Associations between salivary cytokines and oral health, age, and sex in healthy children.

Human saliva is a complex fluid containing proteins such as salivary cytokines, which can be used for diagnostic purposes, particularly among the pediatric population. This study aimed to assess the concentrations of salivary cytokines in healthy children and adolescents and determine their associations with age, sex, and oral and dental findings. Healthy children and adolescents aged 4-18 years were enrolled in this cross-sectional study. The concentrations of the following salivary cytokines were measured by Luminex technology: IFN-γ, IL-1α, IL-1ß, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IP-10, TNF-α, and VEGF-A. Additionally, oral and dental parameters were recorded using a standardized protocol. A total of 128 participants (mean age, 10.7 years; males, 50.8%) were enrolled. The levels of 1ß, IL-6, IL-8, and IL-10 were significantly higher in those with gingivitis. Increased salivary flow rates were negatively correlated with IL-1α, IL-1ß, IL-6, IL-8, IL-10, TNF-α, and VEGF-A concentrations. The findings of this study showed that the concentrations of most of the salivary cytokines were positively correlated with age and the presence of oral pathologies (such as gingivitis and caries) and negatively correlated with salivary flow rate.

Bacillus Calmette-Guérin Skin Reaction Predicts Enhanced Mycobacteria-Specific T-Cell Responses in Infants: A Post Hoc Analysis of a Randomized Controlled Trial.

Rationale: Scar formation following bacillus Calmette-Guérin (BCG) vaccination has been associated with lower all-cause mortality; the relation between scar and mycobacteria-specific protection against tuberculosis is debated. Objectives: To evaluate the association between BCG skin reaction and mycobacteria-specific immune responses. Methods: A post hoc analysis was done among 214 infants in Australia randomized to vaccination with one of three BCG vaccine strains (BCG-Denmark, BCG-Japan, or BCG-Russia) given at birth or BCG-Denmark given at 2 months of age. Measurements and Main Results: BCG skin reaction size and characteristics 10 weeks after vaccination were related to the in vitro mycobacteria-specific immune responses measured in stimulated whole blood. The size and characteristics of the skin reaction correlated positively with in vitro immune responses, even after adjusting for BCG vaccine strain and age at vaccination. Specifically, the reaction size and characteristics correlated with the proportion of mycobacteria-specific polyfunctional CD4+ T cells after stimulation with BCG and PPD and, to a lesser extent, after stimulation with Mycobacterium tuberculosis or Mycobacterium ulcerans. A similar correlation was observed with concentrations of IFN-γ, IL-2, tumor necrosis factor, and IL-13 in the supernatant after stimulation with BCG, PPD, and M. tuberculosis and to some degree for the proportions of mycobacteria-specific polyfunctional CD8+ T cells and CD107+ cytotoxic cells. Conclusions: BCG skin reaction correlated with the magnitude of mycobacteria-specific T-cell responses. As T-cell responses play a key role in defense against mycobacteria, the relationship between BCG scar formation and protection against tuberculosis should be revisited. This may also extend to the need for BCG revaccination in scar-negative individuals.Clinical trial registered with www.australianclinicaltrials.gov.au/clinical-trial-registries (ACTRN12608000227392).

Subclinical Tuberculosis in Children: Diagnostic Strategies for Identification Reported in a 6-year National Prospective Surveillance Study.

BACKGROUND: Subclinical tuberculosis (TB) is well recognized and defined as a disease state with absent or nonrecognized symptoms. The study identifies factors associated with subclinical TB and diagnostic strategies in a low-burden, high-resource country. METHODS: Data were collected between December 2013 and November 2019 through the Swiss Pediatric Surveillance Unit (SPSU). Children with culture/molecular confirmed TB, or who were treated with ≥3 antimycobacterial drugs, were included. RESULTS: A total of 138 (80%) children with TB disease were included in the final analysis, of which 43 (31%) were subclinical. The median age of children with subclinical compared to symptomatic TB was 3.7 (interquartile range [IQR] 2.2-7) and 9.7 (IQR 2.7-14.3) years, respectively (P = .003). The cause of investigation for TB was recorded in 31/43 (72.1%) of children with subclinical TB and included contact exposure in 25 (80.6%) of children. In children with subclinical TB, diagnosis was made by a combination of the following abnormal/confirming results: culture/molecular + immunodiagnostic + chest radiography in 12 (27.9%) cases, immunodiagnostic + chest radiography in 19 (44.2%) cases, culture/molecular + chest radiography in 2 (4.7%) cases, culture + immunodiagnostic in 1 (2.3%) case, chest radiography only in 8 (18.6%) cases, and immunodiagnostic only in 1 (2.3%) case. CONCLUSIONS: A notable proportion of children with TB had subclinical disease. This highlights the importance of non-symptom-based TB case finding in exposed children and refugees from high-TB-prevalence settings. TB screening in these asymptomatic children should therefore include a combination of immunodiagnostic testing and imaging followed by culture and molecular testing.

Pediatric Tuberculosis Disease during Years of High Refugee Arrivals: A 6-Year National Prospective Surveillance Study.

BACKGROUND: In Europe, surveillance and monitoring of pediatric tuberculosis (TB) remains important, particularly in the light of migration in recent years. The aim of the study was to evaluate incidence rates of childhood TB and detailed diagnostic pathways and treatment. METHODS: Data were collected through the Swiss Pediatric Surveillance Unit (SPSU) from December 2013 to November 2019. Monthly -notifications are obtained from the 33 pediatric hospitals in the SPSU, and a detailed questionnaire was sent out upon notification. Inclusion criteria were children and adolescents aged up to 15 years with culture- or molecular-confirmed TB disease or for whom a treatment with ≥3 antimycobacterial drugs had been initiated. Data were compared with age-matched notification data from the Swiss Federal Office of Public Health (FOPH). RESULTS: Of the 172 cases notified to SPSU, a detailed questionnaire was returned for 161 (93%) children, of which 139 met the inclusion criteria. Reasons for exclusion were age >15 years, double reporting, and not fulfilling the criteria for TB disease. During the same time period, 172 pediatric TB cases were reported to the FOPH, resulting in an incidence of 2.1 per 100,000, ranging from 1.4 to 2.8 per year, without a clear trend over time. In the 64 (46.0%) foreign-born children, incidence rates were higher and peaked in 2016, with 13.7 per 100,000 (p = 0.018). The median interval between arrival in Switzerland and TB diagnosis was 5 (IQR 1-21) months, and 80% were diagnosed within 24 months of arrival. In 58% of the cases, TB disease was confirmed by culture or molecular assays. Age >10 years, presence of fever, or weight loss were independent factors associated with confirmed TB. CONCLUSION: The annual pediatric TB incidence rate only varied among foreign-born children and was highest in 2016 when refugee influx peaked in Europe. Importantly, most foreign-born children with TB were diagnosed within 2 years after arrival in Switzerland. Thus, the early period after arrival in Switzerland is associated with a higher risk of TB disease in children, and this should be considered for screening guidance in refugees.

Cytokines in saliva as biomarkers of oral and systemic oncological or infectious diseases: A systematic review.

Recent evidence suggests that salivary cytokines provide information about both oral conditions and systemic diseases. This review summarizes evidence for the use of salivary cytokines as biomarkers for oral and systemic diseases. We included studies in adults and children with a focus on the latter, due to the importance of non-invasive diagnostic methods in the paediatric age group. A systematic review was performed using Medline and Web of Science covering the period of January 1996 to December 2019 according to the preferred reporting items for systematic reviews. Thirty-four studies were included in the final analysis, for a total of 2407 patients and healthy controls. Pro-inflammatory cytokines including interleukin (IL)-1ß, IL-2, IL-6 and tumor necrosis factor (TNF)-α were associated with the severity of oral mucosal tissue damage in patients with cancer, and IL-1ß may be an early marker of graft-versus-host disease. Salivary interferon-γ levels were correlated with oral complications and the presence of the underlying disease in HIV-infected individuals, and salivary cytokine patterns may be useful for diagnosing tuberculosis. In summary, current data illustrate that salivary cytokines are associated with oral inflammation, making them potential biomarkers for disease diagnosis and treatment efficacy. Because of the simplicity of saliva collection, this method may be useful in pediatric studies and in resource-limited settings.