宏基因组下一代测序对儿童细菌性脑膜炎中肺炎链球菌的诊断价值。
The diagnostic value of metagenomic next-generation sequencing for identifying Streptococcus pneumoniae in paediatric bacterial meningitis.
机构信息
Key Laboratory of Major Diseases in Children, Ministry of Education, Department of Infectious Diseases, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No. 56 Nan Lishi Road, Beijing, 100045, China.
Tianjin Medical Laboratory, BGI-Tianjin, Tianjin, China.
出版信息
BMC Infect Dis. 2019 Jun 4;19(1):495. doi: 10.1186/s12879-019-4132-y.
BACKGROUND
There is currently no research on the diagnostic value of metagenomic next-generation sequencing (mNGS) for a single pathogens in CSF. The aim of this study was to analyse the value of mNGS for identifying Streptococcus pneumoniae (S. pneumoniae) in paediatric bacterial meningitis.
METHODS
Bacterial meningitis (BM) cases from October 23, 2014, to December 31, 2016, and December 1, 2017, to July 31, 2018 at Beijing Children's Hospital were reviewed. Clinical features and pathogens were analysed.
RESULTS
We diagnosed 135 patients with BM in this study. A total of 43 S. pneumoniae were identified by combination methods. 26/135 (19.3%) patients had positive results in S. pneumoniae by blood and/or cerebrospinal fluid (CSF) culture. Alere BinaxNow®Streptococcus pneumoniae Antigen test was positive in 35/135(25.9%) cases. 32/135 (23.7%) S. pneumoniae were identified by mNGS. Six CSF samples were identified as S. pneumoniae only by mNGS technology. Taking culture as the gold standard, the sensitivity and specificity of mNGS for diagnosing S. pneumoniae meningitis were 73.1 and 88.1%, respectively. The positive predictive value (PPV) and negative predictive value (NPV) of diagnosing S. pneumoniae meningitis by mNGS were 59.4 and 93.2%, respectively. When comparison between mNGS and combined tests (culture and Alere BinaxNow®Streptococcus pneumoniae Antigen test), the sensitivity and specificity of mNGS for S. pneumoniae identification were 70.3 and 93.9%, the PPV and NPV in the identification of S. pneumoniae by mNGS were 81.4 and 89.3%, respectively. The difference in number of unique reads of S. pneumoniaein from CSF sample (< 14 days onset) and CSF sample (> 14 days from onset) was statistically significant (170.5 VS. 13, P = 0.019). The difference in the collected time of CSF for culture and mNGS was statistically significant (4 days VS. 14 days, P < 0.001).
CONCLUSIONS
mNGS has high sensitivity and specificity for S. pneumoniae identification. The pathogen load (number of unique reads) of S. pneumonia is related to the CSF collection time. mNGS was less affected than culture by the use of antibiotics before CSF collection.
背景
目前尚无关于宏基因组下一代测序（mNGS）在单一病原体脑脊液检测中诊断价值的研究。本研究旨在分析 mNGS 对儿童细菌性脑膜炎中肺炎链球菌（S. pneumoniae）鉴定的价值。
方法
回顾 2014 年 10 月 23 日至 2016 年 12 月 31 日和 2017 年 12 月 1 日至 2018 年 7 月 31 日在北京儿童医院诊断的细菌性脑膜炎（BM）病例。分析临床特征和病原体。
结果
本研究共诊断 135 例 BM 患者。共通过联合方法鉴定出 43 株 S. pneumoniae。26/135（19.3%）患者血和/或脑脊液（CSF）培养 S. pneumoniae 阳性。Alere BinaxNow®肺炎链球菌抗原检测 35/135（25.9%）例阳性。mNGS 鉴定出 32/135（23.7%）S. pneumoniae。6 份 CSF 样本仅通过 mNGS 技术鉴定为 S. pneumoniae。以培养为金标准，mNGS 诊断 S. pneumoniae 脑膜炎的灵敏度和特异性分别为 73.1%和 88.1%。mNGS 诊断 S. pneumoniae 脑膜炎的阳性预测值（PPV）和阴性预测值（NPV）分别为 59.4%和 93.2%。mNGS 与联合检测（培养和 Alere BinaxNow®肺炎链球菌抗原检测）比较时，mNGS 鉴定 S. pneumoniae 的灵敏度和特异性分别为 70.3%和 93.9%，mNGS 鉴定 S. pneumoniae 的 PPV 和 NPV 分别为 81.4%和 89.3%。CSF 样本中（发病后<14 天）和 CSF 样本中（发病后>14 天）肺炎链球菌的独特读取数差异有统计学意义（170.5 VS. 13，P=0.019）。培养和 mNGS 收集 CSF 的时间差异有统计学意义（4 天 VS. 14 天，P<0.001）。
结论
mNGS 对 S. pneumoniae 的鉴定具有较高的灵敏度和特异性。S. pneumoniae 的病原体载量（独特读取数）与 CSF 采集时间有关。与培养相比，mNGS 受 CSF 采集前抗生素使用的影响较小。
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