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Su Y, Wang M, Wang Q, Hu B, Pan J. Imaging and serum antigen levels that influence the treatment and prognosis of cryptococcosis in immunocompetent and immuno-compromised patients: A 10-year retrospective study. Drug Discov Ther 2025; 19:68-73. [PMID: 40010732 DOI: 10.5582/ddt.2025.01006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/28/2025]
Abstract
This article was to summarize the treatment course and prognosis of immunocompetent and immunocompromised patients with pulmonary cryptococcal infections and to analyse the relevant factors. The chisquared test was used to test for differences in categorical variables, and the independent samples t test was used to compare continuous variables. Multivariable analyses using the Cox proportional hazards model were used to estimate the effect of prognostic factors on treatment time and improvement time. A total of 243 patients were included in the analysis. Immunocompetent patients with diffuse imaging infiltrates had an extension of the treatment course within six months (P = 0.048) and an extension of the improvement days within four weeks (P = 0.008). In immunocompromised patients, an antigen assay ≥ 40 (P = 0.013) is an unfavourable factor leading to an extension of treatment by nine months. The serum antigen assay in 26/98 (26.53%) immunocompetent patients who did not turn negative when the treatment had finished was significantly lower than that in 14/29 (48.28%) immunocompromised patients (P = 0.027). All patients who underwent surgical resection had a good prognosis. Diffuse imaging infiltrates suggest longer treatment days and a longer improvement time in immunocompetent patients. Higher serum antigen levels in immunocompromised patients indicate longer treatment. Serum antigen assays in immunocompromised patients are difficult to negative.
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Affiliation(s)
- Yi Su
- Department of Infectious Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Meixia Wang
- Department of Hospital Infection Management, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, Fujian, China
| | - Qingqing Wang
- Department of Infectious Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Bijie Hu
- Department of Infectious Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jue Pan
- Department of Infectious Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
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Ueno K, Nagamori A, Honkyu NO, Kwon-Chung KJ, Miyazaki Y. Lung-resident memory Th2 cells regulate pulmonary cryptococcosis by inducing type-II granuloma formation. Mucosal Immunol 2025:S1933-0219(25)00022-4. [PMID: 39984054 DOI: 10.1016/j.mucimm.2025.02.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 02/03/2025] [Accepted: 02/15/2025] [Indexed: 02/23/2025]
Abstract
Lung-resident memory T cells (lung TRMs) settle in the lung and respond rapidly to external antigens, and are therefore considered to have great potential for development of respiratory vaccines. Here, we demonstrate that lung-resident memory Th2 cells (lung TRM2) protect against pulmonary mycosis caused by Cryptococcus gattii. We developed novel whole-cell intranasal vaccines using a heat-inactivated C.gattii capsule-deficient strain cap59Δ, which induced ST-2+ Gata-3+ lung TRM2 specifically responding to C.gattii whole-cell antigen. Lung fungal burden and survival rate were significantly improved in immunized mice after infection challenge. The immunosuppressive agent FTY720 did not impact vaccine effectiveness, and adoptive transfer of lung TRMs into Rag-1-deficient mice decreased the lung fungal burden. In IL-4/IL-13 double-knockout (DKO) mice, immunization did not efficiently induce eosinophil recruitment and granuloma formation, and the fungal burden was not decreased after infection challenge. Co-culture of lung TRM2 with myeloid lineages induced multinucleated giant cells (MGCs) in the presence of antigen, which phagocytosed live C.gattii cells without opsonization, whereas lung TRM2 from DKO mice did not induce MGCs. These findings provide a new model in which lung TRM2 suppress C.gattii infection via granuloma induction.
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Affiliation(s)
- Keigo Ueno
- Department of Fungal Infection, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.
| | - Akiko Nagamori
- Department of Fungal Infection, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan
| | - Nahoko Oniyama Honkyu
- Department of Fungal Infection, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan
| | - Kyung J Kwon-Chung
- Molecular Microbiology Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive, Building 10, Bethesda, MD 20892, United States
| | - Yoshitsugu Miyazaki
- Department of Fungal Infection, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan
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Shi J, Chen J, Ding Q, Qian G, Zhang Z, Song Q. Lateral flow assay as radiological prognosis factor of pulmonary cryptococcosis: a single center retrospective study in China. Front Cell Infect Microbiol 2025; 14:1497082. [PMID: 39906214 PMCID: PMC11790446 DOI: 10.3389/fcimb.2024.1497082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Accepted: 12/18/2024] [Indexed: 02/06/2025] Open
Abstract
Background Lateral flow assay (LFA) has demonstrated high sensitivity and specificity for diagnosing cryptococcosis. However, its role in predicting therapeutic efficacy for pulmonary cryptococcosis (PC) remains underexplored. Methods We conducted a retrospective analysis of HIV-negative patients with PC to describe the clinical profile and identify potential predictors of radiological prognosis. Results All the 168 participants received antifungal therapy with a triazole agent. Of these, 84.5% experienced partial or complete absorption of pulmonary lesions. The results of the gamma test, chi-square trend test, and ordinal logistic regression all indicated that both baseline LFA and changes in LFA after treatment were significant predictors of imaging prognosis. The degree of radiological improvement was inversely associated with the baseline LFA positive grade(P for linear-by-linear association: 0.011, Spearman correlation coefficient = -0.17; γ= -0.368, P = 0.045). Patients with a decrease in LFA after therapy had significantly better radiological outcomes compared to those with equal or increased LFA(linear-by-linear association, P = 0.014, Spearman correlation coefficient = 0.188; γ = 0.371, P = 0.012). Additionally, favorable outcomes were more likely in patients with lesions confined to the right lung. Conclusions LFA shows potential of monitoring radiological outcomes in pulmonary cryptococcosis.
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Affiliation(s)
- Jiejun Shi
- Department of Infectious Diseases, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
| | - Jianhua Chen
- Department of Radiology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
| | - Qianjiang Ding
- Department of Radiology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
| | - Guoqing Qian
- Department of Infectious Diseases, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
| | - Zeqin Zhang
- Department of Cardiology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
| | - Qifa Song
- Medical Data Center, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China
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Su Y, Qian Y, Wang Q, Zhang Y, Hu B, Pan J. Clinical characteristics and aetiological analysis of combined central and pulmonary cryptococcal infection: Clinical cases. Drug Discov Ther 2025; 18:397-400. [PMID: 39662931 DOI: 10.5582/ddt.2024.01081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2024]
Abstract
This paper presents a summary of seven cases of combined pulmonary and central cryptococcal infection and analyses of their clinical features, treatment and prognosis. No clear correlation was identified between the intracranial cryptococcal capsular antigen titre and either the intracranial pressure or the amount of protein in the cerebrospinal fluid. Pulmonary lesions may develop in any of the lung lobes and manifest in multiple forms. Infection at the central level is predominantly meningitis. As the central cerebrospinal fluid (CSF) capsular antigen titre can be considerably elevated even when serum capsular antigen titres are markedly low, lumbar puncture and subsequent analysis are essential for every case of pulmonary cryptococcal infection. Patients with renal insufficiency or who refused intravenous treatment opted for oral fluconazole therapy, and their prognoses were favourable.
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Affiliation(s)
- Yi Su
- Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yiyi Qian
- Zhongshan Hospital, Fudan University, Shanghai, China
| | - Qingqing Wang
- Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yao Zhang
- Zhongshan Hospital, Fudan University, Shanghai, China
| | - Bijie Hu
- Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jue Pan
- Zhongshan Hospital, Fudan University, Shanghai, China
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Yu XY, Zhang L, Hu Y, Zhu Z, Zhu Y, Li X. Comparing the Performance of Two Cryptococcal Antigen Detection Tests: Chemiluminescence vs Colloidal Gold Methods. Infect Drug Resist 2024; 17:5639-5647. [PMID: 39711827 PMCID: PMC11663370 DOI: 10.2147/idr.s491846] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Accepted: 12/10/2024] [Indexed: 12/24/2024] Open
Abstract
Objective To compare the performance of a new chemiluminescence method with that of the traditional colloidal gold method for cryptococcal antigen (CrAg) detection. Methods Cryptococcosis is a global invasive mycosis associated with significant morbidity and mortality. Cryptococcal antigen (CrAg) testing from serum and cerebrospinal fluid (CSF) has been regarded as the gold standard for early diagnosis. In this study, a total of 140 samples (92 serum and 48 cerebrospinal fluid samples) from 140 patients with suspected cryptococcosis collected between January 2022 and September 2023 at Zhejiang Provincial People's Hospital were tested via a fully automated chemiluminescent immunoassay analyser (SuperFlex) from Suzhou Xinbo and a cryptococcal antigen detection kit (colloidal gold method) from the IMMY Company of the United States. Results According to the diagnostic criteria for cryptococcosis, 55 of the 140 suspected patients were diagnosed with cryptococcosis (39.3%), including 47 with pulmonary cryptococcosis (PC) and 8 with cryptococcal meningitis (CM). The degree of agreement between chemiluminescence and the colloidal gold method was analysed via Cohen's kappa coefficient, which was 0.970 (P<0.01). The sensitivities of the chemiluminescence and colloidal gold methods were 98.2% and 96.4%, respectively, and their specificities were 100% and 98.8%, respectively. The area under the receiver operating characteristic (ROC) curve were 0.996 for chemiluminescence and 0.9759 for the colloidal gold method. The area under the curve (AUC) of the two methods did not differ significantly (P=0.086). Conclusion For the detection of CrAg, the new chemiluminescence method is highly consistent with the traditional colloidal gold method and has higher sensitivity and specificity for the diagnosis of cryptococcosis.
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Affiliation(s)
- Xiao-yun Yu
- Centre of Laboratory Medicine, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China
| | - Lei Zhang
- Centre of Laboratory Medicine, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China
| | - Yueyue Hu
- Centre of Laboratory Medicine, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China
| | - Zhongliang Zhu
- Centre of Laboratory Medicine, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China
| | - Yongze Zhu
- Centre of Laboratory Medicine, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China
| | - Xi Li
- Centre of Laboratory Medicine, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China
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Su Y, Zhang Y, Wang Q, Hu B, Pan J. Imaging of pulmonary cryptococcosis with consolidations or diffuse infiltrates suggests longer clinical treatment in non-HIV patients. Biosci Trends 2024; 18:476-481. [PMID: 39443117 DOI: 10.5582/bst.2024.01288] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2024]
Abstract
This article was to summarize the clinical features and treatment course in patients with pulmonary cryptococcal infections with different imaging manifestations and to analyse the relevant factors. Categorical variables are described in this paper as percentages, and continuous variables are expressed as medians and quartiles or means and standard deviations. Factors associated with prolonged treatment of pulmonary cryptococcosis with different imaging manifestations were estimated via multivariable analyses with the Cox proportional hazards model. A total of 238 patients were analysed. A significant proportion of patients with diabetes mellitus constituted 18% to 25% of patients with multiple nodules and diffuse infiltrates (p = 0.026). The serum antigen level was markedly elevated in patients with diffuse infiltrates and consolidation (p < 0.001). A significant proportion of patients who presented with solitary nodules were initially diagnosed through thoracic surgery conducted to remove the lesion (p < 0.001). The treatment duration for patients with pulmonary cryptococcosis presenting as single or multiple nodules on imaging was shorter than the traditionally considered 6 months (p < 0.001). Imaging revealed that pulmonary cryptococcosis most commonly involved the right lower lung. Serum antigen assays, the number of infectious lobes, the presence of extrapulmonary lesions and the presence of lesions in the lower right lobe were suggested to be predictive indicators for a longer treatment duration. There was no significant difference in the percentage of patients who used amphotericin B or amphotericin B liposomes among patients with the four different types of imaging presentations.
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Affiliation(s)
- Yi Su
- Department of Infectious Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Yao Zhang
- Department of Infectious Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Qingqing Wang
- Department of Infectious Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Bijie Hu
- Department of Infectious Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Jue Pan
- Department of Infectious Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China
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Yang Y, Shang J, Xu S, Wang Z. Dose Optimization of Fluconazole After Initial Treatment Failure in Pulmonary Cryptococcosis in an Obese Patient with Type 2 Diabetes and Cirrhosis: A Case Report. Infect Drug Resist 2024; 17:4993-5000. [PMID: 39554469 PMCID: PMC11566214 DOI: 10.2147/idr.s491615] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 10/30/2024] [Indexed: 11/19/2024] Open
Abstract
Background Pulmonary cryptococcosis is a fungal infection of the lungs, particularly challenging to treat in patients with multiple comorbidities such as obesity, type 2 diabetes, and cirrhosis. Fluconazole is a first-line medication for the treatment of pulmonary cryptococcosis, but currently there is a lack of clinical medication experience in obese patients with multiple comorbidities, especially in dose adjustment after treatment failure. Case Introduction This case report describes the experience of fluconazole in the treatment of pulmonary cryptococcal infection in a 45-year-old Chinese male with obesity, type 2 diabetes, and cirrhosis. The patient had a history of antifungal therapy for two weeks before admission, but the cough and hemoptysis were not improved. The treatment failed. After admission, it was recommended to use a conventional dose of fluconazole as an antifungal regimen according to the guidelines. However, the treatment effect was still unsatisfactory, due to the patients' cough, hemoptysis, and fever symptoms were not relieved. During this period, it was newly found that the patient had cirrhosis and type 2 diabetes and had not previously controlled blood glucose. Considering the above situation, combined with the pharmacokinetic characteristics of fluconazole and the patient's weight reaching 113 kg, the team readjusted the fluconazole medication regimen, and ultimately, the pulmonary infection improved without significant adverse reactions. Results We found that it was more suitable for patients with obesity to calculate the dose of fluconazole by the lean weight. By estimation, the patient was finally given a loading dose of 800 mg fluconazole, and his condition improved significantly. After two weeks of medication, it was adjusted to a maintenance dose of 600 mg until the pulmonary infection in the patient disappeared. Conclusion This case suggests that fluconazole antifungal therapy for pulmonary cryptococcal infection should fully consider the risk of comorbidities in patients. If necessary, medication dosage can be adjusted according to weight, and it is recommended to use lean bodyweight for evaluation and optimization. In addition, close attention should be paid to liver and kidney function.
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Affiliation(s)
- Yang Yang
- Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Jin Shang
- Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Shuyun Xu
- Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
| | - Zhen Wang
- Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China
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Dai C, Bai D, Lin C, Li KY, Zhu W, Lin J, Lu F, Chen Q, Luo W, Zhu B, Lin Y. The relationship between lung CT features and serum cryptococcal antigen titers in localized pulmonary cryptococcosis patients. BMC Pulm Med 2024; 24:441. [PMID: 39251951 PMCID: PMC11386080 DOI: 10.1186/s12890-024-03259-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Accepted: 08/30/2024] [Indexed: 09/11/2024] Open
Abstract
BACKGROUND To explore the associations of computed tomography (CT) image features with the serum cryptococcal antigen (CrAg) titers measured by the lateral flow assay (LFA) in localized pulmonary cryptococcosis patients. METHODS A retrospective analysis of patients with pathologically confirmed pulmonary cryptococcosis admitted to the First Affiliated Hospital of Xiamen University from January 2016 to December 2022 was performed. Clinical data, CT results, serum CrAg-LFA test results, and follow-up data were collected and analyzed. RESULTS A total of 107 patients with localized pulmonary cryptococcosis were included, of which 31 had a single lesion in chest CT and the other 76 had multiple lesions. The positivity rate was (94.74% vs 64.52%) and titers of serum CrAg-LFA (1.77 ± 0.87 vs 0.91 ± 0.98) in the multiple lesion group were higher than those in the single lesion group, respectively. Multivariate linear regression analysis showed that the serum CrAg titers were positively associated with the number of lesions (β, 0.08; 95% CI, 0.05 to 0.12) and the lesion size (β, 0.40; 95% CI, 0.31 to 0.50) after adjusting other covariates. The serum CrAg-LFA titers of 60 pulmonary cryptococcosis patients showed a decreasing trend with the reduction in pulmonary lesion size after effective therapy. CONCLUSION In pulmonary cryptococcosis patients, the number and size of lung lesions are positively correlated with the titers of the serum CrAg-LFA test. The CrAg-LFA test could be a useful tool for the diagnosis, severity assessment, and therapeutic monitoring of localized pulmonary cryptococcosis patients.
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Affiliation(s)
- Chunmei Dai
- Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, No.55 Zhenhai Road, Xiamen, 361003, China
- Clinical Medicine Department of Fujian Medical University, Fujian, China
| | - Dongyu Bai
- Department of Pathology, the First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
| | - Chunbei Lin
- Department of Internal Medicine, the First Hospital of Zhangzhou China Merchants Economic and Technological Development Zone, Zhangzhou, Fujian, China
- Department of Internal Medicine, Zhangzhou Development Zone Branch of the First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Ke-Yi Li
- Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, No.55 Zhenhai Road, Xiamen, 361003, China
| | - Wenliang Zhu
- Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, No.55 Zhenhai Road, Xiamen, 361003, China
| | - Juan Lin
- Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, No.55 Zhenhai Road, Xiamen, 361003, China
- Clinical Medicine Department of Fujian Medical University, Fujian, China
| | - Fang Lu
- Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, No.55 Zhenhai Road, Xiamen, 361003, China
- Clinical Medicine Department of Fujian Medical University, Fujian, China
| | - Qiujuan Chen
- Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, No.55 Zhenhai Road, Xiamen, 361003, China
- Clinical Medicine Department of Fujian Medical University, Fujian, China
| | - Wen Luo
- Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, No.55 Zhenhai Road, Xiamen, 361003, China
- Clinical Medicine Department of Fujian Medical University, Fujian, China
| | - Bo Zhu
- Xiamen Key Laboratory of Genetic Testing, Department of Laboratory Medicine, The First Affiliated Hospital of Xiamen University, No. 55 Zhenhai Road, Xiamen, 361003, China.
| | - Yihua Lin
- Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, No.55 Zhenhai Road, Xiamen, 361003, China.
- Clinical Medicine Department of Fujian Medical University, Fujian, China.
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Palmucci JR, Sells BE, Giamberardino CD, Toffaletti DL, Dai B, Asfaw YG, Dubois LG, Li Z, Theriot B, Schell WA, Hope W, Tenor JL, Perfect JR. A ketogenic diet enhances fluconazole efficacy in murine models of systemic fungal infection. mBio 2024; 15:e0064924. [PMID: 38619236 PMCID: PMC11077957 DOI: 10.1128/mbio.00649-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Accepted: 03/21/2024] [Indexed: 04/16/2024] Open
Abstract
Invasive fungal infections are a significant public health concern, with mortality rates ranging from 20% to 85% despite current treatments. Therefore, we examined whether a ketogenic diet could serve as a successful treatment intervention in murine models of Cryptococcus neoformans and Candida albicans infection in combination with fluconazole-a low-cost, readily available antifungal therapy. The ketogenic diet is a high-fat, low-carbohydrate diet that promotes fatty acid oxidation as an alternative to glycolysis through the production of ketone bodies. In this series of experiments, mice fed a ketogenic diet prior to infection with C. neoformans and treated with fluconazole had a significant decrease in fungal burden in both the brain (mean 2.66 ± 0.289 log10 reduction) and lung (mean 1.72 ± 0.399 log10 reduction) compared to fluconazole treatment on a conventional diet. During C. albicans infection, kidney fungal burden of mice in the keto-fluconazole combination group was significantly decreased compared to fluconazole alone (2.37 ± 0.770 log10-reduction). Along with higher concentrations of fluconazole in the plasma and brain tissue, fluconazole efficacy was maximized at a significantly lower concentration on a keto diet compared to a conventional diet, indicating a dramatic effect on fluconazole pharmacodynamics. Our findings indicate that a ketogenic diet potentiates the effect of fluconazole at multiple body sites during both C. neoformans and C. albicans infection and could have practical and promising treatment implications.IMPORTANCEInvasive fungal infections cause over 2.5 million deaths per year around the world. Treatments for fungal infections are limited, and there is a significant need to develop strategies to enhance antifungal efficacy, combat antifungal resistance, and mitigate treatment side effects. We determined that a high-fat, low-carbohydrate ketogenic diet significantly potentiated the therapeutic effect of fluconazole, which resulted in a substantial decrease in tissue fungal burden of both C. neoformans and C. albicans in experimental animal models. We believe this work is the first of its kind to demonstrate that diet can dramatically influence the treatment of fungal infections. These results highlight a novel strategy of antifungal drug enhancement and emphasize the need for future investigation into dietary effects on antifungal drug activity.
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Affiliation(s)
- Julia R Palmucci
- Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
| | - Blake E Sells
- Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
- Department of Medicine, Washington University in St. Louis, St. Louis, Missouri, USA
| | - Charles D Giamberardino
- Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
| | - Dena L Toffaletti
- Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
| | - Baodi Dai
- Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
| | - Yohannes G Asfaw
- Department of Laboratory Animal Resources, Duke University Medical Center, Durham, North Carolina, USA
| | - Laura G Dubois
- Duke Proteomics and Metabolomics Core Facility, Duke University, Durham, North Carolina, USA
| | - Zhong Li
- Duke Proteomics and Metabolomics Core Facility, Duke University, Durham, North Carolina, USA
| | - Barbara Theriot
- Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA
| | - Wiley A Schell
- Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
| | - William Hope
- Antimicrobial Pharmacodynamics and Therapeutics, University of Liverpool, Liverpool Health Partners, Liverpool, United Kingdom
| | - Jennifer L Tenor
- Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
| | - John R Perfect
- Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
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Kanata K, Shirai T, Ito Y, Ichijo K, Uehara M. Pulmonary cryptococcosis suspected due to inhalation of swallow excreta presenting with multiple infiltrative shadows. Respir Med Case Rep 2024; 49:102014. [PMID: 38559327 PMCID: PMC10973641 DOI: 10.1016/j.rmcr.2024.102014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 03/12/2024] [Accepted: 03/14/2024] [Indexed: 04/04/2024] Open
Abstract
A 70-year-old woman had been treated with methotrexate for rheumatoid arthritis by a rheumatologist who opened a clinic near our hospital. In January of a certain year, she had respiratory symptoms of cough, sputum, and fever. Laboratory test results showed a white blood cell count of 8600/μL (neutrophil count of 5330/μL, lymphocyte count of 2490 μ/L), C-reactive protein (CRP) of 3.30 mg/dL. Chest radiography showed multiple infiltrative shadows in the right middle and lower lobes. Bronchoalveolar lavage fluid (BAL) lymphocyte count was increased (65.1%), and histopathological findings were consistent with numerous bowl-shaped cryptococcus cells stained black by Grocott staining. Added measurement of serum cryptococcal antigen titers was 4096-fold. Treatment with fluconazole 400 mg/day was initiated, and her symptoms resolved; the shadows of the lung fields improved. When asked in detail, the cryptococcus infection route was suspected from swallow excreta. There have been no reported cases of pulmonary cryptococcosis suspected due to inhalation of swallow excreta presenting with multiple infiltrative shadows.
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Affiliation(s)
- Kei Kanata
- Department of Respiratory Medicine, Shimada General Medical Center, Shizuoka, Japan
| | - Toshihiro Shirai
- Department of Respiratory Medicine, Shizuoka General Hospital, Shizuoka, Japan
| | - Yutaro Ito
- Department of Respiratory Medicine, Shimada General Medical Center, Shizuoka, Japan
| | - Koshiro Ichijo
- Department of Respiratory Medicine, Shimada General Medical Center, Shizuoka, Japan
| | - Masahiro Uehara
- Department of Respiratory Medicine, Shimada General Medical Center, Shizuoka, Japan
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11
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Dai Q, Wang Y, Ying Q, Ye Q. Cryptococcosis with pulmonary cavitation in an immunocompetent child: a case report and literature review. BMC Infect Dis 2024; 24:162. [PMID: 38321369 PMCID: PMC10845742 DOI: 10.1186/s12879-024-09061-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Accepted: 01/26/2024] [Indexed: 02/08/2024] Open
Abstract
BACKGROUND Pulmonary cryptococcosis (PC) rarely occurs in immunocompetent children. CASE PRESENTATION A 13-year-old boy was admitted to the First Affiliated Hospital of Ningbo University in February 2023 with complaints of cough and chest pain. Physical examination showed slightly moist rales in the right lung. Chest computed tomography (CT) suggested a lung lesion and cavitation. Blood routine test, lymphocyte subsets, immunoglobulin, and complement tests indicated that the immune system was normal. However, the serum cryptococcal antigen test was positive. Next-generation sequencing revealed Cryptococcus infection. The child was diagnosed with PC and was discharged after treating with fluconazole 400 mg. Four months later, chest CT showed that the lung lesion diminished, and reexamination of serum cryptococcal antigen test turned positive. CONCLUSION PC should be considered in an immunocompetent child with pulmonary cavities with nonspecific symptoms.
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Affiliation(s)
- Qiaoyan Dai
- Department of Pediatrics, The First Affiliated Hospital of Ningbo University, Ningbo, 315000, China
- Zhejiang University School of Medicine, Hangzhou, 310000, China
| | - Yingshuo Wang
- Department of Pulmonology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, 310000, China
| | - Qianqian Ying
- Department of Pediatrics, The First Affiliated Hospital of Ningbo University, Ningbo, 315000, China
- Department of pediatrics, Ningbo First Hospital, Ningbo, 315000, China
| | - Qidong Ye
- Department of Pediatrics, The First Affiliated Hospital of Ningbo University, Ningbo, 315000, China.
- Department of pediatrics, Ningbo First Hospital, Ningbo, 315000, China.
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12
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Wang H, Chen X, Wang Y, Yu D, Zhou Y, Liu Y, Tang Y, Wang M. Pulmonary cryptococcosis coexisting with lung adenocarcinoma: A case report and review of the literature. Oncol Lett 2024; 27:47. [PMID: 38106523 PMCID: PMC10722552 DOI: 10.3892/ol.2023.14179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Accepted: 11/22/2023] [Indexed: 12/19/2023] Open
Abstract
Pulmonary cryptococcosis (PC) is an invasive pulmonary fungal disease caused by Cryptococcus neoformans or Cryptococcus gattii. It often presents as a single nodule or mass on radiology, which is easily misdiagnosed as lung cancer or metastases. However, cases of PC coexisting with lung cancer are rare and when this scenario is encountered in clinical practice, it is easy to be misdiagnosed as metastatic lung cancer. The present study reported the case of a 65-year-old immunocompetent patient with PC coexisting with lung adenocarcinoma. Percutaneous lung biopsy was performed on the nodule in the anterior segment of the left upper lobe and the nodule in the posterior basal segment of the left lower lobe, which were diagnosed as primary adenocarcinoma and cryptococcus, respectively. Lung cancer was treated by surgery and PC was treated successfully by antifungal treatment. During the 5-year follow-up, contrast-enhanced CT showed no recurrence of either disease. This case reminds us of the possibility of dualism in the diagnosis of multiple pulmonary nodules based on CT examination, such as the coexistence of lung carcinoma and PC. In addition, early diagnosis and treatment contribute to good prognosis.
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Affiliation(s)
- Hansheng Wang
- Department of Pulmonary and Critical Care Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China
| | - Xiao Chen
- Department of Laboratory, Shiyan Maternal and Child Health Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China
| | - Yunyun Wang
- Department of Thoracic Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China
| | - Dan Yu
- Department of Pathology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China
| | - Yanhui Zhou
- Department of Pulmonary and Critical Care Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China
| | - Yan Liu
- Department of Pulmonary and Critical Care Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China
| | - Yijun Tang
- Department of Pulmonary and Critical Care Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China
| | - Meifang Wang
- Department of Pulmonary and Critical Care Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China
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13
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Beardsley J. Pathogens of importance in lung disease-Implications of the WHO fungal priority pathogen list. Respirology 2024; 29:21-23. [PMID: 37956991 PMCID: PMC10952795 DOI: 10.1111/resp.14623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Accepted: 10/25/2023] [Indexed: 11/21/2023]
Affiliation(s)
- Justin Beardsley
- University of Sydney Infectious Disease InstituteSydneyNew South WalesAustralia
- Westmead Institute for Medical ResearchSydneyNew South WalesAustralia
- Department of Infectious DiseasesWestmead Hospital, NSW HealthSydneyNew South WalesAustralia
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14
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Bilal H, Zhang D, Shafiq M, Khan MN, Chen C, Khan S, Wang Q, Cai L, Awais M, Hu H, Zeng Y. Cryptococcosis in Southern China: Insights from a Six-Year Retrospective Study in Eastern Guangdong. Infect Drug Resist 2023; 16:4409-4419. [PMID: 37435235 PMCID: PMC10332366 DOI: 10.2147/idr.s417968] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Accepted: 06/27/2023] [Indexed: 07/13/2023] Open
Abstract
Objective Cryptococcosis is a fatal infection that can affect both immunocompetent and immunocompromised patients, and it is little understood in China's various regions. This research aimed to look at the epidemiology, risk factors, and antifungal susceptibility pattern of Cryptococcus neoformans in eastern Guangdong, China. Methods A six-year (2016-2022) retrospective study was conducted at Meizhou People's Hospital, China. Demographical, clinical, and laboratory data of cryptococcal patients were collected from hospital records and statistically analyzed using the chi-square and ANOVA tests. Results Overall, 170 cryptococcal infections were recorded, of which meningitis accounted for 78 (45.88%), cryptococcemia for 50 (29.41%), and pneumonia for 42 (24.7%). The number of cases increased 8-fold during the study duration. The median age of patients was 58 years (Inter quartile range: 47-66), and the high proportion of cases was from the male population (n = 121, 71.17%). The underlying diseases were identified only in 60 (35.29%) patients, of which 26 (15.29%) were severely immunocompromised, and 26 (15.29%) others were mildly immunocompromised. A statistically significant difference was reported for chronic renal failure, and anemia (p < 0.05) persisted in cases of three infection types. A high number of non-wild type (NWT) isolates were found against amphotericin B (n=13/145, 8.96%), followed by itraconazole (n=7/136, 5.15%) and voriconazole (n=4/158, 2.53%). Only six isolates (3.79%) were multidrug-resistant, four of which were from cryptococcemia patients. Compared to meningitis and pneumonia, cryptococcemia revealed a higher percentage of NWT isolates (p < 0.05). Conclusion In high-risk populations, cryptococcal infections require ongoing monitoring and management.
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Affiliation(s)
- Hazrat Bilal
- Department of Dermatology, Second Affiliated Hospital of Shantou University Medical College, Shantou, 515041, People’s Republic of China
| | - Dongxing Zhang
- Department of Dermatology, Meizhou Dongshan Hospital, Meizhou, Guangdong Province, 514023, People’s Republic of China
- Department of Dermatology, Meizhou People’s Hospital, Meizhou, Guangdong Province, 514023, People’s Republic of China
| | - Muhammad Shafiq
- Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, People’s Republic of China
| | - Muhammad Nadeem Khan
- Faculty of Biological Sciences, Department of Microbiology, Quaid-I-Azam University, Islamabad, 45320, Pakistan
| | - Canhua Chen
- Clinical Laboratory, Meizhou People’s Hospital, Meizhou, Guangdong Province, 514023, People’s Republic of China
| | - Sabir Khan
- Department of Dermatology, Second Affiliated Hospital of Shantou University Medical College, Shantou, 515041, People’s Republic of China
| | - Qian Wang
- Department of Dermatology, Second Affiliated Hospital of Shantou University Medical College, Shantou, 515041, People’s Republic of China
- Department of Medical-Surgical and Experimental Sciences University of Sassari Neurology Unit, Azienda Ospedaliera Universitaria (AOU), Sassari, Italy
| | - Lin Cai
- Department of Dermatology, Second Affiliated Hospital of Shantou University Medical College, Shantou, 515041, People’s Republic of China
| | - Muhammad Awais
- Department of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming, Yunnan, People’s Republic of China
| | - Haibin Hu
- The First Clinical Medical college, Guangdong Medical University, Zhanjiang, 523808, People’s Republic of China
| | - Yuebin Zeng
- Department of Dermatology, Second Affiliated Hospital of Shantou University Medical College, Shantou, 515041, People’s Republic of China
- Department of Dermatology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610021, People’s Republic of China
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15
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Dantas KC, de Freitas—Xavier RS, Spina Lombardi SCF, Júnior AM, da Silva MV, Criado PR, de Freitas VLT, de Almeida TMB. Comparative analysis of diagnostic methods for the detection of Cryptococcus neoformans meningitis. PLoS Negl Trop Dis 2023; 17:e0011140. [PMID: 36877731 PMCID: PMC10019727 DOI: 10.1371/journal.pntd.0011140] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 03/16/2023] [Accepted: 02/05/2023] [Indexed: 03/07/2023] Open
Abstract
BACKGROUND Cryptococcosis is a devastating opportunistic infection in immunocompromised individuals, primarily in people living with HIV/AIDS. This study evaluated a protocol for the early diagnosis of meningitis due to C. neoformans, utilizing established molecular techniques from serum and CSF samples. METHODS The 18S and 5.8S (rDNA-ITS) sequence-specific nested PCR assays were compared with direct India ink staining and the latex agglutination test for detection of C. neoformans in serum and cerebrospinal fluid (CSF) from 49 Brazilian suspected meningitis patients. Results were validated with samples obtained from 10 patients negative for cryptococcosis and HIV, and by analysis of standard C. neoformans strains. PRINCIPAL FINDINGS The 5.8S DNA-ITS PCR was more sensitive (89-100%) and specific (100%) than the 18S rDNA PCR and conventional tests (India ink staining and latex agglutination) for identification of C. neoformans. While the 18S PCR exhibited a sensitivity (72%) similar to that of the latex agglutination assay in serum samples, it was superior to the latex agglutination assay when testing CSF, with a sensitivity of 84%. However, the latex agglutination was superior to the 18SrDNA PCR in specificity in CSF (92%). The 5.8S DNA-ITS PCR yielded the highest levels of accuracy (96-100%) of any test for detection (serological and mycological) of C. neoformans in both serum and CSF. CONCLUSION Use of the nested 5.8S PCR was superior to other techniques for the diagnosis of cryptococcosis. The possibility of using serum, a non-invasively collected material, in a targeted 5.8S PCR analysis to identify Cryptococcus spp. is recommended, especially in immunosuppressed patients. Our results indicate that nested 5.8S PCR can increase the diagnostic capability of cryptococcosis, and we suggest its use to monitor patients in the future.
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Affiliation(s)
- Katia Cristina Dantas
- Department of Pathology, Sao Paulo University Medical School, Sao Paulo, Brazil
- * E-mail:
| | | | | | - Alfredo Mendroni Júnior
- Laboratory of Medical Investigation in Pathogenesis and Targeted Therapy in OncoImmuno-Hematology (LIM-31), Department of Hematology, Hospital das Clínicas -HCFMUSP, Faculty of Medicine, University of São Paulo, São Paulo, Brazil
| | - Marcos Vinicius da Silva
- Emilio Ribas Institute of Infectious Diseases, Consultant, Ministry of Health, Department of Medicine, Catholic University of Sao Paulo, and Professor, Program in Postgraduate Sciences and Coordination of Disease Control, Department of State Health, São Paulo, Brazil
| | | | - Vera Lúcia Teixeira de Freitas
- Laboratory of Medical Investigation in Imunology (LIM-48), Department of Infectious and Parasitic Diseases, Sao Paulo University Medical School, Sao Paulo, Brazil
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16
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Disseminated cryptococcal infection with pulmonary involvement presenting as diffuse cavitary nodules in an immunocompromised patient: a case report. BMC Pulm Med 2023; 23:38. [PMID: 36707820 PMCID: PMC9883961 DOI: 10.1186/s12890-023-02332-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Accepted: 01/18/2023] [Indexed: 01/29/2023] Open
Abstract
BACKGROUND Disseminated cryptococcal infection is especially prone to occur in immunosuppressed hosts. We herein report the case of an immunosuppressed girl with disseminated cryptococcal infection in whom pulmonary cryptococcosis (PC) presented as diffuse cavitary pulmonary nodules, a finding which has rarely been reported. CASE PRESENTATION A 16-year-old immunocompromised girl presented with fever and a non-productive cough. A chest computed tomography (CT) scan revealed diffuse pulmonary nodules with cavities. Subsequent results were consistent with disseminated cryptococcosis with Cryptococcus identified in her blood, bone marrow and cerebrospinal fluid cultures. Thus, the patient was diagnosed with disseminated cryptococcal infection with PC, cryptococcus meningitis, cryptococcus osteomyelitis and cryptococcus sepsis. After antifungal treatment, the patient demonstrated both clinical and chest radiological improvement. CONCLUSION The atypical clinical manifestations of a disseminated cryptococcal infection and the rare manner of chest CT findings of PC reported in our case are easy to misdiagnose. It is necessary to carry out a thorough search for a definitive diagnosis using various methods.
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17
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Sato K, Kawakami K. Mouse Model of Latent Cryptococcal Infection and Reactivation. Methods Mol Biol 2023; 2667:87-98. [PMID: 37145277 DOI: 10.1007/978-1-0716-3199-7_6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/06/2023]
Abstract
AbstractCryptococcus neoformans is an opportunistic fungal pathogen that frequently causes fatal meningoencephalitis in patients with impaired immune responses. This fungus, an intracellularly growing microbe, evades host immunity, leading to a latent infection (latent C. neoformans infection: LCNI), and cryptococcal disease is developed by its reactivation when host immunity is suppressed. Elucidation of the pathophysiology of LCNI is difficult due to the lack of mouse models. Here we show the established methods for LCNI and reactivation.
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Affiliation(s)
- Ko Sato
- Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
- Department of Intelligent Network for Infection Control, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
| | - Kazuyoshi Kawakami
- Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
- Department of Intelligent Network for Infection Control, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
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18
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Xiong C, Lu J, Chen T, Xu R. Comparison of the clinical manifestations and chest CT findings of pulmonary cryptococcosis in immunocompetent and immunocompromised patients: a systematic review and meta-analysis. BMC Pulm Med 2022; 22:415. [PMID: 36369001 PMCID: PMC9652893 DOI: 10.1186/s12890-022-02175-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Accepted: 09/26/2022] [Indexed: 11/12/2022] Open
Abstract
Objective The purpose of our study was to perform a meta-analysis and systematic review to compare differences in clinical manifestations and chest computed tomography (CT) findings between immunocompetent and immunocompromised pulmonary cryptococcosis (PC) patients. Methods An extensive search for relevant studies was performed using the PubMed, EMBASE, Cochrane Library, and Web of Sciences databases from inception to September 30, 2021. We included studies that compared the clinical manifestations and chest CT findings between immunocompetent and immunocompromised PC patients. Study bias and quality assessment were performed using the Newcastle–Ottawa Scale (NOS). Results Nine studies involving 248 immunocompromised and 276 immunocompetent PC patients were included in our analysis. The NOS score of each eligible study was above 5, indicating moderate bias. The proportion of elderly patients (> = 60 years old) in the immunosuppressed group was significantly higher than that in the immunocompetent group (OR = 2.90, 95% CI (1.31–6.43), Z = 2.63, p = 0.01). Fever (OR = 7.10, 95% CI (3.84–13.12), Z = 6.25, p < 0.000) and headache (OR = 6.92, 95% CI (2.95–16.26), Z = 4.44, p < 0.000) were more common in immunosuppressed patients. According to thin-section CT findings, lesions were more frequently distributed in the upper lobe (OR = 1.90, 95% CI (1.07–3.37), Z = 2.2, p = 0.028) in immunocompromised individuals. The proportions of patients with cavity sign (OR = 5.11, 95% CI (2.96–8.83), Z = 5.86, p = 0.00), ground-glass attenuation (OR = 5.27, 95% CI (1.60–17.35), Z = 2.73, p = 0.01), and mediastinal lymph node enlargement (OR = 2.41, 95% CI (1.12–5.20), Z = 2.24, p = 0.03) were significantly higher in immunocompromised patients. Conclusion No significant differences in nonspecific respiratory symptoms were found between immunocompromised and immunocompetent PC patients. Nevertheless, fever and headache were more common in immunocompromised patients. Among the CT findings, cavity, ground-glass attenuation, and mediastinal lymph node enlargement were more common in immunocompromised individuals. Supplementary Information The online version contains supplementary material available at 10.1186/s12890-022-02175-9.
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19
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Howard-Jones AR, Sparks R, Pham D, Halliday C, Beardsley J, Chen SCA. Pulmonary Cryptococcosis. J Fungi (Basel) 2022; 8:1156. [PMID: 36354923 PMCID: PMC9696922 DOI: 10.3390/jof8111156] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Revised: 10/26/2022] [Accepted: 10/29/2022] [Indexed: 07/25/2023] Open
Abstract
Pulmonary cryptococcosis describes an invasive lung mycosis caused by Cryptococcus neoformans or Cryptococcus gattii complex. It is often a high-consequence disease in both immunocompromised and immunocompetent populations, and may be misdiagnosed as pulmonary malignancy, leading to a delay in therapy. Epidemiology follows that of cryptococcal meningoencephalitis, with C. gattii infection more common in certain geographic regions. Diagnostic tools include histopathology, microscopy and culture, and the detection of cryptococcal polysaccharide antigen or Cryptococcus-derived nucleic acids. All patients with lung cryptococcosis should have a lumbar puncture and cerebral imaging to exclude central nervous system disease. Radiology is key, both as an adjunct to laboratory testing and as the initial means of detection in asymptomatic patients or those with non-specific symptoms. Pulmonary cryptococcomas (single or multiple) may also be associated with disseminated disease and/or cryptococcal meningitis, requiring prolonged treatment regimens. Optimal management for severe disease requires extended induction (amphotericin B and flucytosine) and consolidation therapy (fluconazole) with close clinical monitoring. Susceptibility testing is of value for epidemiology and in regions where relatively high minimum inhibitory concentrations to azoles (particularly fluconazole) have been noted. Novel diagnostic tools and therapeutic agents promise to improve the detection and treatment of cryptococcosis, particularly in low-income settings where the disease burden is high.
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Affiliation(s)
- Annaleise R. Howard-Jones
- Centre for Infectious Diseases & Microbiology Laboratory Services, New South Wales Health Pathology—Institute of Clinical Pathology & Medical Research, Westmead Hospital, Westmead, NSW 2145, Australia
- Faculty of Medicine and Health, University of Sydney, Camperdown, NSW 2145, Australia
- Sydney Institute for Infectious Diseases, The University of Sydney, Sydney, NSW 2006, Australia
| | - Rebecca Sparks
- Centre for Infectious Diseases & Microbiology Laboratory Services, New South Wales Health Pathology—Institute of Clinical Pathology & Medical Research, Westmead Hospital, Westmead, NSW 2145, Australia
| | - David Pham
- Centre for Infectious Diseases & Microbiology Laboratory Services, New South Wales Health Pathology—Institute of Clinical Pathology & Medical Research, Westmead Hospital, Westmead, NSW 2145, Australia
| | - Catriona Halliday
- Centre for Infectious Diseases & Microbiology Laboratory Services, New South Wales Health Pathology—Institute of Clinical Pathology & Medical Research, Westmead Hospital, Westmead, NSW 2145, Australia
| | - Justin Beardsley
- Faculty of Medicine and Health, University of Sydney, Camperdown, NSW 2145, Australia
- Sydney Institute for Infectious Diseases, The University of Sydney, Sydney, NSW 2006, Australia
- Westmead Institute for Medical Research, Westmead, NSW 2145, Australia
| | - Sharon C.-A. Chen
- Centre for Infectious Diseases & Microbiology Laboratory Services, New South Wales Health Pathology—Institute of Clinical Pathology & Medical Research, Westmead Hospital, Westmead, NSW 2145, Australia
- Faculty of Medicine and Health, University of Sydney, Camperdown, NSW 2145, Australia
- Sydney Institute for Infectious Diseases, The University of Sydney, Sydney, NSW 2006, Australia
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20
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Takazono T, Hidaka Y, Morimoto S, Tashiro M, Ashizawa N, Hirayama T, Takeda K, Iwanaga N, Hosogaya N, Yamamoto K, Fushimi K, Yanagihara K, Mukae H, Izumikawa K. A comparison of liposomal amphotericin B alone and in combination with flucytosine in the treatment of non-HIV Cryptococcal meningitis: A nationwide observational study. Mycoses 2022; 65:897-902. [PMID: 35802067 DOI: 10.1111/myc.13493] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2022] [Revised: 06/23/2022] [Accepted: 06/30/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND Cryptococcal meningitis (CM) is an opportunistic infectious disease that occurs in immunocompromised hosts, not only in patients living with HIV, but also in patients without HIV. The evidence regarding the treatment for CM in patients without HIV is mainly found in small retrospective studies and is extremely limited. OBJECTIVES In the present study, we compared the efficacy of liposomal amphotericin B (L-AMB) alone and in combination with flucytosine (5-FC) for the induction treatment of CM in patients without HIV. PATIENTS/METHODS Data was gathered from the Japanese Diagnosis Procedure Combination database obtained from hospitals throughout Japan. The study included 517 patients without HIV but having CM who fulfilled the inclusion and exclusion criteria. We analyzed the average effect of adding 5-FC to L-AMB treatment using the survival time within 14 days of the diagnosis after adjustment of the baseline clinical characteristics with associations with both selections of the treatment and the prognosis. RESULTS A total of 146 and 217 CM patients received L-AMB and L-AMB with 5-FC, respectively, within 7 days of diagnosis. L-AMB with 5-FC showed better prognosis than L-AMB on day 14 (mortality 6% vs. 11%, hazard ratio, 0.5775; 95% confidence interval, 0.2748-1.213; p = 0.1, Wald test). CONCLUSIONS From the results of this real-world database study, we revealed that the combination therapy of 5-FC on L-AMB for induction therapy might have an advantage on the survival time of NHNT patients with CM as well as PLHIV patients with CM.
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Affiliation(s)
- Takahiro Takazono
- Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.,Department of Respiratory Medicine, Nagasaki University Hospital, Nagasaki, Japan
| | - Yusuke Hidaka
- Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.,Department of Respiratory Medicine, Nagasaki University Hospital, Nagasaki, Japan.,Department of General Internal Medicine, National Hospital Organization Nagasaki Medical Center, Nagasaki, Japan
| | - Shimpei Morimoto
- Innovation Platform & Office for Precision Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.,Nagasaki University Hospital, Clinical Research Center, Nagasaki, Japan
| | - Masato Tashiro
- Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.,Infection Control and Education Center, Nagasaki University Hospital, Nagasaki, Japan
| | - Nobuyuki Ashizawa
- Department of Respiratory Medicine, Nagasaki University Hospital, Nagasaki, Japan.,Infection Control and Education Center, Nagasaki University Hospital, Nagasaki, Japan
| | - Tatsuro Hirayama
- Department of Respiratory Medicine, Nagasaki University Hospital, Nagasaki, Japan.,Department of Pharmacotherapeutics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Kazuaki Takeda
- Department of Respiratory Medicine, Nagasaki University Hospital, Nagasaki, Japan.,Infection Control and Education Center, Nagasaki University Hospital, Nagasaki, Japan
| | - Naoki Iwanaga
- Department of Respiratory Medicine, Nagasaki University Hospital, Nagasaki, Japan
| | - Naoki Hosogaya
- Nagasaki University Hospital, Clinical Research Center, Nagasaki, Japan
| | - Kazuko Yamamoto
- Department of Respiratory Medicine, Nagasaki University Hospital, Nagasaki, Japan
| | - Kiyohide Fushimi
- Department of Health Policy and Informatics, Tokyo Medical and Dental University Graduate School, Tokyo, Japan
| | - Katsunori Yanagihara
- Department of Laboratory Medicine, Nagasaki University Hospital, Nagasaki, Japan
| | - Hiroshi Mukae
- Department of Respiratory Medicine, Nagasaki University Hospital, Nagasaki, Japan
| | - Koichi Izumikawa
- Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.,Infection Control and Education Center, Nagasaki University Hospital, Nagasaki, Japan
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21
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Xin Z, Li B, Xue W, Lin W, Zhao Q, Zhang X. Pulmonary cryptococcosis mimicking lung cancer: 3 case report. Int J Surg Case Rep 2022; 94:106973. [PMID: 35658271 PMCID: PMC9093010 DOI: 10.1016/j.ijscr.2022.106973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Revised: 03/25/2022] [Accepted: 03/25/2022] [Indexed: 11/28/2022] Open
Affiliation(s)
- Zhifei Xin
- Hebei General Hospital, Shijiazhuang, Hebei, China
| | - Bowen Li
- Hebei General Hospital, Shijiazhuang, Hebei, China; North China University of Science and Technology, Tangshan, Hebei, China
| | - Wenfei Xue
- Hebei General Hospital, Shijiazhuang, Hebei, China
| | - Wei Lin
- Hebei General Hospital, Shijiazhuang, Hebei, China
| | - Qingtao Zhao
- Hebei General Hospital, Shijiazhuang, Hebei, China
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22
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Wang H, Wang L, Luo Z, Li D, Luo G, Ren T, You H, Liu Y, Tang Y, Wang M. The performance of rapid on-site evaluation of touch imprints of lung tissue biopsies for the diagnosis of pulmonary cryptococcosis in patients without HIV infection. Mycoses 2022; 65:635-642. [PMID: 35377478 DOI: 10.1111/myc.13441] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 03/25/2022] [Accepted: 03/29/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND AND OBJECTIVE The diagnosis of pulmonary cryptococcosis depends on serum testing, histopathology and mycological culture; there are few studies on touch imprints of lung tissue biopsies for the diagnosis of pulmonary cryptococcosis in patients without HIV infection. The purpose of the current study was to investigate the accuracy and timeliness of on-site touch imprint cytology in the diagnosis of pulmonary cryptococcosis during CT-guided percutaneous lung biopsy. METHODS We retrospectively analyzed the diagnosis and treatment of 56 patients with final proof of pulmonary cryptococcosis through histopathology and culture or surgical resection from September 2015 to February 2021. Diagnostic methods and treatment and the turnaround time for diagnosis were analyzed. RESULTS The sensitivity of rapid on-site evaluation was 89.3%, and the sensitivity of serology, histopathology and mycological culture was 53.6%, 91.1%, 61.5%, respectively, compared with the final diagnosis. The average turnaround time to diagnose pulmonary cryptococcosis by on-site touch imprint cytology was 8.3 ± 0.9 min, which was significantly faster than serum testing, histopathology and mycological culture. CONCLUSION On-site touch imprint cytology showed good sensitivity and timeliness in the diagnosis of pulmonary cryptococcosis. In addition, it contributed to the triage of biopsies based on the preliminary diagnosis. On-site touch imprint cytology should be applied and promoted in the diagnosis of pulmonary cryptococcosis during biopsy.
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Affiliation(s)
- Hansheng Wang
- Department of Pulmonary and Critical Care Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, P.R. China
| | - Lei Wang
- Department of Laboratory, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, P.R. China
| | - Zhengning Luo
- Center of Adult Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100037, P.R. China
| | - Dan Li
- Department of Pathology, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, P.R. China
| | - Guoshi Luo
- Department of Pulmonary and Critical Care Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, P.R. China
| | - Tao Ren
- Department of Pulmonary and Critical Care Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, P.R. China
| | - Hui You
- Department of Pulmonary and Critical Care Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, P.R. China
| | - Yan Liu
- Department of Pulmonary and Critical Care Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, P.R. China
| | - Yijun Tang
- Department of Pulmonary and Critical Care Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, P.R. China
| | - Meifang Wang
- Department of Pulmonary and Critical Care Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, P.R. China
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23
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Video-assisted thoracoscopic surgery for primary pulmonary cryptococcosis. J Formos Med Assoc 2022; 121:2237-2247. [DOI: 10.1016/j.jfma.2022.04.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 04/06/2022] [Accepted: 04/19/2022] [Indexed: 02/07/2023] Open
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24
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Tucker M, Sheikh AM, Villanueva MS. Rapidly enlarging pulmonary mass due to immune reconstitution inflammatory syndrome (IRIS) in an immunocompetent host with pulmonary Cryptococcus neoformans. BMJ Case Rep 2022; 15:e247495. [PMID: 35351746 PMCID: PMC8966528 DOI: 10.1136/bcr-2021-247495] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/17/2022] [Indexed: 11/04/2022] Open
Abstract
An immunocompetent man presented with Cryptococcus neoformans disease manifesting as a large pulmonary mass (cryptococcoma). Despite an initial induction course of 4 weeks of liposomal amphotericin B (LAmB), followed by 8 weeks of fluconazole, the cryptococcoma enlarged in size. Ten days into a second course of induction therapy with LAmB and flucytosine, the cryptococcoma markedly increased in size with encroachment on critical vascular structures. Due to concern for immune reconstitution inflammatory syndrome (IRIS), prednisone was added with significant decrease in the size of the mass. To our knowledge, this is the first reported case of pulmonary cryptococcal-IRIS in an immunocompetent host.
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Affiliation(s)
- Mollie Tucker
- Infectious Diseases, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Abdul Majeed Sheikh
- Infectious Diseases, Charlotte Hungerford Hospital, Torrington, Connecticut, USA
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25
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Hsiao PJ, Cheng H, Kao YH, Wang YH, Chiu CC, Chiang WF, Kuo CC, Chuu CP, Wu KA. Comparison of laboratory diagnosis, clinical manifestation, and management of pulmonary cryptococcosis: Report of the clinical scenario and literature review. Clin Chim Acta 2022; 524:78-83. [PMID: 34843703 DOI: 10.1016/j.cca.2021.11.017] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Revised: 10/04/2021] [Accepted: 11/17/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND Pulmonary cryptococcosis is an opportunistic aggressive mycosis in immunocompromised patients, but it can be increasingly seen in immunocompetent patients. It is still challenging to make a rapid and accurate diagnosis due to the various clinical manifestations and limitations in the diagnostic tools. METHOD A 54-year-old man presented with intermittent productive cough and fever for 1 week. A chest X-ray demonstrated multiple consolidations in both lungs. Blood biochemistry indicated elevated immunoglobulin G levels. Including sputum cultures, polymerase chain reaction (PCR) tests for severe acute respiratory syndrome coronavirus 2, influenza A and B virus were all negative. Computed tomography of the chest showed ground-glass opacities with a nodular pattern. The serum cryptococcal antigen test was positive; however, the cerebral spinal fluid was negative. The diagnosis of pulmonary cryptococcal infection was made. An initial bronchoscopy was performed unsuccessfully and the patient received intravenous fluconazole therapy for 2 weeks. Due to poor improvement of clinical condition, he then underwent a surgical lung biopsy. The pathology revealed several encapsulated yeast cells, diffuse pulmonary interstitial fibrosis, noncaseating granulomas surrounded by T lymphocytes and multinucleated giant cells with intracellular inclusions, confirming pulmonary yeast infection associated with hypersensitivity pneumonitis. Ultimately, fungal cultures of the pathology samples revealed Cryptococcus neoformans. Subsequently antifungal therapy combined with oral steroid treatment, his general condition improved. After a total of 6 months of antifungal therapy, the patient recovered completely. CONCLUSIONS Applicable laboratory diagnosis can help facilitate the accurate and rapid diagnosis of pulmonary cryptococcosis. This report elected to provide an update on the topic of laboratory diagnosis, clinical manifestation, and management of pulmonary cryptococcosis.
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Affiliation(s)
- Po-Jen Hsiao
- Division of Nephrology, Department of Internal Medicine, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan; Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Department of Life Sciences, National Central University, Taoyuan, Taiwan.
| | - Han Cheng
- Department of Internal Medicine, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan
| | - Yung-Hsi Kao
- Department of Life Sciences, National Central University, Taoyuan, Taiwan
| | - Yuan-Hung Wang
- Department of Internal Medicine, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan; Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chih-Chiun Chiu
- Division of Infectious Disease, Department of Internal Medicine, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan; Division of Infectious Disease and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Wen-Fang Chiang
- Division of Nephrology, Department of Internal Medicine, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan; Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chih-Chun Kuo
- Division of Metabolism and Endocrinology, Department of Internal Medicine, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan
| | - Chih-Pin Chuu
- Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli County, Taiwan; Graduate Program for Aging, China Medical University, Taichung, Taiwan
| | - Kuo-An Wu
- Division of Pulmonary & Critical Care Medicine, Department of Internal Medicine, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan
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26
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Sato K, Matsumoto I, Suzuki K, Tamura A, Shiraishi A, Kiyonari H, Kasamatsu J, Yamamoto H, Miyasaka T, Tanno D, Miyahara A, Zong T, Kagesawa T, Oniyama A, Kawamura K, Kitai Y, Umeki A, Kanno E, Tanno H, Ishii K, Tsukita S, Kawakami K. Deficiency of lung-specific claudin-18 leads to aggravated infection with Cryptococcus deneoformans through dysregulation of the microenvironment in lungs. Sci Rep 2021; 11:21110. [PMID: 34702961 PMCID: PMC8548597 DOI: 10.1038/s41598-021-00708-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 10/15/2021] [Indexed: 12/25/2022] Open
Abstract
Cryptococcus deneoformans is an opportunistic fungal pathogen that infects the lungs via airborne transmission and frequently causes fatal meningoencephalitis. Claudins (Cldns), a family of proteins with 27 members found in mammals, form the tight junctions within epithelial cell sheets. Cldn-4 and 18 are highly expressed in airway tissues, yet the roles of these claudins in respiratory infections have not been clarified. In the present study, we analyzed the roles of Cldn-4 and lung-specific Cldn-18 (luCldn-18) in host defense against C. deneoformans infection. luCldn-18-deficient mice exhibited increased susceptibility to pulmonary infection, while Cldn-4-deficient mice had normal fungal clearance. In luCldn-18-deficient mice, production of cytokines including IFN-γ was significantly decreased compared to wild-type mice, although infiltration of inflammatory cells including CD4+ T cells into the alveolar space was significantly increased. In addition, luCldn-18 deficiency led to high K+ ion concentrations in bronchoalveolar lavage fluids and also to alveolus acidification. The fungal replication was significantly enhanced both in acidic culture conditions and in the alveolar spaces of luCldn-18-deficient mice, compared with physiological pH conditions and those of wild-type mice, respectively. These results suggest that luCldn-18 may affect the clinical course of cryptococcal infection indirectly through dysregulation of the alveolar space microenvironment.
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Affiliation(s)
- Ko Sato
- Department of Intelligent Network for Infection Control, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. .,Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
| | - Ikumi Matsumoto
- Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Koya Suzuki
- Laboratory of Biological Science and Laboratory of Biosciences, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, Japan.,Research Institute for Diseases of Old Age and Department of Clinical Laboratory Medicine, Graduate School of Medicine, Juntendo University, Tokyo, Japan
| | - Atsushi Tamura
- Laboratory of Biological Science and Laboratory of Biosciences, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, Japan
| | - Aki Shiraishi
- Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan
| | - Hiroshi Kiyonari
- Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan
| | - Jun Kasamatsu
- Department of Intelligent Network for Infection Control, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Hideki Yamamoto
- Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.,Center for Transdisciplinary Research, Institute of Research Promotion, Niigata University, Niigata, Japan
| | - Tomomitsu Miyasaka
- Division of Pathophysiology, Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi, Japan
| | - Daiki Tanno
- Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.,Department of Clinical Laboratory, Fukushima Medical University, Fukushima, Japan
| | - Anna Miyahara
- Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Tong Zong
- Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Takafumi Kagesawa
- Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Akiho Oniyama
- Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Kotone Kawamura
- Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Yuki Kitai
- Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Aya Umeki
- Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Emi Kanno
- Department of Science of Nursing Practice, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Hiromasa Tanno
- Department of Science of Nursing Practice, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Keiko Ishii
- Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Sachiko Tsukita
- Laboratory of Biological Science and Laboratory of Biosciences, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, Japan
| | - Kazuyoshi Kawakami
- Department of Intelligent Network for Infection Control, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.,Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
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27
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Hu Y, Ren SY, Xiao P, Yu FL, Liu WL. The clinical and radiological characteristics of pulmonary cryptococcosis in immunocompetent and immunocompromised patients. BMC Pulm Med 2021; 21:262. [PMID: 34389002 PMCID: PMC8361630 DOI: 10.1186/s12890-021-01630-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Accepted: 08/03/2021] [Indexed: 12/12/2022] Open
Abstract
Background We characterized the clinical features, radiographic characteristics, and response to treatment of immunocompetent and immunocompromised patients with pulmonary cryptococcosis (PC). Methods We retrospectively reviewed the medical records and radiological profiles of patients diagnosed with PC who received surgical resection between May 2015 and November 2020 in a tertiary referral center. Results A total of 21 males and 18 females were included in the study. 23 patients were immunocompetent and 20 out of the 39 were asymptomatic. Immunocompetent patients were diagnosed with PC at a younger age than immunocompromised patients (48.9 vs 57.1 years, P = 0.02). Single nodule pattern was the most frequent lesion pattern (33 out of 39, 84.6%) and right upper lobe was the most common site of location (15 out of 47, 31.9%). The majority of lesions were located peripherally (38 out of 47, 80.9%) and most lesions were 1–2 cm in diameter (30 out of 47, 63.8%). Cavitation was more likely to occur in immunocompromised patients (5 out of 11, 45.5%) than in immunocompetent patients (6 out of 36, 16.7%) (P = 0.04) and there was complete resolution of PC in all patients treated with anti-fungal therapy. Conclusions Immunocompetent patients were diagnosed with PC at a younger age than immunocompromised patients. Single nodule pattern was the most frequent lesion pattern in PC patients. Cavitation was more likely to occur in immunocompromised patients than in immunocompetent patients.
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Affiliation(s)
- Yan Hu
- Department of Thoracic Surgery, The Second Xiangya Hospital of Central South University, No. 139 Renmin Road, Changsha, 410011, China
| | - Si-Ying Ren
- Department of Respiratory and Critical Care Medicine, The Second Xiangya Hospital of Central South University, Changsha, 410011, China
| | - Peng Xiao
- Department of Cardiothoracic Surgery, The Third Xiangya Hospital of Central South University, Changsha, 410013, China
| | - Feng-Lei Yu
- Department of Thoracic Surgery, The Second Xiangya Hospital of Central South University, No. 139 Renmin Road, Changsha, 410011, China
| | - Wen-Liang Liu
- Department of Thoracic Surgery, The Second Xiangya Hospital of Central South University, No. 139 Renmin Road, Changsha, 410011, China.
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Hosoda C, Ishiguro T, Uozumi R, Ueda M, Takata N, Takayanagi N. Characteristics of pulmonary cryptococcosis in patients with rheumatoid arthritis. BMJ Open Respir Res 2021; 8:8/1/e000805. [PMID: 34326152 PMCID: PMC8323392 DOI: 10.1136/bmjresp-2020-000805] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Accepted: 07/05/2021] [Indexed: 11/17/2022] Open
Abstract
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.
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Affiliation(s)
- Chiaki Hosoda
- Department of Respiratory Medicine, Saitama Cardiovascular and Respiratory Center, Saitama, Japan .,Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Takashi Ishiguro
- Department of Respiratory Medicine, Saitama Cardiovascular and Respiratory Center, Saitama, Japan
| | - Ryuji Uozumi
- Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Miyuki Ueda
- Department of Radiology, Saitama Cardiovascular and Respiratory Center, Saitama, Japan
| | - Naomi Takata
- Department of Radiology, Saitama Cardiovascular and Respiratory Center, Saitama, Japan
| | - Noboru Takayanagi
- Department of Respiratory Medicine, Saitama Cardiovascular and Respiratory Center, Saitama, Japan
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29
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Yamamura D, Xu J. Update on Pulmonary Cryptococcosis. Mycopathologia 2021; 186:717-728. [PMID: 34181160 DOI: 10.1007/s11046-021-00575-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Accepted: 06/22/2021] [Indexed: 12/24/2022]
Abstract
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.
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Affiliation(s)
- Deborah Yamamura
- Microbiology Department, Hamilton Regional Laboratory Medicine Program, Hamilton General Hospital, Hamilton, ON, L8L 2X2, Canada.,Department of Pathology and Molecular Medicine, McMaster University, Hamilton, L8S 4K1, Canada
| | - Jianping Xu
- Department of Biology, McMaster University, Hamilton, L8S 4K1, Canada.
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30
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Hussein M, Haq IU, Hameed M, Alabbas A, Hadi HA, Elarabi A, Al-Bozom I. Isolated pulmonary cryptococcosis in a patient with Crohn's disease treated with infliximab: A case report and literature review. Respir Med Case Rep 2021; 33:101459. [PMID: 34401295 PMCID: PMC8349031 DOI: 10.1016/j.rmcr.2021.101459] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 06/07/2021] [Accepted: 06/16/2021] [Indexed: 02/06/2023] Open
Abstract
Tumor necrosis factor-alpha (TNF-α) inhibitors are widely used to treat various inflammatory conditions, where they have demonstrated excellent efficacy and tolerability. However, increased risk of infections is one of the most important concerns associated with these agents. Reactivation of tuberculosis and fungal infections have emerged as significant infective complications of anti-TNF-α therapy. Cryptococcus infection is an opportunistic fungal infection that can occur in patients receiving anti-TNF-α treatment. We report a rare case of isolated pulmonary cryptococcosis in a patient undergoing anti-TNF-α therapy for Crohn's disease. Our case should alert clinicians to the increased incidence and atypical presentation of pulmonary cryptococcosis in patients receiving anti-TNF-α treatment.
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Affiliation(s)
- Mousa Hussein
- Hamad Medical Corporation, Pulmonology Department, Qatar
| | - Irfan Ul Haq
- Hamad Medical Corporation, Pulmonology Department, Qatar
| | - Mansoor Hameed
- Hamad Medical Corporation, Pulmonology Department, Qatar
| | - Abbas Alabbas
- Hamad Medical Corporation, Pulmonology Department, Qatar
| | - Hamad Abdel Hadi
- Hamad Medical Corporation, Infectious Diseases Department, Qatar
| | - Anam Elarabi
- Hamad Medical Corporation, Pulmonology Department, Qatar
| | - Issam Al-Bozom
- Department of Laboratory Medicine and Pathology, Hamad Medical Corporation, Doha, Qatar
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31
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Li Z, Wang M, Zeng P, Chen Z, Zhan Y, Li S, Lin Y, Cheng J, Ye F. Examination of a Chinese-made cryptococcal glucuronoxylomannan antigen test in serum and bronchoalveolar lavage fluid for diagnosing pulmonary cryptococcosis in HIV-negative patients. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2021; 55:307-313. [PMID: 34052144 DOI: 10.1016/j.jmii.2021.05.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Revised: 04/21/2021] [Accepted: 05/06/2021] [Indexed: 11/26/2022]
Abstract
BACKGROUND We presented the performance of a Chinese-made cryptococcal glucuronoxylomannan (GXM) antigen test using serum and bronchoalveolar lavage fluid (BALF) samples in the HIV-negative Chinese population. METHODS Between February 2017 and January 2019, HIV-negative patients with pulmonary cryptococcosis were recruited and followed-up every three months, including completion of a chest CT examination and collection of serum and BALF samples. RESULTS Here, thirty-seven confirmed and ten clinically diagnosed patients were recruited. Furthermore, samples from 174 noncryptococcosis patients that may cause false positives were also collected. The sensitivity of a lateral flow assay (LFA) for detecting cryptococcal GXM antigen in serum and BALF samples from confirmed cases was 97% and 95%, respectively, and the specificity was 98.2% and 93%, respectively, and the differences in these values between the BALF and serum samples were not significant. The serum cryptococcal GXM antigen value showed a positive correlation (r: 0.581, p < 0.001) with pulmonary lesion size, while the BALF value showed no correlation (r: 0.253, p: 0.13). The positivity rate of BALF was higher than that of serum when the diameter of the pulmonary lesion was small (diameter less than 20 mm). Moreover, the serum cryptococcal GXM antigen levels showed an overall decreasing trend with the decrease in pulmonary lesion size after antifungal therapy in patient follow-up. CONCLUSIONS The Chinese-made cryptococcal GXM antigen test has better sensitivity and specificity for diagnosing pulmonary cryptococcosis in the HIV-negative Chinese population, and it could be used to diagnose and to monitor this disease.
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Affiliation(s)
- Zhengtu Li
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China
| | - Mingdie Wang
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China
| | - Peiying Zeng
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China
| | - Zhaoming Chen
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China
| | - Yangqing Zhan
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China
| | - Shaoqiang Li
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China
| | - Ye Lin
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China
| | - Jing Cheng
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China
| | - Feng Ye
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.
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32
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Archuleta S, Gharamti AA, Sillau S, Castellanos P, Chadalawada S, Mundo W, Bandali M, Oñate J, Martínez E, Chastain DB, DeSanto K, Shapiro L, Schwartz IS, Franco-Paredes C, Henao-Martínez AF. Increased mortality associated with uncontrolled diabetes mellitus in patients with pulmonary cryptococcosis: a single US cohort study. Ther Adv Infect Dis 2021; 8:20499361211004367. [PMID: 33815790 PMCID: PMC7992770 DOI: 10.1177/20499361211004367] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Accepted: 02/26/2021] [Indexed: 12/12/2022] Open
Abstract
Background: Diabetes mellitus is an established risk factor for bacterial infections, but its role in cryptococcosis is unclear. The study aimed to determine whether uncontrolled diabetes (HbA1c >7%) was an independent risk factor for mortality in cryptococcosis. Methods: A retrospective case–control study partially matched by age and gender was performed in patients tested for Cryptococcus infection at the University of Colorado Hospital from 2000 to 2019. A multivariable logistic regression model was used to identify mortality predictors. Cox proportional hazard model was used for survival analysis. Results: We identified 96 cases of cryptococcosis and 125 controls. Among cases, cryptococcal meningitis (49.0%) and pneumonia (36.5%) constituted most infections. Cases with pulmonary cryptococcosis with uncontrolled diabetes had a higher mortality at 10 weeks (50% versus 7%, p = 0.006) and 1 year (66.7% versus 13.8%, p = 0.005) compared to pulmonary cases with controlled or no diabetes. Unadjusted Cox proportional hazard model found an increased rate of death for uncontrolled diabetes at 10 weeks [hazard ratio 8.4, confidence interval (CI): 1.4–50.8, p = 0.02] and 1 year (hazard ratio 7.0, CI: 1.7–28.4, p = 0.007) among pulmonary cryptococcosis cases. Multivariable analysis showed a significantly increased odds of 10 weeks [odds ratio (OR) = 4.3, CI: 1.1–16.5, p = 0.035] and 1 year (OR = 5.0, CI: 1.4–18.3, p = 0.014) mortality for uncontrolled diabetes among pulmonary cryptococcosis cases. After adjustment for gender, age, and case/control, for every 1% increase in HbA1c levels, the odds of pulmonary cryptococcosis mortality at 1 year increased by 11% (OR = 1.6, CI 95%: 1.1–2.3, p = 0.006). Conclusion: Uncontrolled diabetes is associated with worse outcomes in pulmonary cryptococcosis, including a 4-fold and 6-fold increased odds of death at 10 weeks and 1 year, respectively. Glucose control interventions should be explored to improve clinical outcomes in patients with pulmonary cryptococcosis.
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Affiliation(s)
- Solana Archuleta
- School of Medicine, Division of Infectious Diseases, University of Colorado Denver, Aurora, CO, USA
| | - Amal A Gharamti
- Department of Internal Medicine, American University of Beirut, Beirut, Lebanon
| | - Stefan Sillau
- Department of Neurology, Division of Infectious Diseases, University of Colorado Denver, Aurora, CO, USA
| | | | | | - William Mundo
- School of Medicine, Division of Infectious Diseases, University of Colorado Denver, Aurora, CO, USA
| | - Mehdi Bandali
- School of Medicine, Division of Infectious Diseases, University of Colorado Denver, Aurora, CO, USA
| | | | | | - Daniel B Chastain
- Department of Clinical and Administrative Pharmacy, University of Georgia College of Pharmacy, Albany, GA, USA
| | - Kristen DeSanto
- Health Sciences Library, University of Colorado Denver, Aurora, Colorado, USA
| | - Leland Shapiro
- Department of Medicine, Division of Infectious Diseases, University of Colorado Denver, Aurora, CO, USA
| | - Ilan S Schwartz
- Division of Infectious Diseases, Department of Medicine, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB, Canada
| | - Carlos Franco-Paredes
- Department of Medicine, Division of Infectious Diseases, University of Colorado Denver, Aurora, CO, USA
| | - Andrés F Henao-Martínez
- Department of Medicine, Division of Infectious Diseases, University of Colorado Denver, 12700 E. 19th Avenue, Mail Stop B168, Aurora, CO 80045, USA
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Liang L, Liang Z, She D, Chen L. A case-control study of human immunodeficiency virus-negative patients with cryptococcemia and cryptococcal meningitis in a Chinese tertiary care hospital during 10 years. J Int Med Res 2021; 49:300060520984658. [PMID: 33472466 PMCID: PMC7829516 DOI: 10.1177/0300060520984658] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
OBJECTIVE This study aimed to characterize patients with cryptococcemia and compare the clinical features of cryptococcemia and cryptococcal meningitis. METHODS This was a retrospective, case-control study. We retrospectively identified blood cultures with Cryptococcus spp. growth. Controls were hospitalized patients who suffered from cryptococcal meningitis, but did not experience cryptococcemia. Controls and cases were matched by admission date, age, sex, and body weight. Clinical information was analyzed by two independent reviewers. RESULTS Eight patients with cryptococcemia and eight patients with cryptococcal meningitis were included. They were all negative for human immunodeficiency virus. The most common underlying disease was primary nephrotic syndrome. All patients presented with fever. The incidence of headache, nausea/vomiting, seizures, and cough/expectoration was significantly lower in patients with cryptococcemia than in those with cryptococcal meningitis. All clinical strains of Cryptococcus, except for one, were sensitive to fluconazole, voriconazole, itraconazole, amphotericin B, and flucytosine in vitro. The rate of receiving an amphotericin B-containing regimen was significantly higher in patients with cryptococcal meningitis than in those with cryptococcemia. In-hospital mortality was significantly higher in cryptococcemia cases compared with cryptococcal meningitis cases. CONCLUSION Cryptococcemia is an unusual infection characterized by a high mortality. Cryptococcemia requires early identification and prompt antifungal therapy.
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Affiliation(s)
- Liling Liang
- Department of Respiratory Medicine, The First Medical Centre of 104607Chinese PLA General Hospital, Beijing, China
| | - Zhixin Liang
- Department of Respiratory Medicine, The First Medical Centre of 104607Chinese PLA General Hospital, Beijing, China
| | - Danyang She
- Department of Respiratory Medicine, The First Medical Centre of 104607Chinese PLA General Hospital, Beijing, China
| | - Liang'an Chen
- Department of Respiratory Medicine, The First Medical Centre of 104607Chinese PLA General Hospital, Beijing, China
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Nsenga L, Kajjimu J, Olum R, Ninsiima S, Kyazze AP, Ssekamatte P, Kibirige D, Baluku JB, Andia-Biraro I, Bongomin F. Cryptococcosis complicating diabetes mellitus: a scoping review. Ther Adv Infect Dis 2021; 8:20499361211014769. [PMID: 33996076 PMCID: PMC8111545 DOI: 10.1177/20499361211014769] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2020] [Accepted: 04/13/2021] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND A better understanding of the epidemiology of cryptococcal infection in HIV-negative individuals is an international research interest. Immune dysfunction in diabetes mellitus (DM) significantly increases the risk of acquiring and reactivation of infection due to Cryptococcus neoformans. Risk factors and outcomes of cryptococcosis in DM are not well documented. OBJECTIVE The objective of this study was to determine the clinical characteristics and outcomes of cryptococcal infections in persons living with DM. METHODS MEDLINE (via PubMed), EMBASE, and the Cochrane Library databases were searched in November 2020. The searches covered the period between 1980 and 2020.We included studies that reported confirmed cryptococcosis in patients with DM. Reference lists of included articles were also searched, and additional studies were included if appropriate. No language restriction was applied. Single case reports, case series and original articles were included whereas review articles were excluded. RESULTS A total of 28 studies (24 single case reports, 4 retrospectives) were included involving 47 unique patients from Asia (17 cases), North America (six cases), South America (three cases) and Africa (two cases). Men constituted 75% (n = 18) of the cases. Median age was 60.5 (range: 27-79) years. The majority of the patients had cryptococcal meningitis (68.1%, n = 32) followed by disseminated cryptococcosis (6.4%, n = 7), and others (isolated cutaneous disease one, peritonitis one, pleural one, thyroid one, adrenal one). Diagnosis was achieved through either culture and microscopy (38/47), cryptococcal antigen tests (9/47) or histopathology (9/47) singly or in a combination. All-cause mortality was 38.3% (n = 18). Among those with meningitis mortality was 36.2%. CONCLUSION A wide spectrum of cryptococcal infections with varying severity occurs in DM. Mortality remains unacceptably high. There is a need for more studies to characterize better cryptococcal disease in DM.
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Affiliation(s)
- Lauryn Nsenga
- School of Medicine, Kabale University, Kabale, Uganda
| | - Jonathan Kajjimu
- Faculty of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda
| | - Ronald Olum
- Department of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda
| | - Sandra Ninsiima
- Department of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda
| | - Andrew Peter Kyazze
- Department of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda
| | - Phillip Ssekamatte
- Department of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda
| | - Davis Kibirige
- Department of Medicine, Uganda Martyrs Lubaga Hospital, Kampala, Uganda
- Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine, Uganda Research Unit, Entebbe, Uganda
| | - Joseph Baruch Baluku
- Division of Pulmonology, Kiruddu National Referral Hospital, Kampala, Uganda
- Department of Programs, Mildmay Uganda, Wakiso, Uganda
| | - Irene Andia-Biraro
- Department of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda
- Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine, Uganda Research Unit, Entebbe, Uganda
| | - Felix Bongomin
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Gulu University, P.O. Box, 166, Gulu, Uganda
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Ueno K, Yanagihara N, Shimizu K, Miyazaki Y. Vaccines and Protective Immune Memory against Cryptococcosis. Biol Pharm Bull 2020; 43:230-239. [PMID: 32009111 DOI: 10.1248/bpb.b19-00841] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Cryptococcosis is a potentially lethal disease caused by fungal pathogens including Cryptococcus neoformans and Cryptococcus gattii species complex. These fungal pathogens live in the environment and are associated with certain tree species and bird droppings. This infectious disease is not contagious, and healthy individuals may contract cryptococcal infections by inhaling the airborne pathogens from the environment. Although cleaning a contaminated environment is a feasible approach to control environmental fungal pathogens, prophylactic immunization is also considered a promising method to regulate cryptococcal infections. We review the history of the development of cryptococcal vaccines, vaccine components, and the various forms of immune memory induced by cryptococcal vaccines.
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Affiliation(s)
- Keigo Ueno
- Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases
| | - Nao Yanagihara
- Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases.,Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science
| | - Kiminori Shimizu
- Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science
| | - Yoshitsugu Miyazaki
- Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases
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36
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Fujimoto S, Oda N, Fujioka Y, Mitani R, Takata I. An Elderly Patient with Pulmonary Cryptococcosis with Mediastinal Lymphadenopathy Who Was Successfully Treated with Amphotericin B and Flucytosine. Intern Med 2020; 59:2547-2551. [PMID: 32581163 PMCID: PMC7662044 DOI: 10.2169/internalmedicine.4753-20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Pulmonary cryptococcosis develops not only in immunocompromised patients but also in immunocompetent patients. However, lymph node involvement is relatively rare in immunocompetent patients. We herein report the case of an 80-year-old man who was not in an apparent immunocompromised state but was diagnosed with pulmonary cryptococcosis with mediastinal lymphadenopathy. The patient was resistant to fluconazole and voriconazole monotherapy; thus, his lung lesions significantly worsened. He eventually responded well to a combination therapy of amphotericin B and flucytosine, which was administered according to the treatment strategy for disseminated diseases.
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Affiliation(s)
| | - Naohiro Oda
- Department of Internal Medicine, Fukuyama City Hospital, Japan
| | - Yusuke Fujioka
- Department of Internal Medicine, Fukuyama City Hospital, Japan
| | - Reo Mitani
- Department of Internal Medicine, Fukuyama City Hospital, Japan
| | - Ichiro Takata
- Department of Internal Medicine, Fukuyama City Hospital, Japan
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37
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Bramantono B, Danial A, Hadi U. A case of an AIDS patient with Cryptococcus neoformans infection. Pan Afr Med J 2020; 36:88. [PMID: 32774647 PMCID: PMC7392875 DOI: 10.11604/pamj.2020.36.88.20406] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Accepted: 11/01/2019] [Indexed: 11/30/2022] Open
Abstract
Cryptococcosis is the most common fungal disease in HIV-infected persons. It is known as the AIDS-defining illness for 60-70% of HIV-infected patients. Before antiretroviral therapy (ARV) was discovered, fungal and other opportunistic infections were a major problem for people with advanced HIV/AIDS. Presented here is a case of a 43-year-old man who was newly diagnosed HIV, in which he was admitted due to shortness of breath and decreased consciousness. His clinical symptoms, physical examination, laboratory and radiologic findings indicated a Cryptococcus neoformans infection. The patient had received treatment using anti-fungal and ARV that showed a clinical improvement during observation.
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Affiliation(s)
- Bramantono Bramantono
- Tropical and Infectious Disease Division, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Dr. Soetomo Teaching Hospital, Surabaya, East Java, Indonesia
| | - Ahmad Danial
- Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Dr. Soetomo Teaching Hospital, Surabaya, East Java, Indonesia
| | - Usman Hadi
- Tropical and Infectious Disease Division, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Dr. Soetomo Teaching Hospital, Surabaya, East Java, Indonesia.,Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Dr. Soetomo Teaching Hospital, Surabaya, East Java, Indonesia
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38
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Soni A, Athwal PSS, Kahlon S, Gogia A. Pulmonary Cryptococcosis in a Human Immunodeficiency Virus Negative Patient: A Case Report. Cureus 2020; 12:e9006. [PMID: 32775086 PMCID: PMC7402539 DOI: 10.7759/cureus.9006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Cryptococcosis is a major life-threatening fungal infection in patients with severe HIV infection and other immunocompromised states. Lung and central nervous system (CNS) are the most commonly involved organs in disseminated cryptococcosis. Others include skin, prostate, medullary cavity of bones, eyes, heart, liver, etc. Pulmonary cryptococcosis may be misdiagnosed because of comparatively nonspecific clinical and radiological features. We report the case of a 61-year-old male patient who is a known case of gastroesophageal reflux disease (GERD), myasthenia gravis, and steroid-induced diabetes mellitus. He was diagnosed with gangrenous cholecystitis at another institution but refused surgery. At our hospital, he experienced loss of consciousness in the out-patient department (OPD) and was therefore admitted for further evaluation where he was found to have pulmonary cryptococcosis and pancytopenia. Pulmonary cryptococcosis is usually found in HIV-positive immunosuppressed patients. However, sometimes it is also seen in HIV-negative patients, and they tend to have a good prognosis with adequate treatment.
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Affiliation(s)
- Aakriti Soni
- Internal Medicine, Himalayan Institute of Medical Sciences, Gurgaon, IND
| | | | - Sukhmanii Kahlon
- Internal Medicine, Medical University of the Americas, Camps, KNA
| | - Atul Gogia
- Internal Medicine, Sir Ganga Ram Hospital, New Delhi, IND
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Wu HH, Chen YX, Fang SY. Pleural effusion in an immunocompetent host with cryptococcal pneumonia: A case report. World J Clin Cases 2020; 8:1295-1300. [PMID: 32337205 PMCID: PMC7176623 DOI: 10.12998/wjcc.v8.i7.1295] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 03/06/2020] [Accepted: 03/26/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Pulmonary cryptococcosis is an opportunistic infection that mainly occurs among immunocompromised patients although it can sometimes occur in immunocompetent individuals. However, the imaging findings of pulmonary cryptococcosis in immunocompetent hosts differ from those in immunosuppressed patients. In addition, the most common imaging findings of isolated pulmonary cryptococcosis are single or multiple nodules. Cavities and the halo sign are, however, prevalent in immunosuppressed patients. In immunocompetent patients, lung consolidation, pleural effusion or cavities are scarce.
CASE SUMMARY A 29-year-old Asian male was admitted to our hospital with complaints of cough and fever that had persisted for a month. As a chest computed tomography scan showed consolidation in his left lower lobe, he was initially diagnosed with pneumonia and received antibiotic treatment. A second review of the chest computed tomography image revealed multiple cavities and pleural effusion. Flexible fiberoptic bronchoscopy was subsequently performed, bronchoalveolar lavage fluid and serum cryptococcal antigen tests were positive. Cryptococcus capsules were observed in bronchoalveolar lavage fluid ink stain. Histopathological examination of a percutaneous lung biopsy from the left lower lobe further revealed granulomatous inflammation, and periodic acid-Schiff staining showed red-colored yeast walls, signifying pulmonary cryptococcosis. The patient was then treated with a daily dose of fluconazole (0.4 g), but the cough and fever still persisted. We therefore changed treatment to voriconazole (0.2 g, twice a day), and the patient’s clinical outcome was satisfactory.
CONCLUSION Although rare, clinicians should not disregard the possibility of cavities and pleural effusion occurring in immunocompetent hosts without underlying diseases.
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Affiliation(s)
- Huan-Huan Wu
- Department of Respiratory Medicine, Dongyang Hospital Affiliated to Wenzhou Medical University, Dongyang 322100, Zhejiang Province, China
| | - Yan-Xiao Chen
- Department of Evidence-base Medicine, Dongyang Hospital Affiliated to Wenzhou Medical University, Dongyang 322100, Zhejiang Province, China
| | - Shuang-Yan Fang
- Department of Respiratory Medicine, Dongyang Hospital Affiliated to Wenzhou Medical University, Dongyang 322100, Zhejiang Province, China
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40
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Kalyango N, Kwizera R, Baluku JB, Bongomin F. Intra-cavitary pulmonary cryptococcoma in poorly controlled diabetes mellitus. Med Mycol Case Rep 2020; 28:1-3. [PMID: 32154097 PMCID: PMC7056601 DOI: 10.1016/j.mmcr.2020.02.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Revised: 02/17/2020] [Accepted: 02/21/2020] [Indexed: 01/09/2023] Open
Abstract
A 59-year-old HIV-negative Ugandan man presented with a long-standing history of respiratory symptoms and was found to have an intra-cavitary pulmonary cryptococoma by chest imaging and sputum culture. The serum cryptococcal antigen was negative. The sputum Xpert® MTB RIF Ultra assay was negative. He was previously treated for cavitary pulmonary tuberculosis. The patient had poorly controlled diabetes (HbA1c, 9.3%). The patient was successfully treated with oral fluconazole.
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Affiliation(s)
- Najibu Kalyango
- Department of Medicine, College of Health Sciences, Makerere University, Kampala, P.o.Box, 7072, Uganda
| | - Richard Kwizera
- Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, P.o.Box, 7072, Uganda
| | - Joseph B Baluku
- Department of Pulmonology, Mulago National Referral Hospital, Kampala, P.o.Box, 7051, Uganda
| | - Felix Bongomin
- Department of Medicine, College of Health Sciences, Makerere University, Kampala, P.o.Box, 7072, Uganda.,Department of Microbiology and Immunology, Faculty of Medicine, Gulu University, Gulu, P.o.Box 166, Uganda
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41
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Min J, Huang K, Shi C, Li L, Li F, Zhu T, Deng H. Pulmonary Cryptococcosis: comparison of Cryptococcal antigen detection and radiography in Immunocompetent and Immunocompromised patients. BMC Infect Dis 2020; 20:91. [PMID: 32000709 PMCID: PMC6993350 DOI: 10.1186/s12879-020-4818-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2019] [Accepted: 01/23/2020] [Indexed: 12/23/2022] Open
Abstract
Background We compared the cryptococcal antigen detection and imaging findings between immunocompetent and immunocompromised patients in whom pulmonary cryptococcosis had been diagnosed. The aim of our study was to determine whether the patient’s immune status and radiography affect the detection of cryptococcal antigen. Methods According to whether they took immunosuppressive drugs or not, seventy and eight adult patients with pulmonary cryptococcosis were divided into two groups: the immunocompetent group and the immunocompromised group. According to the detection of CrAg, each group was divided into the CrAg+ group and the CrAg- group. Then, clinical records, laboratory examinations and computed tomography findings were collected and analyzed. Results No difference was found in baseline characteristics, clinical symptoms, and laboratory investigations. By comparing CrAg detection in these two groups, it was found that the number of CrAg+ cases in the immunocompetent group was more than that in the immunocompromised group. And in the immunocompetent group, diffuse lesions were more common in CrAg+ group and limited lesions were more frequently observed in CrAg- group. Conclusions The patient’s immune status and radiography would affect the detection of cryptococcal antigen. And serum CrAg could be a useful tool for the diagnosis of pulmonary cryptococcosis in immunocompetent patients with extensive lung involvement.
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Affiliation(s)
- Jingqi Min
- Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China
| | - Kunlun Huang
- Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China
| | - Chanmei Shi
- Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China
| | - Laifu Li
- Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China
| | - Fuye Li
- Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China
| | - Tao Zhu
- Department of Pulmonary and Critical Care Medicine, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Huojin Deng
- Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
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42
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Ueno K, Yanagihara N, Otani Y, Shimizu K, Kinjo Y, Miyazaki Y. Neutrophil-mediated antifungal activity against highly virulent Cryptococcus gattii strain R265. Med Mycol 2020; 57:1046-1054. [PMID: 30668754 DOI: 10.1093/mmy/myy153] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2018] [Revised: 12/10/2018] [Accepted: 12/13/2018] [Indexed: 01/08/2023] Open
Abstract
Vaccine-induced immune responses, including neutrophil, macrophage, and T-cell responses, ameliorate cryptococcosis caused by Cryptococcus gattii. However, whether neutrophils can exert fungicidal activity against C. gattii remains to be elucidated. Therefore, in this study, we investigated the neutrophil-mediated fungicidal effect against C. gattii R265 in vitro and compared it to the related fungal pathogen, Cryptococcus neoformans standard strain H99. We found that neutrophils recognized, phagocytosed, and killed C. gattii R265 in the presence of fresh mouse serum. This antifungal effect required phagocytosis and serine protease activity but not nicotinamide adenine dinucleotide phosphate oxidase activity. We also demonstrated that C. gattii R265 was more resistant to oxidative and nitrosative stress than C. neoformans H99. Together, these findings indicate that neutrophils can exert fungicidal activity against highly virulent C. gattii, at least under in vitro conditions.
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Affiliation(s)
- Keigo Ueno
- Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan
| | - Nao Yanagihara
- Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.,Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, 6-3-1 Niijuku, Katsushika-ku, Tokyo 125-8585, Japan
| | - Yoshiko Otani
- Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.,Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, 6-3-1 Niijuku, Katsushika-ku, Tokyo 125-8585, Japan
| | - Kiminori Shimizu
- Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, 6-3-1 Niijuku, Katsushika-ku, Tokyo 125-8585, Japan
| | - Yuki Kinjo
- Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan.,Department of Bacteriology, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan.,Jikei Center for Biofilm Science and Technology, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan
| | - Yoshitsugu Miyazaki
- Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan
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43
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Izumikawa K, Kakeya H, Sakai F, Shibuya K, Sugita T, Takazono T, Takata T, Tashiro M, Teruya K, Nakamura S, Noguchi H, Hiruma M, Makimura K, Miyazaki T, Miyazaki Y, Yamagishi Y, Yoshida K, Watanabe A. Executive Summary of JSMM Clinical Practice Guidelines for Diagnosis and Treatment of Cryptococcosis 2019. Med Mycol J 2020; 61:61-89. [PMID: 33250505 DOI: 10.3314/mmj.20.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Affiliation(s)
- Koichi Izumikawa
- Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences
| | - Hiroshi Kakeya
- Department of Infection Control Science, Osaka City University Graduate School of Medicine
| | - Fumikazu Sakai
- Department of Diagnostic Radiology, Saitama Medical University International Medical Center
| | - Kazutoshi Shibuya
- Department of Pathology, Omori Hospital, Toho University School of Medicine
| | - Takashi Sugita
- Department of Microbiology, Meiji Pharmaceutical University
| | - Takahiro Takazono
- Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences
| | - Tohru Takata
- Department Oncology, Hematology, and Infectious Diseases, Fukuoka University Hospital
| | - Masato Tashiro
- Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences
| | - Katsuji Teruya
- AIDS Clinical Center, National Center for Global Health and Medicine
| | - Shigeki Nakamura
- Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases.,Department of Microbiology, Tokyo Medical University
| | | | | | - Koichi Makimura
- Medical Mycology, Graduate School of Medicine, Teikyo University
| | - Taiga Miyazaki
- Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences
| | - Yoshitsugu Miyazaki
- Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases
| | - Yuka Yamagishi
- Department of Clinical Infectious Diseases, Aichi Medical University Graduate School of Medicine
| | - Koichiro Yoshida
- Department of Medical Safety Management, Division of Infection Control and Prevention, Kindai University Hospital
| | - Akira Watanabe
- Division of Clinical Research, Medical Mycology Research Center, Chiba University
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Huang J, Lan C, Li H, Chen S, Lin Q, Weng H. Concomitant lung adenocarcinoma and pulmonary cryptococcosis confirmed by pathologic examinations. Medicine (Baltimore) 2019; 98:e18316. [PMID: 31852116 PMCID: PMC6922476 DOI: 10.1097/md.0000000000018316] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Revised: 10/18/2019] [Accepted: 11/07/2019] [Indexed: 02/08/2023] Open
Abstract
To describe the characteristics of concomitant lung cancer and pulmonary cryptococcosis (PC) cases.A total of 8 patients with lung cancer and coexisting PC, who were admitted to Fuzhou Pulmonary Hospital of Fujian from 1st January 2009 to 31st December 2015 and whose diagnoses were confirmed by pathological examinations, were studied.One patient had a history of diabetes mellitus and 1 had a history of treated with surgery. The lesions in 7 cases manifested as nodular shadows; only 1 case showed the lesion of the 2 diseases mergedmixed together, and it manifested as a large flake-like infiltrated shadow in the same lobe. The histological type in all of the patients was lung adenocarcinoma. Lung cancer stage was advanced (III-IV) in 25.0% of the cases. The 5 patients who received surgery and drug treatment are presently healthy following resection. Recurrence and metastasis of lung cancer following surgery occurred in 2 patients in whom the tumor was controlled again after anti-tumor treatment. One patient with advanced lung cancer and PC was treated with antifungal therapy in combination with antineoplastic chemotherapy, but she failed to improve and died 10 months after symptom onset during the follow-up period.PC coexisting with pulmonary carcinoma is rare. PC can manifest as pulmonary nodules and mimic malignant lesions, so it must be considered during a differential diagnosis of pulmonary nodules, especially in immunosuppressed patients.
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Affiliation(s)
- Jinbao Huang
- Department of Respiratory and Critical Care Medicine
| | | | - Hongyan Li
- Department of Respiratory and Critical Care Medicine
| | | | - Qinghua Lin
- Department of Pathology, Fuzhou Pulmonary Hospital of Fujian, Educational Hospital of Fujian Medical University, Fuzhou, China
| | - Heng Weng
- Department of Respiratory and Critical Care Medicine
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Setianingrum F, Rautemaa-Richardson R, Denning DW. Pulmonary cryptococcosis: A review of pathobiology and clinical aspects. Med Mycol 2019; 57:133-150. [PMID: 30329097 DOI: 10.1093/mmy/myy086] [Citation(s) in RCA: 156] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2018] [Accepted: 09/05/2018] [Indexed: 01/13/2023] Open
Abstract
Pulmonary cryptococcosis is an important opportunistic invasive mycosis in immunocompromised patients, but it is also increasingly seen in immunocompetent patients. The main human pathogens are Cryptococcus neoformans and C. gattii, which have a worldwide distribution. In contrast to cryptococcal meningitis, pulmonary cryptococcosis is still underdiagnosed because of limitations in diagnostic tools. It can mimic lung cancer, pulmonary tuberculosis, bacterial pneumonia, and other pulmonary mycoses both clinically and radiologically. Pulmonary nodules are the most common radiological feature, but these are not specific to pulmonary cryptococcosis. The sensitivity of culture of respiratory samples for Cryptococcus is poor and a positive result may also reflect colonisation. Cryptococcal antigen (CrAg) with lateral flow device is a fast and sensitive test and widely used on serum and cerebrospinal fluid, but sera from patients with pulmonary cryptococcosis are rarely positive in the absence of disseminated disease. Detection of CrAg from respiratory specimens might assist the diagnosis of pulmonary cryptococcosis but there are very few data. Molecular detection techniques such as multiplex reverse transcription polymerase chain reaction (RT-PCR) could also provide better sensitivity but these still require validation for respiratory specimens. The first line of treatment for pulmonary cryptococcosis is fluconazole, or amphotericin B and flucytosine for those with central nervous system involvement. Pulmonary cryptococcosis worsens the prognosis of cryptococcal meningitis. In this review, we summarize the biological aspects of Cryptococcus and provide an update on the diagnosis and management of pulmonary cryptococcosis.
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Affiliation(s)
- Findra Setianingrum
- Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, University of Manchester, UK
- Parasitology Department, Universitas Indonesia, Jakarta, Indonesia
| | - Riina Rautemaa-Richardson
- Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, University of Manchester, UK
- Mycology Reference Centre Manchester, ECMM Centre of Excellence in Clinical and Laboratory Mycology and Clinical Studies, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK
- Department of Infectious Diseases, Wythenshawe Hospital Manchester University NHS Foundation Trust, Manchester, UK
| | - David W Denning
- Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, University of Manchester, UK
- Department of Infectious Diseases, Wythenshawe Hospital Manchester University NHS Foundation Trust, Manchester, UK
- National Aspergillosis Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, UK
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Hou X, Kou L, Han X, Zhu R, Song L, Liu T. Pulmonary cryptococcosis characteristics in immunocompetent patients-A 20-year clinical retrospective analysis in China. Mycoses 2019; 62:937-944. [PMID: 31287920 PMCID: PMC6852394 DOI: 10.1111/myc.12966] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2019] [Revised: 07/03/2019] [Accepted: 07/05/2019] [Indexed: 12/28/2022]
Abstract
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.
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Affiliation(s)
- Xiaomeng Hou
- Department of Pulmonary Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Lei Kou
- Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio
| | - Xiaozhen Han
- Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio
| | - Rui Zhu
- Department of Medical Record, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Lan Song
- Department of Radiology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
| | - Tao Liu
- Department of Pulmonary Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
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Huang J, Li H, Lan C, Zou S, Zhang H, Wang X, Weng H. Concomitant severe influenza and cryptococcal infections: A case report and literature review. Medicine (Baltimore) 2019; 98:e15544. [PMID: 31083210 PMCID: PMC6531193 DOI: 10.1097/md.0000000000015544] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Concomitant influenza and cryptococcal infections are rare. Herein, we describe an unusual case of an avian influenza A (H7N9) infection with several severe mixed bacterial infections and systemic super-infection with Cryptococcus neoformans presenting as ventilator-associated pneumonia (VAP) and bloodstream infection in a previously immunocompetent man during hospitalization.A 58-year-old man was admitted to our hospital complaining of hyperpyrexia, dyspnoea, cough, and phlegm with blood. A chest computed tomography scan revealed multiple ground-glass opacities and consolidation in both lungs with right pleural effusion. An initial sputum test was positive for influenza A (H7N9) virus. After antiviral treatment and other supportive measures, the patient's condition improved. However, the patient's condition deteriorated again approximately 2 weeks after admission, and bronchoalveolar lavage fluid (BALF) and blood cultures were positive for C. neoformans. Therapy with intravenous liposomal amphotericin B and fluconazole was started. After a 2-week antifungal treatment, BALF and blood cultures were negative for C. neoformans. However, the patient had persistent lung infiltrates with severe pulmonary fibrosis with a prolonged course of disease. On hospital day 40, BALF and blood cultures were both positive for multidrug-resistant Stenotrophomonas maltophilia. Finally, the patient developed septic shock, disseminated intravascular coagulation and multi-organ failure and succumbed to treatment failure.Cryptococcal infection can occur in patients with severe influenza during hospitalization with a more severe condition, and the clinician should be aware of this infection.
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Affiliation(s)
- Jinbao Huang
- Department of Respiratory and Critical Care Medicine
| | - Hongyan Li
- Department of Respiratory and Critical Care Medicine
| | | | - Shenghua Zou
- Department of Clinical Laboratory, Fuzhou Pulmonary Hospital of Fujian, Educational Hospital of Fujian Medical University, Fuzhou, China
| | | | - Xinhang Wang
- Department of Respiratory and Critical Care Medicine
| | - Heng Weng
- Department of Respiratory and Critical Care Medicine
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Tajima K, Yamanaka D, Ishibashi KI, Adachi Y, Ohno N. Solubilized melanin suppresses macrophage function. FEBS Open Bio 2019; 9:791-800. [PMID: 30984552 PMCID: PMC6443868 DOI: 10.1002/2211-5463.12615] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Revised: 02/20/2019] [Accepted: 02/22/2019] [Indexed: 11/18/2022] Open
Abstract
Melanin‐producing Cryptococcus and Aspergillus are highly invasive and can suppress or escape the immune system of the host. Since non‐melanin‐producing strains do not affect the immune system, melanin may play a role in immune system suppression. Artificial melanin synthesized using conventional methods is insoluble, making structural and functional analysis of this chemical difficult. In this study, we describe a melanin solubilization method based on polymerization of homogentisic acid (solubilizing component) and an equivalent amount of L‐DOPA in the presence of laccase. In addition, we investigated the effect of melanin on the immune system. Homogentisic acid and L‐DOPA mixed melanin (HALD), the synthetic solubilized melanin, did not exert a cytotoxic effect on mouse macrophages. HALD suppressed cytokine and reactive oxygen species production by macrophages when they were stimulated by fungal components. HALD also suppressed the phagocytosis of fungal components by macrophages. These results suggest that HALD can suppress the function of macrophages without causing cytotoxicity.
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Affiliation(s)
- Katsuya Tajima
- Tokyo University of Pharmacy and Life Sciences Hachioji Japan
| | | | | | | | - Naohito Ohno
- Tokyo University of Pharmacy and Life Sciences Hachioji Japan
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Zhu T, Luo WT, Chen GH, Tu YS, Tang S, Deng HJ, Xu W, Zhang W, Qi D, Wang DX, Li CY, Li H, Wu YQ, Li SJ. Extent of Lung Involvement and Serum Cryptococcal Antigen Test in Non-Human Immunodeficiency Virus Adult Patients with Pulmonary Cryptococcosis. Chin Med J (Engl) 2018; 131:2210-2215. [PMID: 30203796 PMCID: PMC6144838 DOI: 10.4103/0366-6999.240815] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
Abstract
Background: Serum cryptococcal antigen (CrAg) test is the most used noninvasive method to detect cryptococcal infection. However, false-negative CrAg test is not uncommon in clinical practice. Then, the aim of this study was to investigate the factors associated with false-negative CrAg test among non-human immunodeficiency virus (HIV) adult patients with pulmonary cryptococcosis and its clinical features. Methods: One hundred and fourteen non-HIV adult patients with pulmonary cryptococcosis, proven by biopsy, were retrospectively reviewed. Finally, 85 patients were enrolled; 56 were CrAg positive (CrAg+ group) and 29 were negative (CrAg− group). It was a cross-sectional study. Then, baseline characteristics, underlying diseases, clinical symptoms, laboratory findings, and chest radiological findings were reviewed and analyzed. Chi-square test was used to analyze categorical variable. Odds ratio (OR) was used to measure correlation. Student's t-test was obtained to analyze continuous variable. Results: No difference in baseline characteristics, underlying diseases, clinical symptoms, and laboratory findings were found between two groups (P > 0.05 in all). Nevertheless, diffuse extent lesion was 82.1% in CrAg+ group and 10.3% in CrAg− group (χ2= 40.34, P < 0.001; OR = 39.87). Conclusions: Among patients with limited pulmonary involvement, a negative serum CrAg does not preclude the diagnosis of pulmonary cryptococcosis. However, among patients with extensive pulmonary involvement, serum CrAg is a useful diagnostic tool for pulmonary cryptococcosis. Furthermore, we also noticed that the untypical and mild presentations with extensive pulmonary lesion might be the features of pulmonary cryptococcosis, which needs further investigation.
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Affiliation(s)
- Tao Zhu
- Department of Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Wan-Ting Luo
- Southern Medical University, Guangzhou, Guangdong 510280, China
| | - Gui-Hua Chen
- Department of Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Yue-Sheng Tu
- Southern Medical University, Guangzhou, Guangdong 510280, China
| | - Shuo Tang
- Department of Orthopedic Medicine, Shenzhen Nanshan Hospital, Shenzhen, Guangdong 518052, China
| | - Huo-Jin Deng
- Department of Respiratory Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong 510280, China
| | - Wei Xu
- Southern Medical University, Guangzhou, Guangdong 510280, China
| | - Wei Zhang
- Department of Respiratory Medicine, First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan 610500, China
| | - Di Qi
- Department of Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Dao-Xin Wang
- Department of Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Chang-Yi Li
- Department of Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - He Li
- Department of Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Yan-Qiao Wu
- Department of Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Shen-Jin Li
- Department of Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
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50
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Shuai SY, Xiong L, He XL, Yu F, Xia Q, Zhou Q. A unique case report of endobronchial cryptococcosis and review of the literature. Respir Med Case Rep 2018; 25:247-252. [PMID: 30302308 PMCID: PMC6174268 DOI: 10.1016/j.rmcr.2018.09.014] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2018] [Revised: 09/22/2018] [Accepted: 09/22/2018] [Indexed: 12/11/2022] Open
Abstract
Cryptococcosis is an infection caused by the yeast-like fungus Cryptococcus neoformans. Pulmonary cryptococcosis is typically identified as a single mass or as multiple nodules, while endobronchial lesions are quite rare. Here we report an uncommon case of pulmonary cryptococcosis presenting as endobronchial lesion in an immunocompetent patient. A 49-year-old male patient complained of intermittent cough with hemoptysis for two years. Computerized tomography of the chest showed a filling defect in the basal segment of the right lower lobe bronchus. A flexible bronchoscopic examination revealed a white smooth-surfaced polypoid lesion completely occluding the medial basal segment of the right lower lobe bronchus. The diagnosis was confirmed by bronchial biopsy under bronchoscopy, and the histopathologic findings showed the organisms were Cryptococcal neoformans. The patient was treated with fluconazole at a dose of 400 mg daily. The endobronchial lesion was found rapidly diminished after 18 days of therapy, and disappeared after 6.5 months of therapy by repeated fiberoptic bronchoscopy. Then the patient continued fluconazole for another 2.5 months. During the total 16 months' follow-up visits, the patient repeated CT scanning for five times, the results of which were all normal. The patient's symptoms disappeared as well, and now he is still under follow-up. This case highlights the fact that pulmonary cryptococcosis can present as endobronchial lesions even in immunocompetent subjects, mimicking lung tumor. Pathological confirmation is important to establish the definite diagnosis.
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Affiliation(s)
- Shi-Yuan Shuai
- Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Liang Xiong
- Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xin-Liang He
- Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Fan Yu
- Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qin Xia
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qiong Zhou
- Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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