The contribution of genetic variation of streptococcus pneumoniae to the clinical manifestation of invasive pneumococcal disease
MetadataShow full item record
© 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.
Showing items related by title, author, creator and subject.
Phage-derived protein induces increased platelet activation and is associated with mortality in patients with invasive pneumococcal diseaseTunjungputri, R.N.; Mobegi, Fredrick ; Cremers, A.J.; van der Gaast-de Jongh, C.E.; Ferwerda, G.; Meis, J.F.; Roeleveld, N.; Bentley, S.D.; Pastura, A.S.; van Hijum, S.A.F.T.; van der Ven, A.J.; de Mast, Q.; Zomer, A.; de Jonge, M.I. (2017)To improve our understanding about the severity of invasive pneumococcal disease (IPD), we investigated the association between the genotype of Streptococcus pneumoniae and disease outcomes for 349 bacteremic patients. A ...
Identification of novel genetic loci associated with thyroid peroxidase antibodies and clinical thyroid diseaseO'Leary, Peter (2014)Autoimmune thyroid diseases (AITD) are common, affecting 2-5% of the general population. Individuals with positive thyroid peroxidase antibodies (TPOAbs) have an increased risk of autoimmune hypothyroidism (Hashimoto's ...
The molecular epidemiology and evolution of the Panton-Valentine leukocidin-positive, methicillin-resistant Staphylococcus aureus strain USA300 in Western AustraliaMonecke, S.; Ehricht, R.; Slickers, P.; Tan, H.; Coombs, Geoffrey (2009)Between 2003 and 2008, 76 clinical isolates of the Panton-Valentine leukocidin-positive Staphylococcus aureus strain 'West Australian methicillin-resistant Staphylococcus aureus (MRSA)-12'(WA MRSA-12) were recovered from ...