Screening for cryptococcal antigenemia and analyzsis of the related cryptococcal lesions in hospitalized human immunodeficiency virus infected patients

Zhiliang Hu, Wei Chen, Yaling Chen, Yuan Liu, Yun Chi, Cong Cheng, Yongfeng Yang
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Abstract

Objective To evaluate the prevalence of cryptococcal antigenemia and explore the related cryptococcal lesions in hospitalized human immunodeficiency virus (HIV)-infected patients. Methods Medical records of 517 HIV-infected patients, including patients' age, sex, clinical features, previous medical history, laboratory tests, chest CT, treatment and the response to treatment, in the Second Hospital of the Nanjing between January 2016 and February 2018 were retrospectively analyzed. The serum cryptococcal antigen (sCrAg) was detected by lateral flow immunoassay. The χ2 test or Fisher exact test was used to perform the statistical analysis. Results Among 517 HIV-infected cases, 51 were sCrAg positive, of whom 96.1% (49 cases) were men. The cases with CD4+ T lymphocyte count <100×106 cells/L accounted for 66.2% (342 cases), while 90.2% (46 cases) in sCrAg-positive patients showed CD4+ T lymphocyte count <100×106 cells/L with statistical significance (χ2=14.6, P<0.01). Multivariable analysis revealed that CD4+ T lymphocyte count <100 ×106 cells/L was independent risk factor for cryptococcal antigenemia (OR=4.7; 95%CI: 1.8-12.5, P<0.01). Clinical cryptococcal diseases were found in 76.4% (39/51) of patients with cryptococcal antigenemia, and cryptococcal meningitis (CM), pulmonary cyptococcosis (PC) and cryptococcal septicemia were found in 56% (28/50), 52.9% (27/51) and 44.4% (16/36) of the patients, respectively. Cryptoccal disease was not identified in 21.6% (11/51) of the patients with cryptococcal antigenemia (isolated cryptococcal antigenemia). The median (range) sCrAg titers of the patients with and without CM were 1∶1 280 (1∶10-1∶2 560) and 1: 15 (1∶2-1∶2 560), respectively (P<0.01). The proportion of CM in patients with sCrAg titers ≤1∶5, 1∶10-1∶320 and ≥1∶640 were 0 (0/10), 50% (10/20) and 90% (18/20), respectively. When cryptococcal infection was restricted to the lung, 87.5% (7/8) of the patients had sCrAg titers ≤1∶20. 30% (3/10) of the patients with sCrAg titers ≤1∶5 had PC. The median (range) sCrAg titers of the patients with cryptococcal septicemia and with isolated cryptococcal antigenemia were 1∶1 280 (1∶10-1∶2 560) and 1∶5 (1∶2-1∶320), respectively. Conclusions The prevalence of cryptococcal antigenmia is high in hospitalized HIV-infected patients. Most patients with cryptococcal antigenemia have developed cryptococcal diseases. The sCrAg titer in HIV patients may, in some extend, predicts the condition of cryptococcal infection. sCrAg titers ≥1∶640 are strongly suggestive of CM. Patients with sCrAg titers ≤1∶5 seems unlikely to have CM or cryptococcal septicemia, however, clinician should still be alarmed of possible PC. Key words: HIV; Meningitis, cryptococcal; Cryptococcal antigenemia; Pulmonary cryptococcosis; Cryptococcal septicemia
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人类免疫缺陷病毒感染住院患者隐球菌抗原血症筛查及相关隐球菌病变分析
目的了解人类免疫缺陷病毒(HIV)感染住院患者隐球菌抗原血症的流行情况,探讨相关隐球菌病变情况。方法回顾性分析2016年1月至2018年2月南京市第二医院517例hiv感染者的病历,包括患者的年龄、性别、临床特征、既往病史、实验室检查、胸部CT、治疗情况和治疗反应。采用侧流免疫法检测血清隐球菌抗原(sCrAg)。采用χ2检验或Fisher精确检验进行统计分析。结果517例hiv感染者中,sCrAg阳性51例,其中男性49例,占96.1%。CD4+ T淋巴细胞计数<100×106 cells/L占66.2%(342例),scrag阳性患者中CD4+ T淋巴细胞计数<100×106 cells/L占90.2%(46例),差异有统计学意义(χ2=14.6, P<0.01)。多变量分析显示CD4+ T淋巴细胞计数<100 ×106 cells/L是隐球菌抗原血症的独立危险因素(OR=4.7;95%ci: 1.8 ~ 12.5, p <0.01)。隐球菌抗原血症患者临床隐球菌病发生率为76.4%(39/51),隐球菌性脑膜炎(CM)、肺隐球菌病(PC)和隐球菌败血症分别为56%(28/50)、52.9%(27/51)和44.4%(16/36)。21.6%(11/51)隐球菌抗原血症(分离性隐球菌抗原血症)患者未发现隐球菌病。有无CM患者sCrAg滴度中位(范围)分别为1∶1 280(1∶10 ~ 1∶2 560)、1∶15(1∶2 ~ 1∶2 560),差异有统计学意义(P<0.01)。sCrAg滴度≤1∶5、1∶10-1∶320、≥1∶640患者中CM的比例分别为0(0/10)、50%(10/20)、90%(18/20)。当隐球菌感染局限于肺部时,87.5%(7/8)的患者sCrAg滴度≤1∶20。sCrAg滴度≤1∶5的患者中有30%(3/10)发生PC。隐球菌败血症和分离性隐球菌抗原血症患者sCrAg滴度中位(范围)分别为1∶1 280(1∶10 ~ 1∶2 560)和1∶5(1∶2 ~ 1∶320)。结论住院hiv感染者隐球菌抗原血症发生率较高。大多数隐球菌抗原血症患者发生隐球菌疾病。HIV患者的sCrAg滴度在一定程度上可以预测隐球菌感染的情况。sCrAg滴度≥1∶640强烈提示CM。sCrAg滴度≤1∶5的患者不太可能发生CM或隐球菌败血症,但仍应警惕PC的可能。关键词:HIV;隐球菌脑膜炎;隐球菌antigenemia;肺隐球菌病;隐球菌败血症
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