Case Of Pulmonary Aspergillosis Research Articles

Invasive Pulmonary Aspergillosis in Lung Transplant Recipients: Retrospective Clinical Analysis from a Tertiary Transplant Center.

Aspergillosis is the most common invasive fungal infection among lung transplant recipients (LTRs). Although its incidence is lower than that of bacterial or viral infections, it poses a similar or even higher mortality rate due to challenges in early diagnosis, limited treatment options, and various complications. Therefore, we aimed to evaluate the pulmonary aspergillosis cases in our tertiary lung transplant center. A retrospective analysis of 146 LTRs was performed. The demographic data, microbiological and histopathological test results, and radiological findings used for Aspergillus identification were recorded. Aspergillus spp. was detected in 13 of 146 LTRs (9%), mean age 42.5 ± 14.06 years, an average of 18.9 months after lung transplantation. 3 cases (23%) had Aspergillus growth in tissue culture, and 2 (15.4%) showed fungal elements with septal hyaline fibrils in tissue pathology. Aspergillus spp Polymerase chain reaction (PCR) was positive in bronchoalveolar lavage of 8 (61.5%) cases. In addition, 4 (30.7%) cases had relevant tomography findings. The most common pathogens were A. Terreus (21%), A. Fumigatus (14%), and A. Flavus (14%). The mortality rate was 15%. LTRs are at high risk of Aspergillus spp infections. Early diagnosis with microbiological, histopathological, and radiological tests, in addition to well-established prevention strategies, prophylaxis, and treatment will provide a better survival rate for patients.

Environmental factors associated with invasive mold infections at a tertiary-care hospital

Background: Invasive mold infections (IMIs) in hospitalized patients can result in significant morbidity and mortality. Environmental factors, such as hospital construction and negative air-pressure rooms (NAPRs), have been associated with hospital-acquired IMI. Increased utilization of NAPRs during the COVID-19 pandemic created a unique opportunity to examine the impact of NAPRs on IMI risk. Methods: From 2018 to present, a new pavilion was being constructed adjacent to our hospital. The Theradoc platform was used to identify positive mold cultures among adult patients hospitalized at our institution between March 1, 2017, and October 15, 2022. We performed a retrospective chart review of 262 mold isolates to determine patient demographics, timing of IMI, and their relationship to hospital construction and exposure to NAPR. IMI incidence was compared across 3 observation periods: (A) before hospital construction; (B) during hospital construction alone; and (C) during hospital construction and NAPR enhancement during the COVID-19 surge. Hospital-acquired IMI was defined as an infection that occurred >72 hours after admission. A REDCap database was created for data storage and R software was used for data analysis. Results: Of the 262 mold isolates identified, 61 cases were classified as IMI, of which 29 were hospital-acquired IMI. The mean age of IMI patients was 51.8 years, and 55.2% were male. Among them, 20.7% were exposed to NAPR during admission; 65.5.% were immunocompromised; and 2 patients were diagnosed with COVID-19. The all-cause mortality rate among hospital-acquired IMI cases was 79.3% (23 of 29). Also, 82.8% of hospital-acquired IMI cases were respiratory in nature, with 83.3% of these cases due to Aspergillus spp. Yearly rates of hospital-acquired IMI were 3.0 before construction versus 5.6 during construction (periods B and C). Yearly rates of hospital-acquired IMI, respiratory IMI, and invasive pulmonary aspergillosis by period were as follows: Period A had 3 hospital-acquired IMI cases per year, 2 hospital-acquired respiratory IMI cases per year, and 3 hospital-acquired invasive pulmonary aspergillosis cases per year. Period B had 4.5 hospital-acquired IMI cases per year, 3.5 hospital-acquired respiratory IMI cases per year, and 3.0 hospital-acquired invasive pulmonary aspergillosis cases per year. Period C had 6.5 hospital-acquired IMI cases per year, 5.4 hospital-acquired respiratory IMI cases per year, and 5.0 hospital-acquired invasive pulmonary aspergillosis cases per year. Conclusions: Hospital-acquired IMI was associated with a high mortality. Our data demonstrate a >2-fold increase in yearly incidence of hospital-acquired IMI before construction compared with during construction in association with increased implementation of NAPR. We have now reversed the trend in NAPR at our hospital’s designated COVID-19 units.Disclosures: None

Clinico-mycological profile of suspected pulmonary aspergillosis cases

Abstract Introduction: Aspergillus is one of the most ubiquitous airborne saprophytic fungi. Humans constantly inhale numerous conidia of this fungus. The conidia are normally eliminated in the immunocompetent host by innate immune mechanisms. With increase in the number of immunocompromised patients, there has been a dramatic increase in severe and fatal invasive aspergillosis (IA). The present study was aimed to know the clinico-mycological profile of suspected pulmonary aspergillosis cases. Methods: The present study was a prospective study conducted over a period of 1 year in the department of microbiology in admitted cases with clinical suspicion of pulmonary aspergillosis. Samples such as sputum, bronchoalveolar lavage, endotracheal secretions, fine-needle aspiration or biopsy and blood (for serological analysis) were collected and processed as per standard protocol. Results: Over a period of 1 year, 89 cases were included in the study. Their mean age was 58.7 years. Majority were male (60.6%). The most common presentation was cough (89.9%), followed by chest pain (57.3%) and fever (56.2% most common chest X-ray finding was homogeneous haziness (40.4%). Fungal smear was positive in 55.1% and 61.8% showed fungal growth. Galactomannan (GM) and (1-3)-β-D glucan positivity were 56% and 83.3%, respectively. The mortality was observed in 21.4% of patients. Conclusions: The study demonstrated that GM assay and (1-3)-β-D glucan assay are useful diagnostic modalities with a high sensitivity and specificity for the detection of pulmonary aspergillosis in high-risk patients along with positive fungal culture. Thus, these tests are early markers for IA.

POST-COVID-19 PULMONARY ASPERGILLOSIS AND MUCORMYCOSIS CO-INFECTION IN A PATIENT WITH DIABETES: A COMBINED CHALLENGING COMPLICATION

TYPE: Abstract TOPIC: Chest Infections PURPOSE: The recent emergence of COVID-19 disease had been associated with rare, invasive and life threatening fungal infections such as pulmonary aspergillosis and mucormycosis caused by Aspergillus fumigatus and Rhizopus arrhizus respectively with higher case fatality rate(>50%) especially among immunocompromised patients, diabetes mellitus, usage of steroids & other immunomodulators and covid infection itself. Here,we describe a case of Pulmonary aspergillosis and mucormycosis occuring in a 62 years old male diabetic patient who had history of COVID-19 infection 42 days back. After confirmation of diagnosis and aggressive therapeutic measures, he was discharged after 6 weeks of indoor treatment. The treatment depends on early and precise diagnosis followed by long term use of combination of antifungal agents and surgical intervention when necessary. Thus careful assessment and early diagnosis could lead to early therapeutic interventions and ultimately better outcomes. METHODS: Diagnosis on the basis of imaging CT Thorax findings- 52*48 mm thick walled cavity lesion with surrounding area of consolidation- reverse halo sign in right lower lobe and bronchoscopy guided TBLB & HPE findings were positive for aspergillus and mucormycosis. RESULTS: Both bronchoscopic and TBLB are effective tools to diagnose aspergillus and mucomycosis infection.In the treatment part, if feasible, attempts to reverse the underlying predisposing factors should be made. CONCLUSIONS: This case report highlights the need for healthcare professionals to be aware that combined pulmonary aspergillosis and mucormycosis can present as secondary complications of COVID-19 coinfection in diabetics. CLINICAL IMPLICATIONS: The combined risk factors of diabetes mellitus, COVID-19 and recent corticosteroid treatment contributed to both infections in our patient. DISCLOSURE: Nothing to declare. KEYWORD: COVID-19 , Pulmonary , Aspergillosis , Mucormycosis , Diabetes mellitus

Clinical features and risk factors of pulmonary tuberculosis complicated with pulmonary aspergillosis.

This study was carried out to explore the clinical features and risk factors of pulmonary tuberculosis complicated with pulmonary aspergillosis. Through a retrospective analysis of 3,000 patients with pulmonary tuberculosis history or active pulmonary tuberculosis complicated with pulmonary aspergillosis in the inpatient department of pulmonary tuberculosis in Shandong Provincial Public Health Clinical Center from January 2017 to January 2021, 70 cases of pulmonary aspergillosis were selected and diagnosed. In addition, 70 patients with pulmonary tuberculosis without other fungal infections in the same period were randomly selected as the control group. The risk factors of pulmonary tuberculosis complicated with pulmonary aspergillosis were analyzed by multi-factor logistic analysis, and the clinical characteristics of pulmonary tuberculosis complicated with pulmonary aspergillosis were analyzed by collecting the basic information of patients, drug use of pulmonary tuberculosis, imaging characteristics, past medical history, and test indicators. Univariate analysis showed that the single risk factors of pulmonary tuberculosis complicated with pulmonary aspergillosis were: the types of pulmonary tuberculosis (initial diagnosis or previous reexamination), hormone application time, antibiotic application time (rifampicin), hemoptysis/sputum blood, C-reactive protein, and pulmonary cavity were significantly correlated with pulmonary tuberculosis complicated with pulmonary aspergillosis (p-value <0.05). The proportion of patients with pulmonary tuberculosis complicated with pulmonary aspergillosis was higher than that of patients with simple pulmonary tuberculosis in the follow-up of pulmonary tuberculosis, the time of antibiotics application ≥ 1 month, the time of hormone application ≥ 1 week and C-reactive protein. The incidence of hemoptysis/blood in sputum in the clinical symptoms of pulmonary aspergillosis group (24/70) was higher than that of simple pulmonary tuberculosis group (20/70), and the difference was statistically significant (p-value < 0.05). Multivariate logistic regression analysis showed that there were significant differences between the two groups in the two indexes of "hormone application time ≥ 1 week" and "antibiotic application time ≥ 1 month" (p-value < 0.05). Hemoptysis/blood in sputum can be considered as the main clinical feature of pulmonary tuberculosis complicated with pulmonary aspergillosis. The main risk factors for pulmonary tuberculosis complicated with pulmonary aspergillosis were the application time of antibiotics ≥ 1 month and the application time of hormones ≥ 1 week.

Characteristics of Invasive Pulmonary Fungal Diseases Diagnosed by Pathological Examination.

Objective To explore the characteristics of invasive pulmonary fungal disease and the spectrum of pathogens causing invasive pulmonary fungal disease diagnosed by pathological examination using fungal stains. Methods Patients with an invasive pulmonary fungal disease diagnosed by histopathological analysis through the use of fungal stains (including Grocott's methenamine silver and periodic acid-Schiff stains) were included in this study. The clinical records, radiological reports, pathology, and fungal culture results were reviewed. Results Forty-eight invasive pulmonary fungal disease patients diagnosed by histopathological analysis in the Tianjin Haihe Hospital (including 8 cases obtained by pulmonary resection, 35 cases by fiberoptic bronchoscopic biopsy, and 5 cases by percutaneous lung biopsy) were included. There were 24 male and 24 female patients, aged 21–80 years (53 ± 13 years). There were 37 cases of pulmonary aspergillosis, 4 cases of pulmonary cryptococcosis, 2 cases of pulmonary mucormycosis, and 5 in which pathogens were not determined due to limited tissue availability. Among 48 cases, 32 specimens were submitted to fungal culture. No fungus was detected in culture, although 26 cases of fungus infections were diagnosed by histopathological analysis. Only 3 cases were consistent between histopathological and culture results. In 3 cases, the pathogen was identified as Aspergillus spp. by the histopathological analysis, while the contrasting fungal culture results identified Candida albicans. Conclusion Candida albicans pneumonia was rare, while aspergillosis was common in invasive pulmonary fungal disease diagnosed by histopathological analysis. The majority of patients with an invasive pulmonary fungal disease were culture-negative. Although culture can clarify the fungal pathogen species, it has low sensitivity. Pathological examination with fungal stains has its advantages in diagnosing fungal disease; therefore, more attention should be paid to the role of pathological examination in the diagnosis of fungal disease.

20 günlük bir süt kuzusunda pulmoner aspergillozis vakası

In this study, a case of pulmonary aspergillosis was described in a 20-day-old suckling lamb. Lamb suffering from high fever, anorexia, weakness and balance disorder was brought to the Department of Pathology of Kafkas University Faculty of Veterinary Medicine for necropsy. According to the anamnesis obtained from the animal owner, an intense and random drug treatment was administered to the animal. Following the systemic necropsy of the animal, various tissue samples were taken from for histopathological and microbiological analysis. On macroscopic examination, a yellowish-white colored focus in a diameter of 2x2 mm was detected in only one area of the animal's lung. Histopathological examinations revealed a granuloma in the lung. In the center of this granuloma, in addition to severe necrosis, neutrophils and fungal hyphae were detected. In the PAS staining of the lung tissue, it was noted that these hyphae took the stain and gave a positive reaction in terms of fungus. Ziehl-Neelsen staining of the lung and liver tissues revealed that these tissues were negative for tuberculosis. As a result of histopathological and microbiological analysis, this case, which is rarely seen in dairy lambs, was diagnosed as pulmonary aspergillosis.

Chronic Lung Injury After Trimodality Therapy for Locally Advanced Non-Small Cell Lung Cancer

Trimodality therapy is a treatment option for patients with locally advanced non-small cell lung cancer (LA-NSCLC). Thoracic radiation has both early (radiation pneumonitis) and late (chronic lung injury [CLI]) adverse effects on the lung. While CLI is expected to result in various problems in long-term survivors, these manifestations have not been precisely investigated. We enrolled 112 LA-NSCLC patients who had received induction chemoradiotherapy followed by surgery, and then undergone follow-up computed tomography (CT) every 6 months for greater than 1 year. All chest CT images were reviewed to evaluate any injury of the pulmonary parenchyma. CLI at 1 year after surgery and its progression were observed in 94 (84%) and 38 (34%) patients, respectively. Progressive lung fibrosis as the first manifestation of CLI progression was most frequent after right middle and lower lobectomy. Cavity formation was the subsequent manifestation after progressive lung fibrosis , and chronic infection was the final stage of CLI. The cumulative rate of chronic infection was 76.4% at 10 years in patients with cavity formation. Ten patients with chronic infection included 7 cases of pulmonary aspergillosis and 2 cases of cavity infections with methicillin-resistant Staphylococcus aureus or Stenotrophomonas maltophilia. Among them, 4 patients required surgical interventions including completion pneumonectomy or fenestration. CLI is a common incidence after trimodality therapy for LA-NSCLC. CLI frequently results in cavity formation, which is a precursor of highly refractory chronic infections requiring surgical intervention. Appropriate management needs to be established for CLI developing after trimodality therapy.

Invasive pulmonary aspergillosis in immunocompetent patients hospitalised with influenza A-related pneumonia: a multicenter retrospective study

BackgroundIncreasing cases of pulmonary aspergillosis (IPA) in immunocompetent patients with severe influenza have been reported. Howevere, the risk factors for occurence and death are largely unknown.MethodsData of hospitalised patients with influenza A-related pneumonia (FluA-p) obtained from five teaching hospitals from 2031 to 2018, were reviewed. Univariate and multivariate logistical regression analyses were performed to determine the risk factors involved in the acquisition and 60-day mortality in IPA patients.ResultsOf the 693 FluA-p patients included in the study, 3.0% (21/693) were IPA patients with a 60-day mortality of 42.9% (9/21). Adjusted for confounders, a Cox proportional hazard model showed that IPA was associated with increased risk for 60-day mortality [hazard ratio (HR) 4.336, 95% confidence interval (CI) 1.191–15.784, p = 0.026] in FluA-p patients. A multivariate logistic regression model confirmed that age (odd ratio (OR) 1.147, 95% CI 1.048–1.225, p = 0.003), systemic corticosteroids use before IPA diagnosis (OR 33.773, 95% CI 5.681–76.764, p < 0.001), leukocytes > 10 × 109/L (OR 1.988, 95% CI 1.028–6.454, p = 0.029) and lymphocytes < 0.8 × 109/L on admission (OR 34.813, 95% CI 1.676–73.006, p = 0.022), were related with the acquisition of IPA. Early neuraminidase inhibitor use (OR 0.290, 95% CI 0.002–0.584, p = 0.021) was associated with a decreased risk for a 60-day mortality in IPA patients.ConclusionsOur results showed that IPA worsen the clinical outcomes of FluA-p patients. The risk factors for the acquisition and death were helpful for the clinicians in preventing and treating IPA.

Epidemiology, laboratory diagnosis and clinical aspects of fungal pulmonary infections in 384 patients hospitalized in pulmonary units in Guilan province, Iran.

Background and Objectives:The respiratory tract is the most common site for developing fungal infections. People who have a weakened immune system are more susceptible to respiratory system involvement with fungi. Fungal infections of the respiratory tract are largely unrecognized and their true burden is elusive. Therefore, the aim of the current study was to evaluate the clinical spectrum, demographic characteristics, risk factors, and etiology of fungal respiratory infections in 384 patients hospitalized in pulmonary units of Razi hospital, Guilan province, Iran.Materials and Methods:A total of 384 lung specimens (192 Bronchoalveolar lavages (BAL) and 192 sputa) were obtained from patients who met the inclusion criteria. All samples were analyzed by direct microscopy and culture. Fungal identification was accomplished by internal transcribed spacer (ITS) and beta-tubulin sequencing. Also, in patients suspected to invasive pulmonary aspergillosis BAL specimens were tested for galactomannan (GM) antigen. According to the host factors (clinical symptoms, radiology findings and predisposing factors which were defined as inclusion criteria), and the positive results in direct examination, culture and serology (GM for aspergillosis) the infection was confirmed.Results:Fungal respiratory infection was confirmed in 137 cases (35.67%) including 86 (62.77%) males and 51 (37.23%) females and the highest prevalence of infection was found in the age group of 46–72 years (n=75, 54.74%). Cough (n=129, 94.16%), dyspnea (n=111, 81.02%), purulent sputum (n=85, 62.04%) and weight loss (n=77, 56.2%) were the predominant symptoms. Tuberculosis (n=34, 24.81%), taking chemotherapy regimen (n=30, 21.89%) and diabetes mellitus (n=27, 19.70%) were the predominant underlying conditions. Candida albicans (37.22%) and Candida tropicalis (21.89%) represent the two most commonly isolated species in the current study. Furthermore, according to revised EORTC/MSG (2008) definitions for invasive fungal infections, from 5 cases of pulmonary aspergillosis, 2 (40%) cases of probable invasive pulmonary aspergillosis (IPA) and 3 (60%) cases of possible IPA were diagnosed.Conclusion:According to the results of this study, infected infants with congenital CMV infection could identify at early stage by testing Guthrie cards (within 21 days of life). Furthermore, since there is a lack of CMV knowledge in our population, educating and effective counseling by obstetricians/gynecologists to the pregnant women are recommended.

Emergence of azole resistant-Aspergillus fumigatus infections during STAT3-deficiency

Introduction. Signal transducer and activator of transcription 3 (STAT3) deficiency is a rare primary immunodeficiency associated with increased susceptibility to bacterial and fungal infections, notably pulmonary aspergillosis.Aim. We describe the emergence of azole-resistant Aspergillus fumigatus infections in STAT3-deficient patients.Methodology. During a retrospective study of 13 pulmonary aspergillosis cases in STAT3-deficient patients conducted in France, we identified patients infected with azole-resistant A. fumigatus isolates.Results. Two out of the 13 STAT3-deficient patients with aspergillosis had azole-resistant A. fumigatus infection, indicating an unexpectedly high prevalence of resistance. The first patient with STAT3 deficiency presented several flares of allergic bronchopulmonary aspergillosis-like episodes. He was chronically infected with two azole-resistant A. fumigatus isolates (TR34/L98). Despite prolonged antifungal treatment, including caspofungin and amphotericin B, the patient was not able to clear the azole-resistant A. fumigatus. The second patient had chronic cavitary pulmonary aspergillosis (CCPA). The A. fumigatus isolate was initially azole susceptible but harboured three F46Y, M172V and E427K point mutations. Despite prolonged antifungal therapies, lesions worsened and the isolate became resistant to all azoles. Surgery and caspofungin treatments were then required to cure CCPA. Resistance was probably acquired from the environment (TR34/L98) in the first case whereas resistance developed under antifungal treatments in the second case. These infections required long-term antifungal treatments and surgery.Conclusions. The emergence of azole-resistant A. fumigatus infections in STAT3-deficiency dramatically impacts both curative and prophylactic antifungal strategies. Physicians following patients with primary immune-deficiencies should be aware of this emerging problem as it complicates management of the patient.

Potential value of serum Aspergillus IgG antibody detection in the diagnosis of invasive and chronic pulmonary aspergillosis in non-agranulocytic patients

BackgroundAt present, serum Aspergillus IgG and IgM antibody detection is mainly used in the diagnosis of chronic pulmonary aspergillosis (CPA), but its value in the diagnosis of invasive pulmonary aspergillosis (IPA) in non-agranulocytic patients is still unclear. IgM can be used as a marker of acute infection to help diagnose acute infection-related diseases. IgG is a marker of long-term infection and is used to assist in the diagnosis of pre-existing or chronic infection-related diseases. The aim of this study was to investigate and compare the value of serum Aspergillus IgG and IgM antibody detection in the diagnosis of IPA and CPA in non-agranulocytic patients.MethodsFifty-eight cases of pulmonary aspergillosis (37 IPA and 21 CPA cases), 15 cases of community-acquired bacterial pneumonia and 50 cases in the healthy control group were collected. The serum (1,3)-β-D-glucan test (G test) was performed with a chromogenic method, and the galactomannan test (GM test) and Aspergillus IgG and IgM antibody detection were performed by commercial enzyme-linked immunosorbent assay (ELISA) in all patients. The sensitivity and specificity, cut-off value and area under the curve (AUC) of Aspergillus IgG and IgM antibodies were further obtained by receiver operating characteristic (ROC) curves.ResultsThe positive rate of the G test, Aspergillus IgG antibody detection and the GM test also showed notable differences among the IPA, CPA, community-acquired bacterial pneumonia and healthy groups (P = 0.006, P < 0.001 and P = 0.217, respectively). Only the positive rate of the GM test showed a significant difference between the IPA and CPA groups (P = 0.04). ROC curves indicated that Aspergillus IgG antibody detection had a higher specificity in the IPA group than in the CPA group (0.952). The detection of Aspergillus IgG antibody can preferably distinguish IPA from community-acquired bacterial pneumonia and healthy controls (sensitivity = 0.923, specificity = 0.459, cut-off value = 134.46, AUC = 0.727). It can also distinguish CPA from community-acquired bacterial pneumonia and healthy controls (sensitivity = 0.952, specificity = 0.692, cut-off value = 75.46, AUC = 0.873).ConclusionsSerum Aspergillus IgG antibody detection may have certain clinical value in the diagnosis of IPA and CPA in non-agranulocytic patients.

Infections Associated with CAR T Therapy for Treatment of Hematological Malignancies

Introduction: Chimeric antigen receptor t cells (CAR T) therapy is an innovative adoptive immunotherapy being used for the treatment of CD19+ive B cell hematological malignancies, especially B cell acute lymphoblastic leukemia (B-ALL), non-Hodgkin's lymphomas (NHL) and chronic lymphocytic Leukemia (CLL). This treatment holds the potential to be highly effective and potentially less toxic alternative to cytotoxic chemotherapy for patients with relapsed and refractory (R/R) disease.This therapeutic modality is associated with a variety of side effects which includes cytokine release syndrome (CRS), neurotoxicity, B cell aplasia, hypogammaglobulinemia and resultant high risk infections. There is paucity of data about infection related complications with CAR-T therapy. In this review, we focus on the infections associated with B cell targeting CART cell therapy for the treatment of hematological malignancies. Methods: We conducted a systematic review (following PRISMA guidelines) by completing a comprehensive PubMed, Cochrane Library and ClinicalTrials.gov search on May 15th2019. Our search strategy included using search and MeSH terms related to CAR T therapy, hematological malignancies, Infections, safety and mortality. We were able to identify 279 articles from PubMed, 26 from Cochrane, 5 from Clinical Trials.org and 7 from Web of Science. After screening we selected 13 prospective published trials (n=555) for data extraction. We manually extracted data and summarized our results. RESULTS: Total included trials were 13, and trial level data from 555 patient was summarized in Table 1. Commonly used targets were CD19 ( B cell malignancies), and BCMA (Multiple Myeloma). CAR T were used for the treatment of diseases B-cell acute lymphoblastic leukemia ( ALL), B cell NHL, CLL, and Multiple myeloma (MM). Out of the available data, the two most frequent infections were upper respiratory tract infections (RTI) and blood stream infections. Other infections observed were the lower RTI, urinary tract infections (UTI), clostridium difficile (C. Diff), meningitis, mucocutaneous herpes infections, cellulitis, mucormycosis, and aspergillosis. A Phase 1/2 trial (NCT00924326 / B-NHL / CD19 Target) demonstrated 43 cases of septicemia (23.2%), 4 cases of UTI (9.3%) and 1 case each of cellulitis (2.3%), opportunistic infections (2.3%), upper RTI and lower RTI (2.3%). Phase 1 trial (NCT01029366 / B lymphoma, leukemia / CD19 target / n=20) showed 3 cases (15%) of pneumonia, 1 case each of C Diff, Pseudomonas and salmonella (5%) infections. A Phase 2 trial (NCT02030834, B NHL, CD19 target, n=63) treated patients showed 34% patients experienced infection which included sepsis, UTI, upper and lower RTI, skin, small intestine and mucosal infections. A phase 1 trial ( NCT01840566, n=17, NHL, CD19 target) demonstrated cases of mucormycosis ( n=unknown) and 7 case of pneumonia (41.1%). In phase 2 trial (NCT02030847, B ALL, CD19, n=30) treated patients experienced cases of sepsis (10%), Pneumonia (6.7%) and 1 case each of oral Candidiasis, C Diff, influenza and meningitis (10%). A phase 1 trial (NCT01044069, n=53, RR ALL, CD19 target) showed incidence of 11 cases of blood stream infections (20.1%), 9 cases of upper RTI (16.9), 2 cases of UTI (3.8%), 2 cases of pneumonia (3.8%), 3 cases of pulmonary aspergillosis (5.7%) and a case of herpes infection (1.9). Phase 2 trial (NCT01747486, CLL, CD19, n=42) demonstrated 2 cases of sepsis (4.7%), 2 cases of influenza (4.7), 3 cases of upper respiratory tract infections (7.1%) and 2 cases of pneumonia (4.7%). NCT02215967, Phase 1 trial ( Multiple Myeloma, BCMA target, n=12) was associated with 3 cases of upper RTI (25%) and 1 case of UTI (8.3%). Table 2 summarizes additional ongoing CAR T cell trials. Conclusion: CAR T cell therapy is gaining popularity and its indications are expanding. Its complications need to be closely studied for potential infections amongst other side effects. Clinical trial results have likely under-reported infections associated with CAR-T therapy because of overlapping presentation with cytokine release syndrome (CRS), neurotoxicity and limited follow-up reported in the published trials. Additional studies with longer follow up duration are required to identify the true risk of infectious complications of CAR T therapy in patients with hematological malignancies. Real word data on CAr T patients can also reveal long term infectious complications. Disclosures Anwer: In-Cyte: Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: CAR-T therapy. We are summarizing infectious complications of CAR-T therapy and their projects under development.

A call to arms: Mustering secondary metabolites for success and survival of an opportunistic pathogen.

Aspergillus fumigatus is a ubiquitous saprophytic mold able to grow on a diversity of material ranging from decayed organic matter in the environment to space station cupolas [1]. Yet this fungus is equally adept as a serious opportunistic pathogen, causing pulmonary aspergillosis and the more deadly invasive aspergillosis (IA). There are an estimated 3,000,000 cases of pulmonary aspergillosis annually and more than 200,000 cases of IA each year reaching a mortality rate of up to 90% in the most susceptible populations [2]. Difficulties in treating IA include delayed detection and increasing resistance to antifungal treatment. Like many opportunistic fungi, there is no one gene that makes A. fumigatus such a threatening pathogen. One unique feature of this pathogen is its arsenal of small molecules that impact disease development. Secondary metabolites are characterized as bioactive molecules of low molecular weight that are not required for growth of the organism but instead aid survival in harsh environments, resisting desiccation and UV stress and improving competition with other microbes. For A. fumigatus, these benefits extend to aiding growth not only in the environment but in the human body as well. Some secondary metabolites combat the host immune system by affecting immune cell function or by shielding the fungus against host attack, whereas others allow the fungus to acquire essential, scarce cofactors. The following synopsis of secondary metabolites produced by the opportunistic human pathogen A. fumigatus highlights how microbial metabolites, although undoubtedly evolved as environmental protectants, can impact infectious disease development (Fig 1). Although we delineate the roles of each metabolite by category for ease of discussion (e.g., “on the offensive,” “scavenging the battlefield,” “arms race”), the reader should note that each metabolite may have several biological roles for the fungus, in part illustrated in Fig 1. Open in a separate window Fig 1 Roles of Aspergillus fumigatus secondary metabolites. A list of the secondary metabolites produced by A. fumigatus, flanked by their proposed roles in the environment (right) and the host (left). Metabolites with a “?” indicate that the compound has not been examined in a niche. Bracketed numerals (e.g., [22]) indicate the reference associated with the role of the metabolite. Nidulanin A is a proposed metabolite produced by A. fumigatus, whereas all other metabolites are characterized end-product metabolites from a biosynthetic gene cluster. ROS, reactive oxygen species; TNF-α, tumor necrosis factor alpha.

Spectrum of Pulmonary Aspergillosis in Hyper-IgE Syndrome with Autosomal-Dominant STAT3 Deficiency

Autosomal-dominant signal transducer and activator of transcription 3 (STAT3) deficiency predisposes to recurrent bacterial pneumonia, complicated by bronchiectasis and cavitations. Aspergillosis is a major cause of morbidity in these patients. However, its diagnosis, classification, and treatment are challenging. We aimed to assess the prevalence and describe the clinical, mycological, and radiological presentation and related therapy and outcome of Aspergillus infections of the respiratory tract in the STAT3-deficient patients of the National French cohort. We performed a retrospective study of all pulmonary aspergillosis cases in STAT3-deficient patients (n=74). Clinical and mycological data were collected up to October 2015 and imaging was centralized. Twenty-one episodes of pulmonary aspergillosis in 13 (17.5%) STAT3-deficient patients were identified. The median age at first episode was 13 years (interquartile range, 10-26 years). Ninety percent of patients had previous bronchiectasis or cavitations. Infections were classified as follows: 5 single aspergilloma, 9 chronic cavity pulmonary aspergillosis, 5 allergic bronchopulmonary aspergillosis-like disease, and 2 mixed forms of concomitant allergic bronchopulmonary aspergillosis-like disease and chronic cavity pulmonary aspergillosis. No invasive aspergillosis cases were identified. Aspergillus species were isolated in 71% of episodes and anti-Aspergillus antibodies in 93%. Eleven episodes were breakthrough infections. Antifungal treatment was prolonged, with a median of 13 months, and 6 patients (7 episodes) required surgery, with a high rate of postsurgical complications. One patient died and 6 had a relapse. Chronic and allergic forms of aspergillosis occurred in 17.5% of STAT3-deficient patients, mostly in lung cavities. Almost half had recurrences, despite prolonged antifungal treatment and/or surgery.

Histologically confirmed pulmonary aspergillosis in patients with light and moderate immunosuppression

In the article a modern forms of pulmonary aspergillus infection are describes in detail, which are widely spread fungi in nature, and which can be saprophytes relatively to the human body or cause severe, diverse in clinical and anatomical manifestations, lesions of the human lungs. The review of modern classifications of pulmonary aspergillosis, as well as clinical and X-ray characteristics of individual forms of infectious lesions, is presented. In addition, data on the diagnostics of this infection are summarized, taking into account the forms of disease, the causes of the emerging diagnostic problems. In particular, the importance of background pathology and the state of immunity as prerequisites for the development of aspergillus infection is noted. The results of a personal analysis of 19 cases of pulmonary aspergillosis verified by histological examination are presented. Background diseases and/or conditions that served as the basis for the development of pulmonary aspergillosis, the level of immunosuppression of patients, and the clinical picture of the disease were studied in detail.

A case of pulmonary aspergillosis in white storks

Aspergillosis is a fungal infection affecting respiratory system both in mammals and avian species. It is more commonly encountered in birds, in comparison with its mammalian counterpart. Mostly isolated strains are Aspergillus fumigatus (95%) and Aspergillus flavus (5%). Affected lungs and air sacs reveal miliary to gross lesions like gray-yellowish or white-grayish granulomatous foci surrounded by white halos indicative of inflammatory infiltration. Five storks found dead in the rural areas near Istanbul were submitted to our faculty between years 2008 and 2014. Two of them were thought to be younger than 1-year-old and the other three were older than one year of age. Necropsies were performed right after their submissions. Aspergillosis lesions were observed in the lungs and thoracic air sacs of the first four storks. In addition to these changes the lesions were detected at the aortic bifurcation and on the testicular and renal capsule of the fifth stork. Histopathology revealed encapsulated granulomas with foci of caseous necrosis at the center surrounded by numerous macrophages, heterophil leukocytes, lymphocytes and foreign body giant cells in all the storks. Following the gross, histopathological and mycological examinations the agents were detected as Aspergillus fumigatus. Although, the number of reported deaths due to Aspergillosis is not high in storks, we believe that these birds are quite susceptible to the disease and stress factors such as migration increases the risk of pathogenicity. This report was designed as a contribution to literature since there is only one reported case available with respect to aspergillosis associated death in storks and stress factors such as migration may also predispose storks to the disease.

Pulmonary aspergillosis after treatment with infliximab in Still's disease and a literature review of Still's disease and pulmonary aspergillosis.

The use of anti-tumor necrosis factor alpha (anti-TNF-α) agents has increased during the past decade in rheumatology practice. Opportunistic infections have been reported with anti-TNF-α agents in clinical trials and post-marketing usage. Aspergillus infection is a rare opportunistic infection that is associated with immunosuppression, and there are reported cases of pulmonary aspergillosis in various rheumatic diseases treated with anti-TNF-α agents. Here, we present the first case of pulmonary aspergillosis associated with infliximab treatment in a patient with Still's disease.

Elastin increases biofilm and extracellular matrix production of Aspergillus fumigatus.

Aspergillus fumigatus is an opportunistic saprobe fungus that accounts for 90% of cases of pulmonary aspergillosis in immunosuppressed patients and is known for its angiotropism. When it reaches the respiratory tract, A. fumigatus interacts with structural components and blood vessels of the lungs, such as elastin. To understand the effect of this structural component, we examined the effect of elastin on the production and development of the biofilm of A. fumigatus. In RPMI containing 10 mg/mL of elastin, a significant increase (absorbance p < 0.0001; dry weight p < 0.0001) in the production of biofilm was observed in comparison to when RPMI was used alone, reaching a maximum growth of 18.8 mg (dry weight) of biofilm in 72 h. In addition, elastin stimulates the production (p = 0.0042) of extracellular matrix (ECM) and decreases (p = 0.005) the hydrophobicity during the development of the biofilm. These results suggest that elastin plays an important role in the growth of A. fumigatus and that it participates in the formation of thick biofilm.

経気管支鏡的にアンホテリシン B 注入療法を行い, 空洞壁を経時的に観察しえた肺アスペルギルス症の 1 例

経気管支鏡的にアンホテリシン B 注入療法を行い, 空洞壁を経時的に観察しえた肺アスペルギルス症の 1 例