Efficacy of Messenger RNA-1273 Against Severe Acute Respiratory Syndrome Coronavirus 2 Acquisition in Young Adults From March to December 2021

BACKGROUND: The efficacy of messenger RNA (mRNA)-1273 against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is not well defined, particularly among young adults. METHODS: Adults aged 18-29 years with no known history of SARS-CoV-2 infection or prior vaccination for coronavirus disease 2019 (COVID-19) were recruited from 44 US sites from 24 March to 13 September 2021 and randomized 1:1 to immediate vaccination (receipt of 2 doses of mRNA-1273 vaccine at months 0 and 1) or the standard of care (receipt of COVID-19 vaccine). Randomized participants were followed up for SARS-CoV-2 infection measured by nasal swab testing and symptomatic COVID-19 measured by nasal swab testing plus symptom assessment and assessed for the primary efficacy outcome. A vaccine-declined observational group was also recruited from 16 June to 8 November 2021 and followed up for SARS-CoV-2 infection as specified for the randomized participants. RESULTS: The study enrolled 1149 in the randomized arms and 311 in the vaccine-declined group and collected >122 000 nasal swab samples. Based on randomized participants, the efficacy of 2 doses of mRNA-1273 vaccine against SARS-CoV-2 infection was 52.6% (95% confidence interval, -14.1% to 80.3%), with the majority of infections due to the Delta variant. Vaccine efficacy against symptomatic COVID-19 was 71.0% (95% confidence interval, -9.5% to 92.3%). Precision was limited owing to curtailed study enrollment and off-study vaccination censoring. The incidence of SARS-CoV-2 infection in the vaccine-declined group was 1.8 times higher than in the standard-of-care group. CONCLUSIONS: mRNA-1273 vaccination reduced the incidence of SARS-CoV-2 infection from March to September 2021, but vaccination was only one factor influencing risk. CLINICAL TRIALS REGISTRATION: NCT04811664

Shift Work Predicts Increases in Lipopolysaccharide-Binding Protein, Interleukin-10, and Leukocyte Counts in a Cross-Sectional Study of Healthy Volunteers Carrying Low-Grade Systemic Inflammation

The disruption of inflammatory responses is a potential mechanism behind the harmful effects of shift work and is associated with increased risk of hypertension, stroke, obesity, diabetes, and cancer. These responses are linked to the proliferation of leukocytes in shift workers, suggesting a systemic signal as a potential mediator. The purpose of this study was to assess the relationship between systemic inflammation, leukocyte counts, and systemic endotoxemia in samples from a diverse cohort of day workers and shift workers. Participants (normothermic and normotensive) were healthy volunteers, non-smoking, and drug- and medication-free. The following outcomes were measured: C-reactive protein, TNF-α, IL-6, IL-1β, IL-10, leukocyte counts (monocytes, lymphocytes, and neutrophils), and lipopolysaccharide-binding protein (LBP). Risk factors that increase systemic inflammation, such as blood pressure, sleep loss, and cortisol, were also assessed. The results indicated that shift workers slept significantly less than day workers and had significantly increased concentrations of all of the cytokines measured as well as plasma cortisol. Regression models found that after controlling for covariates, shift-work exposure predicted the significant increase observed in IL-10, leukocyte counts, and LBP. Our results suggest that acute increases in low-grade systemic endotoxemia are unresolved during chronic shift-work exposure. This ongoing immune challenge may underlie the disrupted inflammatory responses characteristic of shift-work-related pathologies. Systemic endotoxemia may represent a novel target to investigate the early effects of exposure to shift-work schedules

Geographic and racial variation in asthma prevalence and emergency department use among Medicaid-enrolled children in 14 southern states

BACKGROUND: Despite evidence-based prevention and practice guidelines, asthma prevalence, treatment, and outcomes vary widely at individual and community levels. Asthma disproportionate/ly affects low-income and minority children, who comprise a large segment of the Medicaid population. METHODS: 2007 Medicaid claims data from 14 southern states was mapped for 556 counties to describe the local area variation in 1-year asthma prevalence rates, emergency department (ED) visit rates, and racial disparity rate ratios. RESULTS: One-year period prevalence of asthma ranged from 2.8% in Florida to 6.4% in Alabama, with a median prevalence rate of 4.1%. At the county level, the prevalence was higher for Black children and ranged from 1.03% in Manatee County, FL, to 21.0% in Hockley County, TX. Black–White rate ratios of prevalence ranged from 0.49 in LeFlore County, MS, to 3.87 in Flagler County, FL. Adjusted asthma ED visit rates ranged from 2.2 per 1000 children in Maryland to 16.5 in Alabama, with a median Black–White ED-visit rate ratio of 2.4. Rates were higher for Black children, ranging from 0.80 per 1000 in Wicomico County, MD, to 70 per 1000 in DeSoto County, FL. Rate ratios of ED visits ranged from 0.25 in Vernon Parish, LA, to 25.28 in Nelson County, KY. CONCLUSIONS AND RELEVANCE: Low-income children with Medicaid coverage still experience substantial variation in asthma prevalence and outcomes from one community to another. The pattern of worse outcomes for Black children also varies widely across counties. Eliminating this variation could substantially improve overall outcomes and eliminate asthma disparities

Geographic surveillance of community associated MRSA infections in children using electronic health record data

Abstract Background Community- associated methicillin resistant Staphylococcus aureus (CA-MRSA) cause serious infections and rates continue to rise worldwide. Use of geocoded electronic health record (EHR) data to prevent spread of disease is limited in health service research. We demonstrate how geocoded EHR and spatial analyses can be used to identify risks for CA-MRSA in children, which are tied to place-based determinants and would not be uncovered using traditional EHR data analyses. Methods An epidemiology study was conducted on children from January 1, 2002 through December 31, 2010 who were treated for Staphylococcus aureus infections. A generalized estimated equations (GEE) model was developed and crude and adjusted odds ratios were based on S. aureus risks. We measured the risk of S. aureus as standardized incidence ratios (SIR) calculated within aggregated US 2010 Census tracts called spatially adaptive filters, and then created maps that differentiate the geographic patterns of antibiotic resistant and non-resistant forms of S. aureus. Results CA-MRSA rates increased at higher rates compared to non-resistant forms, p = 0.01. Children with no or public health insurance had higher odds of CA-MRSA infection. Black children were almost 1.5 times as likely as white children to have CA-MRSA infections (aOR 95% CI 1.44,1.75, p < 0.0001); this finding persisted at the block group level (p < 0.001) along with household crowding (p < 0.001). The youngest category of age (< 4 years) also had increased risk for CA-MRSA (aOR 1.65, 95%CI 1.48, 1.83, p < 0.0001). CA-MRSA encompasses larger areas with higher SIRs compared to non-resistant forms and were found in block groups with higher proportion of blacks (r = 0.517, p < 0.001), younger age (r = 0.137, p < 0.001), and crowding (r = 0.320, p < 0.001). Conclusions In the Atlanta MSA, the risk for CA-MRSA is associated with neighborhood-level measures of racial composition, household crowding, and age of children. Neighborhoods which have higher proportion of blacks, household crowding, and children < 4 years of age are at greatest risk. Understanding spatial relationship at a community level and how it relates to risks for antibiotic resistant infections is important to combat the growing numbers and spread of such infections like CA-MRSA

Risk of Skin and Soft Tissue Infections among Children Found to be Staphylococcus aureus MRSA USA300 Carriers

The purpose of this study was to examine community-associated methicillin resistant Staphylococcus aureus (CA-MRSA) carriage and infections and determine risk factors associated specifically with MRSA USA300. A case control study was conducted in a pediatric emergency department. Nasal and axillary swabs were collected, and participants were interviewed for risk factors. The primary outcome was the proportion of S. aureus carriers among those presenting with and without a skin and soft tissue infection (SSTI). S. aureus carriers were further categorized into MRSA USA300 carriers or non MRSA USA300 carriers. We found MRSA USA300 carriage rate was higher in children less than 2 years of age, those with an SSTI, children with recent antibiotic use, and those with a family history of SSTI. MRSA USA300 carriers were also more likely to have lower income compared to non MRSA USA300 carriers and no S. aureus carriers. Rates of PVL genes were higher in MRSA carriage isolates with an SSTI, compared to MRSA carriage isolates of patients without an SSTI with an association between MRSA USA300 carriage and presence of PVL in those diagnosed with an abscess

Applying fecal microbiota transplantation (FMT) to treat recurrent Clostridium difficile infections (rCDI) in children

Background: Fecal Microbiota Transplantation (FMT) is an innovative means of treating recurrent Clostridium difficile infection (rCDI), through restoration of gut floral balance. However, there is a lack of data concerning the efficacy of FMT and its impact on the gut microbiome among pediatric patients. This study analyzes clinical outcomes and microbial community composition among 15 pediatric patients treated for rCDI via FMT. Methods: This is a prospective, observational, pilot study of 15 children ≤18 years, who presented for rCDI and who met inclusion criteria for FMT at a pediatric hospital and pediatric gastroenterology clinic. Past medical history and demographics were recorded at enrollment and subsequent follow-up. Specimens of the donors’ and the patients’ pre-FMT and post-FMT fecal specimen were collected and used to assess microbiome composition via 16S rRNA gene sequencing. Results: FMT successfully prevented rCDI episodes for minimum of 3 months post-FMT in all patients, with no major adverse effects. Three patients reported continued GI bleeding; however, all three also had underlying Inflammatory Bowel Disease (IBD). Our analyses confirm a significant difference between pre-and post-FMT gut microbiome profiles (Shannon diversity index), whereas no significant difference was observed between post-FMT and donor microbiome profiles. At the phyla level, post-FMT profiles showed significantly increased levels of Bacteroidetes and significantly decreased levels of Proteobacteria. Subjects with underlying IBD showed no difference in their pre-and post-FMT profiles. Conclusion: The low rate of recurrence or re-infection by C. difficile, coupled with minimal adverse effects post-FMT, suggests that FMT is a viable therapeutic means to treat pediatric rCDI. Post-FMT microbiomes are different from pre-FMT microbiomes, and similar to those of healthy donors, suggesting successful establishment of a healthier microbiome

Shedding of porcine circovirus type 1 DNA and rotavirus RNA by infants vaccinated with Rotarix®

Thirty-three infants aged ∼2 months had serial stool samples collected after receipt of Rotarix® vaccine dose 1, and were assessed for shedding of porcine circovirus type 1 DNA and Rotavirus group A RNA by molecular methods. We did not find strong evidence that porcine circovirus type 1 replication occurred. Porcine circovirus type 1 genome with the same sequence as that in Rotarix® was detected in a few infants as late as day ≥ 13; while this timing could suggest there may have been replication and not just transient passage through the gastrointestinal tract, the lack of increase in copy number in any infant supports transient passage and there are inherent limitations to the results. We found that 21% of infants did not shed Rotarix® RVA RNA beyond the day 3 sample, which may suggest lack of vaccine virus replication. Of the infants in whom Rotarix RVA RNA shedding continued, peak copy numbers were reached on days 3–5 for ∼40%, and after day 5 in ∼60%, and shedding can be prolonged (≥ 45 days)