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Data on antifungal susceptibility of Cryptococcus neoformans are limited in Japan. A total of 89 C. neoformans strains isolated from 83 non-human immunodeficiency virus-infected patients with cryptococcosis between 1997 and 2021 in Nagasaki, Japan, were investigated. Using the reference method M27-Ed4 by the Clinical and Laboratory Standards Institute, the minimum inhibitory concentration for 90% of isolates of fluconazole, itraconazole, voriconazole, amphotericin B, and flucytosine were 4, 0.125, 0.06, 0.5, and 4 µg/ml, respectively, which were below the reported epidemiological cutoff values, without any detectable non-wild-type strains. Our findings imply no increasing trend of antifungal-resistant C. neoformans in Nagasaki, Japan. [ABSTRACT FROM AUTHOR]

Pneumocystis jirovecii pneumonia (PCP) is an opportunistic and life-threatening pulmonary infection with an increasing prevalence among individuals who are human immunodeficiency virus (HIV)-negative. Evidence regarding diagnostic testing of PCP in this patient population is insufficient. We evaluated the performance of serum (1, 3)-β- d -glucan (BDG) using the Fungitec G-test MK kit for diagnosing PCP in non-HIV patients. We retrospectively analyzed data from 219 non-HIV adult patients who underwent bronchoscopy and were tested for P. jirovecii DNA by PCR using lavage samples from the lower respiratory tract. Fifty PCP patients and 125 non-PCP patients were included. The most common underlying diseases were malignancies and systemic autoimmune diseases. Using the serum BDG Fungitec G-test MK test to diagnose PCP, the area under the receiver operating characteristic curve (AUC) was 0.924, whereas the modified cut-off value of 36.6 pg/mL had a sensitivity and specificity of 92.0% and 84.8%, respectively. The AUC for patients with systemic autoimmune diseases was 0.873, and the accuracy of serum BDG test declined when using methotrexate (MTX). In conclusion, the serum BDG test was useful for diagnosing PCP in non-HIV patients; however, the results should be carefully interpreted in case of MTX administration. [ABSTRACT FROM AUTHOR]

There is an urgent need for development of better diagnostic strategies to improve outcomes in patients with invasive pulmonary aspergillosis (IPA). We hypothesized that lung perfusion single-photon emission computed tomography (SPECT) may be more sensitive and specific than computed tomography (CT) of the chest for detection of IPA because it is an angioinvasive pulmonary infection with characteristics that are different from those of bacterial pneumonia. We used SPECT with injection of technetium-99m-labeled macroaggregated albumin ([99mTc]MAA) to measure pulmonary perfusion in noninfected mice, mice with IPA, and mice with bacterial pneumonia. Histopathologic analysis was performed to evaluate the correlation between the perfusion defect and mould invasion. We also attempted to quantitatively evaluate the SPECT images to identify differences in decreased perfusion levels in affected areas in the mouse lung. Histopathologic analysis in the IPA mouse model showed a clear match between areas with a perfusion defect and the presence of mold, indicating that the location of the perfusion defect on a SPECT image reflects angioinvasion of the mould in the lungs. Some of these perfusion defects could be seen before appearance of the infiltrate of CT images. Quantitative analysis confirmed that perfusion in the affected areas was significantly decreased in the IPA model but not in the bacterial pneumonia model (P  < .0001). This imaging method may be preferable to the alternative methods presently used to identify the presence of mold in a patient's lungs. [ABSTRACT FROM AUTHOR]

We clarified the performance of a cryptococcal glucuronoxylomannan (GXM) antigen test using bronchoalveolar lavage fluid (BALF) samples, in an HIV-negative Japanese population. Between March 2008 and December 2014, we examined cryptococcal GXM antigens in both serum and BALF specimens from 429 cases at Nagasaki University hospital. The diagnoses, underlying diseases, chest computed tomography findings, and cryptococcal GXM antigen test results were retrospectively investigated. Twenty-three patients were confirmed to have pulmonary cryptococcosis, another six were clinically diagnosed with cryptococcosis because they were seropositive for the GXM antigen, and five possible cryptococcosis cases had BALF samples that were positive for the GXM antigen and serum samples that were negative. The test's sensitivities for detecting cryptococcal GXM antigens in serum and BALF samples, for confirmed cases, were 73.9% and 82.6%, respectively, and their respective specificities were 98.5% and 97.8%. Three of the five putative patients with cryptococcosis were treated with antifungal agents; the pulmonary lesions decreased in size in all treated patients. Both the BALF and serum GXM antigen titers showed positive correlations with the lesion sizes; however, the serum antigen titers showed a higher correlation (r = 0.490, P = .0033) than did the BALF titres (r = 0.312, P = .0724). The rate of GXM-positive BALF samples was higher than the rate for serum samples, especially for patients with pulmonary lesion diameters ≤25 mm. Testing for the presence of the cryptococcal GXM antigen in BALF specimens might contribute to the early diagnosis of pulmonary cryptococcosis. [ABSTRACT FROM AUTHOR]

Cryptococcosis is primarily caused by two Cryptococcus species, i.e., Cryptococcus neoformans and C. gattii. Both include several genetically diverse subgroups that can be differentiated using various molecular strain typing methods. Since little is known about the molecular epidemiology of the C. neoformans/ C. gattii species complex in Japan, we conducted a molecular epidemiological analysis of 35 C. neoformans isolates from non-HIV patients in Nagasaki, Japan and 10 environmental isolates from Thailand. All were analyzed using URA5-restriction fragment length polymorphism (RFLP) and multilocus sequence typing (MLST). Combined sequence data for all isolates were evaluated with the neighbor-joining method. All were found to be serotype A and mating type MATα. Thirty-two of the 35 clinical isolates molecular type VNI, while the three remaining isolates were VNII as determined through the URA5-RFLP method. Thirty-one of the VNI isolates were identified as MLST sequence type (ST) 5, the remaining one was ST 32 and the three VNII isolates were found to be ST 43. All the environmental isolates were identified as molecular type VNI (four MLST ST 5 and six ST 4). Our study shows that C. neoformans isolates in Nagasaki are genetically homogeneous, with most of the isolates being ST 5. [ABSTRACT FROM AUTHOR]

Aspergillus udagawae and A. fumigatus share similar morphological features but they differ genetically. There is also an important clinical distinction as A. udagawae is less sensitive to amphotericin B than A. fumigatus. We encountered a rare case of bronchial infection due to A. udagawae that was successfully treated with voriconazole. An 82-year-old woman with diabetes mellitus complained of bloody sputum. Bronchoscopy revealed a white plugged region at the origin of the right bronchi B5. Cytological study revealed a clot composed of filamentous fungi and Aspergillus spp. was detected by culture. Molecular analysis revealed that the causative agent was A. udagawae, and voriconazole was used for the treatment. In comparison to A. fumigatus, the A. udagawae strain isolated in this case was less sensitive to amphotericin B, less virulent in immunosuppressed mice, and more sensitive to hydrogen peroxide, features that are almost identical to those of the previously reported isolates of the fungus. We should be aware of the emergence of new Aspergillus species that might pose a clinical threat. [ABSTRACT FROM AUTHOR]

Although the diagnostic significance of isolating Aspergillus spp. from respiratory cultures has been studied in immunocompromised hosts with invasive pulmonary aspergillosis (IPA), little is known of such infections in immunocompetent patients with other forms of aspergillosis. In this study of adult pneumology ward patients, we examined the association between Aspergillus spp. and disease prevalence. Laboratory records from April 1998 to March 2009 were reviewed to identify patients with Aspergillus spp. in respiratory samples. Correlations between the isolated species and clinical characteristics of patients were evaluated. During the study period, 165 Aspergillus spp. isolates were detected in the respiratory cultures of 139 patients. Of these patients, 62 (45%) were colonized with Aspergillus spp. and displayed no clinical symptoms of aspergillosis, while 77 (55%) had a form of pulmonary aspergillosis, characterized as either chronic necrotizing pulmonary aspergillosis (CNPA) (48%), aspergilloma (29%), IPA (13%), or allergic bronchopulmonary aspergillosis (ABPA) (10%). The dominant species were Aspergillus fumigatus (41%), A. niger (32%), and A. versicolor (12%). A. fumigatus was most commonly isolated in patients with IPA, aspergilloma, and CNPA, whereas A. niger was the dominant species in colonized patients and those with ABPA. Isolation of an Aspergillus spp. from respiratory samples does not confirm it as the etiologic pathogen because airway colonization by Aspergillus spp. is a common feature in several chronic lung diseases. Repeated isolation of the identical Aspergillus species and detection of anti- Aspergillus antibodies and/or Aspergillus antigens in sera are needed to determine the isolate represents the etiologic agent of disease. [ABSTRACT FROM AUTHOR]

Aspergillus species cause a range of respiratory diseases in humans. While immunocompromised patients are at risk for the development of invasive infection with these opportunistic molds, patients with underlying pulmonary disease can develop chronic airway infection with Aspergillus species. These conditions span a range of inflammatory and allergic diseases including Aspergillus bronchitis, allergic bronchopulmonary aspergillosis, and severe asthma with fungal sensitization. Animal models are invaluable tools for the study of the molecular mechanism underlying the colonization of airways by Aspergillus and the host response to these non-invasive infections. In this review we summarize the state-of-the-art with respect to the available animal models of noninvasive and allergic Aspergillus airway disease; the key findings of host-pathogen interaction studies using these models; and the limitations and future directions that should guide the development and use of models for the study of these important pulmonary conditions., (© The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)