antigen and multiple pathogens for prevention of relapse and infection after haemopoietic stem cell transplant (HSCT) for myeloid malignancies (the INTACT trial).

7039 Background: Disease relapse and infection cause significant morbidity and mortality after allogeneic HSCT for acute myeloid leukemia (AML) and myelodysplasia (MDS). Wilms’ tumour 1 (WT1) and preferentially expressed antigen in melanoma (PRAME) are both commonly overexpressed in these conditions. We assessed the safety of a novel combination of tumour associated antigen (TAA) and multipathogen (MP) specific T cells administered prophylactically after HSCT in a phase 1 trial. Methods: Patients with overexpression of WT1 or PRAME by ddPCR on diagnostic tumour samples were eligible. TAA and MP specific T cells were ex vivo expanded from stem cell donors by stimulating apheresis derived mononuclear cells with tumour, viral or fungal peptides. T cells specific for CMV, EBV, Adenovirus (AdV) and Aspergillus (Asp) antigens were produced separately and pooled in equal parts into a MP product. Patients received 1 infusion of MP specific and up to 4 infusions of TAA specific T cells at 4-weekly intervals from 28 days post HSCT (cell dose 2x107/m2 per infusion). Results: Ten HSCT recipients have received a total of 38 infusions. Median age was 48 years (17-67), disease AML (n = 6) or high risk MDS (n = 4), DRI intermediate (n = 4) or high (n = 6), conditioning myeloablative (n = 8) or reduced intensity (n = 2), donor source sibling (n = 7) or matched unrelated (n = 3). Median expression of WT1 on diagnostic bone marrow was 1442 copies/104 copies ABL (0-3870), PRAME 131 copies/104 copies ABL (4-12300). Patients received WT1 (n = 4), PRAME (n = 5) or both WT1 and PRAME specific T cells (n = 1). Mean tumour antigen specificity in the TAA product was 1.4% and 13.3% of CD3+ cells for WT1 and PRAME respectively. Mean total pathogen specificity in the MP product was approximately 44% (CMV = 14.0%, EBV = 14.8% and AdV = 11.6% of CD3+ cells, Asp = 14.8% of CD4+ cells). All patients received MP specific T cells. No immediate infusion related adverse events were reported. At a median 540 days post transplant (80-1265), 8 of 10 patients remain alive and in complete disease remission. Two patients did not proceed after completing 3 of 5 infusions due to the development of graft versus host disease (GVHD); both are in remission. There were 2 deaths; one patient with progressive disease who had persistent high risk MDS pre and post HSCT, and one with multiorgan failure who had multiple post transplant complications (venoocclusive disease, sepsis, GVHD), both prior to infusion. Low level viral reactivations occurred (CMV n = 5, EBV n = 7, BKV n = 3, HHV6 n = 4, AdV n = 1), however none required treatment and there were no cases of viral tissue disease or EBV PTLD. There were no invasive fungal infections. Conclusions: Prophylactic infusions of donor derived WT1/PRAME and multipathogen specific T cells post HSCT are well tolerated and associated with low rates of infection and relapse. Clinical trial information: NCT02895412.

Invasive Aspergillosis Manifesting As An Intracardiac Mass In A Heart Transplant Patient

<h3>Introduction</h3> Invasive aspergillosis (IA) is the third most common form of invasive fungal infections in immunocompromised patients, and has the second highest mortality rate at 30-70%. Invasion of lung parenchyma is the most common presentation, but can rarely present as aspergillus endocarditis. To our knowledge, IA presenting as a mass lesion in the heart is very rare and has never been reported in an orthotopic heart transplant (OHT) patient. We present a case of invasive aspergillus manifesting as an intracardiac mass in the right atrium (RA) in a heart transplant patient who survived. <h3>Patient presentation</h3> This is a 68 year-old-male with ischemic cardiomyopathy s/p OHT in June 2019 complicated by Aspergillus fumigatus sternal osteomyelitis requiring complete sternectomy on chronic antifungal therapy who was readmitted for right shoulder pain and failure to thrive. On admission, the patient was afebrile and hemodynamically stable. Pertinent workup showed transthoracic echocardiogram (TTE) with right atrial (RA) mass confirmed to be 3.5 × 3.3 cm by transesophageal echocardiogram (TEE) attached to interatrial septum. Initial malignancy workup was negative. Further infectious work up was remarkable for Aspergillus antigens. Intra-cardiac echocardiogram (ICE) and TEE techniques were utilized to locate and culture the mass. Argon epitome was placed into the mass under fluoroscopic and intracardiac echo guidance, extracting two specimens. Gross examination suggested identical specimens without any evidence of endocardium or lipomatous tissue. Initial pathology showed findings consistent with a thrombus but no evidence of fungal organisms, inflammation or malignancy. However, cultures from the specimen revealed Aspergillus fumigatus. Unfortunately, the patient was deemed a poor surgical candidate for resection due to other comorbidities and attempts are being made for long term antifungal therapy in management. <h3>Discussion</h3> Opportunistic infections such as invasive fungal infections are the leading cause of mortality in heart transplant recipients. Approximately 65% of OHT cases will have an infection within the first year of surgery. In a single institution, both incidence and mortality of IA in heart transplant recipients declined over the years. Despite this decrease, it remains a common pathogen observed in immunocompromised populations, specifically in solid organ transplantations. Most IA present as pulmonary disease as the route of entry for aspergillus conidia particles is inhalation, but rarely has intracardiac manifestations. To our knowledge, this is the first case report of invasive aspergillosis in a heart transplant recipient who had rare systemic manifestations including intra-cardiac mass and sternal osteomyelitis.

480 - Urine Aspergillus Antigen Detection As an Aid to Diagnose Invasive Aspergillosis

480 - Urine Aspergillus Antigen Detection As an Aid to Diagnose Invasive Aspergillosis

53 - Urine Aspergillus Antigen Detection to Screen for Invasive Aspergillosis in at-Risk Patients Treated for Hematologic Malignancies

53 - Urine Aspergillus Antigen Detection to Screen for Invasive Aspergillosis in at-Risk Patients Treated for Hematologic Malignancies

Which came first, allergic bronchopulmonary aspergillosis or asthma?

Aspergillosis includes a group of disorders caused by Aspergillus species that affect the respiratory system most commonly. The clinical spectrum of respiratory aspergillosis is divergent. Allergic bronchopulmonary aspergillosis is a result of hypersensitivity to Aspergillus antigens. Although it is known for many years, pathogenesis is not entirely clarified and there are no exact diagnostic criteria. The results are diagnostic delay, incompletely known management that can cause serious disability. Keywords: allergic; bronchopulmonary; aspergilosis; asthma.

279. Clinical Characteristics of Critically Ill Patients with COVID-19 and Invasive Pulmonary Aspergillosis: A Case Series From Mexico City

BackgroundCOVID-19 has emerged as a global public health emergency and has been the main cause of intensive care admission during the pandemic. COVID-19-associated pulmonary aspergillosis (CAPA) has been reported in case series of critically ill patients. However, the criteria for CAPA diagnosis has been inconsistent among most of the reports. Mexico has been widely affected by SARS-CoV-2. We present a series of CAPA cases at a teaching hospital in Mexico City.MethodsWe performed a retrospective analysis of COVID-19 patients admitted to the ABC Medical Center from May 1st, 2020, to May 1st, 2021. Including only those with critical COVID-19 who required invasive mechanical ventilation (IMV). Patients with a diagnosis of CAPA were analyzed. We followed the 2020 ECMM/ISHAM consensus criteria for CAPA diagnosis. Aspergillus antigen testing in tracheal aspirate and serum was done with Aspergillus-specific galactomannoprotein (GP) ELISA (Euroimmun Medizinische Labordiagnostika).ResultsAmong the 230 admitted patients who required IMV, we identified 49 (21.3%) cases of CAPA, 46 probable CAPA and 3 proven CAPA. Nineteen (38%) of those died in the hospital. The mean age was 64.5 ± 12.6 years and 11 were female. Proven CAPA was diagnosed with culture in three cases (one A. niger, one A. terreus and one A. fumigatus). Probable CAPA was diagnosed by a positive serum GP in 27 (55.1%) patients and by a positive bronchoalveolar lavage (BAL) GP in 29 (59.2%) cases. Seven patients had both serum and BAL positive GP. Forty-six (93.9%) patients received corticosteroids, and 22 (49.9%) were treated with tocilizumab before CAPA diagnosis. All but one received isavuconazole as CAPA treatment. We detected 35 (71.4%) patients who had a bacterial co-infection. Eighteen of those died (51.4%) compared to only one dead in the subgroup without coinfections (7.1%). The mean time from hospital admission to CAPA diagnosis was 6.2 days (SD 7.1) among those who survived compared to 13.2 (SD 6.3) days in those who died p< 0.01. ConclusionCAPA had a lower prevalence than previously reported in other series. However, it appears to be linked to high mortality when it occurs with other bacterial coinfections and when it is diagnosed late from admission. Disclosures All Authors: No reported disclosures

Evaluation of the EUROIMMUN Aspergillus antigen immunoenzyme assay in serum and bronchoalveolar lavage fluid samples

IntroductionThe most widely used marker for the diagnosis of invasive aspergillosis (IA) is the detection of galactomannan by ELISA. This study describes the evaluation of the results obtained by Euroimmun Aspergillus antigen ELISA (EIA-GM-E) in serum samples and bronchoalveolar lavage fluid (BAL) from patients at risk of IA, and compares these results with those obtained by Bio-Rad Galactomannan EIA (EIA-GM-BR). MethodsAnonymous retrospective case–control comparative study in 64 serum samples and 28 BAL from 51 patients. ResultsOverall agreement of the results of the two assays was observed in 72 of 92 samples (78.3%). The sensitivity of EIA-GM-BR and EIA-GM-E in serum samples was 88.9% and 43.2%, respectively, and 100% and 88.9% for BAL. The specificity of EIA-GM-BR and EIA-GM-E in serum samples was 91.9% for both assays, and 68.4% and 84.2% in BAL. There were no statistically significant differences in the results of both assays. ConclusionsBoth methods show good results for the discrimination of patients with IA when BAL is tested, or serum in case of EIA-GM-BR.

VACCINATED WITH A TWIST: BREAKTHROUGH COVID-19 IN AN IMMUNOCOMPROMISED PATIENT

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: With ongoing efforts to vaccinate the public against SARS-CoV2, there have been reports of breakthrough COVID-19 cases. We report a case of an immunocompromised patient who was infected despite being fully vaccinated. CASE PRESENTATION: 63-year-old female with COPD, rheumatoid arthritis on abatacept, prednisone, & methotrexate (MTX), and Sweet syndrome presented to the ED with acute non-exertional chest pain, palpitations, and dyspnea at rest. She denied fevers or chills but reported diarrhea and vomiting. She had no history of or exposure to COVID-19 and had completed her 2-dose mRNA SARS-CoV-2 vaccination 45 days prior. On presentation she was in respiratory distress, hypotensive, tachycardic, and tachypneic. She was saturating at 86% on room air, requiring supplemental O2. Physical exam was significant for scattered bilateral wheezes. CBC showed no leukocytosis. CRP was elevated. Lactic acid, ferritin and LDH were within normal limits. D-dimer was higher than the age-adjusted cutoff;CTA of the chest revealed no PE but showed bilateral ground glass opacities with consolidations. She tested positive for SARS-CoV-2. She was admitted for severe sepsis from COVID-19 pneumonitis and started on dexamethasone and remdesivir. SARS-CoV-2 IgG antibodies were positive. Given her immunocompromised status, bronchoscopy with BAL was performed and revealed copious thick secretions. Gram stain and bronchial brushings were negative for bacterial etiologies. Lavage culture was positive for aspergillus antigen and cytology revealed markedly enlarged reactive cells. Galactomannan serum antigen was positive. She was discharged on day 9 with a prolonged course of voriconazole. She had residual dyspnea on exertion but did not require supplemental O2. A nasal swab to test for variant strains was still pending. DISCUSSION: The COVID vaccine proved effective in preventing severe COVID-19 infections but trials excluded immunocompromised patients. This case of infection despite vaccination and detectable IgG titers reveals suboptimal protection. From data on pre-existing vaccines in immunocompromised patients, MTX is known to reduce immunogenicity. Our patient remained on immunosuppressants after vaccination, which may have contributed to her subsequent viral and fungal infections. Rheumatology guidelines suggest holding MTX for one to two weeks after vaccination to improve vaccine response. Employing this strategy will maximize immunogenicity against SARS-CoV-2 in immunocompromised patients. CONCLUSIONS: The American College of Rheumatology recommends vaccinating patients with rheumatological conditions against SARS-CoV-2. This case highlights individual patient factors to consider in the battle against COVID-19 in immunosuppressed patients. Non-viral infections must also be considered despite the ongoing pandemic. Determining protective antibody titers can guide booster vaccine recommendations. REFERENCE #1: Sonani B, Aslam F, Goyal A, Patel J, Bansal P. COVID-19 vaccination in immunocompromised patients. Clin Rheumatol. 2021;40(2):797-798. doi:10.1007/s10067-020-05547-w REFERENCE #2: Day AL, Winthrop KL, Curtis JR. The effect of disease-modifying antirheumatic drugs on vaccine immunogenicity in adults. Cleve Clin J Med. 2020;87(11):695-703. Published 2020 Nov 2. doi:10.3949/ccjm.87a.20056 REFERENCE #3: COVID-19 Vaccine Clinical Guidance Summaryfor Patients with Rheumatic and Musculoskeletal Diseases DISCLOSURES: No relevant relationships by Vernon Chan, source=Web Response No relevant relationships by Dana Daoud, source=Web Response No relevant relationships by Jeet Lund, source=Web Response