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The rising number of immunocompromised people has increased concerns about fungal infections as a severe public health issue. Invasive pulmonary fungal infections (IPFIs) are prevalent and often fatal, particularly for those with weakened immune systems. Understanding IPFIs is crucial. The work aims to offer a concise overview of the field's characteristics, main research areas, development paths, and trends. This study searched the Web of Science Core Collection on June 5, 2024, collecting relevant academic works from 2003 to 2023. Analysis was conducted using CiteSpace, VOSviewer, Bibliometrix Package in R, Microsoft Excel 2019, and Scimago Graphica. The study indicated that the USA, the University of Manchester, and Denning DW led in productivity and impact, while the Journal of Fungi topped the list in terms of publication volume and citations. High-frequency terms include "fungal infection," "invasive," "diagnosis," and "epidemiology." Keyword and trend analysis identified "influenza," "COVID-19," "invasive pulmonary aspergillosis," and "metagenomic next-generation sequencing" as emerging research areas. Over the last 2 decades, research on IPFI has surged, with topics becoming more profound. These insights offer key guidance on current trends, gaps, and the trajectory of IPFI studies., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Cryptococcosis is progressively acknowledged among people, irrespective of the human with or without immunodeficiency virus (HIV). This change in epidemiology has been recorded in recent years, prompting closer examination and a broader understanding of the disease manifestations and risk factors., Methods: The data of cryptococcal infections in China during 11 years were retrospectively analyzed. According to the position of infection, the patients were categorized into the pulmonary infection group and extrapulmonary infection group. The composition of the two groups was compared, and the potential risk factors of disseminated infection were analyzed. Logistic regression was used to analyze the prognostic risk factors of the disease., Results: A total of 165 patients were enrolled. 113 (68.5%) were male, and the age was 47.49 (18-82) years. 101 cases (61.2%) had a normal immune function and 64 cases (38.8%) had impaired immune function. 45 patients had extrapulmonary infection, involving the central nervous system, bone and joint, skin and bloodstream, and 120 patients had simple pulmonary infection. The mortality of the extrapulmonary infection group (48.9%) was significantly higher than that of the pulmonary infection group (0.8%). According to univariate logistic regression analysis, immune status (hazard ratio [HR], 4.476; 95% confidence interval [CI], 1.725-11.618; P = 0.002), infection position ([HR], 113.826; [CI], 14.607-886.967; P < 0.001), white blood cell count, ([HR],1.209;[CI], 1.054-1.386; P = 0.007), hemoglobin ([HR], 0.970; [CI], 0.955-0.986; P < 0.001), platelet count ([HR], 0.993; [CI], 0.987-0.999; P = 0.026), neutrophil percentage ([HR], 1.115; [CI], 1.065-1.168; P < 0.001), lymphocyte percentage ([HR], 0.875; [CI], 0.827-0.927; P < 0.001), neutrophil-to-lymphocyte Ratio (NLR) ([HR], 1.144; [CI], 1.072-1.221; P < 0.001), monocyte percentage ([HR], 0.752; [CI], 0.618-0.915; P = 0.004) were related to the prognosis. Multivariate logistic regression analysis showed that the infection position was remained related to the prognosis with statistical significance ([HR], 0.018; [CI], 0.001-0.384; P = 0.001)., Conclusion: Extrapulmonary infection of Cryptococcosis is an important risk factor for prognosis. High levels of neutrophils and NLR, and low levels of lymphocytes and monocytes may lead to disseminated infection of Cryptococcosis. Further studies are needed to reduce the occurrence rate of extrapulmonary infection and mortality., (© 2024. The Author(s).)

Background: Data on mixed mould infection with COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated pulmonary mucormycosis (CAPM) are sparse., Objectives: To ascertain the prevalence of co-existent CAPA in CAPM (mixed mould infection) and whether mixed mould infection is associated with early mortality (≤7 days of diagnosis)., Methods: We retrospectively analysed the data collected from 25 centres across India on COVID-19-associated mucormycosis. We included only CAPM and excluded subjects with disseminated or rhino-orbital mucormycosis. We defined co-existent CAPA if a respiratory specimen showed septate hyphae on smear, histopathology or culture grew Aspergillus spp. We also compare the demography, predisposing factors, severity of COVID-19, and management of CAPM patients with and without CAPA. Using a case-control design, we assess whether mixed mould infection (primary exposure) were associated with early mortality in CAPM., Results: We included 105 patients with CAPM. The prevalence of mixed mould infection was 20% (21/105). Patients with mixed mould infection experienced early mortality (9/21 [42.9%] vs. 15/84 [17.9%]; p = 0.02) and poorer survival at 6 weeks (7/21 [33.3] vs. 46/77 [59.7%]; p = 0.03) than CAPM alone. On imaging, consolidation was more commonly encountered with mixed mould infections than CAPM. Co-existent CAPA (odds ratio [95% confidence interval], 19.1 [2.62-139.1]) was independently associated with early mortality in CAPM after adjusting for hypoxemia during COVID-19 and other factors., Conclusion: Coinfection of CAPA and CAPM was not uncommon in our CAPM patients and portends a worse prognosis. Prospective studies from different countries are required to know the impact of mixed mould infection., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Introduction: Dimorphic fungi cause infection following the inhalation of spores into the pulmonary system. In the lower respiratory tract, the conidia transform into yeasts, which are engulfed by alveolar macrophages and may be destroyed without disease manifestation. However, in some immunocompromised individuals, they may persist and cause active fungal disease characterized by formation of granulomas in the infected tissues, which may mimic Mycobacterium tuberculosis (MTB)., Objective: To determine the prevalence of pulmonary dimorphic fungal infections among HIV/AIDS patients with non-TB chronic cough at Mulago National Referral and Teaching Hospital in Kampala, Uganda., Methods: Sputum samples were collected from 175 consented HIV/AIDS patients attending the immuno-suppression syndrome (ISS) clinic at the hospital. Upon Xpert MTB/RIF sputum testing, 21 patients tested positive for MTB, and these were excluded from further analysis. The other 154 sputum negative samples were then subjected to PCR for dimorphic fungi at MBN Clinical Laboratories. Singleplex PCR was used to detect the target sequences in selected respective genes of each dimorphic fungal species of interest. DNA amplicons were detected based on gel electrophoresis., Results: Dimorphic fungi were detected in 16.2% (25/154) of the studied population. Of these 9.1% (14/154) had Blastomyces dermatitidis and 7.1% (11/154) had Talaromyces marneffei. The remaining 84% of the studied participants had no dimorphic fungi. Histoplasma capsulatum, Coccidioides immitis and Paracoccidioides brasiliensis were not detected in any of the participants., Conclusion: Dimorphic fungi (B. dermatitidis and T. marneffei) were found in 16.2% of the HIV/AIDS patients with non-TB chronic cough in Kampala, Uganda. We recommend routine testing for these pathogens among HIV/AIDS patients with chronic cough., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Background: Histoplasmosis is mainly described as a disseminated disease in people living with HIV (PLHIV). Compared to historical descriptions in immunocompetent individuals, knowledge is lacking on the detailed clinical and radiological findings and outcomes of pulmonary histoplasmosis (PH). Overlooked or misdiagnosed with other AIDS-defining condition, prognostic of PLHIV may be at risk because of inappropriate care., Methods: A retrospective multicentric study was conducted in PLHIV from French Guiana between January 1988 and October 2019. Proven PH were documented through mycological direct examination, culture, or histology. Patients with concomitant respiratory infections were excluded., Results: Among 65 patients, sex ratio M:F was 2.4 with a median age of 39 years [IQR 25-75%: 34-44]. Median CD4 count was 24 cells/mm 3 [11-71], with histoplasmosis as the AIDS-defining condition in 88% and concomitant AIDS-defining conditions in 29%. Clinical findings were fever (89%), cough (58%), dyspnea (35%), expectoration (14%), and hemoptysis (5%). Sixty-one X-rays and 24 CT-scans were performed. On X-rays, an interstitial lung disease was mainly found (77%). On CT-scans, a nodular pattern was predominant (83%): mostly miliary disease (63%), but also excavated nodules (35%). Consolidations were present in 46%, associated with miliary disease in 21%. Thoracic lymphadenopathies were found in 58%, mainly hilar and symmetric (33%). Despite antifungal treatment, case-fatality rate at one month was 22%., Conclusion: When faced with an interstitial lung disease on X-rays or a miliary pattern on CT-scans in advanced PLHIV, physicians in endemic areas, apart from tuberculosis or pneumocystosis, should include histoplasmosis as part of their differential diagnoses., (© 2023. The Author(s).)

Invasive fungal disease (IFD) during neutropenia goes along with a high mortality for patients after allogeneic hematopoietic cell transplantation (alloHCT). Low-dose computed tomography (CT) thorax shows good sensitivity for the diagnosis of IFD with low radiation exposure. The aim of our study was to evaluate sequential CT thorax scans at two time points as a new reliable method to detect IFD during neutropenia after alloHCT. We performed a retrospective single-center observational study in 265/354 screened patients admitted for alloHCT from June 2015 to August 2019. All were examined by a low-dose CT thorax scan at admission (CT t 0 ) and after stable neutrophil recovery (CT t 1 ) to determine the incidences of IFD. Furthermore, antifungal prophylaxis medications were recorded and cohorts were analyzed for statistical differences in IFD incidence using the sequential CT scans. In addition, IFD cases were classified according to EORTC 2008. At CT t 0 in 9.6% of the patients, an IFD was detected and antifungal therapy initiated. The cumulative incidence of IFD in CT t 1 in our department was 14%. The use of Aspergillus-effective prophylaxis through voriconazole or posaconazole decreased CT thorax t 1 suggesting IFD is statistically significant compared to prophylaxis with fluconazole (5.6% asp-azol group vs 16.3% fluconazole group, p = 0.048). In 86%, CT t 1 was negative for IFD. Low-dose sequential CT thorax scans are a valuable tool to detect pulmonary IFDs and guide antifungal prophylaxis and therapies. Furthermore, a negative CT t 1 scan shows a benefit by allowing discontinuation of antifungal medication sparing patients from drug interactions and side effects., (© 2022. The Author(s).)

Purpose of Review: This review is an overview of the recent progress made for the diagnosis and understanding of fungal lung disease in people with cystic fibrosis (CF), with a focus on Aspergillus fumigatus , the most common filamentous fungus in the CF airway. Currently, the longstanding question of the clinical significance of Aspergillus fumigatus and other fungi in CF respiratory cultures, in the absence of allergy, remains. Clinical criteria and biomarkers are needed to classify fungal lung disease and determine who may warrant therapy., Recent Findings: Several retrospective and prospective studies have described the prevalence of A. fumigatus and other fungi in the CF lung and factors contributing to the changes in fungal epidemiology. Selective fungus culture testing for the detection of fungi in CF sputa has been well studied, yet a standardized fungus culture protocol has yet to be defined. Culture-independent molecular studies and other fungal diagnostic testing have been conducted in the CF population, leading to efforts to better understand the clinical role of these tests. Recent works have aimed to determine whether chronic A. fumigatus colonization is associated with lung disease progression measured by FEV 1 percentage predicted, structural lung disease, lung clearance index and respiratory quality-of-life. However, the existing knowledge gaps remain: definition of a fungal respiratory infection, the association between fungal infection and clinical outcomes, and indications for antifungal therapy., Summary: Significant progress has been made for the detection and diagnosis of fungal lung disease. Yet, the role and impact of A. fumigatus and other fungal infections on respiratory health in people with CF remains to be determined., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Over the past few decades, the clinical features of pulmonary cryptococcosis (PC) have progressed; however, there is a lack of data on the manifestations of PC over time. To investigate the differences in the clinical characteristics of PC across different time periods, we retrospectively reviewed 130 non-acquired immunodeficiency syndrome (AIDS) patients diagnosed with pathologically or microbiologically confirmed PC from 1990-2020. Among the 130 patients with PC, 24 (18.5%) exhibited immunosuppression, and 44 (33.8%) had underlying diseases. In radiology, 118 (90.8%) presented with subpleural lesions, and 68 (53.1%) presented with nodules with diameters ranging from 1-5 cm. Seventy-five (57.7%) patients underwent surgery alone. The clinical features of PC at different time periods showed that hospitalization days decreased (P = 0.009), and the number of patients with symptoms decreased over time. The number of patients exhibiting isolated lesions decreased (P = 0.022), and the number of patients exhibiting subpleural lesions increased (P = 0.020). In addition, the number of patients with lesions presenting 3-10 mm nodules increased (P = 0.028). In conclusion, an increasing number of patients have been diagnosed with PC over the last 30 years. The timing of PC diagnosis has shifted to the early stages of disease progression. Pulmonary lesions caused by cryptococcosis are easily misdiagnosed and may require unnecessary surgical treatment. Further research is needed to identify the lung lesions caused by cryptococcosis.

Histoplasmosis, blastomycosis, and coccidioidomycosis are endemic fungal infections in North America. Many infections are subclinical, and many symptomatic infections are mild. Pneumonia is the most common clinical manifestation. All can occur in immunocompetent and immunocompromised patients, with the latter at greater risk for disseminated and more severe disease. As with other acute respiratory illness, imaging can play a role in diagnosis. Knowledge of the acute and chronic imaging findings of endemic fungal infections is important for radiologists so that they can assist in establishing these often-elusive diagnoses, recognize normal evolution of imaging findings of infection, and identify complications., Competing Interests: Disclosure The author has nothing to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Blastomycosis, coccidioidomycosis, and histoplasmosis cause various symptoms and syndromes, which may present similarly to other infections such as bacterial or viral community-acquired pneumonia, influenza, and tuberculosis., Methods: We used the IBM MarketScan Research Databases to identify adult outpatients with International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM), diagnosis codes during 2016-2017 for blastomycosis, coccidioidomycosis, histoplasmosis, pneumonia (viral, bacterial, Streptococcus pneumoniae, and unspecified pneumonia), influenza; tuberculosis, and other lower and upper respiratory infections. We compared symptoms on and in the 90 days before diagnosis between patients with these diagnosis codes., Results: Fever was less common in blastomycosis (2.6%), histoplasmosis (5.3%), and coccidioidomycosis (9.4%) than in patients with influenza (18.5%) or pneumonia (12.6-16.3%). Fungal diseases resembled bacterial, viral, and unspecified pneumonias for many pulmonary symptoms. However, cough was more common with coccidioidomycosis (31.4%) and less common with histoplasmosis (14.0%) and blastomycosis (13.1%) versus influenza (20.2%). Although less frequent, solitary pulmonary nodule (5.2-14.4%), enlarged lymph nodes (3.7-9.0%), hyperhidrosis (<2%), and erythema nodosum (<2%) were particularly suggestive of fungal diseases., Conclusions: Despite limitations inherent in administrative coding, this analysis of symptom codes across disease types suggests that fungal diseases may be difficult to clinically distinguish from other causes of pneumonia except when certain uncommon symptoms are present. Healthcare providers caring for patients with pneumonia, especially if nonresponsive to conventional treatment, should consider fungal diseases as possible etiologies., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Recently, the prevalence trend of pulmonary fungal infection (PFI) has rapidly increased. Changes in the risk factors for, distributions of underlying diseases associated with and clinical characteristics of some individual PFIs have been reported in the past decade. However, data regarding PFIs remain uncertain. This study reports the epidemiological characteristics and trends of PFIs over time in recent years. We applied an automated natural language processing (NLP) system to extract clinically relevant information from the electronic health records (EHRs) of PFI patients at the First Affiliated Hospital of Guangzhou Medical University. Then, a trend analysis was performed. From January 1, 2013, to December 31, 2019, 40,504 inpatients and 219,414 outpatients with respiratory diseases were screened, in which 1368 inpatients and 1313 outpatients with PFI were identified. These patients were from throughout the country, but most patients were from southern China. Upward trends in PFIs were observed in both hospitalized patients and outpatients ( P <0.05). The stratification by age showed that the incidence of hospitalized patients aged 14-30 years exhibited the most obvious upward trend, increasing from 9.5 per 1000 patients in 2013 to 88.3 per 1000 patients in 2019. Aspergillosis (56.69%) was the most common PFI, but notably, the incidence rates of Talaromyces marneffei , which used to be considered uncommon, exhibited the most rapid increases. In younger PFI patients, the incidence and trend of PFIs have increased. Infection by previously uncommon pathogens has also gradually increased. Increased attention should be paid to young PFI patients and uncommon PFI pathogen infections.

With the widespread use of antibacterial drugs and increasing number of immunocompromised patients, pulmonary fungal infections are becoming more common. However, the incidence of pulmonary fungal and bacterial co-infection is rarely reported. In this study, 119 patients definitively diagnosed with pulmonary fungal infections between July 2018 and March 2020 were assessed using metagenomic next-generation sequencing (mNGS) as well as traditional pathogen detection to gauge the incidence of fungal and bacterial co-infection and evaluate the associated risk factors. We found that of the 119 patients with fungal infections, 48 (40.3%) had pulmonary fungal and bacterial co-infection. We identified immunocompromised status and the presence of one or more pulmonary cavities as risk factors associated with fungal and bacterial co-infection. The most commonly isolated fungi species were Aspergillus, Pneumocystis , and Rhizopus. The most commonly isolated bacterial species were Pseudomonas aeruginosa, Acinetobacter baumannii , and Stenotrophomonas maltophilia. Seventy-nine (66.4%) patients had received empirical antibiotic treatment before their pathogenic test results became available, and 41.7% (fungal infection group) and 38.7% (fungal and bacterial co-infection group) of the patients had their antibacterial drug dosage changed accordingly. This mNGS-based study showed that the incidence of fungal and bacterial co-infection is significant. Our research outcomes can, thus, guide the use of antibacterial drugs in the treatment of clinical fungal infections., Competing Interests: Authors JC and XL were employed by company Guangzhou Sagene Biotechnology Company, Limited. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhao, Song, Yang, Yang, Chen, Li, Wang and Feng.)

Pulmonary cryptococcosis is a common but underdiagnosed opportunistic fungal infection in both immunocompromised and immunocompetent patients. The causal agents include at least eight evolutionary distinct haploid lineages as well as their hybrids of the human pathogenic Cryptococcus complex. In this update, we review recent advances in epidemiology, mode of transmission, risk factors, diagnostic methods, and therapy of pulmonary cryptococcosis. Our review suggests significant challenges and opportunities for research, from bedside to benchside and back to bedside., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Fungal infections have become crucial factors that threaten the prognosis and survival of blood disease patients. Here, we aim to analyze the epidemiological characteristics and early and advanced CT (computed tomography) manifestations of patients with invasive pulmonary fungal infections secondary to blood system diseases. 65 hospitalized patients from October 2018 to October 2020 with invasive pulmonary fungal infections secondary to blood diseases were enrolled. Blood diseases were recorded according to clinical and imaging data, and the serum galactomannan test (GM test) was conducted. Two senior radiologists analyzed the CT data and recorded the distribution of the lesions and CT signs. We analyzed and counted the first chest CT scan images of patients with nodule/mass type secondary to hematological diseases and invasive pulmonary fungal infection. The first CT nodules or mass-type lesions were statistically significant in nodule size, the number of lesions, distribution, and accompanying signs. Pulmonary fungal infection was common in both lungs during 7-day, 14-day, and 30-day follow-up CT. We also found that the nodular mass type was the main manifestation in the positive group of the GM test. Both the positive group and the negative group had the highest incidence of nodules. The incidence of air crescent signs in nodules or mass lesions in the positive group was higher than in the negative group, and the difference was statistically significant. To conclude, follow-up CT signs after antifungal treatment were highly sensitive to the early diagnosis of hematological diseases and secondary invasive pulmonary Eumycetes infection, which could be used for clinical treatment to provide help. GM test results were also related to CT manifestations such as air crescent sign, cavity, and halo sign., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2021 Jun-Wei Wang et al.)

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.)

Background: The incidence of secondary pulmonary infections is not well described in hospitalized COVID-19 patients. Understanding the incidence of secondary pulmonary infections and the associated bacterial and fungal microorganisms identified can improve patient outcomes., Objective: This narrative review aims to determine the incidence of secondary bacterial and fungal pulmonary infections in hospitalized COVID-19 patients, and describe the bacterial and fungal microorganisms identified., Method: We perform a literature search and select articles with confirmed diagnoses of secondary bacterial and fungal pulmonary infections that occur 48 h after admission, using respiratory tract cultures in hospitalized adult COVID-19 patients. We exclude articles involving co-infections defined as infections diagnosed at the time of admission by non-SARS-CoV-2 viruses, bacteria, and fungal microorganisms., Results: The incidence of secondary pulmonary infections is low at 16% (4.8-42.8%) for bacterial infections and lower for fungal infections at 6.3% (0.9-33.3%) in hospitalized COVID-19 patients. Secondary pulmonary infections are predominantly seen in critically ill hospitalized COVID-19 patients. The most common bacterial microorganisms identified in the respiratory tract cultures are Pseudomonas aeruginosa, Klebsiella species, Staphylococcus aureus, Escherichia coli, and Stenotrophomonas maltophilia. Aspergillus fumigatus is the most common microorganism identified to cause secondary fungal pulmonary infections. Other rare opportunistic infection reported such as PJP is mostly confined to small case series and case reports. The overall time to diagnose secondary bacterial and fungal pulmonary infections is 10 days (2-21 days) from initial hospitalization and 9 days (4-18 days) after ICU admission. The use of antibiotics is high at 60-100% involving the studies included in our review., Conclusion: The widespread use of empirical antibiotics during the current pandemic may contribute to the development of multidrug-resistant microorganisms, and antimicrobial stewardship programs are required for minimizing and de-escalating antibiotics. Due to the variation in definition across most studies, a large, well-designed study is required to determine the incidence, risk factors, and outcomes of secondary pulmonary infections in hospitalized COVID-19 patients., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Fungal pneumonia is a dreaded complication encountered after kidney transplantation, complicated by increased mortality and often associated with graft failure. Diagnosis can be challenging because the clinical presentation is non-specific and diagnostic tools have limited sensitivity and specificity in kidney transplant recipients and must be interpreted in the context of the clinical setting. Management is difficult due to the increased risk of dissemination and severity, multiple comorbidities, drug interactions and reduced immunosuppression which should be applied as an important adjunct to therapy. This review will focus on the main causes of fungal pneumonia in kidney transplant recipients including Pneumocystis, Aspergillus, Cryptococcus, mucormycetes and Histoplasma. Epidemiology, clinical presentation, laboratory and radiographic features, specific characteristics will be discussed with an update on diagnostic procedures and treatment., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background and Objective: A high frequency of infections complicating rheumatoid arthritis (RA) has been reported due to the immunomodulatory effect of RA or to agents with immunosuppressive effects used in its treatment. We aimed to assess clinical and radiological characteristics of pulmonary cryptococcosis in patients with and without RA., Methods: We retrospectively reviewed the medical records of 52 patients with pulmonary cryptococcosis and divided them into two groups, those with RA and without RA, and compared clinical characteristics and radiological findings between them., Results: Eleven (21.2%) of the 52 patients had RA. Median follow-up periods were 51.2 (range: 1.1-258.7) months for patients with RA and 19.1 (range: 0.63-246.9) months for patients without RA. Among the patients with RA, 81.8% were women, with a mean age of 68.1 years. Female sex and respiratory comorbidities were significantly more frequent in patients with RA than in patients without RA. Frequencies of concomitant cryptococcal meningitis and respiratory failure were not different between the groups. There were no significant differences in frequency of any radiological findings, locations and number between the two groups. Among patients with RA, all but one responded well to antifungal treatment. During the antifungal treatment course, one (9.1%) patient with RA died of cryptococcosis. Despite continuing antirheumatic drugs, no patients had recurrence of pulmonary cryptococcosis during follow-up., Conclusion: Other than some differences in background, there were no clinical, radiological or prognostic differences between the patients with and without RA with pulmonary cryptococcosis. The administration of antirheumatic therapy had no negative effect on the clinical course of antifungal treatment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Coccidioidomycosis, caused by the dimorphic pathogenic fungi Coccidioides immitis and Coccidioides posadassi, is endemic to the southwestern United states and Central and South America. The incidence of coccidioidomycosis continues to increase. Coccidioidomycosis is typically a self-limiting influenza-like respiratory illness; however, it can lead to disseminated disease outside of the lungs. Not all nondisseminated cases require therapy, but antifungal therapy is typically beneficial requiring treatment ranging from months to lifelong. Clinical factors related to treatment decisions include severity of symptoms, radiography, coccidioidomycosis serologic results, and concurrent medical problems including immunosuppression. This review summarizes the epidemiology, clinical manifestations, and treatment options., Competing Interests: Disclosure All authors, no conflicts., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Sparse data exists about patients with cystic fibrosis (CF) and their risk of contracting coccidioidiomycosis or Valley Fever, which is highly endemic in southern Arizona. A retrospective review of medical records of 79 adult CF patients residing in Arizona was performed. Two cases only of coccidioidomycosis were documented between in the 790 patient years. However, false-positive serologies were found in 15 patients. This 10-year retrospective review of 79 adult CF patients found that there was a lower prevalence of coccidioidomycosis in CF patients compared to that of the general population of the area., Lay Summary: Patients with cystic fibrosis (CF) suffer from chronic lung infection. Little is known about CF and fungal infection. Coccidioidomycosis is a fungal infection common in Arizona and this study shows a lower infection rate from Coccidioidomycosis in CF patients compared to the general population., (© The Author(s) 2020. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Rationale: Whether severe coronavirus disease (COVID-19) is a significant risk factor for the development of invasive fungal superinfections is of great medical interest and remains, for now, an open question. Objectives: We aim to assess the occurrence of invasive fungal respiratory superinfections in patients with severe COVID-19. Methods: We conducted the study on patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related pneumonia admitted to five ICUs in France who had respiratory and serum sampling performed for specific screening of fungal complications. Measurements and Main Results: The study population included a total of 145 patients; the median age was 55 years old. Most of them were male ( n  = 104; 72%), were overweight ( n  = 99; 68%), and had hypertension ( n  = 83; 57%) and diabetes ( n  = 46; 32%). Few patients presented preexisting host risk factors for invasive fungal infection ( n  = 20; 14%). Their global severity was high; all patients were on invasive mechanical ventilation, and half ( n  = 73, 54%) were on extracorporeal membrane oxygenation support. Mycological analysis included 2,815 mycological tests (culture, galactomannan, β-glucan, and PCR) performed on 475 respiratory samples and 532 sera. A probable/putative invasive pulmonary mold infection was diagnosed in 7 (4.8%) patients and linked to high mortality. Multivariate analysis indicates a significantly higher risk for solid organ transplant recipients (odds ratio,  = 4.66; interquartile range, 1.98-7.34; P  = 0.004). False-positive fungal test and clinically irrelevant colonization, which did not require the initiation of antifungal treatment, was observed in 25 patients (17.2%). Conclusions: In patients with no underlying immunosuppression, severe SARS-CoV-2-related pneumonia seems at low risk of invasive fungal secondary infection, especially aspergillosis.

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.)

As the global COVID-19 pandemic spreads worldwide, new challenges arise in the clinical landscape. The need for reliable diagnostic methods, treatments and vaccines for COVID-19 is the major worldwide urgency. While these goals are especially important, the growing risk of co-infections is a major threat not only to the health systems but also to patients' lives. Although there is still not enough published statistical data, co-infections in COVID-19 patients found that a significant number of patients hospitalized with COVID-19 developed secondary systemic mycoses that led to serious complications and even death. This review will discuss some of these important findings with the major aim to warn the population about the high risk of concomitant systemic mycoses in individuals weakened by COVID-19.

Objectives: To describe the epidemiology, management and outcome of individuals with mucormycosis; and to evaluate the risk factors associated with mortality., Methods: We conducted a prospective observational study involving consecutive individuals with proven mucormycosis across 12 centres from India. The demographic profile, microbiology, predisposing factors, management and 90-day mortality were recorded; risk factors for mortality were analysed., Results: We included 465 patients. Rhino-orbital mucormycosis was the most common (315/465, 67.7%) presentation followed by pulmonary (62/465, 13.3%), cutaneous (49/465, 10.5%), and others. The predisposing factors included diabetes mellitus (342/465, 73.5%), malignancy (42/465, 9.0%), transplant (36/465, 7.7%), and others. Rhizopus species (231/290, 79.7%) were the most common followed by Apophysomyces variabilis (23/290, 7.9%), and several rare Mucorales. Surgical treatment was performed in 62.2% (289/465) of the participants. Amphotericin B was the primary therapy in 81.9% (381/465), and posaconazole was used as combination therapy in 53 (11.4%) individuals. Antifungal therapy was inappropriate in 7.6% (30/394) of the individuals. The 90-day mortality rate was 52% (242/465). On multivariate analysis, disseminated and rhino-orbital (with cerebral extension) mucormycosis, shorter duration of symptoms, shorter duration of antifungal therapy, and treatment with amphotericin B deoxycholate (versus liposomal) were independent risk factors of mortality. A combined medical and surgical management was associated with a better survival., Conclusions: Diabetes mellitus was the dominant predisposing factor in all forms of mucormycosis. Combined surgical and medical management was associated with better outcomes. Several gaps surfaced in the management of mucormycosis. The rarer Mucorales identified in the study warrant further evaluation., (Copyright © 2019 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate the clinical features and outcomes of cryptococcal meningitis (CM) in HIV-negative patients with and without lung infections., Methods: We retrospectively reviewed the medical records of HIV-negative patients with CM admitted to two university hospitals in Southwest China over the past 5 years., Results: Seventy-one patients were included, of whom 35 (49.3%) had lung disease. Compared with patients without lung infection, CM patients with lung infection tended to be male and younger (≤30 years), experienced more fever, less vomiting and fewer central nervous system symptoms; more often had low white blood cell (WBC) counts (<20 × 10 6 /L), and fewer often had ethmoid sinusitis, maxillary sinusitis, paranasal sinusitis, and otitis media. Cryptococcus neoformans isolates from these patients were sensitive to itraconazole, voriconazole, fluconazole, and amphotericin B but resistant to flucytosine. CM patients with lung infection had higher mortality at discharge compared with patients without lung infection (8.6% vs. 0%). Multivariable analyses showed that a WBC count <20 × 10 6 /L was significantly associated with poor treatment outcome (odds ratio 0.01, 95% confidence interval 0-0.83)., Conclusion: HIV-negative CM patients with lung infections tended to be male and younger. Fever, fewer central nervous system symptoms, and WBC counts <20 × 10 6 /L were characteristic of this patient group.

Background: Diabetes mellitus is a public health problem in Mexico, and the trend of the disease is increasing. From 2000 to 2017, 7.32 million new cases were diagnosed, with pulmonary mycoses being one of the most serious complications., Aims: To describe the frequency and the clinical characteristics of patients diagnosed with pulmonary mycoses, and to identify the risk factors associated with this entity., Methods: Case-control study, paired by gender (1:1-3) and age (± 5 years), that analyzed patients with pulmonary mycosis (mucormycosis, histoplasmosis, coccidioidomycosis, blastomycosis, aspergillosis, cryptococcosis, paracoccidioidomycosis) and studied the risk factors present in each patient., Results: From the 162 patients studied, 56 suffered pulmonary mycosis and 106 were controls. The median of the age was 51 and 50 years for the cases and for the controls, respectively. Multiple logistic regression analysis showed that patients with diabetes mellitus had an odds ratio of 8,3 (p < 0.001), and patients with a history of tuberculosis had an odds ratio of 8,8 (p < 0.001)., Conclusions: Our results show that 52% of the patients with pulmonary mycoses had a history of diabetes mellitus. Diabetes mellitus is a relevant risk factor for pulmonary mycoses, which are usually diagnosed in advanced stages and have a high mortality., (Copyright © 2020 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: The new Rasamsonia spp. complex can develop invasive infection in immunosuppression or chronic pulmonary disease. It has potential to be misidentified as other genera due to morphological similarities. Nowadays, there is a gap of knowledge on this fungi., Objectives: To provide knowledge base of risk factors and therapeutic decisions in invasive Rasamsonia spp. complex infection., Patients/methods: Cases of invasive infection due to Rasamsonia spp. (formerly Geosmithia/Penicillium spp.) from FungiScope ® registry and all reported cases from a literature were included., Results: We identified 23 invasive infections due to Rasamsonia spp., six (26.1%) in the FungiScope ® registry. Main risk factors were chronic granulomatous disease (n = 12, 52.2%), immunosuppressive treatment (n = 10, 43.5%), haematopoietic stem cell transplantation (n = 7, 30.4%), graft-versus-host disease and major surgery (n = 4, 17.4%, each). Predominantly affected organs were the lungs (n = 21, 91.3%), disease disseminated in seven cases (30.4%). Fungal misidentification occurred in 47.8% (n = 11), and sequencing was used in 69.6% of the patients (n = 16) to diagnose. Breakthrough infection occurred in 13 patients (56.5%). All patients received antifungal treatment, mostly posaconazole (n = 11), caspofungin (n = 10) or voriconazole (n = 9). Combination therapy was administered in 13 patients (56.5%). Susceptibility testing showed high minimum inhibitory concentrations for azoles and amphotericin B, but not for echinocandins. No preferable treatment influencing favourable outcome was identified. Overall mortality was 39% (n = 9)., Conclusion: Rasamsonia spp. are emerging fungi causing life-threatening infections, especially in immunocompromised and critically ill patients. Mortality is high. Treatment is challenging and clinicians dealing with this patient population should become aware of this infection constituting a medical emergency., (© 2019 The Authors. Mycoses published by Blackwell Verlag GmbH.)

Since mould-active azole prophylaxis has become a standard approach for patients with high-risk haematologic diseases, the epidemiology of invasive fungal infections (IFIs) has shifted towards non-Aspergillus moulds. It was aimed to identify the epidemiology and characteristics of non-Aspergillus invasive mould infections (NAIMIs). Proven/probable NAIMIs developed in patients with haematologic diseases were reviewed from January 2011 to August 2018 at Catholic Hematology hospital, Seoul, Korea. There were 689 patients with proven/probable invasive mould infections; of them, 46 (47 isolates) were diagnosed with NAIMIs. Fungi of the Mucorales order (n = 27, 57.4%) were the most common causative fungi, followed by Fusarium (n = 9, 19.1%). Thirty-four patients (73.9%) had neutropenia upon diagnosis of NAIMIs, and 13 (28.3%) were allogeneic stem cell transplantation recipients. The most common site of NAIMIs was the lung (n = 27, 58.7%), followed by disseminated infections (n = 8, 17.4%). There were 23.9% (n = 11) breakthrough IFIs, and 73.9% (n = 34) had co-existing bacterial or viral infections. The overall mortality at 6 and 12 weeks was 30.4% and 39.1%, respectively. Breakthrough IFIs (adjusted hazards ratio [aHR] = 1.99, 95% CI: 1.3-4.41, P = .031) and surgical treatment (aHR = 0.09, 95% CI: 0.02-0.45, P = .003) were independently associated with 6-week overall mortality. NAIMIs were not rare and occur as a complex form of infection often accompanied by breakthrough/mixed/concurrent IFIs and bacterial or viral infections. More active diagnostic efforts for NAIMIs are needed., (© 2019 The Authors. Mycoses Published by Blackwell Verlag GmbH.)

Diagnosis of fungal co-infections in patients suffering from pulmonary tuberculosis has critical importance. Therefore, we aimed to determine the prevalence of candida coinfection in patients with pulmonary tuberculosis. The present systematic review of cross-sectional studies was conducted based on the Preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA) Protocol. Studies published online in English from January 2001 to March 2019 were assessed. Literature search was done in Web of Science, MEDLINE/PubMed, and Scopus databases and search engines using keywords combinations of "pulmonary fungi", "pulmonary coinfection", OR "pulmonary mycosis", "pulmonary fungal infections/agents", OR "polymicrobial infection", OR "secondary infection", OR "mixed infections", "pulmonary candidiasis", "fungi coinfection", "fungal co-colonization", AND "pulmonary tuberculosis", OR "pulmonary TB", AND "Asia", AND "Africa". Data was analyzed using Comprehensive Meta-Analysis software (CMA). Heterogeneity between studies was evaluated by Cochran's Q and I 2 tests. The pooled prevalence of candida coinfection among patients with pulmonary tuberculosis was 25.7% (95% CI: 23.7-27.9). C. albicans was the most prevalent Candida spp. with a pooled prevalence of 65.8% (95% CI: 54.3-75.7). Risk factors of candida coinfection were smoking, diabetes, advanced age, and low body mass index. The present review showed a high rate of candida coinfection among patients suffering from pulmonary tuberculosis. So, appropriate measures are necessary to early diagnose and treat these infections., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Paracoccidioidomycosis (PCM) is one of the most relevant systemic endemic mycoses in Latin American countries, especially in South American countries, with endemic and hyperendemic areas. The real burden of PCM may be underestimated because of a lack of compulsory case notification. Recent phylogenetic data revealed that Paracoccidioides brasiliensis comprises several cryptic species including P. brasiliensis and P. lutzii . However, the genetic biodiversity of Paracoccidioides does not affect the clinical manifestations or therapeutic response to therapy. Lung involvement is a common finding, especially in patients experiencing the chronic form of the disease, and, because of its similarities with tuberculosis, clinicians must be alert to the possibility of PCM in patients with chronic respiratory manifestations and epidemiological risk factors for this fungal disease., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Coccidioidomycosis is an infection caused by the geographically restricted dimorphic fungus, Coccidioides . Coccidioidomycosis occurs endemically in the southwestern and western United States, mainly in focused regions of Arizona and California where the incidence is highest, and in Central and South America. Patients with impaired immunity, especially those with impaired cellular immunity, are at higher risk of severe and disseminated disease. In this review, we describe the fungal ecology and mycology, epidemiology, pathophysiology, and normal immune defenses to Coccidioides as well as address current concepts in diagnosis, treatment, and continued care of patients with pulmonary coccidioidomycosis. We also present and answer our most frequently asked questions regarding patients with primary pulmonary coccidioidomycosis., Competing Interests: No conflict of interest to disclose., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

In the middle of a pandemic, patients with cough and fever are thought to have SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2). It should be remembered that in the desert southwest of the United States, we have an ongoing epidemic of coccidioidomycosis (CM). There are additionally many other respiratory illnesses that could be confused with CoV-2 or overlooked. This is a case report of CoV-2 engrafted on chronic cavitary pulmonary CM. In a time where the coronavirus pandemic is becoming rampant, we demonstrate the case of a coinfection with cavitary pulmonary CM. In this case, the importance of detection of the coronavirus and treatment of the coinfection is explored.

Background: Pulmonary cryptococcosis (PC) is not considered an rare, opportunistic infection anymore. The immunocompetent population accounts for an increasing proportion of the morbidity., Objective: This study investigated the clinical characteristics of PC patients spanning 20 years, in a referral centre of China., Patients/methods: We retrospectively investigated the clinical data of 99 patients with PC who were diagnosed at Peking Union Medical College Hospital (PUMCH) from January 1998 to December 2017., Results: Pulmonary cryptococcosis incidence in PUMCH has seen sharp increase in two decades. There were 40.4% (40/99), 17.2% (17/99) and 42.4% (42/99) immunocompetent, mildly immunocompromised and severe immunocompromised patients, respectively. Significantly higher (P = .035) male predominance in immunocompetent and mildly immunocompromised groups (68.4%, 39/57) compared with severe immunocompromised group (45.2%, 19/42) was found. Overall, 27.5% (11/40) immunocompetent patients reported a significant difference (P = .02) in history of more than weekly drinking, higher than mildly or severe immunocompromised. No significant difference occurred in symptoms and radiographic characteristics among the groups. In pulmonary computerised tomography findings, the non-air pathway feature was the dominant distribution characteristics in all patients with PC (P = .002). The gap in body dissemination frequency between immunocompetent combined with mildly immunocompromised (5.26%, 3/57) and severe immunocompromised (19.0%, 8/42) was marginally significant (P = .05)., Conclusions: Gender and alcohol drinking could be PC risk factors of concern in patients without severe immunodeficiency. No significant difference occurred in symptoms or radiographic characteristics between patients with different levels of immune status. The unique radiographic non-air pathway distribution in the lung may be the feature of Cryptococcus invasion that may enhance accurate diagnosis., (© 2019 The Authors. Mycoses published by Blackwell Verlag GmbH.)

Tucson, Arizona, USA, is a highly coccidioidomycosis-endemic area. We conducted a retrospective review of 815 patients in Tucson over 2.7 years. Of 276 patients with coccidioidomycosis, 246 had a delay in diagnosis; median delay was 23 days. Diagnosis delay was associated with coccidioidomycosis-related costs totaling $589,053 and included extensive antibacterial drug use.

Exposure to mould is a potential risk factor for asthma in both adults and children. In adult, the relation between exposure, sensitization and symptoms has been demonstrated in severe asthmatics sensitized to Alternaria. For children, exposure to mould in childhood is a risk factor for asthma in both atopic and non-atopic individuals. Exposure or sensitization to moulds are a risk factor for severe asthma and/or exacerbations in children. There appears to be a causal relationship between exposure and asthma. This link seems less significant in adults. However, in adults mould sensitive asthma seems to determine a phenotype of severe asthma associated with more marked obstructive lung disease. Moulds can stimulate either innate or the acquired immunity. They are responsible for a marked Th2 inflammation leading to more severe asthma. Besides the immunological mechanisms, toxic mechanisms can also intervene. It is therefore not correct to reduce the effect of moulds, particularly in respiratory symptoms, to only allergic mechanisms., (Copyright © 2019 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

We developed an electronic records methodology to programmatically estimate the date of first appearance of coccidioidomycosis symptoms in patients. We compared the diagnostic delay with overall healthcare utilization charges. Many patients (46%) had delays in diagnosis of >1 month. Billed healthcare charges before diagnosis increased with length of delay.

In this present study, for the first time, we evaluated the cystic fibrosis (CF) patients for the Scedosporium species and their antifungal susceptibility against eight antifungal agents. During one-year period, 90 Sputum samples were collected from Iranian CF patients. All samples were evaluated by direct microscopic examination, culture onto four different media including Malt extract agar, Inhibitory mold agar, Brain Heart Infusion and Scedo-Select III. The mold isolated fungi were identified by PCR-Sequencing of ITS and β-tubulin genes. In-vitro antifungal susceptibility was performed according to the Clinical & Laboratory Standards Institute (CLSI) M38-A2 guidelines. Out of 90 CF patients, 47 (52.2%) were male. The age of the patients ranged from 1 to 34 years (median of 15.84 ± 7.41 years). Overall, 3 (3.3%) cases were positive for Scedosporium spp. of which two isolates were characterized as Scedosporium boydii and one isolate as S. ellipsoideum. Among Aspergillus genus, A. flavus (29.4%) was the most prevalent species followed by A. tubingensis (24.7%), A. niger (17.0%) and A. fumigatus (14.5%). The minimum effective concentration ranges of micafungin, anidulafungin, and caspofungin were 0.008-0.031 μg/mL, 0.0625-0.25 μg/mL, and 0.0625-0.25 μg/mL, respectively. All isolates of Scedosporium species showed high minimum inhibitory concentration to the triazoles tested, except voriconazole. Our results showed that A. flavus and Scedosporium species are the most prevalent molds isolated from CF patient populations in Iran. Our findings have also showed that Scedo-Select III can be used as a reliable culture media for isolation of Scedosporium spp. in clinical samples., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: The objective of our study was to characterize and update the radiologic patterns of pediatric pulmonary blastomycosis, and correlate the radiologic patterns with patient age., Materials and Methods: Patients 0-18 years old with pulmonary blastomycosis who underwent chest imaging from 2005 to 2016 were included in this study. The following data were collected: age, sex, clinical information, and imaging findings including presence of extrapulmonary involvement and scarring on follow-up examinations. Concordance between radiography and CT was analyzed., Results: Thirty-six patients (28 boys and eight girls) ranging in age from 3 months to 17 years (mean, 10.5 years) were identified. Consolidation was found in 94.4% of patients and was unilateral in 76.5% of cases and bilateral in 23.5%. Upper (70.6%) and middle (47.1%) lobes were more frequently involved. Air bronchograms were identified in 76.5% of patients with consolidations, masslike consolidation was found in 55.9%, cavitation in 38.2%, and bubbly pattern (i.e., multiple small cavities) in 32.4%. In all patients younger than 5 years, consolidations involved multiple lobes. In 67.6% of patients, consolidations were associated with the following additional pulmonary or pleural abnormalities: pulmonary nodules (50% of patients), diffuse patchy opacification (26.5%), reticulonodular pattern (41.2%), atelectasis (5.9%), pleural effusion (20.6%), and hilar lymphadenopathy (23.5%). Pulmonary scarring was found in 70.4% of patients. Five patients had extrapulmonary involvement. The concordance between radiography and CT was excellent for location and extension of consolidation and diagnosis of cavitation, bubbly pattern, and nodules., Conclusion: The most common pattern of lung involvement from pulmonary blastomycosis in our series was a combination of consolidations with bilateral lung nodules and reticulonodular opacification.

As human populaces develop, they are progressively squeezed into higher living densities. The same is true for horticulture and animals expected to bolster these communities. Despite the high potential for zoonotic transmission, connections among humans and cattle have been understudied; however, Candida albicans remains the most important medical mycosis. The genesis of the mycobiome can vary, and interactions between humans and cattle are progressively being perceived as a key interface for disease transmission. αINT1 is a unique gene from Candida albicans; hence, it has been used for detection as well as intraspecific and interspecific phylogenetic analysis of C. albicans collected from human patients and cattle with pulmonary distress in urban-rural populations. A total of 1,921 specimens were examined by direct microscopy and culture to recover yeast associated with human infection. Identification was performed by micromorphology using an API 20C AUX system. The fungal species identified in bovine nasal specimens were Alternaria species (15%), Penicillium species, and C. albicans (6.7%). Other fungal species, such as Aspergillus niger, Torulopsis species, Mucor species (5%), Aspergillus flavus, Fusarium species, Trichosporon species (3.3%), C. rugosa, C. tropical, and Saccharomyces species (1.7%), were also isolated. In human sputum specimens, C. albicans (20%) and C. parapsilosis (2.7%) were the only reported yeast species in our samples. The four identified C. albicans species (two human and two cattle) were subjected to αINT1 gene sequence analysis, which confirmed major phylogenetic relationships among human and cattle isolates. This finding highlights the public health importance of bovines as a potential source for C. albicans zoonotic transmission to humans in an urban-rural community. Additionally, the close relationship between circulating C. albicans strains recorded in Egypt and the United States indicates the possible cross-species transmission of C. albicans between imported foreign and native cattle breeds.

Introduction: Systemic endemic mycoses are prevalent in specific geographical areas of the world and are responsible for high rates of morbidity and mortality in these populations, and in immigrants and travelers returning from endemic regions. The most common fungal infections that can affect the lungs of immunocompetent patients include histoplasmosis, coccidioidomycosis, paracoccidioidomycosis, blastomycosis, sporotrichosis, aspergillosis, and cryptococcosis. Diagnosis and management of these diseases remain challenging, especially in non-endemic areas due to the lack of experience. Therefore, recognition of the various radiologic manifestations of pulmonary fungal infections associated with patients' clinical and epidemiologic history is imperative for narrowing the differential diagnosis. Areas covered: This review discusses the clinical and radiological findings of the main endemic fungal diseases affecting the lungs in immunocompetent patients. Specific topics discussed are their etiology, epidemiology, pathogenesis, clinical manifestations, methods of diagnosis, pathology and main imaging findings, especially in computed tomography. Expert commentary: Imaging plays an important role in the diagnosis and management of pulmonary fungal infection and may reveal useful signs. Although definitive diagnosis cannot be made based on imaging features alone, the use of a combination of epidemiologic, clinical and imaging findings may permit the formulation of an adequate differential diagnosis.

Background: Blastomyces helicus (formerly Emmonsia helica) is a dimorphic fungus first isolated from a man with fungal encephalitis in Alberta, Canada. The geographic range, epidemiology, and clinical features of disease are unknown., Methods: We reviewed human and veterinary isolates of B. helicus identified among Blastomyces and Emmonsia isolates at the University of Alberta Microfungus Collection and Herbarium, University of Texas Health San Antonio's Fungus Testing Laboratory, and Associated Regional and University Pathologists Laboratories. Isolates were selected based on low Blastomyces dermatitidis DNA probe values and/or atypical morphology. Species identification was confirmed for most isolates by DNA sequence analysis of the internal transcribed spacer with or without D1/D2 ribosomal RNA regions. Epidemiological and clinical data were analyzed., Results: We identified isolates from 10 human and 5 veterinary cases of B. helicus infection; all were referred from western regions of Canada and the United States. Isolates remained sterile in culture, producing neither conidia nor sexual spores in the mycelial phase, but often producing coiled hyphae. Isolates were most frequently cultured from blood and bronchoalveolar lavage in humans and lungs in animals. Most infected persons were immunocompromised. Histopathological findings included pleomorphic, small or variably sized yeast-like cells, with single or multiple budding, sometimes proliferating to form short, branching, hyphal-like elements. Disease carried a high case-fatality rate., Conclusions: Blastomyces helicus causes fatal pulmonary and systemic disease in humans and companion animals. It differs from B. dermatitidis in morphological presentation in culture and in histopathology, by primarily affecting immunocompromised persons, and in a geographic range that includes western regions of North America.

Cryptococcosis is a common invasive fungal infection (IFI) in solid organ transplant (SOT) recipients. Little is known about cryptococcosis in lung transplant (LTx) recipients despite having one of the highest risks of infection. The aim of this study was to describe demographic and clinical features of cryptococcal infection in LTx recipients. We performed a retrospective, observational study of cryptococcal infection in LTx recipients at The Alfred Hospital in Melbourne, Australia, from 2012 to 2017. A total of 11 cases were identified. Seven patients (64%) were male and the median age was 54.7 years (range 34-69 years). Diagnosis occurred at a median of 233 days (range 1-3650 days) post-transplant. Nine patients (82%) had isolated pulmonary infection of whom 7 (78%) were asymptomatic. All were treated with oral antifungal therapy and 1 required surgical resection of infected lung. Two patients (18%) had disseminated infection; 1 with pulmonary and central nervous system (CNS) infection and 1 with isolated CNS infection. Both patients presented with headache and brain imaging demonstrated cerebral edema, myelinosis, and leptomeningeal enhancement. One of these patients died. This study highlights the fact that cryptococcal infection should remain a consideration in asymptomatic LTx recipients, especially in the presence of non-specific nodules on chest imaging, and that the presence of headache in these patients requires urgent investigation for CNS infection., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Pulmonary tuberculosis is one of the most important health concerns. Pulmonary fungal infections have clinical and radiological characteristics similar to tuberculosis which may be easily misdiagnosed as tuberculosis. This study aimed to evaluate tuberculosis (TB) status and coinfection of TB with pulmonary fungal infections in patients referred to reference laboratory of health centers Ghaemshahr city during 2007-2017., Methods: This cross-sectional study was conducted during eleven years, between 2007-2017, on 3577 patients with suspected TB referred to health centers of Ghaemshahr City. For isolation, sputum smear preparation and Ziehl-Neelson staining in companying with microscopy direct observation and KOH 10% + white Calcofluor staining was used. The culture of fungi was performed on Sabouraud Dextrose agar, Czapek and chrome agar media. Then, data were analyzed using SPSS software (version 16) through Student's t-test, Fisher test, and Odds Ratio. P values <0.05 were considered statistically significant., Results: Of 3577 patients, 10731 smears were prepared, 3.6% (n=130) of patients were identified as smear-positive pulmonary tuberculosis, 86.4% (n=3090) were smear negative and 10% (n=357) drug-resistant TB. The mean age of patients was 48±1.8 years. With increasing age, the prevalence of TB has increased which was statistically significant (P value <0.05). Prevalence of tuberculosis in the age group over than 57 years in males and females had an ascending trend. Amongst the positive tuberculosis patients, 16/130 cases (12.3%) had the coinfection of TB with fungi microorganisms., Conclusion: Our findings showed the coinfection of fungi agents in patients with tuberculosis that should be considered.

In the literature, cases of blastomycosis in Canada have been documented in provinces bordering the Great Lakes, including Ontario and Quebec, as well as Manitoba. This is the first study to our knowledge reporting cases of mycosis seen in southern Saskatchewan suggesting a broader area of endemicity. We searched the Regina Qu'Appelle Health Region (RQHR) Microbiology Laboratory for all culture-confirmed cases of Blastomyces from January 2000 to December 2015 and identified 15 cases. Thirteen cases were reviewed, identifying common presenting symptoms, misdiagnosis, comorbidities, travel history, time from presentation to diagnosis, diagnostic specimen, treatment, and clinical outcome. Nine patients had no travel to areas known to be endemic to environmental blastomycosis. Eight patients presented with respiratory symptoms, four with skin lesions, four with constitutional symptoms, and one presented with chest pain after a fall. Initial misdiagnosis occurred in nine (69%) of the 13 cases, and all six patients that died of the disease were misdiagnosed. These six patients (46%) were acutely ill with refractory disseminated disease, leading to respiratory failure. It is probable that Blastomyces is present as an endemic fungus in the soil of southern Saskatchewan. Possibly due to a lack of awareness of this pathogen in the area, initial misdiagnoses were common and likely contributed to significant morbidity and mortality.

Background: Severe coccidioidal pneumonia with acute respiratory distress syndrome (ARDS) is associated with high mortality. Extracorporeal membrane oxygenation (ECMO) has been applied successfully to other severe fungal pneumonia associated with ARDS. We review our experience with the use of ECMO in severe coccidioidal ARDS., Objectives: To review indications and outcome of ECMO in severe pulmonary coccidioidomycosis., Methods: Three cases of severe ARDS caused by coccidioidomycosis are presented. All were managed with ECMO. Clinical course, complications, antifungal therapy and outcome are reviewed., Results: Three cases of severe coccidioidal ARDS survived after treatment with ECMO. Common complications included bacterial pneumonia, encephalopathy and critical illness myopathy. They received liposomal amphotericin during ECMO, and transitioned to azole therapy. All required prolonged hospitalization and rehabilitation., Conclusions: ECMO was life-saving in cases of coccidioidal ARDS. Common complications included pneumonia, encephalopathy and critical illness myopathy. All cases were successfully managed with liposomal amphotericin followed by azole therapy. They required prolonged hospitalization and rehabilitation., (Copyright © 2018 Elsevier Inc. All rights reserved.)