Rationale: Laboratory and clinical evidence suggests synergy between rhinoviruses and Streptococcus pneumoniae in the pathogenesis of respiratory tract infections. However, it is unclear whether rhinoviruses promote pneumococcal acquisition and transmission. Objectives: To describe the impact of rhinovirus infection on the acquisition and transmission of pneumococci within families with children. Methods: We investigated 29 families with at least two children. The follow-up started at the onset of respiratory infectious symptoms in any family member and consisted of daily symptom diary and nasal swab samples from each participant twice per week for 3 weeks. Swabs were taken by the parents and sent to a study clinic by mail. Rhinoviruses were detected by reverse transcription–polymerase chain reaction and typed by sequencing. Pneumococci were identified by an antigen test and by standard culture methods, serotyping, and whole-genome sequencing. The effect of rhinovirus infection on the rates of pneumococcal acquisition and within-family transmission was estimated from the observed acquisition events and person-times spent uncolonized, using Poisson regression. Measurements and Main Results: Rhinovirus was detected in 38 subjects (30%) at the onset and in 86 subjects (67%) during the follow-up. S. pneumoniae was detected on the first day in 9 (7%) and during follow-up in 38 (30%) subjects. Children with rhinovirus infection had a 4.3-fold rate of pneumococcal acquisition from the community (95% confidence interval, 1.1–15.4) and a 14.8-fold rate of within-family transmission (95% confidence interval, 3.1–69.6) compared with children without rhinovirus infection. Conclusions: Rhinovirus infection within families facilitates acquisition and within-family transmission of S. pneumoniae.

We aimed to explore the role of TLR4 (rs4986790) polymorphism in the nasopharyngeal (NP) bacterial colonization and its consequent impact on the development of childhood asthma. A semi-quantitative culture of NP swabs was performed on 473 children at 2 months of age and on 213 children at 13 months of age. TLR4 polymorphism was analyzed for 396 children. Children were followed from birth to the age of 7.5 years and the final outcome was physician-diagnosed asthma. The associations between TLR4 genotype, bacterial colonization, and asthma were analyzed. Children with TLR4 AG or GG genotype were more often colonized with Moraxella catarrhalis at 2 months of age (p = 0.009) and Haemophilus influenzae at 13 months of age (p = 0.018). Children who were colonized with H. influenzae at 13 months of age had a significantly higher risk of later development of asthma (p = 0.004). M. catarrhalis or H. Influenzae colonization at 2 months of age or TLR4 genotype Asp299Gly were not associated with the development of childhood asthma. TLR4 Asp299Gly polymorphism was associated with an increased risk of colonization of M. catarrhalis and H. influenzae in children. The colonization with H. influenzae at 13 months of age was associated with a higher risk of later development of childhood asthma.

Bacterial meningitis (BM) is a severe disease caused by various bacterial pathogens. Toll-like receptors (TLRs) protect humans from invading pathogens. In this study, we determined whether single nucleotide polymorphisms (SNPs) of TLR4 and TLR9 are associated with susceptibility to and outcome of BM in Angolan children. Samples were taken from 241 patients and 265 age-matched ethnic controls. The SNPs TLR4 rs4986790 (896A > G) and TLR9 rs187084 (−1486T > C) were determined by high-resolution melting analysis (HRMA). The frequency of variant genotypes in TLR4 was significantly higher in patients with Haemophilus influenzae meningitis than controls (odds ratio (OR), 2.5; 95% confidence interval (CI), 1.2–5.4; p = 0.021), whereas the frequency of variant genotypes in TLR9 was significantly lower in patients with H. influenzae meningitis than controls (OR, 0.4; 95% CI, 0.2–0.9; p = 0.036). No such differences were found with other causative pathogens, such as Streptococcus pneumoniae and Neisseria meningitidis. At the time of discharge, patients with meningitis caused by Gram-negative bacteria who were carriers of variant TLR4 genotypes had a higher risk of ataxia (OR, 12.91; 95% CI, 1.52–109.80; p = 0.019) and other neurological sequelae (OR, 11.85; 95% CI, 1.07–131.49; p = 0.044) than those with the wild-type TLR4 genotype. Our study suggests an association between H. influenzae meningitis and genetic variation between TLR4 and TLR9 in Angolan children.

To analyze the role of interleukin IL-17A and IL-10 polymorphisms in susceptibility to juvenile idiopathic arthritis (JIA), 98 Finnish children and adolescents with JIA were studied. Data from the 1000 Genomes Project, consisting of 99 healthy Finns, served as the controls. The patients were analyzed for four IL-17A and three IL-10 gene-promoter polymorphisms, and the serum IL-17A, IL-17F, IL-10, and IL-6 levels were determined. The IL-17A rs8193036 variant genotypes (CT/CC) were more common among the patients than controls, especially in those with polyarthritis (OR 1.93, 95% CI 1.11–3.36; p = 0.020). IL-17A rs2275913 minor allele A was more common in patients (OR 1.45, 95% Cl 1.08–1.94; p = 0.014) and especially among patients with oligoarthritis and polyarthritis than the controls (OR 1.61, 95%CI 1.06–2.43; p = 0.024). Carriers of the IL-17A rs4711998 variant genotype (AG/AA) had higher serum IL-17A levels than those with genotype GG. However, carriers of the variant genotypes of IL-17A rs9395767 and rs4711998 appeared to have higher IL-17F levels than those carrying wildtype. IL-10 rs1800896 variant genotypes (TC/CC) were more abundant in patients than in the controls (OR 1.97, 95%CI 1.06–3.70; p = 0.042). Carriers of the IL-10 rs1800896 variant genotypes had lower serum levels of IL-17F than those with wildtype. These data provide preliminary evidence of the roles of IL-17 and IL-10 in the pathogenesis of JIA and its subtypes in the Finnish population. However, the results should be interpreted with caution, as the number of subjects included in this study was limited.

Despite extensive vaccinations, pertussis remains endemic and epidemic in multiple countries. The persistence of cases can be partly attributed to the significant individual variation in vaccine responses. This study evaluated the association of baseline cytokines (before booster vaccination) on antibody concentrations to Tdap-vaccine antigens. Healthy Finnish children (7-10y, n = 36), adolescents (11-15y, n = 37), young adults (20-34y, n = 25), and older adults (60-70y, n = 23) received a Tdap3-IPV booster. Serum antibodies against pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (Prn), fimbriae 2/3, diphtheria toxoid (DT), and tetanus toxoid (TT), as well as PT neutralizing antibodies were measured before, one month, and one year after the booster. Baseline serum concentrations of IFN-γ, IL-2, IL-5, IL-10, IL-13, IL-17 A and IL-17F were determined. The proportion of detectable and undetectable baseline cytokines varied between age groups 58.3 % of children had a higher proportion of detectable IL-5, IL-10, IL-13, and IL-17F compared to adolescents (IL-5, 37.8 %; IL-10, 48.6 %; IL-13, 48.6 %; IL-17F, 37.7 %), young adults (IL-5, 36.0 %; IL-10, 28.0 %; IL-13, 36.0 %; IL-17F, 44.0 %), and older adults (IL-5, 26.1 %; IL-10, 21.7 %; IL-13, 39.1 %; IL-17F, 30.4 %). IFN-γ had a lower detectability in children (44.4 %) and young (40.0 %) and older adults (39.1 %) in contrast to adolescents (62.2 %). IL-2 was undetectable in all age groups while the proportion of detectable IL-17 A decreased with age. A mixed model showed that undetectable baseline levels of IFN-γ, IL-2, IL-10, and IL-17 A were associated with higher antibody concentrations in children before and after vaccination, particularly against PT. Positive associations were observed in adolescents for anti-TT concentrations and young adults for anti-FHA IgA concentrations. These findings indicate a possible role of existing cytokines in pertussis booster antibody concentrations in children and warrant further studies in different populations. However, the results should be interpreted with caution as the number of subjects is limited.

Background/Objectives: Bacterial meningitis is a severe disease with a fatality rate of 5–50%. It is mainly caused by Streptococcus pneumoniae or Neisseria meningitidis, which can also cause simultaneous infections outside the central nervous system. Toll-like receptors (TLRs) have an important role in the innate immune system. The TLR2 subfamily comprises the four highly homologous members TLR1, TLR2, TLR6, and TLR10, which also have an important immunomodulatory role in infectious diseases. Methods: The study cohort consists of 190 bacterial meningitis patients aged 1 to 147 months from randomized clinical trials and 268 controls from Luanda, Angola. Polymorphisms of TLR2 (rs111200466) and TLR10 (rs10856837 and rs11096956) were determined using PCR-based methods and Sanger sequencing. The genotyping results were analyzed together with clinical data to determine whether gene polymorphisms of TLR2 and TLR10 are associated with susceptibility and outcome of bacterial meningitis in Angolan children. Results: At admission and during hospitalization, patients with pneumococcal meningitis carrying a variant (ins/del or del/del) of TLR2 rs111200466 had a significantly lower risk of coexisting infections (OR 0.27; 95% CI 0.11–0.65; p = 0.004), particularly pneumonia (OR 0.18; 95% CI 0.06–0.49; p = 0.001). In addition, haplotype analysis demonstrated that a variant genotype of TLR2 rs111200466 together with a wildtype of TLR10 SNPs (rs10856837 and rs11096956) may protect against coexisting pneumonia (OR 0.2; 95% CI 0.06–0.6; p = 0.007). Conclusions: This study suggests an association between coexisting infection and genetic variation in TLR2 and TLR10 of bacterial meningitis in Angolan children.