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.

Molecular Epidemiologic and Geo-Spatial Characterization of Staphylococcus aureus Cultured from Skin and Soft Tissue Infections from United States-Born and Immigrant Patients Living in New York City.

(1) Background: With increasing international travel and mass population displacement due to war, famine, climate change, and immigration, pathogens, such as Staphylococcus aureus (S. aureus), can also spread across borders. Methicillin-resistant S. aureus (MRSA) most commonly causes skin and soft tissue infections (SSTIs), as well as more invasive infections. One clonal strain, S. aureus USA300, originating in the United States, has spread worldwide. We hypothesized that S. aureus USA300 would still be the leading clonal strain among US-born compared to non-US-born residents, even though risk factors for SSTIs may be similar in these two populations (2) Methods: In this study, 421 participants presenting with SSTIs were enrolled from six community health centers (CHCs) in New York City. The prevalence, risk factors, and molecular characteristics for MRSA and specifically clonal strain USA300 were examined in relation to the patients' self-identified country of birth. (3) Results: Patients born in the US were more likely to have S. aureus SSTIs identified as MRSA USA300. While being male and sharing hygiene products with others were also significant risks for MRSA SSTI, we found exposure to animals, such as owning a pet or working at an animal facility, was specifically associated with risk for SSTIs caused by MRSA USA300. Latin American USA300 variant (LV USA300) was most common in participants born in Latin America. Spatial analysis showed that MRSA USA300 SSTI cases were more clustered together compared to other clonal types either from MRSA or methicillin-sensitive S. aureus (MSSA) SSTI cases. (4) Conclusions: Immigrants with S. aureus infections have unique risk factors and S. aureus molecular characteristics that may differ from US-born patients. Hence, it is important to identify birthplace in MRSA surveillance and monitoring. Spatial analysis may also capture additional information for surveillance that other methods do not.

Influence of Mask Wearing during COVID-19 Surge and Non-Surge Time Periods in Two K-12 Public School Districts in Georgia, USA.

BACKGROUND: Into the third year of the COVID-19 pandemic and the second year of in-person learning for many K-12 schools in the United States, the benefits of mitigation strategies in this setting are still unclear. We compare COVID-19 cases in school-aged children and adolescents between a school district with a mandatory mask-wearing policy to one with an optional mask-wearing policy, during and after the peak period of the Delta variant wave of infection. METHODS: COVID-19 cases during the Delta variant wave (August 2021) and post the wave (October 2021) were obtained from public health records. Cases of K-12 students, stratified by grade level (elementary, middle, and high school) and school districts across two counties, were included in the statistical and spatial analyses. COVID-19 case rates were determined and spatially mapped. Regression was performed adjusting for specific covariates. RESULTS: Mask-wearing was associated with lower COVID-19 cases during the peak Delta variant period; overall, regardless of the Delta variant period, higher COVID-19 rates were seen in older aged students. CONCLUSION: This study highlights the need for more layered prevention strategies and policies that take into consideration local community transmission levels, age of students, and vaccination coverage to ensure that students remain safe at school while optimizing their learning environment.

Predicting Low-Level Childhood Lead Exposure in Metro Atlanta Using Ensemble Machine Learning of High-Resolution Raster Cells.

Low-level lead exposure in children is a major public health issue. Higher-resolution spatial targeting would significantly improve county and state-wide policies and programs for lead exposure prevention that generally intervene across large geographic areas. We use stack-ensemble machine learning, including an elastic net generalized linear model, gradient-boosted machine, and deep neural network, to predict the number of children with venous blood lead levels (BLLs) ≥2 to <5 µg/dL and ≥5 µg/dL in ~1 km2 raster cells in the metro Atlanta region using a sample of 92,792 children ≤5 years old screened between 2010 and 2018. Permutation-based predictor importance and partial dependence plots were used for interpretation. Maps of predicted vs. observed values were generated to compare model performance. According to the EPA Toxic Release Inventory for air-based toxic release facility density, the percentage of the population below the poverty threshold, crime, and road network density was positively associated with the number of children with low-level lead exposure, whereas the percentage of the white population was inversely associated. While predictions generally matched observed values, cells with high counts of lead exposure were underestimated. High-resolution geographic prediction of lead-exposed children using ensemble machine learning is a promising approach to enhance lead prevention efforts.

Space-time trends of community-onset Staphylococcus aureus infections in children: a group-based trajectory modeling approach.

PURPOSE: Staphylococcus aureus (S. aureus) remains a serious cause of infections in the United States and worldwide. In the United States, methicillin-resistant S. aureus (MRSA) is the leading cause of skin and soft tissue infections. This study identifies 'best' to 'worst' infection trends from 2002 to 2016, using group-based trajectory modeling approach. METHODS: Electronic health records of children living in the southeastern United States with S. aureus infections from 2002 to 2016 were retrospectively studied, by applying a group-based trajectory model to estimate infection trends (low, high, very high), and then assess spatial significance of these trends at the census tract level; we focused on community-onset infections and not those considered healthcare acquired. RESULTS: Three methicillin-susceptible S. aureus (MSSA) infection trends (low, high, very high) and three MRSA trends (low, high, very high) were identified from 2002 to 2016. Among census tracts with community-onset S. aureus cases, 29% of tracts belonged to the best trend (low infection) for both methicillin-resistant S. aureus and methicillin-susceptible S. aureus; higher proportions occurring in the less densely populated areas. Race disparities were seen with the worst methicillin-resistant S. aureus infection trends and were more often in urban areas. CONCLUSIONS: Group-based trajectory modeling identified unique trends of S. aureus infection rates over time and space, giving insight into the associated population characteristics which reflect these trends of community-onset infection.

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-1ß, 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.

Increased Risk of Sub-Clinical Blood Lead Levels in the 20-County Metro Atlanta, Georgia Area-A Laboratory Surveillance-Based Study.

Lead (Pb) is a naturally occurring, highly toxic metal that has adverse effects on children across a range of exposure levels. Limited screening programs leave many children at risk for chronic low-level lead exposure and there is little understanding of what factors may be used to identify children at risk. We characterize the distribution of blood lead levels (BLLs) in children aged 0-72 months and their associations with sociodemographic and area-level variables. Data from the Georgia Department of Public Health's Healthy Homes for Lead Prevention Program surveillance database was used to describe the distribution of BLLs in children living in the metro Atlanta area from 2010 to 2018. Residential addresses were geocoded, and "Hotspot" analyses were performed to determine if BLLs were spatially clustered. Multilevel regression models were used to identify factors associated with clinical BBLs (≥5 µg/dL) and sub-clinical BLLs (2 to <5 µg/dL). From 2010 to 2018, geographically defined hotspots for both clinical and sub-clinical BLLs diffused from the city-central area of Atlanta into suburban areas. Multilevel regression analysis revealed non-Medicaid insurance, the proportion of renters in a given geographical area, and proportion of individuals with a GED/high school diploma as predictors that distinguish children with BLLs 2 to <5 µg/dL from those with lower (<2 µg/dL) or higher (≥5 µg/dL) BLLs. Over half of the study children had BLLs between 2 and 5 µg/dL, a range that does not currently trigger public health measures but that could result in adverse developmental outcomes if ignored.

Correction to: Geographic surveillance of community associated MRSA infections in children using electronic health record data.

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

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.

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.

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

INTRODUCTION: 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. METHODS: We conducted a case control study 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). We further categorized S. aureus carriers into MRSA USA300 carriers or non-MRSA USA300 carriers. RESULTS: We found the MRSA USA300 carriage rate was higher in children less than two 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 Panton-Valentine leukocidin (PVL) genes were higher in MRSA carriage isolates with an SSTI, compared to MRSA carriage isolates of patients without an SSTI. There was an association between MRSA USA300 carriage and presence of PVL in those diagnosed with an abscess. CONCLUSION: Children younger than two years were at highest risk for MRSA USA300 carriage. Lower income, recent antibiotic use, and previous or family history of SSTI were risk factors for MRSA USA300 carriage. There is a high association between MRSA USA300 nasal/axillary carriage and presence of PVL in those with abscesses.

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).

Sustained Effectiveness of Monovalent and Pentavalent Rotavirus Vaccines in Children.

OBJECTIVE: Using case-control methodology, we measured the vaccine effectiveness (VE) of the 2-dose monovalent rotavirus vaccine (RV1) and 3-dose pentavalent rotavirus vaccine (RV5) series given in infancy against rotavirus disease resulting in hospital emergency department or inpatient care. STUDY DESIGN: Children were eligible for enrollment if they presented to any 1 of 3 hospitals in Atlanta, Georgia with diarrhea ≤10 days duration during January-June 2013 and were born after RV1 introduction. Stool samples were tested for rotavirus by enzyme immunoassay and immunization records were obtained from providers and the state electronic immunization information system. Case-subjects (children testing rotavirus antigen-positive) were compared with children testing rotavirus antigen-negative. RESULTS: Overall, 98 rotavirus-case subjects and 175 rotavirus-negative controls were enrolled. Genotype G12P[8] predominated (n = 87, 89%). The VE of 2 RV1 doses was 84% (95% CI 38, 96) among children aged 8-23 months and 82% (95% CI 41, 95) among children aged ≥24 months. For the same age groups, the VE of 3 RV5 doses was 80% (95% CI 27, 95) and 87% (95% CI 22, 98), respectively. CONCLUSIONS: Under routine use, the RV1 and RV5 series were both effective against moderate-to-severe rotavirus disease during a G12P[8] season, and both vaccines demonstrated sustained protection beyond the first 2 years of life.

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.

Effectiveness of monovalent and pentavalent rotavirus vaccine.

OBJECTIVE: Previous US evaluations have not assessed monovalent rotavirus vaccine (RV1, a G1P[8] human rotavirus strain) effectiveness, because of its later introduction (2008). Using case-control methodology, we measured the vaccine effectiveness (VE) of the 2-dose RV1 and 3-dose pentavalent vaccine (RV5) series against rotavirus disease resulting in hospital emergency department or inpatient care. METHODS: Children were eligible for enrollment if they presented to 1 of 5 hospitals (3 in Georgia, 2 in Connecticut) with diarrhea of ≤10 days' duration during January through June 2010 or 2011, and were born after RV1 introduction. Stools were collected; immunization records were obtained from providers and state electronic immunization information system (IIS). Case-subjects (children testing rotavirus antigen-positive) were compared with 2 control groups: children testing rotavirus negative and children selected from IIS. RESULTS: Overall, 165 rotavirus-case subjects and 428 rotavirus-negative controls were enrolled. Using the rotavirus-negative controls, RV1 VE was 91% (95% confidence interval [CI] 80 to 95) and RV5 VE was 92% (CI 75 to 97) among children aged ≥8 months. The RV1 VE against G2P[4] disease was high (94%, CI 78 to 98), as was that against G1P[8] disease (89%, CI 70 to 96). RV1 effectiveness was sustained among children aged 12 through 23 months (VE 91%; CI 75 to 96). VE point estimates using IIS controls were similar to those using rotavirus-negative controls. CONCLUSIONS: RV1 and RV5 were both highly effective against severe rotavirus disease. RV1 conferred sustained protection during the first 2 years of life and demonstrated high effectiveness against G2P[4] (heterotypic) disease.

Methicillin-resistant Staphylococcus aureus colonization among pediatric health care workers from different outpatient settings.

Staphylococcus aureus colonization rates in pediatric health care workers from different types of outpatient settings were determined from December 2008 through May 2010. Colonization rates for Staphylococcus aureus and, specifically, methicillin-resistant Staphylococcus aureus (MRSA) rates were similar to the rates that have been reported for the general population. The predominant MRSA pulsed-field gel electrophoresis type associated with colonization in these health care workers is not MRSA USA300.

Leveraging state immunization information systems to measure the effectiveness of rotavirus vaccine.

OBJECTIVE: Electronic immunization information systems (IISs) are now established in almost all US states. We used the IIS in Minnesota, Georgia, and Connecticut for immunization data and as the source of 1 of 2 control groups to measure pentavalent rotavirus vaccine (RV5) effectiveness (VE) using case-control methodology. PATIENTS AND METHODS: Case-subjects were vaccine-eligible children who presented to 1 of 5 hospitals or emergency departments with gastroenteritis and had rotavirus antigen detected in stool during any of 3 rotavirus seasons (2007-2009). Two control groups were used: children with gastroenteritis who tested negative for rotavirus and children from the IIS matched by zip code and birth date. In Minnesota and Georgia, immunization records for rotavirus-positive and -negative children were also obtained from providers. RESULTS: Overall, 402 (96%) rotavirus case-subjects and 825 (97%) rotavirus-negative controls who met eligibility criteria were found in the IISs. Ten IIS controls were identified for each case. VE estimates for RV5 were similar across control groups, immunization data sources, and states. VE point estimates for 3 vs 0 doses were 89% to 94% among children aged 8 months or older and 86% to 92% among those aged 24 months or older. VE for 2 doses was ≥90% among children aged 8 months or older, and VE for 1 dose was 66% among those aged 6 weeks through 5 months. CONCLUSIONS: Three RV5 doses confer sustained protection against rotavirus disease during the first 3 years of life in US children. Two RV5 doses also seem to provide good protection. IISs can be valuable tools for assessing the effectiveness of vaccines administered to young children.

Community-associated infections in children--update on community-associated methicillin-resistant Staphylococcus aureus for the practitioner.

Nationally, the incidence of infections in children due to resistant Staphylococcus aureus originating from the community (CA-MRSA) is increasing at alarming rates. The predominant clinical syndrome caused by CA-MRSA in children is skin and soft tissue infections (SSTIs), and many of these children suffer from recurrence of these SSTIs. Most studies published in the medical literature have evaluated infection and colonization due to resistant staphylococcal bacteria among people with previously identified risk factors, eg, indwelling catheters, chronic illnesses. Established risk factors for MRSA infection include recent hospitalization or surgery, stay at long-term care facility, history of prolonged antibiotic use, and history of injection drug use. However, little is known about the risk factors associated with CA-MRSA in children. This paper will summarize the current epidemiology surrounding CA-MRSA, the associated clinical syndromes and most common presentations, and the latest strategies to not only treat but to prevent the recurrence of the infections caused by this resistant bacterium, which originated from the community.