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Objective To investigate the association between genetic polymorphisms of Dectin-2 and pulmonary cryptococcosis.Methods A total of 134 non-human immunodeficiency virus (HIV)patients with pulmonary cryptococcosis and 464 healthy controls were included in this case control study.The peripheral leucocyte DNA was extracted and genotyping was performed by multiplex SNaPshot technology.The single nucleotide polymorphism (SNP)of rs11045418 located at 5′-flanking locus of Dectin-2 gene was genotyped.Patients without predisposing conditions were compared independently.The differences of gene polymorphism distributions compared between pulmonary patients and healthy control, and between patients without predisposing conditions and healthy control.All data were analyzed withχ2 tests.Results Among the total 134 patients,82 patients had no predisposing factors.Thirty two patients met the proven diagnosis criteria and 102 patients were probable pulmonary cryptococcosis.According to the site of infection, 72 patients had local infection in lungs and 62 patients had disseminated cryptococcosis.Three samples failed in genotyping,one of which was a patient without predisposing factor.Compared with the control group,there was a trend of increasing proportion of heterozygote rs11045418 CT in the 131 pulmonary cryptococcosis patients (59% vs 50%,P =0.069,OR=1.44,95%CI :0.97-2.13),and the heterozygote was significantly increased in 81 patients without predisposing conditions(64% vs 50%,P =0.017,OR= 1 .82,95 %CI :1 .11 -2.95 ).No significant difference of genotype distribution was found between the local and disseminated infection patients.Conclusion Our study shows that rs11045418 CT heterozygote in Dectin-2 is associated with the susceptibility of pulmonary cyrptococcosis among non-HIV-infected Chinese patients,which indicated that the change of Dectin-2 receptor may play a role in the pathogenesis of pulmonary cyrptococcosis.
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Objective To describe the distributions of FCGR polymorphisms in human immunodeficiency virus (HIV)-uninfected patients with cryptococcosis,and to investigate the association of FCGR polymorphisms with the susceptibility to cryptococcosis.Methods The distributions of the four functional polymorphisms,including FCGR2A 131H/R,FCGR3A 158F/V,FCGR3B NA1/NA2,and FCGR2B 232I/T were compared between 198 cryptococcosis patients and 190 healthy controls.The polymorphisms distribution patterns were also compared between patients with central nervous system (CNS) infection and those without CNS infection.Genotyping of eight single nucleotide polymorphism (SNP) in FCGR were performed by multiplex SNaPshot technology using DNA extracted from blood samples.The comparison between patients and controls was performed by chi square test or Fisher exact test.Results Compared to healthy controls,the frequency of FCGR2B 232I/I increased (65％ vs 53％,x2 =4.27,P=0.039,OR=1.652,95％CI:1.02-2.67) and that of FCGR2B 232I/T decreased (27％ vs 40％,x2 =5.77,P=0.016.OR=0.542,95％CI:0.33-0.90) in patients with cryptococcal meningitis.Among immunocompetent patients,the frequency of FCGR2B 232I/I was also over-presented (69％ vs 53％,x2=4.53,P =0.033,OR=1.958,95％CI:1.05-3.66) and the FCGR2B 232I/T genotype was also less frequently observed (24％ vs 40％,x2=5.14,P=0.023,OR=0.467,95％CI:0.24-0.91) compared to healthy controls.There were 117 cases with CNS infection and 81 non-CNS infection cases.The genotype of FCGR2A 131R/Rwas over-presented (19％ vs 6％,x2 =6.48,P=0.011,OR=3.52,95％CI:1.27-9.73) and the FCGR2B 232I/T genotype was under-presented (27 ％ vs 46 ％,x2 =7.56,P =0.006,OR=0.431,95％CI:0.24-0.79) in patients with CNS infection compared with those without CNS infection.Furthermore,the frequency of FCGR2B 232I/I genotypes increased (69％ vs47％,x2 =5.47,P=0.019,OR=2.479,95％CI:1.15-5.34) and the frequency of FCGR2B 232I/T decreased (24％ vs 51％,x2 =8.66,P=0.003,OR=0.307,95％CI:0.14-0.68) in immunocompetent patients with CNS infection compared with those without CNS infection.Conclusions FCGR2A 131H/R and FCGR2B 232I/T are associated with the susceptibility to cryptococcal CNS infection,which suggests that FcγRⅡA and FcγRⅡB may contribute to the pathogenesis of cryptococcosis.
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Objective To describe the distribution of mannose binding lectin (MBL) genetic polymorphisms in non-acquired immunodeficiency syndrome (AIDS) patients with cryptococcosis in China and to verify the association of MBL polymorphisms with susceptibility to cryptococcosis.Methods The case-controlled genetic association study was conducted and 167 non-AIDS patients with cryptococcosis and 208 healthy controls were recruited. Genome DNA was extracted from the peripheral blood and MBL gene was amplified by polymerase chain reaction (PCR). Six singlenucleotide polymorphisms ( SNP) of MBL gene were sequenced. The association of MBL polymorphisms with susceptibility to cryptococcosis were analyzed. The comparison between patients and controls was performed by chi square test or Fisher's exact test. The differences of MBL plasma concentrations between groups with different MBL genotypes were compared by single factor variance analysis. Results There were no differences between patients and controls in terms of MBL genotype frequencies, haplotypes and genotypes (all P>0. 05). Compared with healthy control, the deficient MBL-producing genotypes were strongly associated with cryptococcal meningitis (16. 5% vs 8. 7%,χ2=4.25, P=0.0392, OR = 2.09), particularly in patients without underlying immunocompromised conditions (21. 4% vs 8. 7%, χ2 =7. 15, P = 0. 0075, OR = 2. 88). Individuals with MBL deficiency genotypes showed significantly higher rates of central nervous system (CNS) cryptococcal infection rather than non-CNS cryptococcosis (16. 5% vs 3. 1%, Fisher's exact test, P = 0. 010, OR = 6. 13).The difference was even more significant in the immunocompetent patients (21. 4% vs 4. 0%, P =0.009, OR= 6. 55). Conclusion MBL deficiency is associated with cryptococcal meningitis and may play a role in CNS Cryptococcus infection.
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Objective To analyze the clinical features of patients with uncommon fungal infections in central nervous system (CNS).Methods Thirty-five patients with uncommon CNS fungal infections who were admitted to Huashan Hospital from 1997 to 2010 were retrospectively reviewed.The pathogens,symptoms and signs.treatments of patients were evaluated.The data were analyzed by rank sum test and Fisher'S exact test.Results Twenty-nine of the 35 patients met the definition criteria of prover CNS fungal infections,while the other 6 had probable diagnosis.Predisposing factors were found in 86% of all patients.The most common pathogens were Aspergillus and Candida species.The symptoms and signs commonly occurred including fever(22 cases),headache(19 cases), cranial neuropathy(12 cases),and meningeal irritation sign(12 cases).High white blood cell count,high protein level,and low glucose level were the main findings of cerebrospinal fluid (CSF) analysis.Patients with cerebral aspergillosis were more frequently accompanied with immunocompromised conditions, and they often got CNS aspergillosis from hematogenous dissemination or direct extension of paranasal sinus infection.Cerebral granuloma and abscess were the common clinical characteristics of CNS aspergillosis.Cerebral candidiasis often arose from neurosurgical surgery or traumatic brain injury,and these patients were usually presented with meningitis.All patients were treated with antifungal drugs and (or) surgical intervention and 77%(27/35) of the patients achieved complete or partial responses. Antifungal agents combined with surgical resection might improve outcome of patients with CNS aspergillosis; while removal or replacement of drainage tubes in combination with antifungal treatment showed satisfactory efficacy in patients with cerebral candidiasis who usually had shunt manipulation. Conclusions The incidence of CNS fungal infection, such as cerebral aspergillosis and candidiasis, is increasing. Early diagnose and therapeutic intervention are crucial for improving outcome.
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Objective To understand the clinical epidemiology of nosocomial candidemia in Huashan Hospital during a 10-year period. Methods One hundred and nine cases of nosocomial candidemia in Huashan Hospital affiliated Fudan University during the period of 1998- 2007 were retrospectively reviewed. The underlying conditions, risk factors, clinical manifestations, treatment and outcome were described. The prognostic factors were analyzed by chi square test or Fisher exact probability test. Multivariate analysis was done by multiple Logistic regression. Results The average annual incidence of nosocomial candidemia during the study period was 0.28/10 000 patients per day.The most common pathogen was C. albicans (59/109,54.1%), followed by C. tropicalis (20/109,18.3%), then C. parapsilosis (11/109, 10. 1%), C. glabrata (11/109, 10.1%), and other Candida spp. (8/109, 7.3% ). Underlying diseases frequently identified included diabetes (50,45.9%), solid malignancy (32, 29.4%), head trauma (13, 11. 9%) and stroke (12, 11.0%).There were 37 cases who died or deteriorated. The overall mortality was 34.0% and the attributable mortality was 22. 0% (24/109). In multivariate prognostic analysis, retention of central venous catheters (OR: 5.42, 95% CI: 1.68-17.41, P＝0.005), corticosteroid medication (OR: 3.69,95% CI: 1.10-12.34, P=0. 034), and severe sepsis on the day of candidemia (OR: 2.94, 95% CI:1.72-15. 21, P = 0. 003) were factors independently correlated to increased mortality. Furthermore,adequate antifungal therapy was the only independent predictor of decreased overall mortality (OR: 0. 27,95% CI: 0. 09-0. 78,P=0.015). Conclusions The incidence of nosocomial candidemia in our hospital has been increasing during the past decade. Timely diagnosis and treatment plays a key role in the management of nosocomial candidemia,