1 Department of Microbial and Cellular Molecular Biology, Addis Ababa University, Ethiopia.
2 Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
Innate Immun. 2019 Apr;25(3):158-167. doi: 10.1177/1753425918806363.
Neisseria meningitidis infections in sub-Saharan Africa usually present with distinct symptoms of meningitis but very rarely as fulminant septicemia when reaching hospitals. In Europe, development of persistent meningococcal shock and multiple organ failure occurs in up to 30% of patients and is associated with a bacterial load of >10/ml plasma or serum. We have prospectively studied 27 Ethiopian patients with meningococcal infection as diagnosed and quantified with real-time PCR in the cerebrospinal fluid (CSF) and serum. All presented with symptoms of meningitis and none with fulminant septicemia. The median N. meningitidis copy number (NmDNA) in serum was < 3.5 × 10/ml, never exceeded 1.8 × 10/ml, and was always 10-1000 times higher in CSF than in serum. The levels of LPS in CSF as determined by the limulus amebocyte lysate assay were positively correlated to NmDNA copy number ( r = 0.45, P = 0.030), levels of IL-1 receptor antagonist, ( r = 0.46, P = 0.017), and matrix metallopeptidase-9 (MMP-9; r = 0.009). We also compared the inflammatory profiles of 19 mediators in CSF of the 26 meningococcal patients (2 died and 2 had immediate severe sequelae) with 16 patients with Streptococcus pneumoniae meningitis (3 died and 3 with immediate severe sequelae). Of 19 inflammatory mediators tested, 9 were significantly higher in patients with pneumococcal meningitis and possibly linked to worse outcome.
在撒哈拉以南非洲,脑膜炎奈瑟菌感染通常表现为明显的脑膜炎症状,但在到达医院时很少表现为暴发性败血症。在欧洲,高达 30%的患者会出现持续性脑膜炎球菌性休克和多器官衰竭,且与血浆或血清中细菌负荷量>10/ml 相关。我们前瞻性地研究了 27 例埃塞俄比亚脑膜炎奈瑟菌感染患者,通过实时 PCR 在脑脊液 (CSF) 和血清中进行诊断和定量。所有患者均表现出脑膜炎症状,无暴发性败血症。血清中脑膜炎奈瑟菌拷贝数 (NmDNA) 的中位数<3.5×10/ml,从未超过 1.8×10/ml,且始终比血清高 10-1000 倍。通过鲎变形细胞溶解物试验确定的 CSF 中 LPS 水平与 NmDNA 拷贝数呈正相关 ( r=0.45,P=0.030),与 IL-1 受体拮抗剂 ( r=0.46,P=0.017) 和基质金属蛋白酶-9 (MMP-9; r=0.009) 呈正相关。我们还比较了 26 例脑膜炎奈瑟菌患者 (2 例死亡,2 例立即出现严重后遗症) 和 16 例肺炎链球菌脑膜炎患者 (3 例死亡,3 例立即出现严重后遗症) CSF 中 19 种炎症介质的炎症特征。在测试的 19 种炎症介质中,9 种在肺炎球菌性脑膜炎患者中显著升高,可能与不良预后有关。