van Kassel Merel N, de Boer Gregory, Teeri Samira A F, Jamrozy Dorota, Bentley Stephen D, Brouwer Matthijs C, van der Ende Arie, van de Beek Diederik, Bijlsma Merijn W
Department of Neurology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands.
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
Lancet Microbe. 2021 Jan;2(1):e32-e40. doi: 10.1016/S2666-5247(20)30192-0.
Streptococcus agalactiae (group B streptococcus) causes invasive disease in all age groups. In the Netherlands, the incidence of group B streptococcal sepsis in early infancy is increasing because of a specific genetic subtype, clonal complex (CC) 17-A1. We assessed the molecular epidemiology, incidence, and mortality of group B streptococcal meningitis in the Netherlands over 30 years.
We used nationwide surveillance data from Jan 1, 1987, to Dec 31, 2016, on all group B streptococcal meningitis and sepsis cases. The surveillance database of the Netherlands Reference Laboratory for Bacterial Meningitis-which receives approximately 90% of cerebrospinal fluid isolates from all patients with bacterial meningitis in the Netherlands-was the data source for the study. All patients with group B streptococcus-positive cerebrospinal fluid cultures (meningitis) and infants (0-89 days) with group B streptococcus-positive blood cultures (sepsis) were included. Patients with missing date of birth were excluded. Multi-locus sequence typing and clade profiles were extracted from whole genome sequences. Serotyping was done by latex agglutination and genome sequencing. Survival data was obtained through Municipal Personal Records.
1501 episodes in 1490 patients were identified: 626 meningitis cases (in patients of all ages) and 875 sepsis cases (in patients aged 0-89 days). Mean annual group B streptococcal meningitis incidence was 1·32 per 1 000 000 population. CC17-A1 caused 16 (5%) of 307 meningitis cases in the first half of the study and 77 (26%) of 296 meningitis cases in the second half of the observation period (p<0·0001). Because of a simultaneous decline in CC19, the overall meningitis incidence remained stable. 27 (8%) of 323 patients with meningitis younger than 3 months died and 14 (21%) of 66 patients older than 3 months died. Patients older than 65 years with sequence type (ST) 24 disease were independently associated with death. Serotype III and ST17 were associated with meningitis in early infancy, serotype III remained associated with meningitis in children younger than 3 months after correcting for ST17 (odds ratio 3·71, 95%CI 2·75-5·01). Serotype Ia, Ib, II, III, and V accounted for 98% of the meningitis cases in patients younger than 3 months and 92% cases in patients older than 3 months.
CC17-A1 is an increasing cause of group B streptococcal meningitis in all age groups. A pentavalent polysaccharide vaccine would cover most meningitis cases.
Netherlands Organization for Health Research and Development and Amsterdam University Medical Centres.
无乳链球菌（B组链球菌）可在各年龄组引发侵袭性疾病。在荷兰，由于一种特定的基因亚型，即克隆复合体（CC）17 - A1，婴儿早期B组链球菌败血症的发病率正在上升。我们评估了荷兰30年间B组链球菌脑膜炎的分子流行病学、发病率和死亡率。
我们使用了1987年1月1日至2016年12月31日全国范围内关于所有B组链球菌脑膜炎和败血症病例的监测数据。荷兰细菌性脑膜炎参考实验室的监测数据库——该实验室接收了荷兰所有细菌性脑膜炎患者约90%的脑脊液分离株——是本研究的数据源。纳入所有脑脊液培养B组链球菌呈阳性（脑膜炎）的患者以及血培养B组链球菌呈阳性（败血症）的婴儿（0 - 89天）。出生日期缺失的患者被排除。从全基因组序列中提取多位点序列分型和进化枝图谱。通过乳胶凝集和基因组测序进行血清分型。生存数据通过市政个人记录获得。
共识别出1490例患者的1501次发病情况：626例脑膜炎病例（各年龄段患者）和875例败血症病例（0 - 89天的患者）。B组链球菌脑膜炎的年均发病率为每100万人口1.32例。在研究的前半段，CC17 - A1导致了307例脑膜炎病例中的16例（5%），在观察期的后半段，导致了296例脑膜炎病例中的77例（26%）（p<0.0001）。由于CC19同时下降，总体脑膜炎发病率保持稳定。3个月以下患脑膜炎患者中27例（8%）死亡，3个月以上患者中66例里有14例（21%）死亡。65岁以上患有序列型（ST）24疾病的患者与死亡独立相关。血清型III和ST17与婴儿早期脑膜炎相关，在校正ST17后，血清型III在3个月以下儿童中仍与脑膜炎相关（比值比3.71，95%置信区间2.75 - 5.01）。血清型Ia、Ib、II、III和V占3个月以下患者脑膜炎病例的98%，占3个月以上患者病例的92%。
CC17 - A1是各年龄组B组链球菌脑膜炎日益增加的病因。一种五价多糖疫苗将覆盖大多数脑膜炎病例。
荷兰卫生研究与发展组织和阿姆斯特丹大学医学中心。
