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Advancements in allogeneic haematopoietic stem cell transplant (alloHSCT) procedures have improved patient outcomes over the last two decades, though invasive fungal infections (IFIs) remain a significant risk. The incidence of IFIs in alloHSCT recipients is estimated at 6%, with a mortality rate of 13%, and Aspergillus species are the most common pathogens involved. Posaconazole is effective in preventing IFIs post-transplant and is standard care during neutropenia or when managing graft-versus-host disease (GvHD) with high-dose steroids. However, azole prophylaxis may cause resistant Aspergillus species like A. calidoustus, which are difficult to treat. We report a case from our institution where a patient developed a dual infection with Aspergillus calidoustus and Talaromyces columbinus after alloHSCT and posaconazole prophylaxis. While A. calidoustus is known to cause IFIs in HSCT recipients, T. columbinus represents a previously unreported occurrence in medical literature. This case underscores the importance of a multifaceted diagnostic strategy, integrating BAL diagnosis, mycological cultures, direct microscopy, fungal speciation, susceptibility testing, and biomarkers. These comprehensive approaches are indispensable for accurate pathogen identification and effective management of IFIs with appropriate antifungal agents., (© 2024. The Author(s).)

Invasive aspergillosis (IA) is a rare but fatal disease among liver transplant recipients (LiTRs). We performed a multicenter 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 8 cases (13%). Twelve-week all-cause mortality of IA was 37%. In multivariate analyses, systemic antibiotic usage (adjusted odds ratio [aOR], 4.74; P = .03) and history of pneumonia (aOR, 48.7; P = .01) were identified as independent risk factors associated with the occurrence of IA. Moreover, reoperation (aOR, 5.99; P = .01), systemic antibiotic usage (aOR, 5.03; P = .04), and antimold prophylaxis (aOR, 11.9; P = .02) were identified as independent risk factors associated with the occurrence of early IA. Among IA cases, Aspergillus colonization (adjusted hazard ratio [aHR], 86.9; P < .001), intensive care unit stay (aHR, 3.67; P = .02), disseminated IA (aHR, 8.98; P < .001), and dialysis (aHR, 2.93; P = .001) were identified as independent risk factors associated with 12-week all-cause mortality, while recent receipt of tacrolimus (aHR, 0.11; P = .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 antimold prophylactic and appropriate treatment strategies against IA., Competing Interests: Declaration of competing interest The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. J. Hand reports research grant funding from Pfizer, Janssen, Scynexis, and GlaxoSmithKline. D. Neofytos has received research support from MSD and Pfizer and consulting fees from MSD, Pfizer, Basilea, and Gilead. N.J. Mueller is on the scientific advisory board of Takeda MSD, and Pfizer and has received travel support from Biotest. M. Luong is on the Scientific Advisory Board of Takeda and Merck. S. Husain reports grant funding from Merck, Astellas, ScynexisInc, Pulmocide, Ltd, and Gilead Sciences Inc, outside the submitted work. All other authors have no potential conflicts., (Copyright © 2024. Published by Elsevier Inc.)

Invasive fungal infections are a serious complication for haematology patients. However, there is no study on this subject in Reunion Island. The aim of this study was to estimate the incidence of invasive fungal infections in patients with haematological malignancies at the University Hospital of Reunion Island. We conducted a descriptive and ambispective study. We included any patient with haematological malignancy presenting with a putative, possible, probable, or proven invasive fungal infection, defined as per the criteria of the European Organisation for Research and Treatment of Cancer/Mycoses Study Group 2019, from January 2018 to December 2022. Data were collected from medical records and identified by ICD-10 coding and laboratory data. Eighty-nine invasive fungal infections were diagnosed in 76 patients. The 5-year incidence rate of invasive fungal infections was 1.7 per 100 person-years (95% Confidence Interval (CI) 1.3-2). Invasive aspergillosis was the most common infection (35/89, 39%), followed by invasive candidiasis (33/89, 37%), mucormycosis (7/89, 8%), and pneumocystosis (7/89, 8%). Most infections occurred in patients with acute myeloid leukaemia (32/89, 36%) and lymphoma (26/89, 29%). Six-month mortality was higher for mucormycosis (71%) than for aspergillosis (34%) and invasive candidiasis (33%). The incidence and distribution of fungal infections in haematology patients were similar to European cohorts, albeit with more mucormycosis, less pneumocystis, and a high proportion of Candida parapsilosis in candidemia., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Rare yeast infections have been slowly increasing, given the increasing numbers of patients who are immunocompromised after hematopoietic stem cell transplantation. A considered approach to the complex, multidisciplinary management of infections that are caused by these pathogens is essential to optimize patient outcomes. We reported the management of two patients with combined rare yeast Trichosporon asahii infections, that suggested we should perform timely multivisceral screening for systemic dissemination of infection, and early treatment and combination of medications may improve prognosis.

A 67 year-old male was admitted in the ICU because of multi-organ failure due to sepsis secondary to Fournier's gangrene. He had sustained radical prostatectomy in the last 48 hours. Peritoneal fluid and fatty tissue biopsies grew Aspergillus Fumigatus without concomitant pulmonary involvement. Postoperative acquisition via exogenous and endogenous routes is discussed, as this nosocomial entity is very rarely reported apart from peritoneal dialysis, especially in non-immunosuppressed patients., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Invasive fungal infections are associated with high morbidity in solid organ transplant recipients. Risk factor modification may help with preventative efforts. The objective of this study was to identify risk factors for the development of fungal infections within the first year following solid organ transplant., Methods: We searched for eligible articles through February 3, 2023. Studies published after January 1, 2001, that pertained to risk factors for development of invasive fungal infections in solid organ transplant were reviewed for inclusion. Of 3087 articles screened, 58 were included. Meta-analysis was conducted using a random-effects model to evaluate individual risk factors for the primary outcome of any invasive fungal infections and invasive candidiasis or invasive aspergillosis (when possible) within 1 y posttransplant., Results: We found 3 variables with a high certainty of evidence and strong associations (relative effect estimate ≥ 2) to any early invasive fungal infections across all solid organ transplant groups: reoperation (odds ratio [OR], 2.92; confidence interval [CI], 1.79-4.75), posttransplant renal replacement therapy (OR, 2.91; CI, 1.87-4.51), and cytomegalovirus disease (OR, 2.97; CI, 1.78-4.94). Both posttransplant renal replacement therapy (OR, 3.36; CI, 1.78-6.34) and posttransplant cytomegalovirus disease (OR, 2.81; CI, 1.47-5.36) increased the odds of early posttransplant invasive aspergillosis. No individual variables could be pooled across groups for invasive candidiasis., Conclusions: Several common risk factors exist for the development of any invasive fungal infections in solid organ transplant recipients. Additional risk factors for invasive candidiasis and aspergillosis may be unique to the pathogen, transplanted organ, or both., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Competing interests: None declared.

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., (© 2023 The Authors. APMIS published by John Wiley & Sons Ltd on behalf of Scandinavian Societies for Pathology, Medical Microbiology and Immunology.)

Competing Interests: Conflict of Interest: No conflict of interests to disclose.

Background: Kidney transplant recipients are at increased risk for invasive aspergillosis (IA), a disease with poor outcomes and substantial economic burden. We aimed to determine risk factors for posttransplant IA by using a national database and to assess the association of IA with mortality and allograft failure., Methods: Using the United States Renal Data System database, we performed a retrospective case-control study of patients who underwent kidney transplant from 1998 through 2017. To evaluate risk factors for IA, we performed conditional logistic regression analysis by comparing characteristics between IA-infected patients and their matched uninfected controls. We performed Cox regression analysis to evaluate the effects of IA on mortality and death-censored allograft failure., Results: We matched 359 patients with IA to 1436 uninfected controls (1:4). IA was diagnosed at a median of 22.5 months (interquartile range, 5.4-85.2 months) after kidney transplant. Risk factors for IA were Black/African American race, duration of pretransplant hemodialysis, higher Elixhauser Comorbidity Index score, weight loss, chronic pulmonary disease, need for early posttransplant hemodialysis, and a history of cytomegalovirus infection. Receiving an allograft from a living donor was protective against IA. IA was a strong independent predictor of 1-year mortality (adjusted hazard ratio [aHR], 5.02 [95% confidence interval {CI}, 3.58-7.04], P < .001). Additionally, IA was associated with 1-year allograft failure (aHR, 3.37 [95% CI, 1.96-5.77], P < .001)., Conclusions: Our findings emphasize the importance of timely transplant to mitigate the risk of posttransplant IA. An individualized approach to disease prevention is essential to decrease mortality and allograft failure., Competing Interests: Potential conflicts of interest. P. V. has received research funding from Cidara Therapeutics, Scynexis, and Ansun Biopharma and has served on the data safety monitoring board for AbbVie (all fees paid to the institution). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Infection by Aspergillus covers a broad clinical spectrum, including invasive pulmonary aspergillosis (IPA) and its disseminated extrapulmonary form, invasive aspergillosis (IA). It typically occurs in severely immunocompromised hosts, but it sometimes affects the immunocompetent population, especially patients with acute diseases being treated at the intensive care unit (ICU) and less often those with chronic conditions. In this article, we report the case of a 50-year-old male, with diabetes mellitus (DM) as the only risk factor, treated for IPA and IA with cardiac and central nervous system (CNS) involvement at a high complexity institution in Cali-Colombia. Clinical presentation and radiological findings are unspecific and require a high level of suspicion. To confirm the case, histological or cytological of the fungus is required; histopathological examination of lung tissue is the gold standard, but it is difficult to perform due to respiratory compromise and high risk of bleeding, so bronchoscopy and bronchoalveolar lavage (BAL) plays an essential role in the diagnostic process. A diagnostic algorithm that includes risk assessment, symptoms, imaging findings, and isolation in cultures is essential to allow the diagnosis and initiation of treatment promptly, which includes a combination of surgery and antifungal medications for long periods, even life-long treatment.

Mucocutaneous mycotic infections are common complications in patients on IL-17 inhibitor therapy. We report a case of a 33-year-old male with severe psoriasis and psoriatic arthritis on secukinumab combined with methotrexate and prednisone with swelling, otorrhea, and pain of the right ear and external auditory canal. Due to progressive hypacusis, a surgical solution was chosen. Tissue samples taken during surgery revealed the presence of Aspergillus fumigatus . Aspergillosis should be suspected in prolonged otorrhea, especially in immunocompromised patients. Without intervention, the disease could be fatal.

Introduction: Invasive Aspergillus infection (IA) in lung transplantation can result in poor outcomes. Itraconazole has been shown to be effective for fungal prophylaxis in lung transplant recipients. However, IA remains a major cause of death after lung transplantation. Therefore, we aimed to clarify the risk factors for IA on itraconazole prophylaxis., Methods: We examined 120 recipients to uncover their IA epidemiology, clinical characteristics, and outcomes. In addition, a case-control study was performed to identify risk factors of IA., Results: Of the 120 patients, 12 developed IA under itraconazole prophylaxis. The patient demographics and clinical characteristics were compared among the following two groups: IA group, 12 patients, and control group, 108 patients. Significant differences were observed in age (p = 0.004), history of interstitial pneumonia (p = 0.032), and CMV infection (p < 0.001) between the groups. Before the onset of IA, 92% (11/12) of the patients received itraconazole with trough concentrations above the therapeutic range. IA developed at 272.9 ± 114.1 days after lung transplantation. Of the 12 patients who developed IA, 66.7% (8/12) had early cessation of cytomegalovirus (CMV) prophylaxis due to toxicity of valganciclovir, as follows: leukocytopenia in 4 patients, and renal dysfunction in 4 patients. Of the 8 patients who stopped valganciclovir, 75% (6/8) developed CMV infection subsequently., Conclusion: This study suggests that older age, history of interstitial pneumonia, and CMV infection may be important risk factors for IA on itraconazole prophylaxis. These results may help clinicians optimize prophylactic strategies for IA., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

There is a matter of debate about the clinical impact of cytomegalovirus (CMV) reactivation on the development of late-onset invasive aspergillosis (IA), which occurs 40 days or later after allogeneic hematopoietic stem cell transplantation (HSCT). Using a Japanese transplant registry database, we analyzed the risk factors for the development of late-onset IA in 21,015 patients who underwent their first allogeneic HSCT between 2006 and 2017. CMV reactivation was defined as the initiation of preemptive anti-CMV antiviral therapy. Overall, there were 582 cases of late-onset IA, which occurred at a median of 95 days after HSCT. The 2-year cumulative incidence was 3.4% (95% confidence interval (CI), 3.0-3.9) in patients with CMV reactivation within 40 days after HSCT and 2.5% (95% CI, 2.3-2.8) in those without it (P < 0.001). In a multivariate analysis, CMV reactivation as a time-dependent covariate was significantly associated with the development of late-onset IA (hazard ratio (HR) 1.40, P < 0.001), as well as grade II-IV acute GVHD, age > 50 and HCT-CI ≥ 3 in the entire cohort. If we focus on the subgroup without grade II-IV acute GVHD, which is generally an indication for systemic corticosteroid therapy (n = 12,622), CMV reactivation was still a significant factor for the development of late-onset IA (HR 1.37, P = 0.045) as well as age > 50 years, HCT-CI ≥ 3, and cord blood transplantation. In conclusion, CMV reactivation was associated with an increased risk of late-onset IA after allogeneic HSCT independently of acute GVHD. Close monitoring for late-onset IA is necessary for patients who develop CMV reactivation even without grade II-IV acute GVHD., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To report a case of infectious necrotizing scleritis secondary to Aspergillus terreus after intravitreal injection therapy., Methods: This is a case report with literature review., Results: A 98-year-old woman receiving intravitreal aflibercept injections for neovascular age-related macular degeneration in the left eye presented with severe pain, redness, and purulent discharge at the injection site. She was initially treated with topical fortified antibiotics, and clinical improvement was achieved, although microbial cultures showed negative results. Two months later, she presented with severe ocular pain and was diagnosed with anterior necrotizing scleritis. Scleral scrapings were collected for cultures, and intensive topical antibiotic therapy was reintroduced. Evaluation for autoimmune etiology and microbiological testing showed negative results. Because of the progression of the scleral necrotic area, empirical therapy with topical voriconazole was initiated, and surgical debridement was performed. Finally, the culture was positive for A. terreus. The modified therapy consisted of topical voriconazole and oral voriconazole for 3 months with an excellent clinical outcome., Conclusions: To our knowledge, this is the first case of fungal necrotizing scleritis secondary to intravitreal injection. Diagnosis was delayed due to its chronic clinical course and the slow fungal growth in culture media, but the combined medical and surgical approach resulted in a satisfactory outcome., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Invasive fungal infections pose a severe threat in unconventional immunocompromised hosts such as cirrhosis. Herein we review the impact of invasive aspergillosis (IA) on the prognosis of cirrhosis patients. An electronic search for full-text articles describing IA in cirrhosis was conducted and the disease outcomes and mortality (point-estimate and comparative risk) were pooled on random-effects meta-analysis. Of 4127 articles, 11 studies (9 with good/fair and 2 with poor quality) were included. IA was associated with high disease severity and multi-organ failures in cirrhosis. The pooled-mortality of IA was 81.8% (95% CI: 64.3-91.8, I2 = 59%, P < 0.01). Estimate's-heterogeneity (I2) was explored through sub-groups, meta-regression, and influential diagnostics. Mortality estimates were higher among subgroups of acute-on-chronic liver failure (ACLF, 86.4%) and intensive care unit (ICU)-admitted patients (84.0%). The odds of mortality related to IA were 8.9 times higher than controls and much higher in ACLF (OR: 22.5) and ICU-admitted patients (OR: 36.4). The odds of mortality in IA were 4.1, 12.9, and 48.6 times higher than bacterial, no-fungal infections, and no-infection controls. There was no asymmetry in mortality estimates or odds ratios and mortality in IA was high irrespective of country of origin, site of infection, proven or probable category, and quality of study. Thus, IA is associated with very high mortality in cirrhosis patients, especially in ACLF and ICU-admitted patients. Intensive research is needed for the rapid diagnosis and treatment of IA in cirrhosis., Lay Summary: We report a high mortality rate of 81.8% in patients with liver cirrhosis and invasive aspergillosis. Higher odds (8.9 times) of death, especially in patients with ACLF or ICU admission were seen. Mortality was not affected by the country of study, site of infection, proven or probable nature of infection category, and quality of study., (© The Author(s) 2021. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Patients treated for adult T-Cell leukemia/lymphoma (ATL) have a poor prognosis and are prone to infectious complications which are poorly described. As the French reference center for ATL, we retrospectively analyzed 47 consecutive ATL (acute, n = 23; lymphoma, n = 14; chronic, n = 8; smoldering, n = 2) patients between 2006 and 2016 (median age 51 years, 96% Afro-Caribbean origin). The 3-year overall survival (OS) was 15.8%, 11.3%, and 85.7% for acute, lymphoma, and indolent (chronic and smoldering) forms respectively. Among aggressive subtypes, 20 patients received, as frontline therapy, high dose of zidovudine and interferon alfa (AZT-IFN⍺) resulting in an overall response rate (ORR) of 39% (complete response [CR] 33%) and 17 chemotherapy resulting of an ORR of 59% (CR 50%). Ninety-five infections occurred in 38 patients, most of whom had an acute subtype (n = 73/95; 77%). During their follow-up, patients receiving frontline chemotherapy or frontline AZT-IFNα developed infections in 74% (n = 14/19) and 89% (n = 24/27) of the cases respectively. Sixty-four (67%) of infections were microbiologically documented. Among them, invasive fungal infections (IFI, n = 11) included 2 Pneumocystis jirovecii pneumonia, 5 invasive aspergillosis, and 4 yeast fungemia. IFI exclusively occurred in patients with acute subtype mostly exposed to AZT-IFNα (n = 10/11) and experiencing prolonged (> 10 days) grade 4 neutropenia. Patients with aggressive subtype experiencing IFI had a lower OS than those who did not (median OS 5.4 months versus 18.4 months, p = 0.0048). ATL patients have a poor prognosis even in the modern era. Moreover, the high rate of infections impacts their management especially those exposed to AZT-IFNα., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Fungal sensitization is associated with poor asthma control. We aimed to determine the prevalence and factors associated with fungal asthma among Ugandan adults. Individuals aged ≥18 years with a new diagnosis of asthma in the last 12 months participating in the African Severe Asthma Program constituted the study population. Skin prick test results, clinical and demographic data were retrieved from the database, and serum Aspergillus fumigatus specific antibodies and total IgE were measured in stored blood. We enrolled 374 patients, median (IQR) age 34 (25-45) years, 286 (76.5%) females and 286 (76.5%) with severe asthma. Prevalence of Aspergillus fumigatus sensitization was 42.0% (95% CI: 37.1-47.0%), allergic bronchopulmonary aspergillosis (ABPA) 3.2% (1.8-5.5%), severe asthma with fungal sensitization (SAFS) 16% (12.7-20.1%) and allergic bronchopulmonary mycosis (ABPM) 2.9% (1.7-5.2%). Older age (55-64 years) (crude odds ratio (cOR) = 2.6), sensitization to at least one allergen (cOR = 9.38) and hypertension (cOR = 1.99) were significantly associated with Aspergillus sensitization, whereas tertiary education level (cOR = 0.29), severe depression (cOR = 0.15) and strong emotions (cOR = 0.47) were not. High occupational exposure to Aspergillus (cOR = 4.26) and contact with moulds (cOR = 14.28) were significantly associated with ABPA. Palpitations (cOR = 5.54), uncontrolled asthma (cOR = 3.54), eczema/dermatitis (cOR = 3.07), poor lung function (cOR = 2.11) and frequent exacerbations (cOR = 1.01) were significantly associated with SAFS. Eczema/dermatitis (cOR = 1.55) was significantly associated with ABPM, but cold weather trigger (cOR = 0.24) was not. Fungal asthma is a significant problem among Ugandans with asthma and should be particularly considered in individuals who remain uncontrolled despite optimal standard of care for asthma, as it is responsive to available and affordable oral antifungal therapy., Lay Summary: This study showed that fungal asthma is a significant problem among Ugandans with asthma with a high prevalence. Fungal asthma should be considered in patients with uncontrolled asthma despite receiving optimal standard of care. This is the first modern attempt to define these endotypes of asthma in Africa., (© The Author(s) 2021. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

We aimed to determine whether T cell-specific STAT3 deletion influences the immune response to Aspergillus in the immunosuppressed context in CD4 Stat3 -/- mice. Immunosuppressed and nonimmunosuppressed CD4 Stat3 -/- mice and littermate Stat3 flox/flox (Stat3 fl/fl ) mice were infected with Aspergillus fumigatus in an aerosol chamber, and the weight, activity, appearance, and respiratory rate of the mice were monitored daily for 21 days to evaluate their survival. Aspergillus infection was confirmed by lung fungal culture counts, histology, and a galactomannan test. Cytokines were measured at 3 days postinfection in bronchoalveolar lavage (BAL) fluid and serum. Immunosuppressed CD4 Stat3 -/- mice began succumbing to infection by day 4, and by day 7, only 30% of mice survived. Immunosuppressed Stat3 fl/fl mice started to succumb to the disease on day 5, and 40% of mice remained by day 7. The nonimmunosuppressed control Stat3 fl/fl and CD4 Stat3 -/- mice maintained their weight over the study period, without any evidence of infection by A. fumigatus by histology. In the BAL fluid, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), interferon gamma (IFN-γ), IL-17A, and IL-22 levels were elevated in Stat3 fl/fl immunosuppressed mice compared to immunosuppressed CD4 Stat3 -/- mice at 3 days postinfection. STAT3 in CD4 + T cells modulates the production of cytokines in the IL-17 pathway in immunosuppressed mice. However, it has no meaningful effect on the clearance of Aspergillus or the concomitant increase in susceptibility to Aspergillus infection., (Copyright © 2021 Gohir et al.)

A 51-year-old woman with headache was referred to our hospital. She had a history of endonasal pituitary surgery 22 years prior and hypertension 10 years prior. The endonasal transsphenoidal pituitary approach was performed via microscopic transseptal approach. Nasal endoscopy revealed whitish cystic wall protruded from the right sphenoid sinus. Functional endoscopic sinus surgery was performed under general anesthesia. After incision of the right sphenoid ostium, yellowish mucoid discharge in the right sphenoid sinus was pushed out from the sphenoid sinus. Histopathology confirmed fungal ball in the sphenoid sinus, which is consistent with aspergillosis sinus. The presence of fungal ball and mucocele are rarely reported, but mucocele and fungal ball found after pituitary surgery are the first and therefore unique in this case.

To investigate risk factors for invasive aspergillosis (IA) after kidney transplantation (KT), we conducted a systematic search in PubMed and EMBASE to identify studies published until June 2020. We included case-control or cohort design studies comprising KT recipients with a diagnosis of IA, defined according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group criteria, and assessed risk factors for the development of IA. Random-effect models meta-analysis served to pool data. We identified eleven case-control studies (319 IA cases and 835 controls). There was an increased risk of IA among recipients with underlying chronic lung diseases (odds ratio [OR] = 7.26; 95% confidence interval [CI] = 1.05-50.06) and among those with diabetic nephropathy (OR = 1.65; 95% CI = 1.10-2.48). Requiring posttransplant hemodialysis (OR = 3.69; 95% CI = 2.13-6.37) or surgical reintervention (OR = 6.28; 95% CI = 1.67-23.66) were also associated with an increased risk. Moreover, a positive link was identified between IA and posttransplant bacterial infection (OR = 7.51; 95% CI = 4.37-12.91), respiratory tract viral infection (OR = 7.75; 95% CI = 1.60-37.57), cytomegalovirus infection or disease (OR = 2.67; 95% CI = 1.12-6.32), and acute graft rejection (OR = 3.01; 95% CI = 1.78-5.09). In contrast, receiving a kidney from a living donor was associated with a reduced risk (OR = 0.65; 95% CI = 0.46-0.93). KT recipients that accumulate several of these conditions should be closely monitored and a low threshold of suspicion for IA should be maintained. Future studies should explore the benefit of mold-active prophylaxis to this subgroup of KT recipients at highest risk., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

An estimated 58 million people have survived tuberculosis since 2000, yet many of them will suffer from post-tuberculosis lung disease (PTLD). PTLD results from a complex interplay between organism, host, and environmental factors and affects long-term respiratory health. PTLD is an overlapping spectrum of disorders that affects large and small airways (bronchiectasis and obstructive lung disease), lung parenchyma, pulmonary vasculature, and pleura and may be complicated by co-infection and haemoptysis. People affected by PTLD have shortened life expectancy and increased risk of recurrent tuberculosis, but predictors of long-term outcomes are not known. No data are available on PTLD in children and on impact throughout the life course. Risk-factors for PTLD include multiple episodes of tuberculosis, drug-resistant tuberculosis, delays in diagnosis, and possibly smoking. Due to a lack of controlled trials in this population, no evidence-based recommendations for the investigation and management of PTLD are currently available. Empirical expert opinion advocates pulmonary rehabilitation, smoking cessation, and vaccinations (pneumococcal and influenza). Exacerbations in PTLD remain both poorly understood and under-recognised. Among people with PTLD, the probability of tuberculosis recurrence must be balanced against other causes of symptom worsening. Unnecessary courses of repeated empiric anti-tuberculosis chemotherapy should be avoided. PTLD is an important contributor to the global burden of chronic lung disease. Advocacy is needed to increase recognition for PTLD and its associated economic, social, and psychological consequences and to better understand how PTLD sequelae could be mitigated. Research is urgently needed to inform policy to guide clinical decision-making and preventative strategies for PTLD., (© 2021 S. Karger AG, Basel.)

Fluconazole is one of the most commonly used drugs for antifungal prophylaxis in childhood leukaemia. However, its interaction with vincristine may induce neuropathy and the emergence of antifungal drug resistance contributes to substantial mortality caused by invasive fungal infections (IFIs). In a retrospective single-centre study, we compared tolerability and outcome of different antifungal prophylaxis strategies in 198 children with acute leukaemia (median age 5·3 years). Until 2010, antifungal prophylaxis with fluconazole was offered to most of the patients and thereafter was replaced by liposomal amphotericin-B (L-AMB) and restricted to high-risk patients only. Vincristine-induced neurotoxicity was significantly reduced under L-AMB, as the percentage of patients with severe constipation decreased (15·4% vs. 3·7%, before vs. after 31 December·2010, P = 0·01) and stool frequency increased by up to 38% in polyene-treated patients (P = 0·005). Before 2011, 10 patients developed confirmed IFIs, most of them were infected with Aspergillus species. After risk adaption in 2011, IFIs were completely prevented (P = 0·007). L-AMB prophylaxis is beneficial in childhood leukaemia patients, as it offers effective antifungal activity with improved tolerability as compared to fluconazole. The potential impact of our risk-adapted antifungal treatment should be included in current prophylaxis guidelines for childhood leukaemia., (© 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Fungal peritonitis in patients undergoing peritoneal dialysis (PD) is very difficult to treat and is associated with significant morbidity and mortality. Among fungal pathogens, Aspergillus peritonitis presents a higher mortality rate when compared to Candida peritonitis and its identification as well as appropriate treatment remains a challenge for the physicians. We critical reviewed all published cases in literature of Aspergillus peritonitis in PD patients. The results showed that a total of 55 cases (51% males) of Aspergillus peritonitis in PD patients were reported from 1968 to 2019. Mean patient age was 49.54±19.63years and mean PD duration prior to fungal infection was 33.31±32.45months. Aspergillus fumigatus was isolated in 17/55 patients, Aspergillus niger in 15, Aspergillus terreus in 9, unidentified Aspergillus spp. in 6, Aspergillus flavus in 4, whereas sporadic cases of other Aspergillus spp. were reported. As far as predisposing factors are concerned, 75% of patients suffered from prior bacterial peritonitis receiving antimicrobial therapy. Initial antifungal treatment was intravenous and/or intraperitoneal administration of amphotericin B formulations monotherapy in 47.2% of patients or in combination with fluconazole in 13.2%, or with itraconazole in 13.2%, or with caspofungin in 3.8%, or with ketoconazole or with 5-FC in 1.9%, each. Peritoneal catheter removal was performed in 85.5% of cases. Mortality rate was 38.2%, while 81.8% of the survived patients switched to hemodialysis. Conclusively, Aspergillus peritonitis diagnosis can be difficult, due to unspecific symptoms. Early treatment with appropriate antifungal agents can be determinant for patient prognosis. Despite appropriate treatment, reported mortality remains high., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

In cystic fibrosis (CF) patients, fungal colonization of the respiratory tract is frequently found. Aspergillus fumigatus is the most frequently recorded and is associated with loss of pulmonary function and allergic disease (ABPA). The knowledge on prevalence rates of filamentous fungi in CF patients in Latin America is scarce. One hundred and seventy-six fungal isolates recovered from the upper respiratory tract of CF patients from Argentina were identified to species by morphology and DNA sequencing. In total, 90% of CF patients were colonized by Aspergillus sp., followed by Exophiala sp. (14%) and Scedosporium sp. (10%). Among Aspergillus, six species complexes (Fumigati, Flavi, Terrei, Nigri, Usti, and Nidulante) and different cryptospecies were found. Among Scedosporium, three species were observed (Scedosporium apiospermum, Scedosporium aurantiacum and Scedosporium boydii). All Exophiala isolates were identified as Exophiala dermatitidis. Rare filamentous fungi were also found. All cases of ABPA were associated to the presence of A. fumigatus. Mixed colonization with other mould or rare fungi was observed in half of them. To our knowledge, this is the first prospective study of mould species in CF using molecular methods in Latin America. This study shows that Aspergillus sp., E. dermatitidis and Scedosporium sp. have a high frequency in CF patients from Argentina, and by far, A. fumigatus was the most commonly cultured species. Continuous clinical surveillance is required to detect the emergence of new fungal pathogens and to detect resistant or difficult-to-treat species capable of chronic colonizing the airways and of hematogenous dissemination in case of lung transplantation., (© The Author(s) 2020. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Background: Acute myeloid leukaemia (AML) patients are at high risk of invasive aspergillosis (IA) after first induction chemotherapy (CHT). Although IA risk factors have been identified, few data are available on impact of IA, occurring during induction phase, on overall AML outcome., Patients and Results: The end point of this multicentre, case-control, study was to evaluate whether IA, occurring after first induction CHT, can affect treatment schedule and patient's outcome. We identified 40 AML patients (cases) who developed IA during first induction phase, 31 probable (77.5%) and 9 proven (22.5%). These cases were matched with a control group (80 AML) without IA, balanced according to age, type of CHT, AML characteristics and cytogenetic-molecular risk factors. The overall response rate to induction CHT was the same in the 2 groups. In the 40 cases with IA, the overall response rate to antifungal treatment was favourable (80%) but it was significantly affected by the achievement of leukaemia complete remission (CR) with induction CHT. In fact, in cases with AML responsive to induction CHT, responses of IA to antifungal therapy were 96% compared to 21% in cases of AML not responsive to induction treatment (P < .0001). The adherence to the schedule and full doses of CHT were reported in 35% of cases (14/40) and in 76% of controls (61/80) (P = .0001; OR 6.7; 95% CI 2.7-16.6). After first induction CHT, a significant higher number of cases (15/40; 37.5%) compared to controls (9/80; 11%) could not receive additional cycles of CHT (P = .0011, OR 4.8; 95% CI 1.9-12.3). The IA-related mortality was 22.5%. The median OS of cases was significantly worse than OS of controls with a difference of 12.3 months (12.1 vs 24.4 months, P = .04). However, the occurrence of IA during first induction phase did not have a significant impact on the OS of cases who achieved a CR of AML with induction CHT which are able to proceed, despite the IA, with their therapeutic program, achieving the same OS as the control group with AML in CR (P = ns)., Conclusions: These data show that IA during first induction CHT can delay the subsequent therapeutic program and has a significant impact on OS, specifically in AML patients who did not achieved a CR of AML with the first course of CHT., (© 2020 Blackwell Verlag GmbH.)

Background: Triazole resistance in Aspergillus fumigatus sensu stricto due to mutations in the cyp51A gene has been widely reported. Data from Argentina, and particularly from cystic fibrosis (CF) patients, are limited., Objectives: To investigate the prevalence and molecular mechanisms of azole resistance in A. fumigatus sensu stricto recovered from this population., Methods: Ninety-three A. fumigatus isolates from 50 CF patients were retrospectively analysed for azole resistance using the standard microbroth dilution method according to CLSI M38-A2 guidelines. Sequencing analysis of the cyp51A gene and its promoter region was conducted in those isolates displaying high MIC values to itraconazole, voriconazole and/or posaconazole., Results: Overall, 14% of isolates displayed high MIC values to at least one azole. Of them, 30.7% had the mutation TR34-L98H. No mutations in the cyp51A gene or its promoter were found in the remaining non-wild-type strains. Therefore, other mechanisms associated with azole resistance can be highly prevalent in these isolates., Conclusions: To the best of our knowledge, this is the first study in Latin America reporting azole-resistant A. fumigatus strains recovered from respiratory secretions of CF patients. Noteworthy, the prevalence of azole resistance in A. fumigatus sensu stricto in the studied Argentinean CF population is alarmingly high., (© 2020 Blackwell Verlag GmbH.)

Background: Invasive mould infections (IMIs) are very rare in patients with lymphoid malignancies. However, IMIs, mostly due to Aspergillus species, have been increasingly reported in such patients receiving ibrutinib (IBR). There is paucity of information regarding non-Aspergillus invasive mould infections (NAIMIs) in this setting, OBJECTIVES: To review our recent experience and the published literature on the topic., Patients/methods: We present a case of invasive sinusitis caused by Fusarium in a patient with refractory chronic lymphocytic leukaemia (CLL) who was treated with IBR and review the 12 published cases of NAIMIs during IBR., Results: Nearly all cases of NAIMIs in the setting of IBR use were encountered in patients with CLL. Mixed fungal infections, brain involvement and late-onset infections were common., Conclusions: Although rare, NAIMIs should be considered in patients who receive IBR., (© 2020 Blackwell Verlag GmbH.)

Supravalvular aortic stenosis is the rarest form of left ventricular outflow tract obstruction. Aspergillus endocarditis is also rare and generally reported in immunocompromised hosts. Here we present a case of an immunocompetent patient with supravalvular aortic stenosis complicated by aortic mycotic pseudoaneurysm due to invasive aspergillosis.

Aspergillus endocarditis (AE) is a rare condition with a mortality rate greater than 60%. While it is generally accepted that both antifungal therapy and surgery are necessary for survival, the optimal antifungal regimen is unclear. A 62-year-old man was diagnosed with AE of a prosthetic aortic valve, complicated by cerebral emboli. He underwent debridement of the aortic valve abscess and valve replacement, and was managed with a combination of liposomal amphotericin B and voriconazole for 7 weeks followed by long-term suppressive azole therapy. He remained well at follow-up 18 months later. Data from a review of case reports published between 1950 and 2010 revealed greater survival rates in patients managed with two or more antifungals as opposed to single agent therapy. We provide an updated literature review with similar findings, suggesting that dual agent antifungal therapy should be considered in patients with AE., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: With the following report we want to present an unusual case of a patient suffering from acute respiratory distress syndrome with early discovery of bacterial pathogens in bronchoalveolar liquid samples that developed a fatal undiscovered disseminated fungal infection., Case Presentation: A 67-year-old man was admitted to our university hospital with dyspnea. Progressive respiratory failure developed leading to admission to the intensive care unit, intubation and prone positioning was necessary. To ensure adequate oxygenation and lung protective ventilation veno-venous extracorporeal membrane oxygenation was established. Despite maximal therapy and adequate antiinfective therapy of all discovered pathogens the condition of the patient declined further and he deceased. Postmortem autopsy revealed Mucor and Aspergillus mycelium in multiple organs such as lung, heart and pancreas as the underlying cause of his deterioration and death., Conclusion: Routine screening re-evaluation of every infection is essential for adequate initiation and discontinuation of every antiinfective therapy. In cases with unexplained deterioration and unsuccessful sampling the possibility for diagnostic biopsies should be considered.

Background: Nosocomial aspergillosis in patients with sepsis has emerged in the past few years. Blockade of PD-1/PD-L pathway has tended to become a promising therapeutic strategy as it improved the outcome of bacterial sepsis and postsepsis secondary fungal infection. Recently, the controversial effects of PD-1 blockade on infectious diseases, including aspergillosis, have been demonstrated; therefore, the efficacy of anti-PD-1 drug still remains to be elucidated., Methods: Cecal ligation and puncture (CLP) was conducted as a mouse sepsis model. Aspergillus fumigatus spores were intravenously inoculated on day 5 post-CLP, when the immune cells succumbed to exhaustion. Amphotericin B was medicated together with or without anti-PD-1 treatment after Aspergillus infection., Results: Amphotericin B alone was not effective to treat the CLP-mice with secondary aspergillosis. In contrast, antifungal medication with the adjunctive anti-PD-1 treatment attenuated the fungal burdens in blood and internal organs, and improved the survival rate of the mice with secondary aspergillosis. These outcomes of PD-1 blockade were concurring with the enhanced CD86 expression on splenocytes, the augmented serum IFN-γ, and the dampened IL-10. Activated T cells from anti-PD-1-treated mice also highly increased IFN-γ and diminished IL-10 production., Conclusion: The blockade of PD-1 on postsepsis aspergillosis presumably reinvigorated exhausted antigen-presenting cells and T cells by upregulating CD86 expression and IFN-γ production, and dampened IL-10 production, which consequently leaded to the attenuation of secondary aspergillosis. The adjunctive anti-PD-1 therapy may become a promising strategy for the advanced immunotherapy against lethal fungal infection.

Rationale: Recent data show that Aspergillus species are prevalent respiratory infections in children with cystic fibrosis (CF). The biological significance of these infections is unknown. Objectives: We aimed to evaluate longitudinal associations between Aspergillus infections and lung disease in young children with CF. Methods: Longitudinal data on 330 children participating in the Australian Respiratory Early Surveillance Team for Cystic Fibrosis surveillance program between 2000 and 2018 who underwent annual chest computed tomography (CT) imaging and BAL were used to determine the association between Aspergillus infections and the progression of structural lung disease. Results were adjusted for the effects of other common infections, associated variables, and repeated visits. Secondary outcomes included inflammatory markers in BAL, respiratory symptoms, and admissions for exacerbations. Measurements and Main Results: Haemophilus influenzae , Staphylococcus aureus , Pseudomonas aeruginosa , and Aspergillus infections were all associated with worse CT scores in the same year ( P overall  < 0.05). Only P. aeruginosa and Aspergillus were associated with progression in CT scores in the year after an infection and worse CT scores at the end of the observation period. P. aeruginosa was most significantly associated with development of bronchiectasis (difference, 0.9; 95% confidence interval, 0.3-1.6; P  = 0.003) and Aspergillus with trapped air (difference, 3.2; 95% confidence interval, 1.0-5.4; P  = 0.004). Aspergillus infections were also associated with markers of neutrophilic inflammation ( P  < 0.001) and respiratory admissions risk ( P  = 0.008). Conclusions: Lower respiratory Aspergillus infections are associated with the progression of structural lung disease in young children with CF. This study highlights the need to further evaluate early Aspergillus species infections and the feasibility, risk, and benefit of eradication regimens.