Department of Clinical Microbiology, Penteli Childrens Hospital, Athens, Greece.
Mol Diagn Ther. 2011 Apr 1;15(2):109-13. doi: 10.1007/BF03256400.
Acute bacterial meningitis is one of the most severe infectious diseases, affecting mainly infants and, secondarily, older children and adolescents. Diagnosis in the early stages is often difficult and despite treatment with appropriate antibiotic therapy, the case fatality rate remains high. In the present study, the incidence of bacterial meningitis was registered in a general pediatric hospital in Athens, Greece, during a 9-year period (2000-2008), and the use of molecular methods in the diagnosis of bacterial meningitis versus the conventional cultural methods was evaluated. The impact of vaccination against meningitis-causing bacteria on the incidence of bacterial meningitis was also assessed.
From a total of 1833 children hospitalized with suspected clinical symptoms and signs of meningitis, all cerebrospinal fluid (CSF) and blood samples were analyzed by white blood cell (WBC) count, measurement of glucose, protein, and C-reactive protein (CRP) levels, as well as by conventional bacteriologic culture methods. If samples showed altered CSF markers that were consistent with meningitis in general, they were further investigated by PCR for bacterial pathogens.
Of the 1833 patients, 289 (15.76%) were found to be positive for meningitis after CSF examination, based on white blood cell count and differentiation, glucose, protein, and CRP. Fifty-six of the 289 (19.37%) had confirmed bacterial meningitis, as diagnosed by either culture and/or PCR. Of these 56 cases, 44 (78.6%) were detected only by PCR, and 12 cases (21.4%) were confirmed by PCR and culture. The predominant microorganism was Neisseria meningitidis serogroup B (n = 40; 71.4%), followed by Streptococcus pneumoniae not typed [NT] (n = 7; 12.5%), Streptococcus spp. (n =4; 7.1%), Haemophilus influenzae NT (n = 2; 3.6%), and S. pneumoniae serotype 3, Streptococcus group B, and S. pneumoniae serotype 18C (each n = 1; 1.8%).
In Greece, according to data from the National Meningitis Reference Laboratory, vaccination against N. meningitidis serogroup C since 2001 led to a 10-fold decrease in the incidence of meningitis cases, vaccination against S. pneumoniae serotypes included in the heptavalent conjugate vaccine since 2005 led to a 3.4-fold incidence decrease, and vaccination against H. influenzae type b since 1992 led almost to an absence of cases. In the population of the present study, none of the cases were caused by the above-mentioned vaccine pathogens, except for one S. pneumoniae serotype 18C case with no history of past vaccination. The introduction of vaccination against meningitis-causing bacteria has drastically decreased the emergence of the infection. The improved molecular amplification assays proved to be superior to conventional bacteriologic methods and should be introduced into routine diagnosis, as well as the epidemiologic surveillance of bacterial meningitis.
急性细菌性脑膜炎是最严重的传染病之一，主要影响婴儿，其次是较大的儿童和青少年。早期诊断往往较为困难，尽管采用了适当的抗生素治疗，但病死率仍然很高。本研究在希腊雅典的一家综合儿科医院登记了 9 年间（2000-2008 年）细菌性脑膜炎的发病率，并评估了分子方法在细菌性脑膜炎诊断中的应用与传统的培养方法。评估了针对引起脑膜炎的细菌的疫苗接种对细菌性脑膜炎发病率的影响。
对所有疑似有临床症状和体征的脑膜炎的 1833 名儿童的所有脑脊液（CSF）和血液样本进行分析，包括白细胞（WBC）计数、葡萄糖、蛋白质和 C-反应蛋白（CRP）水平的测量，以及常规细菌学培养方法。如果样本显示出与一般脑膜炎一致的改变 CSF 标志物，则进一步通过 PCR 检测细菌病原体。
根据白细胞计数和分类、葡萄糖、蛋白质和 CRP，对 1833 名患者进行 CSF 检查后，289 名（15.76%）被确定为脑膜炎阳性。56 例（19.37%）被确认为细菌性脑膜炎，通过培养和/或 PCR 诊断。这 56 例中，44 例（78.6%）仅通过 PCR 检测到，12 例（21.4%）通过 PCR 和培养检测到。主要的微生物是脑膜炎奈瑟菌 B 群血清型（n=40；71.4%），其次是未分型肺炎链球菌（n=7；12.5%）、链球菌属（n=4；7.1%）、流感嗜血杆菌未分型（n=2；3.6%）以及肺炎链球菌 3 型、B 群链球菌和 18C 型肺炎链球菌（各 n=1；1.8%）。
根据国家脑膜炎参考实验室的数据，自 2001 年以来针对脑膜炎奈瑟菌 C 群的疫苗接种使病例发病率降低了 10 倍，自 2005 年以来针对包含在 7 价结合疫苗中的肺炎链球菌血清型的疫苗接种使发病率降低了 3.4 倍，自 1992 年以来针对乙型流感嗜血杆菌的疫苗接种几乎使病例消失。在本研究人群中，除了一例无既往接种史的 18C 型肺炎链球菌病例外，没有一个病例是由上述疫苗病原体引起的。针对引起脑膜炎的细菌的疫苗接种大大减少了感染的发生。改进的分子扩增检测方法优于传统的细菌学方法，应引入常规诊断以及细菌性脑膜炎的流行病学监测。
