新型隐球菌脑膜炎45例临床分析

目的 探讨新型隐球菌脑膜炎（CNM）患者的临床特点,为诊断和治疗提供经验与参考。 方法 回顾性分析2010年1月—2019年6月海南省人民医院收治的45例CNM患者的临床表现及治疗情况。 结果 4.44%（2例）有明确鸽子接触史,22.22%（10例）合并有艾滋病,28.89%（13例）合并有肺结核、肝病等其他基础疾病。主要临床症状为头痛（36/45,80%）,发热（31/45,68.89%）,恶心、呕吐（15/45,33.33%）,复视、视力下降（3/45,6.67%）,意识障碍（4/45,8.89%）,抽搐（2/45,4.44%）,听力下降（1/45,2.22%）,脑膜刺激征阳性（11/45,24.44%）。80%(36例)出现高颅压,20例脑脊液压力大于300 mmH₂O。脑脊液检查显示颅内压升高,脑脊液蛋白、糖、氯化物呈现一高二低现象;20例患者脑脊液培养阳性,分离菌株对氟康唑、5-氟胞嘧啶(5-FC)、两性霉素B(AmB)和伏立康唑的敏感性较高;45例患者中,18例给予AmB联合5-FC治疗,12例接受AmB联合氟康唑治疗,4例接受氟康唑+5-FC治疗,8例单用AmB,3例单用氟康唑治疗,治愈24例,好转2例,有效率57.78%。 结论 CNM患者主要以颅内高压为特点,患者出现发热、头痛、脑膜刺激征阳性,应及时行腰穿,反复行脑脊液涂片及培养明确诊断,隐球菌对多种抗真菌药敏感,临床可个体化采用AmB、氟康唑（或）5-FC的联合方案治疗。     

Cryptococcal meningitis in a patient treated with infliximab

Infliximab, a tumor necrosis factor-alpha inhibitor, is increasingly used for the therapy of different inflammatory conditions. We report the first case of cryptococcal meningitis in a patient treated with infliximab and other immunosuppressive agents, and review a further 5 reported cryptococcal infections. All of them involved fungal pneumonia. Outcome was favorable in all cases.     

艾滋病合并新型隐球菌脑膜炎临床分析

目的通过对25例艾滋病合并新型隐球菌脑膜炎的临床分析,提高对艾滋病合并新型隐球菌脑膜炎的认识。方法对本院2000年8月—2006年2月收治的25例艾滋病合并新型隐球菌脑膜炎病例进行回顾性分析。结果25例新型隐球菌脑膜炎患者均为艾滋病晚期患者,T细胞亚群检测11例:CD4<50/mm39例,CD450~100/mm32例;平均26.18/mm3。在确诊时已合并多种机会感染。结论艾滋病患者合并新型隐球菌脑膜炎病情重,预后差,实验室病原学检查结果是诊断新型隐球菌脑膜炎的主要依据。     

新型隐球菌性脑膜炎109例临床分析

目的了解HIV阴性新型隐球菌性脑膜炎患者的临床特征及其治疗转归。方法回顾性分析109例抗-HIV阴性的新型隐球菌性脑膜炎患者的流行病学资料、临床表现、实验室检查、治疗及预后的情况。结果109例新型隐球菌性脑膜炎患者中,临床表现以剧烈头痛、发热、颅内压升高、脑膜刺激征阳性为主。患者中有基础性疾病者占9．2％。发病前有鸽子接触史者占19-3％,桉树富植区居住史者占61．4％。所有患者颅内压均升高,其中37．6％超过330mmH2O（1mmH2O=0．098kPa）。首次墨汁染色涂片找隐球菌阳性率67．0％,经多次反复查找涂片阳性率100．0％;脑脊液培养隐球菌阳性率89．0％。治疗总有效率为85．3％（93例）,病死率14．7％（16例）。结论对发热、剧烈头痛及颅内压升高,且有鸽子接触史或桉树种植区居住史的患者应考虑新型隐球菌性脑膜炎的可能,一旦诊断应积极控制硕内压,同时给予足量、足疗程的抗真菌药物以提高疗效和降低病死率。     

利用环介导等温扩增技术检测新型隐球菌

目的：建立一种快速检测新型隐球菌的方法。方法根据新型隐球菌的18 S rRNA基因序列设计内外引物各一对,在不同温度下对新型隐球菌进行环介导等温扩增,以探明环介导等温扩增法检测新型隐球菌最适宜的温度。对新型隐球菌、其他几种常见引起脑膜炎的病原菌以及部分种类的念珠菌进行扩增,以研究环介导等温扩增技术检测隐球菌的特异性。将新鲜培养的新型隐球菌稀释后加入非隐球菌感染患者的脑脊液中,模拟脑膜炎感染后的脑脊液环境,以研究环介导等温扩增技术检测新型隐球菌的敏感性。结果环介导等温扩增法检测新型隐球菌在60℃～65℃条件下均能实现良好扩增。环介导等温扩增法对其他病原菌的检测结果均为阴性,仅新型隐球菌的检测结果为阳性,特异性达到100%。用环介导等温扩增法从脑脊液中检测新型隐球菌的最低检出限为102 CFU/ml。用环介导等温扩增技术检测新型隐球菌性脑膜炎,能节省培养及传统鉴定的时间,从DNA的提取至反应结束在2～3h内即可完成,大大减少了诊断所需时间。结论环介导等温扩增是一种灵敏度高,特异性强,耗时短,且操作简便的检测新型隐球菌感染的方法。     

Utility of urine and serum lateral flow assays to determine the prevalence and predictors of cryptococcal antigenemia in HIV-positive outpatients beginning antiretroviral therapy in Mwanza,Tanzania

Background

Detection of subclinical cryptococcal disease using cryptococcal antigen screening among HIV-positive individuals presents a potential opportunity for prevention of both clinical disease and death if patients with detectable cryptococcal antigen are identified and treated pre-emptively. Recently developed point-of-care cryptococcal antigen tests may be useful for screening, particularly in resource-limiting settings, but few studies have assessed their utility.

Methodology

The objectives of this study were to determine the prevalence and factors associated with cryptococcal antigenemia in HIV-positive patients with CD4⁺ T-cell counts ≤200 cells/µL who were initiating ART, and also to evaluate the utility of the point-of-care urine lateral flow assay (LFA) cryptococcal antigen test using two different diluents, compared to gold standard serum antigen testing, as a screening tool. Urine and serum of outpatients initiating antiretroviral therapy at two hospitals in Mwanza were tested for cryptococcal antigen, and demographic and clinical characteristics were obtained using structured questionnaires and patients’ files. Patients with asymptomatic cryptococcal antigenemia received oral fluconazole in accordance with World Health Organization recommendations.

Results

Among 140 patients screened, 10 (7.1%) had asymptomatic cryptococcal antigenemia with a positive serum cryptococcal antigen. Four of these ten patients had CD4 counts between 100 and 200 cells/µL. The prevalence of cryptococcal antigen detected in urine using a standard (older) and a test (newer) diluent were 44 (31.4%) and 19 (13.6%), with Kappa coefficients compared to serum of 0.28 and 0.51 (p<0.001 for both). Compared to the new LFA diluent for urine cryptococcal antigen, the standard diluent had higher sensitivity (100% versus 80%) but lower specificity (74% versus 92%) using serum cryptococcal antigen as a gold standard.

Conclusions

Our findings suggest that HIV-positive outpatients with CD4 counts <200 cells/µL, rather than 100, should be screened for asymptomatic cryptococcal antigenemia given its association with mortality if untreated. Agreement of the urine LFA with the serum LFA was not sufficient to recommend routine screening with urine LFA.     

Anti-Cryptococcal activity of a furanone derivative–antibiofilm and opsonophagocytic potential

Cryptococcus neoformans, an encapsulated fungal pathogen is evolving as a major threat to immune-compromised patients and rarely to healthy individuals also. The cell wall bound capsular polysaccharide, melanin pigment and biofilm formation are major virulence factors that are known to contribute to cryptococcal meningitis. In the present study, a furanone derivative, (E)-5-benzylidenedihydrofuran-2(3H)-one (compound-6) was evaluated against biofilm of seven different strains of C. neoformans in melanized and non-melanized condition. In addition, the efficacy of compound-6 in activation of TLR-2, opsonophagocytosis, and modulation of cytokine expression during phagocytosis were studied. During the biofilm study, we found that moderate capsule size favored biofilm formation. Interestingly, the minimum biofilm eradication concentration (MBEC_0.5) of melanized biofilm was found to be achieved at 1- to 1.7-fold higher MBEC_0.5 of non-melanized cells. The maximum eradication of 77% and 69% of non-melanized and melanized biofilm were observed. The capsule size was reduced to half of its size with marked changes in morphology. Furthermore, expression of TLR2, iNOS and pro-inflammatory cytokines such as TNF-α, IL-12, and IFN-γ were also facilitated by compound-6. The correlation analysis showed a positive correlation between phagocytosis and the expression of TLR-2, iNOS, IL-6, IL-12. Collectively, the significant effect of compound-6, anti-melanization activity, antibiofilmand effective immunomodulant could be an interesting dual strategy drug agonist against cryptococcal meningitis.     

Progressive Cytopenia Developing during Treatment of Cryptococcosis in a Patient with HIV Infection and Bone Marrow Cryptococcal Infection

Cytopenia is a common complication in patients with human immunodeficiency virus (HIV) infection. Identifying the cause is demanding because of the wide range of possible diagnoses. We herein report an HIV-infected patient with disseminated cryptococcosis involving multiple organs including the blood, brain, lungs, and bone marrow, who developed progressive pancytopenia after initiation of anti-fungal treatment with liposomal amphotericin-B (L-AMB) and flucytosine (5FC). The pancytopenia persisted despite early 5FC discontinuation. A bone marrow biopsy revealed cryptococcal infiltration and the blood examination findings recovered quickly after resuming L-AMB. Thus, this HIV-infected patient''s pathological findings and clinical course suggested that the primary cause of the pancytopenia was bone marrow cryptococcosis.     

Cryptococcal infection with ruxolitinib in primary myelofibrosis: A case report and literature review

Cryptococcus neoformans (CN) is an encapsulated yeast that is found worldwide. It causes self‐limiting infections in immunocompetent hosts; however, infections due to CN could be disseminated and potentially life‐threatening in immunocompromised hosts. Herein, we present a patient with primary myelofibrosis who received ruxolitinib and developed disseminated cryptococcosis due to CN. We further discuss immune compromising factors indigenous to myeloproliferative neoplasms, ruxolitinib, and immunological pathways associated with janus kinase inhibition. We further review other cases of cryptococcal infections in patients receiving ruxolitinib reported in the literature. The report underscores the importance of suspecting infections with intracellular pathogens early in the course of illness in patients with higher rates of cumulative immunosuppression. A high clinical suspicion should be maintained when caring for such immunosuppressed patients receiving immunomodulatory agents as severe, disseminated infections can present atypically and lead to worse outcomes.