Carrol Enitan D, Guiver Malcolm, Nkhoma Standwell, Mankhambo Limangeni A, Marsh John, Balmer Paul, Banda Daniel L, Jeffers Graham, White Sarah A, Molyneux Elizabeth M, Molyneux Malcolm E, Smyth Rosalind L, Hart C Anthony
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Department of Paediatrics, College of Medicine, University of Malawi, Blantyre, Malawi.
Pediatr Infect Dis J. 2007 May;26(5):416-22. doi: 10.1097/01.inf.0000260253.22994.61.
In bacteremia owing to Streptococcus pneumoniae, high bacterial counts at presentation have been shown to be predictive of the development of serious invasive disease. Using real-time PCR, we aimed to determine pneumococcal DNA loads in blood and CSF, and their relationship to cytokine concentrations, clinical presentation and outcome.
Children with confirmed meningitis (n = 82) or pneumonia (n = 13) were prospectively recruited, and blood and CSF samples taken for pneumococcal bacterial DNA loads and cytokine determination.
At the time of admission, the median bacterial load in blood was 1.6 x 10 DNA copies/mL (range 0.00-1.54 x 10) and in CSF it was 5.77 x 10 DNA copies/mL (range 4.42 x 10 to 6.15 x 10). Median blood and CSF bacterial loads (log DNA copies/mL) were significantly higher in nonsurvivors than in survivors; blood (3.80 vs. 2.97, P = 0.003), CSF (8.17 vs. 7.50, P = 0.03). In HIV-infected children (n = 59), blood and CSF loads and plasma tumor necrosis factor-alpha, interleukin-1beta (IL-1beta), IL-6 and IL-10 were all significantly higher in nonsurvivors than in survivors, but in HIV-uninfected children (n = 36) this difference was not significant. Blood bacterial loads and plasma cytokine concentrations were significantly associated, and were all significantly higher in children with meningitis than in those with pneumonia. In children with meningitis, median CSF cytokine concentrations were significantly higher than median plasma cytokine concentrations (P < 0.001) and CSF bacterial loads were significantly associated with CSF IL-1beta (P = 0.002) and IL-10 (P = 0.001) concentrations.
Pneumococcal DNA loads are associated with plasma cytokine concentrations, and are higher in meningitis than in pneumonia. High blood and CSF pneumococcal DNA loads are associated with a fatal outcome.
在肺炎链球菌所致菌血症中，就诊时的高细菌计数已被证明可预测严重侵袭性疾病的发生。我们旨在通过实时聚合酶链反应（PCR）测定血液和脑脊液中的肺炎球菌DNA载量，以及它们与细胞因子浓度、临床表现和预后的关系。
前瞻性招募确诊为脑膜炎（n = 82）或肺炎（n = 13）的儿童，并采集血液和脑脊液样本以测定肺炎球菌细菌DNA载量和细胞因子。
入院时，血液中的细菌载量中位数为1.6×10 DNA拷贝/mL（范围0.00 - 1.54×10），脑脊液中的细菌载量中位数为5.77×10 DNA拷贝/mL（范围4.42×10至6.15×10）。非幸存者的血液和脑脊液细菌载量中位数（log DNA拷贝/mL）显著高于幸存者；血液（3.80对2.97，P = 0.003），脑脊液（8.17对7.50，P = 0.03）。在感染人类免疫缺陷病毒（HIV）的儿童（n = 59）中，非幸存者的血液和脑脊液载量以及血浆肿瘤坏死因子-α、白细胞介素-1β（IL-1β）、IL-6和IL-10均显著高于幸存者，但在未感染HIV的儿童（n = 36）中，这种差异不显著。血液细菌载量与血浆细胞因子浓度显著相关，且脑膜炎患儿的所有指标均显著高于肺炎患儿。在脑膜炎患儿中，脑脊液细胞因子浓度中位数显著高于血浆细胞因子浓度中位数（P < 0.001），脑脊液细菌载量与脑脊液IL-1β（P = 0.002）和IL-10（P = 0.001）浓度显著相关。
肺炎球菌DNA载量与血浆细胞因子浓度相关，且脑膜炎中的载量高于肺炎。血液和脑脊液中高肺炎球菌DNA载量与致命结局相关。
