Cases Of Invasive Aspergillosis Research Articles

Report of three azole-resistant Aspergillus fumigatus cases with TR34/L98H mutation in hematological patients in Barcelona, Spain.

We aimed to report the emergence of azole-resistant invasive aspergillosis in hematologic patients admitted to a tertiary hospital in Spain during the last 4months. Prospective, descriptive study was performed to describe and follow all consecutive proven and probable invasive aspergillosis resistant to azoles from hematological cohort during the last 4months. All patients had fungal cultures and antifungal susceptibility or real-time PCR detection for Aspergillus species and real-time PCR detection for azole-resistant mutation. Four cases of invasive aspergillosis were diagnosed in 4months. Three of them had azole-resistant aspergillosis. Microbiological diagnosis was achieved in three cases by means of fungal culture isolation and subsequent antifungal susceptibility whereas one case was diagnosed by PCR-based aspergillus and azole resistance detection. All the azole-resistant aspergillosis presented TR34/L98H mutation. Patients with azole-resistant aspergillosis had different hematologic diseases: multiple myeloma, lymphoblastic acute leukemia, and angioimmunoblastic T lymphoma. Regarding risk factors, one had prolonged neutropenia, two had corticosteroids, and two had viral co-infection. Two of the patients developed aspergillosis under treatment with azoles. We have observed a heightened risk of azole-resistant aspergillosis caused by A. fumigatus harboring the TR34/L98H mutation in patients with hematologic malignancies. The emergence of azole-resistant aspergillosis raises concerns for the community, highlighting the urgent need for increased surveillance and the importance of susceptibility testing and new drugs development.

Invasive Aspergillosis in Liver Transplant Recipients in The Current Era

Invasive aspergillosis (IA) is a rare but fatal disease among liver transplant recipients (LiTRs). We performed a multi-center 1:2 case-control study comparing LiTRs diagnosed with proven/probable IA and controls with no invasive fungal infection. We included 62 IA cases and 124 matched controls. Disseminated infection occurred only in eight cases (13%). 12-week all-cause mortality of IA was 37%. In multivariate analyses, systemic antibiotics usage (adjusted odds ratio [aOR], 4.74; p=0.03) and history of pneumonia (aOR, 48.7; p=0.01) were identified as independent risk factors associated with the occurrence of IA. Moreover, reoperation (aOR, 5.99; p=0.01), systemic antibiotics usage (aOR, 5.03; p=0.04), and anti-mold prophylaxis (aOR, 11.9; p=0.02) were identified as independent risk factors associated with the occurrence of early IA.Among IA cases, Aspergillus colonization (adjusted hazard ration [aHR], 86.9; p<0.001), ICU stay (aHR, 3.67; p=0.02), disseminated IA (aHR, 8.98; p<0.001), and dialysis (aHR, 2.93; p=0.001) were identified as independent risk factors associated with 12-week all-cause mortality; while recent receipt of tacrolimus (aHR, 0.11; p=0.001) was protective. Mortality among LiTRs with IA remains high in the current era. The identified risk factors and protective factors may be useful for establishing robust targeted anti-mold prophylactic and appropriate treatment strategies against IA.

Galactomannan Antigen Assay for the Diagnosis of Invasive Aspergillosis: A Study from a Tertiary Care Hospital of Central India

Invasive Aspergillosis (IA) is a severe and fatal infection, especially in immunocompromised patients. Galactomannan is a polysaccharide antigen present in the cell wall of Aspergillus species, which is secreted into the blood and other body fluids during hyphal growth. Therefore, detecting galactomannan antigen is very useful in diagnosing IA, along with clinical features and radiological findings. The study period was one year (January 2022 to December 2022). The data was collected retrospectively from the medical records and case sheets of all clinically suspected invasive aspergillosis patients. Galactomannan antigen assay was performed using an FDA-approved Platelia Aspergillus EIA test kit, and results were interpreted according to the manufacturer’s instructions (Cut off &gt; 0.5). A total of 236 clinically suspected Invasive Aspergillosis cases were enrolled in the study. Galactomannan positivity was predominantly seen in patients aged 40 – 60 years, with male preponderance. Of 236 patients, 14.40% were immunocompromised, and 85.59% were immunocompetent. According to EORTC/MSG definitions, we got one proven IA case, 21 probable cases (8.89%), and nine (3.81%) possible cases. In immunocompetent individuals also, we observed 48.72% (115/236) galactomannan positivity, especially in old Pulmonary Tuberculosis (PTB) patients. Galactomannan positivity was higher in Broncho alveolar lavage (BAL) samples (n=70, 85.36%) than in serum samples (n=77, 46.67%). We found culture positivity of 14.06%, with Aspergillus fumigatus being the commonest isolate, followed by Aspergillus flavus. There is increased positivity of galactomannan in BAL samples compared to serum; hence BAL is a better specimen for diagnosis of Invasive Pulmonary Aspergillosis (IPA).

Multi-Locus Microsatellite Typing of Colonising and Invasive Aspergillus fumigatus Isolates from Patients Post Lung Transplantation and with Chronic Lung Disease.

Aspergillus fumigatus can cause different clinical manifestations/phenotypes in lung transplant (LTx) recipients and patients with chronic respiratory diseases. It can also precipitate chronic lung allograft dysfunction (CLAD) in LTx recipients. Many host factors have been linked with the severity of A. fumigatus infection, but little is known about the contribution of different A. fumigatus strains to the development of different phenotypes and CLAD. We used multi-locus microsatellite typing (MLMT) to determine if there is a relationship between strain (i.e., genotype) and phenotype in 60 patients post LTx or with chronic respiratory disease across two time periods (1 November 2006-31 March 2009 and 1 November 2015-30 June 2017). The MLMT (STRAf) assay was highly discriminatory (Simpson's diversity index of 0.9819-0.9942) with no dominant strain detected. No specific genotype-phenotype link was detected, but several clusters and related strains were associated with invasive aspergillosis (IA) and colonisation in the absence of CLAD. Host factors were linked to clinical phenotypes, with prior lymphopenia significantly more common in IA cases as compared with A. fumigatus-colonised patients (12/16 [75%] vs. 13/36 [36.1%]; p = 0.01), and prior Staphylococcus aureus infection was a significant risk factor for the development of IA (odds ratio 13.8; 95% confidence interval [2.01-279.23]). A trend toward a greater incidence of CMV reactivation post-A. fumigatus isolation was observed (0 vs. 5; p = 0.06) in LTx recipients. Further research is required to determine the pathogenicity and immunogenicity of specific A. fumigatus strains.

Identification and functional characterization of the putative members of the CTDK-1 kinase complex as regulators of growth and development in Aspergillus nidulans and Aspergillus fumigatus.

Asexual spores are the main vehicle used by fungi to disperse to new niches. The Eurotiomycete Aspergillus nidulans is the main reference for the study of the genetic/molecular control of asexual development. In this species, Flb proteins control the expression of the master gene brlA, and thus, loss-of-function mutations in flb (upstream developmental activation [UDA]) genes block brlA transcription and, consequently, the production of conidiophores, the structures bearing asexual spores known as conidia. However, the aconidial phenotype of specific flb mutants, such as that of the ΔflbB strain, is reverted under salt-stress conditions. Previously, we generated a collection of second-site mutants of ΔflbB unable to conidiate on culture medium supplemented with NaH2PO4 (0.65 M). Here, we identified a Gly347Stop mutation within flpA as responsible for the FLIP57 phenotype and characterized the role of the putative cyclin FlpA and the remaining putative components of the C-terminal domain kinase-1 (CTDK-1) complex in A. nidulans and Aspergillus fumigatus. FlpA, Stk47, and FlpB are necessary (i) for timely germination, (ii) in the transition from metulae to phialides (the cells generating conidia) during conidiophore development, and (iii) for the development of sexual structures (cleistothecia) in A. nidulans. The three proteins are nuclear, and the nucleoplasmic localization of Stk47 depends on the activity of FlpA, which correlates with the retention of Stk47 by FlpA in pull-down assays. Overall, this work links the putative CTDK-1 complex of aspergilli with growth and developmental control. Identification of a mutation in flpA as inhibitor of conidiation in A. nidulans and functional characterization of FlpA, Stk47 and FlpB as putative members of the C-terminal domain kinase complex CTDK-1 in A. nidulans and A. fumigatus.IMPORTANCEAspergillus fumigatus has been included by the World Health Organization in the priority list of fungal pathogens because (i) it causes 90% of invasive aspergillosis cases, with a high mortality rate, and (ii) infections are becoming increasingly resistant to azole antifungals. A. nidulans is an opportunistic pathogen and a saprotroph which has served during the last 80 years as a reference system for filamentous fungi. Here, we characterized the role in morphogenesis and development of the putative transcriptional cyclin/kinase complex CTDK-1 in both aspergilli. The null mutants of the corresponding genes showed delayed germination, aberrant conidiophore development, and inhibition of cleistothecia production. While in higher eukaryotes this complex is formed only by a cyclin and a kinase, the fungal complex would incorporate a fungal-specific third component, FlpB, which would enable the interaction between the kinase (Stk47) and the cyclin (FlpA) and may be used as a target for antifungals.

Commander-in-chief: monocytes rally the troops for defense against aspergillosis.

The detrimental impact of fungal infections to human health has steadily increased over the past decades. In October of 2022, the World Health Organization published the first ever fungal-pathogen priority list highlighting increased awareness of this problem, and the need for more research in this area. There were four distinct fungal pathogens identified as critical priority groups with Aspergillus fumigatus (Af) being the only mold. Af is a common environmental fungus responsible for over 90% of invasive aspergillosis cases worldwide. Pulmonary protection against Af is critically dependent on innate effector cells with essential roles played by neutrophils and monocytes. In this review, we will summarize our current understanding of how monocytes help orchestrate antifungal defense against Af.

Aspergillosis Causing Orbital Subperiosteal Abscess in an Immunocompetent Child: A Rare Presentation.

Orbital abscesses are primarily seen in children as complication of ethmoid bacterial sinusitis. We report a case of invasive aspergillosis causing orbital abscess in an immunocompetent child which resolved with surgery followed by antifungal therapy. This case highlights need for histopathological, and microbiological examination, including fungal culture in such cases.

Clinical Accuracy and Utility of Plasma Microbial Cell-Free DNA Whole-Genome Sequencing for the Diagnosis of Invasive Aspergillosis in Patients with Hematologic Malignancies or Coronavirus Disease 2019.

We evaluated the clinical accuracy and utility of whole-genome sequencing (WGS) of plasma microbial cell-free DNA (cfDNA) as a novel non-invasive method in diagnosing invasive aspergillosis (IA) in patients with hematologic malignancy (HM) or coronavirus disease 2019 (COVID-19). Adults with HM or COVID-19 and suspected IA were recruited. IA cases were retrospectively diagnosed according to EORTC/MSG definitions and ECMM/ISHAM criteria for HM and COVID-19 patients, respectively. The results of cfDNA WGS were compared with the conventional diagnosis. Microbial cfDNA WGS was performed 53 times from 41 participants (19 from HM, 16 from COVID-19, and 7 from the control group). In participants with HM, Aspergillus cfDNA was detected in 100% of proven IA and 91.7% of probable IA cases. In participants with COVID-19, 50.0% of probable IA were positive for Aspergillus in cfDNA WGS. Concordance between Aspergillus cfDNA detection and proven/probable IA conventional diagnosis was significantly higher in participants with HM than in those with COVID-19. IA diagnosed using EORTC/MGS definitions showed significantly high concordance between Aspergillus cfDNA detection and proven/probable IA. Aspergillus cfDNA detection strongly correlated with proven/probable IA diagnosed using EORTC/MSG definitions and could be used as an additional diagnostic tool for IA.

A rare case of invasive pulmonary aspergillosis in an immunocompetent individual

Invasive aspergillosis is a highly lethal opportunistic infection that poses a significant threat to immunocompromised patients. In these patients, the incidence of the disease is increasing, and the mortality rates remain high, so early diagnosis and treatment are very important to improve patient survivability. However, there are few described cases of invasive aspergillosis in immunocompetent patients without any type of comorbidity. We present the case of a 44-year-old immunocompetent woman who presented with a history of productive cough and fever for 1 week. Initially, the clinical and radiological presentation pointed to an infection. Several courses of antibiotics were administrated, with no improvement. Bronchofibroscopy with bronchial biopsies was performed and the bronchoalveolar lavage was negative for all investigations (including fungi). The patient started presenting massive hemoptysis, unresponsive to non-invasive therapies or bronchial artery embolization, requiring pneumonectomy as a life-saving procedure. Definitive diagnosis was made by histological demonstration of tissue invasion by the fungus and growth of Aspergillus in culture. Despite aggressive treatment, the patient is currently under antifungal therapy and respiratory kinesiotherapy, showing great clinical, analytical and radiological improvement. This case emphasizes the importance of maintaining a high index of suspicion and also to remember that invasive aspergillosis can also affect immunocompetent individuals.

Associations between invasive aspergillosis and cytomegalovirus in lung transplant recipients: a nationwide cohort study.

Cytomegalovirus (CMV) and invasive aspergillosis (IA) cause morbidity among lung transplant recipients (LTXr). Early diagnosis and treatment could improve outcomes. We examined rates of CMV after IA and vice versa to assess whether screening for one infection is warranted after detecting the other. All Danish LTXr, 2010-2019, were followed for IA and CMV for 2 years after transplantation. IA was defined using ISHLT criteria. Adjusted incidence rate ratios (aIRR) were estimated by Poisson regression adjusted for time after transplantation. We included 295 LTXr, among whom CMV and IA were diagnosed in 128 (43%) and 48 (16%). The risk of CMV was high the first 3 months after IA, IR 98/100 person-years of follow-up (95% CI 47-206). The risk of IA was significantly increased in the first 3 months after CMV, aIRR 2.91 (95% CI 1.32-6.44). Numbers needed to screen to diagnose one case of CMV after IA, and one case of IA after CMV was approximately seven and eight, respectively. Systematic screening for CMV following diagnosis of IA, and vice versa, may improve timeliness of diagnosis and outcomes for LTXr.

A Rare Case of Aspergillus Granuloma in the Cavernous Sinus of an Immunocompetent Patient

Aspergillosis is an invasive fungal disease that commonly infects immunocompromised hosts. Among the Aspergillus group, A. fumigatus is responsible for most cases of invasive Aspergillosis, mostly occurring in immunocompromised individuals, as well as chronic Aspergillosis and allergic syndromes. Prolonged exposure to Aspergillus is said to cause disease even in immunocompetent host.Hereby discussing a case of a 42-year-old male with headache, drooping of right eyelid and right ophthalmoplegia, right facial pain along the V1 and V2 region with features indicative of cranial nerve palsies involved in cavernous sinus syndrome. With radioimaging not giving clues toward the etiology, an open biopsy was done, was suggestive of fungal Aspergillus granuloma. Hence, the patient was started on voriconazole and clinically improved over time. This emphasizes that although rare with diagnostic barriers such as nonspecific clinical manifestations, deep anatomical location, and completely depending on pathological diagnosis, timely intervention saves the patient.

Fungal infections in Algeria

Invasive and superficial fungal infections are increasingly reported in Algeria, testifying to the increase in their frequency in parallel with the increase in risk factors and the availability of diagnostic means, at least in university hospitals (CHU). The latter, located in the major northern cities, are equipped with high-performance diagnostic tools compared to hospitals in the interior of the country. A comprehensive search of published and grey literature was undertaken. Prevalence and incidence of discrete fungal diseases were estimated using a deterministic modelling approach based on populations at risk. Population (2021) and major underlying disease risk groups were obtained from UNAIDS, WHO Tuberculosis and the international transplant registries as well as published data for asthma and COPD. The health service profile was summarised from national documentation. Among the 43.6 million, including 12.9 million children, living in Algeria, the most prevalent fungal diseases are tinea capitis (>1.5 million), recurrent vaginal candidiasis (>500,000) and allergic fungal lung and sinus disorders (>110,000) and chronic pulmonary aspergillosis (>10,000). Life-threatening invasive fungal infection incidence includes 774 Pneumocystis pneumonia in AIDS, 361 cryptococcal meningitis, 2272 candidaemia and 2639 invasive aspergillosis cases. Fungal keratitis probably affects >6000 eyes each year. Fungal infections are underestimated in Algeria because they are sought in patients with risk factors only after bacterial infections when they should be sought in parallel. The diagnosis is only accessible in hospitals in large cities and the work carried out in mycology is rarely published, making the estimation of the burden of these conditions difficult.

Pediatric Invasive Aspergillosis: a Retrospective Review of 59 Cases.

Invasive aspergillosis (IA) is a major cause of morbidity and mortality. This study aimed to present our 10-year IA experience at a single center. Fifty-nine pediatric patients with IA were included in this study. The male-to-female ratio was 42/17. The median age was 8.75 years. Hematologic malignancy was present in the majority of the patients (40/59, 68%). The mean neutropenia duration was 18.5 days. Cytosine arabinoside was the most common immunosuppressive therapy directed at T cells during IA diagnosis. IA cases were categorized as proven (27%), probable (51%), or possible (22%) according to the 2008 European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. The lungs (78%) were the most common site of IA, and nodules were the most frequent radiological findings (75.5%). In 38 patients (64.4%) receiving antifungal prophylaxis, prophylactic agents included fluconazole (30.5%), liposomal amphotericin B (23.7%), posaconazole (8.5%), and voriconazole (1.7%). Initial treatment was most commonly administered as monotherapy (69.5%). The median antifungal treatment duration was 67 days. Eleven deaths (18.6%) were due to aspergillosis. With the increased use of corticosteroids, biological agents, and intensive immunosuppressive chemotherapy, IA will most likely continue to occur frequently in pediatric patients.

Progression of chronic rhinosinusitis to invasive cerebro-orbital aspergillosis following steroid treatment: A case of induced immunosuppression

Invasive aspergillosis is a classic fungal infection of immunocompromised hosts which rarely manifests in immunocompetent patients. In this report, we present a case of invasive aspergillosis which resulted from induced immunosuppression through corticosteroid treatment of chronic rhinosinusitis. Further investigation is necessary into the epidemiology of mixed fungal rhinosinusitis and providers should be wary of invasive disease in those receiving chronic steroids.

A computational approach to identify novel plant metabolites against Aspergillus fumigatus

Aspergillus fumigatus, a common saprotrophic fungus is one of the most important causative agents of invasive aspergillosis. People with compromised immune systems or lung disorders are at a higher risk of acquiring Aspergillus-related health issues. The global number of invasive aspergillosis cases is expected to be over 300000 per year, with a 50 % death rate even when recognized and treated early. Current noninvasive therapies for fungal infections are azoles. As A. fumigatus resistance to azoles is rising, this study attempted to evaluate several plant metabolites as potential inhibitory agents of A. fumigatus by using in silico method. Five essential proteins including Chitinase, Glycosyl hydrolases, Glycosylphosphatidylinositol anchor, N-myristoyl transferase, and O-mannosyltransferases were selected as target proteins due to their involvement in morphogenetic processes, cell wall polysaccharides biosynthesis, filamentation, survival, organismal characteristics, proliferation, and cell wall integrity. Out of our 20 plant metabolites, four metabolites i.e., Chlorogenic acid, Protopine, Spirostanol, and Viniferin showed the best binding affinity with the key outer membrane protein of A. fumigatus during molecular docking analysis. Viniferin showed the highest binding affinity of about −262.07 and −247.63 with Chitinase and glycosyl hydrolases respectively. Molecular dynamic simulation was used to look further into the stability of the best two protein-ligand complexes. The average RMSD value of 2.4 A° for Chitinase-Viniferin and 2.2 A° for Glycosyl hydrolases-Viniferin complex demonstrated their excellent stability. ADME (absorption, distribution, metabolism, and excretion) analysis of these four plant metabolites showed that none of them had any side effects that might interfere with their drug-likeness efficiency, and no substantial toxic effects or allergenicity were also identified. Thus, all the predicted four plant metabolites can be used as a possible inhibitor of A. fumigatus. Furthermore, we strongly recommend more in vitro and in vivo trials to experimentally strengthen our encouraging outcomes.

Invasive aspergillosis caused by &lt;i&gt;Aspergillus non-fumigatus&lt;/i&gt; after allogeneic hematopoietic stem cell transplantation

Objective. To study the features of invasive aspergillosis (IA) due to A. non-fumigatus versus A. fumigatus in adult (≥ 18 years) recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 2016-2021. Materials and methods. The study included 33 patients with IA caused by A. non-fumigatus (n = 20) and A. fumigatus (n = 13). A comparative analysis of cases of IA, the results of therapy and outcomes in patients after allo-HSCT in the RM Gorbacheva Research Institute was performed. Diagnostic criteria EORTC / MSGERC 2020 were used. Results. Invasive aspergillosis caused by A. non-fumigatus made up the majority (60.6 %) of IA cases with an identified pathogen registered in patients after allo-HSCT in the period from 2016 to 2021. The main etiological agents in the A. non-fumigatus group were A. niger in 13 (65 %) patients, A. flavus – in 4 (20 %). The median day of diagnosis of A. non-fumigatus IAwas + 110 days (17–2093), for A. fumigatus it was + 46 days (2–866) (p = 0.171). Overall 12-week survival was 55 % and 59.2 % in the A. non-fumigatus and A. fumigatus groups, respectively (p = 0.617). The majority of patients in both the A. fumigatus (n = 10, 77 %) and A. non-fumigatus (n = 16, 80 %) groups received voriconazole as initial antifungal therapy. Second-linetherapy was required in 2 (10 %) patients with A. non-fumigatus IA: liposomal amphotericin B and echinocandins with or with-out posaconazole, and 2 (15 %) patients in the A. fumigatus group: liposomal amphotericin B and voriconazole in combination with echinocandins. A comparative analysis showed that in patients from the two groups, none of the assessed signs (gender, age, underlying disease, disease status at the time of transplantation, time from diagnosis to allo-HSCT, source of hematopoietic stem cells, conditioning regimen, donor type, antifungal prophylaxis, cytomegalovirus reactivation, severe acute and chronic graft-versus-host disease) did not differ significantly. Conclusions. A. niger is the main causative agent of IA caused by A. non-fumigatus. Patients characteristics, their treatment and outcomes did not differ significantly between the A. non-fumigatus and A. fumigatus groups.

2095. Associations between Invasive Aspergillosis and Cytomegalovirus Infections in Lung Transplant Recipients

Abstract Background Cytomegalovirus infection (CMV) and invasive aspergillosis (IA) are important causes of morbidity and mortality among lung transplant recipients (LTXr). These opportunistic infections share risk factors, but their interrelationship need further evaluation. Early diagnosis and treatment may improve outcomes. We examined incidence rates of CMV after IA and vice versa to assess whether screening for one of these infections may be indicated when the other is diagnosed. Methods All adults receiving a lung transplant in Denmark from 2010 to 2019 were included and followed for 2 years after lung transplantation. IA was defined using the ISHLT criteria. Standardized screening for CMV and IA was performed during the study period (Figure 1). Incidence rates (IR) and incidence rate ratios (IRR) of CMV and IA was estimated by multivariate Poisson regression adjusted for time after transplantation (time updated), sex, age and high-risk CMV serostatus/IA high-risk condition. In analyses of CMV, we included IA as a time updated variable, and in analyses of IA, we included CMV as a time updated variable. Figure 1Screening protocol for cytomegalovirus (CMV) and invasive aspergillosis following lung transplantation Valganciclovir prophylaxis was administered to patients with CMV serostatus D+/R−, D+/R+, and D−/R+ for three months after transplantation. In 2010-2016 voriconazole was administered as antifungal prophylaxis for all LTXr three months after transplantation. In 2016-2019 posaconazole and inhaled amphotericin B was administered for three months after transplantation for patients at high risk of IA. D, Donor; R, Recipient; PCR, Polymerase Chain Reaction; CMV, cytomegalovirus; BAL, bronchoalveolar lavage; Lung biopsy, transbronchial biopsy Results A total of 295 LTXr with 351 person-years of follow-up (PYFU) for CMV and 440 PYFU for IA were included (Table 1). CMV and IA were diagnosed in 122 (41.4%) and 57 (19.3%) LTXr, respectively (Figure 2). IA diagnosis was proven in 20 and probable in 37 patients (Table 1). Among LTXr diagnosed with IA, 15.8% developed CMV within 3 months, IR 109 per 100 PYFU (95% CI 57-210) (Table 2). The median viral load at CMV diagnosis after IA was 2900 copies/mL (IQR 525-19000). The first 3 months following IA diagnosis there was an increased risk of CMV, although not statistically significant after adjustment for time after LTX with aIRR 1.60 (95% CI 0.80-3.20). Among LTXr diagnosed with CMV, 8.2% developed IA within 3 months, IR 40 per 100 PYFU (95% CI 22-75) (Table 2). In the first 3 months following CMV diagnosis, there was a significantly increased risk of IA, aIRR 2.97 (95% CI 1.47-6.00). Numbers needed to screen to diagnose one case of CMV following IA, and one case of IA following CMV were approximately 6 and 12, respectively. Table 1:Characteristics of lung transplant recipient and infectious outcomes, n (%)*IA high-risk conditions; **Number of patients negative in blood samples but positive in BAL samples (minimum &amp;gt;3000 CMV copies/mL). Invasive aspergillosis defined by the ISHLT criteria including anastomosis infection, tracheobronchitis and pneumonia.TX, Transplantation; COPD, Chronic obstructive pulmonary disease; CMV, cytomegalovirus; D, Donor; R, Recipient; BAL, Bronchoalveolar lavage.Table 2:Incidence rates and incidence rate ratios of cytomegalovirus (CMV) and invasive aspergillosis (IA)1Adjusted for age &amp;gt;50 years, sex, and high-risk CMV serostatus. 2Adjusted for time after transplantation, age &amp;gt;50 years, sex, and high-risk CMV serostatus. 3Adjusted for age &amp;gt;50 years, sex, and IA high-risk underlying condition. 4Adjusted for time after transplantation, age &amp;gt;50 years, sex, and IA high-risk underlying condition.CMV, cytomegalovirus; IR, incidence rate; PYFU, Person-years of follow-up; IRR, incidence rate ratios; aIRR, adjusted incidence rate ratio; CI, confidence interval; TX, transplantation; IA, invasive aspergillosis.Figure 2:Kaplan-Meier survival estimates for CMV infection (A) and invasive aspergillosis (B) after lung transplantation Conclusion Systematic screening for CMV following diagnosis of IA, and vice versa, may improve the timeliness of treatment and thereby outcomes for LTX recipients. Disclosures Maiken C. Arendrup, DMSci, PhD, MD, Chiesi, Gilead: Honoraria|F2G, Cidara, Scynexis: Grant/Research Support Marie Helleberg, PhD, DMSc, AstraZeneca: Advisor/Consultant|Gilead: Advisor/Consultant|Gilead: Honoraria|GSK: Advisor/Consultant|GSK: Honoraria|Janssen: Advisor/Consultant|Roche: Advisor/Consultant|Sobi: Advisor/Consultant.

355. Outcome of patients with non-COVID-19 related Aspergillosis during the COVID-19 pandemic

Abstract Background In March 2020 our Institution was designated a COVID-19 unit, since the start of 2021 conventional medical attention has been reinstalled and it became a hybrid hospital. Our objective was to compare the outcome of patients with Invasive Aspergillosis (IA) without COVID-19 during the COVID-19 pandemic, compared with past controls from a historical cohort, and describe their clinical characteristics. As a secondary objective, we described the characteristics of other Invasive Fungal Infections (IFI) in a similar patient group. Methods Retrospective and descriptive study. The information was obtained from the electronic file. For IFI diagnosis, the EORTC/MSG criteria for proven and probable infection were considered, including the AspiCU modified criteria. The main outcome was death at 6 weeks, time from symptom onset to diagnosis/treatment, and having received antifungal treatment as secondary outcomes. Outcomes were compared to historical IA controls (2:1) from a pre-COVID-19 cohort. The study was approved by the local research and ethics committee. Results From March 2020 to December 2021, 50 IFIs were diagnosed in non-COVID-19 patients, of which 27 (54%) were Invasive Aspergillosis, 10 (20%) Cryptococcosis, 8(16%) histoplasmosis, 4 (8%) mucormycosis, and 1 (2%) Fusariosis. The median age was 44 years (IQR 33-58) and 67% were men. Forty three percent (22/51) had immunosuppression and 35% (18/51) had hematological malignancy, the median time from symptom onset to IFI diagnosis was 30 days (IQR 11-90) and 38% died within 6 weeks. During the pandemic, in Invasive Aspergillosis non COVID-19 patients, the median number of days from symptom onset to start antifungal was 21 (IQR 6-68) vs 5 (IQR 3-10) of IA historic controls (p=0.0005), 81.5% (22/27) vs 93% (50/54) received antifungal treatment (OR 0.88 , 95% CI 0.72-1.0,p=0.13), and IA cases had a mortality of 44% (12/27) vs 41% (22/54) in the historical cohort (p=0.75). We show the IA characteristics in Table 1. Table 1.Clinical characteristics of Patients with Invasive aspergillosis without COVID-19 during COVID-19 pandemic vs historic controlsFigure 1.Invasive fungal infections in non-COVID-19 patients during COVID-19 pandemicFigure 2.Invasive aspergillosis diagnosis methods in non-COVID-19 patients during COVID-19 pandemic GM: Galactomannan antigen Conclusion During the COVID-19 pandemic, patients with IA withouth COVID-19 were diagnosed significantly later. Also, a trend towards increased mortality and lower proportion of antifungal treatment was observed. It is likely a consequence of hospital reconversion during the start of the pandemic. Disclosures All Authors: No reported disclosures.

Blood Mucorales PCR to track down Aspergillus and Mucorales co-infections in at-risk hematology patients: A case-control study.

Serum Mucorales PCR can precede the final diagnosis of invasive mucormycosis by several days or weeks and could therefore be useful as a non-invasive screening tool. We assessed the performance of a commercial Mucorales PCR assay (MucorGenius®, PathoNostics, Maastricht, The Netherlands) on prospectively collected banked sera from hematology patients at risk for invasive mould infections. We evaluated if there is an underestimated incidence of missed Mucorales co-infections in patients with invasive aspergillosis (IA). We tested Mucorales PCR on the sera of all patients with a diagnosis of at least possible IA (EORTC-MSGERC consensus criteria) before the start of any antifungal therapy, and in a control group of similar high-risk hematology patients without IA (in a 1:4 ratio). When a positive Mucorales PCR was observed, at least 5 serum samples taken before and after the positive one were selected. Mucorales PCR was performed in 46 diagnostic serum samples of cases and in 184 controls. Serum Mucorales PCR was positive in 4 cases of IA (8.7%; 12.9% of probable cases) and in 1 control case (0.5%) (p=0.0061, OR=17.43 (1.90-159.96). Post-mortem cultures of the positive control became positive for Rhizopus arrhizus. Mortality of IA cases with and without a positive Mucorales PCR was not significantly different. Only in the PCR positive control case, serial serum samples before and after the diagnostic sample were also positive. It is not entirely clear what a positive Mucorales PCR in these cases implies since the 4 Mucorales PCR positive cases were treated with antifungals with activity against Mucorales. In addition, PCR was positive only once. This study does not provide enough evidence to implement Mucorales PCR screening. However, our findings emphasize once more the importance of considering the possibility of dual mould infections, even in patients with a positive galactomannan detection.

Influenza vaccination is associated with a reduced risk of invasive aspergillosis in high-risk individuals in Taiwan: a population-based cohort study

ABSTRACT Invasive aspergillosis (IA) has become the emerging life-threatening disease in recent years. Influenza has been identified as an independent risk factor for IA. Vaccination is the most effective way to prevent influenza, while whether it can reduce IA in high-risk population still uncertain. We aimed to investigate the association between influenza vaccination and the risk of IA in high-risk population. We performed a population-based cohort study of people who qualified for government-funded influenza vaccination and were at high risk for IA at the start of the influenza season each year between 2016 and 2019. We utilized Taiwan’s National Health Insurance Research Database to identify the influenza vaccination status and IA diagnosis during the follow-up period. We compared the risk of IA between people with and without vaccination using multivariable logistic regression analysis. Out of total 8,544,451 people who were eligible during the 3 influenza seasons, 3,136,477 (36.7%) were vaccinated. A total of 1179 IA cases with the incidence of 13.8 cases per 100,000 high-risk individuals were identified during the follow-up. Compared to non-vaccinated group, vaccinated individuals had a 21% risk reduction of IA (adjusted odds ratio 0.79, 95% confidence interval 0.70–0.90). Influenza vaccination was associated with a lower risk of IA among males, immunosuppressive conditions, malignancy, diabetes, and those having host factors according to the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium. Influenza vaccination is recommended for high-risk population to reduce the risk of IA.