The Contribution of Genetic Variation of Streptococcus pneumoniae to the Clinical Manifestation of Invasive Pneumococcal Disease
The Contribution of Genetic Variation of Streptococcus pneumoniae to the Clinical Manifestation of Invasive Pneumococcal Disease
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DOI：
10.1093/cid/ciy417
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发表时间：
2019-01-01
影响因子：
11.8
通讯作者：
de Jonge, Marien I.
中科院分区：
文献类型：
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作者：
Cremers, Amelieke J. H.;Mobegi, Fredrick M.;de Jonge, Marien I.
背景。侵袭性肺炎球菌病（IPD）的不同临床表现迄今主要由患者特征来解释。在这里，我们研究了肺炎球菌遗传变异对IPD表型的贡献。指数队列包括2000-2011年期间在2家荷兰医院住院的349例肺炎球菌菌血症患者。我们进行了全基因组关联研究，以确定与23种临床IPD表型相关的肺炎球菌谱系、基因和等位基因变异。在全国范围内（n = 482）和肺炎球菌接种后队列（n = 121）中验证了已确定的关联。相对于已知的临床预测因子，已证实的肺炎球菌基因型对临床IPD表型的贡献通过回归分析进行了检验。在IPD患者中，肺炎球菌基因slaA的存在是全国范围内确认的脑膜炎独立预测因子（优势比[OR]， 10.5; P = .001），序列聚类9（血清型7F: OR， 3.68; P = .057）也是如此。位于噬菌体上的一组4个肺炎球菌基因被证实是30天死亡率的独立预测因子（OR, 3.4; P = 0.003）。我们可以在这些患者的血液样本中检测到值得关注的肺炎球菌变异。在这项研究中，肺炎球菌基因型变异的知识改善了IPD有害表现的临床风险评估。这为我们提供了新的机会来靶向、预测或避免与特定肺炎球菌变异相关的致病作用，并表明肺炎球菌基因型信息对IPD的诊断和治疗策略很重要。有必要进行持续监测，以监测动态微生物和易感宿主群体中肺炎球菌变异信息的临床价值。
Background. Different clinical manifestations of invasive pneumococcal disease (IPD) have thus far mainly been explained by patient characteristics. Here we studied the contribution of pneumococcal genetic variation to IPD phenotype.Methods. The index cohort consisted of 349 patients admitted to 2 Dutch hospitals between 2000-2011 with pneumococcal bacteremia. We performed genome-wide association studies to identify pneumococcal lineages, genes, and allelic variants associated with 23 clinical IPD phenotypes. The identified associations were validated in a nationwide (n = 482) and a post-pneumococcal vaccination cohort (n = 121). The contribution of confirmed pneumococcal genotypes to the clinical IPD phenotype, relative to known clinical predictors, was tested by regression analysis.Results. Among IPD patients, the presence of pneumococcal gene slaA was a nationwide confirmed independent predictor of meningitis (odds ratio [OR], 10.5; P = .001), as was sequence cluster 9 (serotype 7F: OR, 3.68; P = .057). A set of 4 pneumococcal genes co-located on a prophage was a confirmed independent predictor of 30-day mortality (OR, 3.4; P = .003). We could detect the pneumococcal variants of concern in these patients' blood samples.Conclusions. In this study, knowledge of pneumococcal genotypic variants improved the clinical risk assessment for detrimental manifestations of IPD. This provides us with novel opportunities to target, anticipate, or avert the pathogenic effects related to particular pneumococcal variants, and indicates that information on pneumococcal genotype is important for the diagnostic and treatment strategy in IPD. Ongoing surveillance is warranted to monitor the clinical value of information on pneumococcal variants in dynamic microbial and susceptible host populations.