The contribution of genetic variation of streptococcus pneumoniae to the clinical manifestation of invasive pneumococcal disease
dc.contributor.author | Cremers, A.J.H. | |
dc.contributor.author | Mobegi, Fredrick | |
dc.contributor.author | Van Der Gaast-De Jongh, C. | |
dc.contributor.author | Van Weert, M. | |
dc.contributor.author | Van Opzeeland, F.J. | |
dc.contributor.author | Vehkala, M. | |
dc.contributor.author | Knol, M.J. | |
dc.contributor.author | Bootsma, H.J. | |
dc.contributor.author | Välimäki, N. | |
dc.contributor.author | Croucher, N.J. | |
dc.contributor.author | Meis, J.F. | |
dc.contributor.author | Bentley, S. | |
dc.contributor.author | Van Hijum, S.A.F.T. | |
dc.contributor.author | Corander, J. | |
dc.contributor.author | Zomer, A.L. | |
dc.contributor.author | Ferwerda, G. | |
dc.contributor.author | De Jonge, M.I. | |
dc.date.accessioned | 2020-08-24T06:51:01Z | |
dc.date.available | 2020-08-24T06:51:01Z | |
dc.date.issued | 2018 | |
dc.identifier.citation | Cremers, A.J.H. and Mobegi, F.M. and Van Der Gaast-De Jongh, C. and Van Weert, M. and Van Opzeeland, F.J. and Vehkala, M. and Knol, M.J. et al. 2018. The contribution of genetic variation of streptococcus pneumoniae to the clinical manifestation of invasive pneumococcal disease. Clinical Infectious Diseases. 68 (1): pp. 61-69. | |
dc.identifier.uri | http://hdl.handle.net/20.500.11937/80729 | |
dc.identifier.doi | 10.1093/cid/ciy417 | |
dc.description.abstract |
© 2018 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. 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. | |
dc.language | English | |
dc.publisher | OXFORD UNIV PRESS INC | |
dc.subject | Science & Technology | |
dc.subject | Life Sciences & Biomedicine | |
dc.subject | Immunology | |
dc.subject | Infectious Diseases | |
dc.subject | Microbiology | |
dc.subject | invasive pneumococcal disease | |
dc.subject | bacterial genomics | |
dc.subject | genome-wide association study | |
dc.subject | clinical prediction | |
dc.subject | molecular diagnostics | |
dc.subject | COMMUNITY-ACQUIRED PNEUMONIA | |
dc.subject | CONJUGATE VACCINATION | |
dc.subject | BACTERIAL-MENINGITIS | |
dc.subject | SEROTYPE | |
dc.subject | PATHOGENESIS | |
dc.subject | ASSOCIATION | |
dc.subject | BACTEREMIA | |
dc.subject | CHILDREN | |
dc.subject | BURDEN | |
dc.subject | DEATH | |
dc.title | The contribution of genetic variation of streptococcus pneumoniae to the clinical manifestation of invasive pneumococcal disease | |
dc.type | Journal Article | |
dcterms.source.volume | 68 | |
dcterms.source.number | 1 | |
dcterms.source.startPage | 61 | |
dcterms.source.endPage | 69 | |
dcterms.source.issn | 1058-4838 | |
dcterms.source.title | Clinical Infectious Diseases | |
dc.date.updated | 2020-08-24T06:51:01Z | |
curtin.department | School of Molecular and Life Sciences (MLS) | |
curtin.accessStatus | Fulltext not available | |
curtin.faculty | Faculty of Science and Engineering | |
curtin.contributor.orcid | Mobegi, Fredrick [0000-0003-0554-9919] | |
curtin.contributor.researcherid | Mobegi, Fredrick [D-1058-2015] | |
dcterms.source.eissn | 1537-6591 | |
curtin.contributor.scopusauthorid | Mobegi, Fredrick [56479121000] |
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