Mother's Milk: A Purposeful Contribution to the Development of the infant Microbiota and immunity

Breast milk is the perfect nutrition for infants, a result of millions of years of evolution. In addition to providing a source of nutrition, breast milk contains a diverse array of microbiota and myriad biologically active components that are thought to guide the infant’s developing mucosal immune system. It is believed that bacteria from the mother’s intestine may translocate to breast milk and dynamically transfer to the infant. Such interplay between mother and her infant is a key to establishing a healthy infant intestinal microbiome. These intestinal bacteria protect against many respiratory and diarrheal illnesses, but are subject to environmental stresses such as antibiotic use. Orchestrating the development of the microbiota are the human milk oligosaccharides (HMOs), the synthesis of which are partially determined by the maternal genotype. HMOs are thought to play a role in preventing pathogenic bacterial adhesion though multiple mechanisms, while also providing nutrition for the microbiome. Extracellular vesicles (EVs), including exosomes, carry a diverse cargo, including mRNA, miRNA, and cytosolic and membrane-bound proteins, and are readily detectable in human breast milk. Strongly implicated in cell–cell signaling, EVs could therefore may play a further role in the development of the infant microbiome. This review considers the emerging role of breast milk microbiota, bioactive HMOs, and EVs in the establishment of the neonatal microbiome and the consequent potential for modulation of neonatal immune system development

Epidemiology of community-onset Staphylococcus aureus infections in pediatric patients: an experience at a Children's Hospital in central Illinois

<p>Abstract</p> <p>Background</p> <p>The nation-wide concern over methicillin-resistant <it>Staphylococcus aureus </it>(MRSA) has prompted many clinicians to use vancomycin when approaching patients with suspected staphylococcal infections. We sought to characterize the epidemiology of community-onset <it>S. aureus </it>infections in hospitalized children to assist local clinicians in providing appropriate empiric antimicrobial therapy.</p> <p>Methods</p> <p>From January 2005–June 2008, children (0–18 years old) admitted to the Children's Hospital of Illinois with community-onset <it>S. aureus </it>infections were identified by a computer-assisted laboratory-based surveillance and medical record review.</p> <p>Results</p> <p>Of 199 patients, 67 (34%) had invasive infections, and 132 (66%) had skin and soft tissue infections (SSTIs). Among patients with invasive infections, <it>S. aureus </it>isolates were more likely to be susceptible to methicillin (MSSA 63% vs. MRSA 37%), whereas patients with SSTIs, <it>S. aureus </it>isolates were more likely to be resistant to methicillin (MRSA 64% vs. MSSA 36%). Bacteremia and musculoskeletal infections were the most common invasive infections in both groups of <it>S. aureus</it>. Pneumonia with empyema was more likely to be caused by MRSA (<it>P </it>= 0.02). The majority (~90%) of MRSA isolates were non-multidrug resistant, even in the presence of healthcare-associated risk factors.</p> <p>Conclusion</p> <p>Epidemiological data at the local level is important for antimicrobial decision-making. MSSA remains an important pathogen causing invasive community-onset <it>S. aureus </it>infections among hospitalized children. In our hospital, nafcillin in combination with vancomycin is recommended empiric therapy in critically ill patients with suspected invasive staphylococcal infections. Because up to 25% of MSSA circulating in our area are clindamycin-resistant, clindamycin should be used cautiously as empiric monotherapy in patients with suspected invasive staphylococcal infections.</p

Staphylococcus aureus Panton-Valentine Leukocidin Contributes to Inflammation and Muscle Tissue Injury

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) threatens public health worldwide, and epidemiologic data suggest that the Panton-Valentine Leukocidin (PVL) expressed by most CA-MRSA strains could contribute to severe human infections, particularly in young and immunocompetent hosts. PVL is proposed to induce cytolysis or apoptosis of phagocytes. However, recent comparisons of isogenic CA-MRSA strains with or without PVL have revealed no differences in human PMN cytolytic activity. Furthermore, many of the mouse studies performed to date have failed to demonstrate a virulence role for PVL, thereby provoking the question: does PVL have a mechanistic role in human infection? In this report, we evaluated the contribution of PVL to severe skin and soft tissue infection. We generated PVL mutants in CA-MRSA strains isolated from patients with necrotizing fasciitis and used these tools to evaluate the pathogenic role of PVL in vivo. In a model of necrotizing soft tissue infection, we found PVL caused significant damage of muscle but not the skin. Muscle injury was linked to induction of pro-inflammatory chemokines KC, MIP-2, and RANTES, and recruitment of neutrophils. Tissue damage was most prominent in young mice and in those strains of mice that more effectively cleared S. aureus, and was not significant in older mice and mouse strains that had a more limited immune response to the pathogen. PVL mediated injury could be blocked by pretreatment with anti-PVL antibodies. Our data provide new insights into CA-MRSA pathogenesis, epidemiology and therapeutics. PVL could contribute to the increased incidence of myositis in CA-MRSA infection, and the toxin could mediate tissue injury by mechanisms other than direct killing of phagocytes

Kawasaki syndrome: an intriguing disease with numerous unsolved dilemmas

More than 40 years have passed since Kawasaki syndrome (KS) was first described. Yet KS still remains an enigmatic illness which damages the coronary arteries in a quarter of untreated patients and is the most common cause of childhood-acquired heart disease in developed countries. Many gaps exist in our knowledge of the etiology and pathogenesis of KS, making improvements in therapy difficult. In addition, many KS features and issues still demand further efforts to achieve a much better understanding of the disease. Some of these problem areas include coronary artery injuries in children not fulfilling the classic diagnostic criteria, genetic predisposition to KS, unpredictable ineffectiveness of current therapy in some cases, vascular dysfunction in patients not showing echocardiographic evidence of coronary artery abnormalities in the acute phase of KS, and risk of potential premature atherosclerosis. Also, the lack of specific laboratory tests for early identification of the atypical and incomplete cases, especially in infants, is one of the main obstacles to beginning treatment early and thereby decreasing the incidence of cardiovascular involvement. Transthoracic echocardiography remains the gold-standard for evaluation of coronary arteries in the acute phase and follow-up. In KS patients with severe vascular complications, more costly and potentially invasive investigations such as coronary CT angiography and MRI may be necessary. As children with KS with or without heart involvement become adolescents and adults, the recognition and treatment of the potential long term sequelae become crucial, requiring that rheumatologists, infectious disease specialists, and cardiologists cooperate to develop specific guidelines for a proper evaluation and management of these patients. More education is needed for physicians and other professionals about how to recognize the long-term impact of systemic problems related to KS

Cost effectiveness analysis of Year 2 of an elementary school-located influenza vaccination program–Results from a randomized controlled trial

BACKGROUND: School-located vaccination against influenza (SLV-I) has the potential to improve current suboptimal influenza immunization coverage for U.S. school-aged children. However, little is known about SLV-I’s cost-effectiveness. The objective of this study is to establish the cost-effectiveness of SLV-I based on a two-year community-based randomized controlled trial (Year 1: 2009–2010 vaccination season, an unusual H1N1 pandemic influenza season, and Year 2: 2010–2011, a more typical influenza season). METHODS: We performed a cost-effectiveness analysis on a two-year randomized controlled trial of a Western New York SLV-I program. SLV-I clinics were offered in 21 intervention elementary schools (Year 1 n = 9,027; Year 2 n = 9,145 children) with standard-of-care (no SLV-I) in control schools (Year 1 n = 4,534 (10 schools); Year 2 n = 4,796 children (11 schools)). We estimated the cost-per-vaccinated child, by dividing the incremental cost of the intervention by the incremental effectiveness (i.e., the number of additionally vaccinated students in intervention schools compared to control schools). RESULTS: In Years 1 and 2, respectively, the effectiveness measure (proportion of children vaccinated) was 11.2 and 12.0 percentage points higher in intervention (40.7 % and 40.4 %) than control schools. In year 2, the cost-per-vaccinated child excluding vaccine purchase ($59.88 in 2010 US$) consisted of three component costs: (A) the school costs ($8.25); (B) the project coordination costs ($32.33); and (C) the vendor costs excluding vaccine purchase ($16.68), summed through Monte Carlo simulation. Compared to Year 1, the two component costs (A) and (C) decreased, while the component cost (B) increased in Year 2. The cost-per-vaccinated child, excluding vaccine purchase, was$59.73 (Year 1) and $59.88 (Year 2, statistically indistinguishable from Year 1), higher than the published cost of providing influenza vaccination in medical practices ($39.54). However, taking indirect costs (e.g., averted parental costs to visit medical practices) into account, vaccination was less costly in SLV-I ($23.96 in Year 1,$24.07 in Year 2) than in medical practices. CONCLUSIONS: Our two-year trial’s findings reinforced the evidence to support SLV-I as a potentially favorable system to increase childhood influenza vaccination rates in a cost-efficient way. Increased efficiencies in SLV-I are needed for a sustainable and scalable SLV-I program

Vaccinating Children against SARS-CoV-2: A Literature Review and Survey of International Experts to Assess Safety, Efficacy and Perceptions of Vaccine Use in Children.

INTRODUCTION: The balance of risks and benefits of COVID-19 vaccination in children is more complex than in adults with limited paediatric data resulting in no global consensus on whether all healthy children should be vaccinated. We sought to assess the safety, efficacy, and effectiveness of childhood vaccination against SARS-CoV-2, as well as better understanding perceptions of vaccination in parents and vaccine experts. METHODS: We performed a literature review for COVID-19 vaccine safety, efficacy, effectiveness, and perceptions. We searched international safety databases for safety data and developed an electronic survey to elicit country-specific COVID-19 immunisation data, including vaccine regulations, policies, rates, and public attitudes solicited from vaccine experts. RESULTS: Nine studies were included in the final safety analysis. Local reactions were frequently reported across all studies and vaccine types. Adverse events reported to surveillance systems tended to be non-serious, and commonly included injection site reactions and dizziness. Twenty-three studies reported immunogenicity, efficacy, and effectiveness data. There were nine randomised control trials of six different vaccine types, which showed seroconversion of neutralising antibodies in vaccinated children ranging from 88% to 100%. The vaccine efficacy for Pfizer and Moderna vaccines ranged from 88% to 100%. There were 118 survey responses representing 55 different countries. Reported vaccination rates ranged from &lt;1% to 98%. Most respondents described "mixed opinions" regarding paediatric vaccination policies in their country. By region, a more positive public attitude towards vaccination correlated with higher vaccination rates. DISCUSSION: In this mixed-methods review, we have found evidence that vaccination against COVID-19 in children is safe, efficacious, and effective. Overall, the combined evidence from both the literature review and survey highlights the need for further data on both the safety and effectiveness of COVID-19 vaccinations in children