One of the overall purposes of this

One of the overall purposes of this work was to catalogue the cell types with evidence of rubella infection in CRS cases. This study extends the description of the pathology of CRS by IHC beyond the single previous report of RV infected protease inhibitors in specimens from a single CRS case almost 50years ago. A complimentary study to catalogue the cell types with evidence of rubella infection from fetuses addressed which RV infected cell types were found during the development of CRS (Nguyen et al., 2015). The only RV positive cell type that was found in the study of fetuses and the current study was neuronal cells. This is not unexpected because the positive cells during progression to CRS and the positive cells in CRS (term babies) may well be different due to transiently infected cells during the progression to CRS. We expect that additional studies of RV positive cell types in RV infected fetuses and in fatal CRS cases will be necessary to fully describe and to understand the molecular pathogenesis and the pathology of CRS. However, as global elimination targets are met, opportunities to conduct such additional studies in the future will diminish (Andrus et al., 2011).
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Introduction Invasive pneumococcal disease (IPD) and invasive meningococcal disease (IMD) are major causes of morbidity and mortality (). Pneumococcal disease remains a frequent infection in children, and in 2005 WHO estimated that 0.7–1 million children aged <5years die of this infection every year worldwide (). For meningococcal disease the incidence is highest in children younger than 1year (MacNeil et al., 2015), and WHO has estimated that the infection was the cause of 171,000 deaths in all age groups worldwide in 2000 (). The most severe presentations of infection with S. pneumoniae and N. meningitidis are meningitis and sepsis (Brouwer et al., 2009). IPD is often preceded by an asymptomatic carrier state (Bogaert et al., 2004). Nasopharyngeal carriage of pneumococci is highest in children aged 1–2years, and IPD primarily affects children under 5years and the elderly (Harboe et al., 2012; Sleeman et al., 2001). Carriage of N. meningitidis is low in the first years of age, increases in teenagers and peaks in young adults aged 20–24 (Caugant et al., 2007). Multiple factors such as age, immunization status, ethnicity, immunosuppression, socioeconomic factors, exposure to respiratory viral diseases and the host\'s genetic profile affect individual risk of IPD and IMD (Harboe et al., 2012; Chapman et al., 2007). Genetic variation in the innate immune system most likely predisposes individuals to these infections. The genetics of the complicated pathways have been elucidated only partially. Activation of nuclear factor (NF)-κB through Toll-like receptor binding is considered to be the central initiating event of host responses to invasion of microbial pathogens, including encapsulated bacteria (Rahman and McFadden, 2011; Clausen et al., 2013). Innate and adaptive immune responses are dependent on activation of the NF-κB pathway (Janssen et al., 2004). The degradation of NF-κB inhibitors including IκB-α, IκB-ε and IκB-ζ (encoded by the genes NFKBIA, NFKBIE, and NFKBIZ) (Chapman et al., 2010a) leads to NF-κB translocation to the nucleus and gene transcription (Chapman and Hill, 2012). Single nucleotide polymorphisms (SNPs) in NFKBIA, NFKBIE, NFKBIZ and related genes have been associated with susceptibility to IPD in adults (Chapman et al., 2006, 2007, 2010a, 2010b; Khor et al., 2007). Studies exploring already described associations between certain SNPs and the susceptibility to diseases are important in order to verify those associations in new, independent studies (Tabor et al., 2002). This study evaluates the association of SNPs in NF-kB inhibitors, and susceptibility to IPD and pneumococcal serotypes in a pediatric population (Chapman et al., 2006, 2007, 2010a, 2010b).