Zoonotic Source Attribution of Salmonella enterica Serotype Typhimurium Using Genomic Surveillance Data, United States.

Increasingly, routine surveillance and monitoring of foodborne pathogens using whole-genome sequencing is creating opportunities to study foodborne illness epidemiology beyond routine outbreak investigations and case-control studies. Using a global phylogeny of Salmonella enterica serotype Typhimurium, we found that major livestock sources of the pathogen in the United States can be predicted through whole-genome sequencing data. Relatively steady rates of sequence divergence in livestock lineages enabled the inference of their recent origins. Elevated accumulation of lineage-specific pseudogenes after divergence from generalist populations and possible metabolic acclimation in a representative swine isolate indicates possible emergence of host adaptation. We developed and retrospectively applied a machine learning Random Forest classifier for genomic source prediction of Salmonella Typhimurium that correctly attributed 7 of 8 major zoonotic outbreaks in the United States during 1998-2013. We further identified 50 key genetic features that were sufficient for robust livestock source prediction.

The effects of maternal smoking on early mucosal immunity and sensitization at 12 months of age.

With the dramatic rise in asthma and respiratory disease, there is an urgent need to determine the effects of common environmental exposures on early immune development. In this study, we examined the effects of maternal smoking as a major adverse exposure in early life, on mucosal immune function and allergen sensitization in the first year of life. A cohort of 60 smokers and 62 non-smokers was recruited in pregnancy, and followed prospectively at 3 and 12 months of age for saliva collection [for immunoglobulin (Ig) A measurements], urine collection (for cotinine levels) and clinical assessments (for allergy and infection history). Allergen skin-prick tests were also performed at 12 months of age. Specific IgA to common colonizing bacteria was measured on saliva samples, including pneumococcal polysaccharide (PS) serotype 14 and non-typeable Haemophilus influenza (NTHI) outer membrane protein 6 (OMP6). Eighty-two mothers and their infants completed the 12-month follow-up period--56 in the maternal non-smoking group and 26 in the maternal smoking group. Maternal smoking was associated with significantly higher total infant salivary IgA at 12 months of age (p = 0.026), and more chronic upper respiratory tract symptoms (p = 0.012). However, there were no differences in the level of specific IgA antibodies to common colonizing bacteria (pneumococcal PS serotype 14 and NTHI OMP6). In general, the IgA levels at 12 months were higher in children who had more chest infections in the first year (Kendall's tau b, 0.282; p = 0.003). There was also a trend of lower respiratory tract symptoms (wheeze) (p = 0.142) in infants of smokers. There were no effects of maternal smoking on the rates of allergen sensitization, atopic dermatitis and food allergy at 12 months of age. In conclusion, maternal smoking did not inhibit the production of anti-microbial IgA, suggesting that other factors are responsible for the increased susceptibility to infection in these infants. The increased mucosal inflammation in these children was not associated with effects on early allergy propensity.

FOXP3 mRNA expression at 6 months of age is higher in infants who develop atopic dermatitis, but is not affected by giving probiotics from birth.

Factors that influence immune regulation in early life may be implicated in the rise in allergic disease, including reduced microbial burden. The aim of the study was to examine the infant regulatory T-cell function in relation to (a) probiotic supplementation for the first 6 months of life and (b) the subsequent development of an early allergic phenotype. Two hundred and thirty-one allergic, pregnant women were recruited into a randomized, controlled trial. The infants received either a probiotic or placebo daily for the first 6 months of life. One hundred and seventy-eight children completed the study, with blood samples available from 118 (60 placebo; 58 probiotic). CD4(+)CD25(+)CTLA4(+)T-regulatory phenotype and allergen-induced FOXP3 mRNA expression were compared in relation to this intervention as well as according to evidence of early disease (atopic dermatitis). The administration of probiotics was not associated with any significant differences in the proportion of circulating CD4(+)CD25(+)CTLA4(+)cells, or in the resting expression of FOXP3. There were also no relationships between these parameters and patterns of gut colonization, and this probiotic did not reduce the risk of atopic dermatitis. Children who developed atopic dermatitis (n = 36/118) had significantly higher induced FOXP3 expression following stimulation with both house dust mite (HDM) (p = 0.017) and ovalbumin (OVA) allergens (p = 0.021) than those that did not develop atopic dermatitis. Although this relationship was seen in both the probiotic and placebo groups, it was more pronounced in the probiotic group. However, regression analysis demonstrated that higher allergen-induced FOXP3 expression was predicted by the presence of atopic dermatitis (p = 0.018) rather than probiotics supplementation (p = 0.217). The higher levels of allergen-induced FOXP3 in atopic dermatitis suggest activation of these compensatory mechanisms rather than a primary defect in this pathway. Probiotic supplementation and gut colonization did not appear to substantially modify these regulatory pathways, or the risk of developing atopic dermatitis.

Probiotic supplementation for the first 6 months of life fails to reduce the risk of atopic dermatitis and increases the risk of allergen sensitization in high-risk children: a randomized controlled trial.

BACKGROUND: Despite preliminary evidence, the role of probiotics in allergy prevention is unclear. OBJECTIVE: To determine whether early probiotic supplementation prevents allergic disease in high-risk infants. METHODS: Newborns of women with allergy (n = 231) received either Lactobacillus acidophilus (LAVRI-A1) or placebo daily for the first 6 months of life. Children were assessed for atopic dermatitis (AD) and other symptoms at 6 and 12 months and had allergen skin prick tests (SPT) at 12 months of age. RESULTS: A total of 178 infants completed the supplementation period. Those in the probiotic group showed significantly higher rates of Lactobacillus colonization (P = .039). At 6 months, AD rates were similar in the probiotic (n = 23/89; 25.8%) and placebo (n = 20/88; 22.7%) groups (P = .629). There was also no difference at 12 months, although the proportion of children with SPT+AD was significantly higher in the probiotic group (P = .045). At 12 months, the rate of sensitization was significantly higher in the probiotic group (P = .030). The presence of culturable Lactobacilli or Bifidobacterium in stools in the first month of life was not associated with the risk of subsequent sensitization or disease; however, the presence of Lactobacillus at 6 months of age was associated with increased risk of subsequent cow's milk sensitization (P = .012). CONCLUSION: Early probiotic supplementation with L acidophilus did not reduce the risk of AD in high-risk infants and was associated with increased allergen sensitization in infants receiving supplements. The long-term significance of the increased rate of sensitization needs to be investigated in further studies. CLINICAL IMPLICATIONS: These findings challenge the role of probiotics in allergy prevention.

HLA-DR expression on neonatal monocytes is associated with allergen-specific immune responses.

BACKGROUND: The specific mechanisms regulating priming of T-cell immunity to common allergens during early childhood remain to be elucidated, though increasing evidence indicates that antigen-presenting cell function is impaired in childhood. OBJECTIVE: Examine the relationship between HLA-DR expression on monocytes and B cells, allergen-specific T-cell responses at birth, and clinical outcomes at 2 years of age. METHODS: Blood mononuclear cells were obtained from 36 healthy neonates who were followed up clinically to the age of 2 years. Expression of HLA-DR by monocytes and B cells was determined at baseline and after in vitro exposure to IFN-gamma, a cytokine that is known to upregulate the expression of HLA-DR. Mononuclear cells were stimulated with endotoxin or a panel of inhalant and food allergens, and cytokine responses and lymphoproliferation were determined after 1 and 5 days, respectively. RESULTS: The magnitude of HLA-DR upregulation on IFN-gamma-stimulated cord blood CD14 + monocytes was consistently correlated with allergen-induced, but not mitogen-induced, lymphoproliferation at birth. HLA-DR upregulation on monocytes was also positively associated with endotoxin-induced IL-12 p70 synthesis (tau = 0.46; P < .001) but inversely related to mite- and ovalbumin-induced IL-13 synthesis ( P = .0006 and P < .003, respectively). HLA-DR expression on unstimulated cord blood monocytes was inversely associated with symptoms of atopic disease at the 2-year follow-up ( P = .015). In contrast, HLA-DR expression on B cells was not associated with these parameters of immune function. CONCLUSIONS: These findings suggest that the maturity of neonatal monocytes and their responsiveness to external stimuli are linked to differing patterns of immune reactivity at birth and to the risk of allergic symptoms in early childhood.

Fish oil supplementation in pregnancy modifies neonatal allergen-specific immune responses and clinical outcomes in infants at high risk of atopy: a randomized, controlled trial.

BACKGROUND: There is growing interest in the potential role of anti-inflammatory n-3 polyunsaturated fatty acids (n-3 PUFAs) in the prevention of allergic disease. OBJECTIVE: We sought to determine whether maternal dietary supplementation with n-3 PUFAs during pregnancy could modify immune responses in infants. METHODS: In a randomized, controlled trial 98 atopic, pregnant women received fish oil (3.7 g n-3 PUFAs per day) or placebo from 20 weeks' gestation until delivery. Neonatal PUFA levels and immunologic response to allergens were measured at birth. RESULTS: Eighty-three women completed the study. Fish oil supplementation (n = 40) achieved significantly higher proportions of n-3 PUFAs in neonatal erythrocyte membranes (mean +/- SD, 17.75% +/- 1.85% as a percentage of total fatty acids) compared with the control group (n = 43, 13.69% +/- 1.22%, P <.001). All neonatal cytokine (IL-5, IL-13, IL-10, and IFN-gamma) responses (to all allergens) tended to be lower in the fish oil group (statistically significant only for IL-10 in response to cat). Although this study was not designed to examine clinical effects, we noted that infants in the fish oil group were 3 times less likely to have a positive skin prick test to egg at 1 year of age (odds ratio, 0.34; 95% confidence interval, 0.11 to 1.02; P =.055). Although there was no difference in the frequency of atopic dermatitis at 1 year of age, infants in the fish oil group also had significantly less severe disease (odds ratio, 0.09; 95% confidence interval, 0.01 to 0.94; P =.045). CONCLUSIONS: These data suggest a potential reduction in subsequent infant allergy after maternal PUFA supplementation. More detailed follow-up studies are required in larger cohorts to establish the robustness of these findings and to ascertain their significance in relation to longer-term modification of allergic disease in children.