Ngo Cuong Chi, Katoh Shungo, Hasebe Futoshi, Dhoubhadel Bhim Gopal, Hiraoka Tomoko, Hamaguchi Sugihiro, Le Anh Thi Kim, Nguyen Anh Thi Hien, Dang Anh Duc, Smith Chris, Yoshida Lay-Myint, Do Cuong Duy, Pham Thuy Thi Thanh, Ariyoshi Koya
Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Trop Med Health. 2021 May 21;49(1):42. doi: 10.1186/s41182-021-00322-2.
Laboratory facilities for etiological diagnosis of central nervous system (CNS) infection are limited in developing countries; therefore, patients are treated empirically, and the epidemiology of the pathogens is not well-known. Tubercular meningitis is one of the common causes of meningitis, which has high morbidity and mortality, but lacks sensitive diagnostic assays. The objectives of this study were to determine the causes of meningitis in adult patients by using molecular assays, to assess the risk factors associated with them, and to explore whether biomarkers can differentiate tubercular meningitis from bacterial meningitis.
We conducted a cross-sectional study in the Department of Infectious Diseases, Bach Mai Hospital, Hanoi, Vietnam, from June 2012 to May 2014. All patients who were ≥ 16 years old and who had meningoencephalitis suggested by abnormal cerebrospinal fluid (CSF) findings (CSF total cell >5/mm3 or CSF protein ≥40 mg/dL) were included in the study. In addition to culture, CSF samples were tested for common bacterial and viral pathogens by polymerase chain reaction (PCR) and for biomarkers: C-reactive protein and adenosine deaminase (ADA).
Total number of patients admitted to the department was 7506; among them, 679 were suspected to have CNS infection, and they underwent lumbar puncture. Five hundred eighty-three patients had abnormal CSF findings (meningoencephalitis); median age was 45 (IQR 31-58), 62.6% were male, and 60.9% were tested for HIV infection. Among 408 CSF samples tested by PCR, out of them, 358 were also tested by culture; an etiology was identified in 27.5% (n=112). S. suis (8.8%), N. meningitis (3.2%), and S. pneumoniae (2.7%) were common bacterial and HSV (2.2%), Echovirus 6 (0.7%), and Echovirus 30 (0.7%) were common viral pathogens detected. M. tuberculosis was found in 3.2%. Mixed pathogens were detected in 1.8% of the CSF samples. Rural residence (aOR 4.1, 95% CI 1.2-14.4) and raised CSF ADA (≥10 IU/L) (aOR 25.5, 95% CI 3.1-212) were associated with bacterial meningitis when compared with viral meningitis; similarly, raised CSF ADA (≥10 IU/L) (aOR 42.2, 95% CI 2.0-882) was associated with tubercular meningitis.
Addition of molecular method to the conventional culture had enhanced the identification of etiologies of CNS infection. Raised CSF ADA (≥10 IU/L) was strongly associated with bacterial and tubercular meningitis. This biomarker might be helpful to diagnose tubercular meningitis once bacterial meningitis is ruled out by other methods.
在发展中国家，用于中枢神经系统（CNS）感染病因诊断的实验室设施有限；因此，患者接受经验性治疗，病原体的流行病学情况尚不为人所知。结核性脑膜炎是脑膜炎的常见病因之一，其发病率和死亡率都很高，但缺乏敏感的诊断检测方法。本研究的目的是通过分子检测方法确定成年患者脑膜炎的病因，评估与之相关的危险因素，并探讨生物标志物是否能区分结核性脑膜炎和细菌性脑膜炎。
2012年6月至2014年5月，我们在越南河内巴维医院传染病科进行了一项横断面研究。所有年龄≥16岁且脑脊液（CSF）检查结果异常（CSF总细胞>5/mm³或CSF蛋白≥40mg/dL）提示脑膜脑炎的患者均纳入研究。除培养外，CSF样本还通过聚合酶链反应（PCR）检测常见细菌和病毒病原体以及生物标志物：C反应蛋白和腺苷脱氨酶（ADA）。
该科室收治的患者总数为7506例；其中，679例疑似患有CNS感染，并接受了腰椎穿刺。583例患者CSF检查结果异常（脑膜脑炎）；中位年龄为45岁（四分位间距31 - 58岁），62.6%为男性，60.9%接受了HIV感染检测。在408份通过PCR检测的CSF样本中，其中358份也进行了培养；确定病因的占27.5%（n = 112）。猪链球菌（8.8%）、脑膜炎奈瑟菌（3.2%）和肺炎链球菌（2.7%）是常见细菌病原体，单纯疱疹病毒（2.2%）、埃可病毒6型（0.7%）和埃可病毒30型（0.7%）是常见病毒病原体。结核分枝杆菌检出率为3.2%。1.8%的CSF样本检测到混合病原体。与病毒性脑膜炎相比，农村居住（调整后比值比4.1，95%可信区间1.2 - 14.4）和CSF中ADA升高（≥10IU/L）（调整后比值比25.5，95%可信区间3.1 - 212）与细菌性脑膜炎相关；同样，CSF中ADA升高（≥10IU/L）（调整后比值比42.2，95%可信区间2.0 - 882）与结核性脑膜炎相关。
在传统培养方法基础上增加分子检测方法提高了CNS感染病因的识别率。CSF中ADA升高（≥10IU/L）与细菌性和结核性脑膜炎密切相关。一旦通过其他方法排除细菌性脑膜炎，这种生物标志物可能有助于诊断结核性脑膜炎。
