Pertussis is a highly contagious respiratory infection caused by Bordetella pertussis bacterium. The mainstay of treatment is macrolide antibiotics that reduce transmissibility, shorten the duration of symptoms and decrease mortality in infants. Recently, the macrolide resistance of B. pertussis has been reported globally but is especially widespread in mainland China. In this review, we aim to summarise the current understanding of the epidemiology, resistance mechanisms and clinical implications of B. pertussis macrolide resistance. Since the first appearance of macrolide-resistant B. pertussis in Arizona, USA, in 1994, only sporadic cases have been reported outside China. In certain parts of China, on the other hand, up to 70–100% of the recent clinical isolates have been found to be macrolide resistant. Reasons for macrolide resistance being centred upon China during the last decade can only be speculated on, but the dominant B. pertussis lineage is different between China and most of the high-income countries. It seems evident that efforts to increase awareness, guide molecular epidemiological surveillance and carry out systematic screening of B. pertussis positive samples for macrolide resistance should be implemented globally. In addition, practices to improve the clinical care of infants with pertussis caused by resistant strains should be studied vigorously.

Pertussis toxin (PT) is considered the main virulence factor causing whooping cough or pertussis. The protein is widely studied and its composition was revealed and sequenced already during the 1980s. The human immune system creates a good response against PT when measured in quantity. However, the serum anti-PT antibodies wane rapidly, and only a small amount of these antibodies are found a few years after vaccination/infection. Therefore, multiple approaches to study the functionality (quality) of these antibodies, e.g., avidity, neutralizing capacity, and epitope specificity, have been investigated. In addition, the long-term B cell memory (Bmem) to PT is crucial for good protection throughout life. In this review, we summarize the findings from functional PT antibody and Bmem studies. These results are discussed in line with the quantity of serum anti-PT antibodies. PT neutralizing antibodies and anti-PT antibodies with proper avidity are crucial for good protection against the disease, and certain epitopes have been identified to have multiple functions in the protection. Although PT-specific Bmem responses are detectable at least five years after vaccination, long-term surveillance is lacking. Variation of the natural boosting of circulating Bordetella pertussis in communities is an important confounding factor in these memory studies.

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.

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.

Serological diagnosis of pertussis is mainly based on anti-pertussis toxin (PT) IgG antibodies. Since PT is included in all acellular vaccines (ACV), serological assays do not differentiate antibodies induced by ACVs and infection. Adenylate cyclase toxin (ACT) is not included in the ACVs, which makes it a promising candidate for pertussis serology with the specific aim of separating infection- and ACV-induced antibodies. A multiplex lateral flow test with PT and ACT antigens was developed to measure serum antibodies from pertussis-seropositive patients (n = 46), healthy controls (n = 102), and subjects who received a booster dose of ACV containing PT, filamentous hemagglutinin, and pertactin (n = 67) with paired sera collected before and one month after the vaccination. If the diagnosis was solely based on anti-PT antibodies, 98.5–44.8% specificity (before and after vaccination, respectively) and 78.2% sensitivity were achieved, whereas if ACT was used in combination with PT, the sensitivity of the assay increased to 91.3% without compromising specificity. No increase in the level of anti-ACT antibodies was found after vaccination. This exploratory study indicates that the use of ACT for serology would be beneficial in combination with a lower quantitative cutoff for anti-PT antibodies, and particularly in children and adolescents who frequently receive booster vaccinations.

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.