Harboe, Z. B. | bioRxiv Science

bioRxiv2018

Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis

Streptococcus pneumoniae is a common nasopharyngeal colonizer, but can also cause life-threatening invasive diseases such as empyema, bacteremia and meningitis. Genetic variation of host and pathogen is known to play a role in invasive pneumococcal disease, though to what extent is unknown. In a genome-wide association study of human and pathogen we show that human variation explains almost half of variation in susceptibility to pneumococcal meningitis and one-third of variation in severity, and identified variants in CCDC33 associated with susceptibility. Pneumococcal variation explained a large amount of invasive potential, but serotype explained only half of this variation. Newly developed methods identified pneumococcal genes involved in invasiveness including pspC and zmpD, and allowed a human-bacteria interaction analysis, finding associations between pneumococcal lineage and STK32C.

genomics↗

bioRxiv2018

Differences in Pneumococcal Serotype Replacement in Individuals with and without Underlying Medical Conditions

BackgroundPneumococcal conjugate vaccines (PCVs) have had a well-documented impact on the incidence of invasive pneumococcal disease (IPD) worldwide. However, declines in IPD due to vaccine-targeted serotypes have been partially offset by increases in IPD due to non-vaccine serotypes. The goal of this study was to quantify serotype-specific changes in the incidence of IPD that occurred in different age groups, with or without certain co-morbidities, following the introduction of PCV7 and PCV13 in the childhood vaccination program in Denmark.\n\nMethodsWe used nationwide surveillance data for IPD in Denmark and a hierarchical Bayesian regression framework to estimate changes in the incidence of IPD associated with the introduction of PCV7 (2007) and PCV13 (2010) while controlling for serotype-specific epidemic cycles and unrelated secular trends.\n\nResults and ConclusionsFollowing the introduction of PCV7 and 13 in children, the net impact of serotype replacement varied considerably by age group and the presence of comorbid conditions. Serotype replacement offset a greater fraction of the decline in vaccine-targeted serotypes following the introduction of PCV7 compared with the period following the introduction of PCV13. Differences in the magnitude of serotype replacement were due to variations in the incidence of non-vaccine serotypes in the different risk groups before the introduction of PCV7 and PCV13. The relative increases in the incidence of IPD caused by non-vaccine serotypes did not differ appreciably in the post-vaccination period. Serotype replacement offset a greater proportion of the benefit of PCVs in strata in which the non-vaccine serotypes comprised a larger proportion of cases prior to the introduction of the vaccines. These findings could help to predict the impact of next-generation conjugate vaccines in specific risk groups.

epidemiology↗