Effectiveness of BNT162b2 COVID-19 primary series vaccination in children aged 5-17 years in the United States: a cohort study.

BACKGROUND: COVID-19 vaccines are authorized for use in children in the United States; real-world assessment of vaccine effectiveness in children is needed. This study's objective was to estimate the effectiveness of receiving a complete primary series of monovalent BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine in US children. METHODS: This cohort study identified children aged 5-17 years vaccinated with BNT162b2 matched with unvaccinated children. Participants and BNT162b2 vaccinations were identified in Optum and CVS Health insurance administrative claims databases linked with Immunization Information System (IIS) COVID-19 vaccination records from 16 US jurisdictions between December 11, 2020, and May 31, 2022 (end date varied by database and IIS). Vaccinated children were followed from their first BNT162b2 dose and matched to unvaccinated children on calendar date, US county of residence, and demographic and clinical factors. Censoring occurred if vaccinated children failed to receive a timely dose 2 or if unvaccinated children received any dose. Two COVID-19 outcome definitions were evaluated: COVID-19 diagnosis in any medical setting and COVID-19 diagnosis in hospitals/emergency departments (EDs). Propensity score-weighted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with Cox proportional hazards models, and vaccine effectiveness (VE) was estimated as 1 minus HR. VE was estimated overall, within age subgroups, and within variant-specific eras. Sensitivity, negative control, and quantitative bias analyses evaluated various potential biases. RESULTS: There were 453,655 eligible vaccinated children one-to-one matched to unvaccinated comparators (mean age 12 years; 50% female). COVID-19 hospitalizations/ED visits were rare in children, regardless of vaccination status (Optum, 41.2 per 10,000 person-years; CVS Health, 44.1 per 10,000 person-years). Overall, vaccination was associated with reduced incidence of any medically diagnosed COVID-19 (meta-analyzed VE = 38% [95% CI, 36-40%]) and hospital/ED-diagnosed COVID-19 (meta-analyzed VE = 61% [95% CI, 56-65%]). VE estimates were lowest among children 5-11 years and during the Omicron-variant era. CONCLUSIONS: Receipt of a complete BNT162b2 vaccine primary series was associated with overall reduced medically diagnosed COVID-19 and hospital/ED-diagnosed COVID-19 in children; observed VE estimates differed by age group and variant era. REGISTRATION: The study protocol was publicly posted on the BEST Initiative website ( https://bestinitiative.org/wp-content/uploads/2022/03/C19-VX-Effectiveness-Protocol_2022_508.pdf ).

Assessment of Neonatal Abstinence Syndrome Surveillance - Pennsylvania, 2019.

The incidence of neonatal abstinence syndrome (NAS), a withdrawal syndrome associated with prenatal opioid or other substance exposure (1), has increased as part of the U.S. opioid crisis (2). No national NAS surveillance system exists (3), and data about the accuracy of state-based surveillance are limited (4,5). In February 2018, the Pennsylvania Department of Health began surveillance for opioid-related NAS in birthing facilities and pediatric hospitals* (6). In March 2019, CDC helped the Pennsylvania Department of Health assess the accuracy of this reporting system at five Pennsylvania hospitals. Medical records of 445 infants who possibly had NAS were abstracted; these infants had either been reported by hospital providers as having NAS or assigned an International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) hospital discharge code potentially related to NAS.† Among these 445 infants, 241 were confirmed as having NAS. Pennsylvania's NAS surveillance identified 191 (sensitivity = 79%) of the confirmed cases. The proportion of infants with confirmed NAS who were assigned the ICD-10-CM code for neonatal withdrawal symptoms from maternal use of drugs of addiction (P96.1) was similar among infants reported to surveillance (71%) and those who were not (78%; p = 0.30). Infants with confirmed NAS who were not assigned code P96.1 typically had less severe signs and symptoms. Accurate NAS surveillance, which is necessary to monitor changes and regional differences in incidence and assist with planning for needed services, includes and is strengthened by a combination of diagnosis code assessment and focused medical record review.

Yersinia enterocolitica Outbreak Associated with Pasteurized Milk.

In July 2019, we investigated a cluster of Yersinia enterocolitica cases affecting a youth summer camp and nearby community in northeastern Pennsylvania. After initial telephone interviews with camp owners and community members, we identified pasteurized milk from a small dairy conducting on-site pasteurization, Dairy A, as a shared exposure. We conducted site visits at the camp and Dairy A where we collected milk and other samples. Samples were cultured for Y. enterocolitica. Clinical and nonclinical isolates were compared using molecular subtyping. We performed case finding, conducted telephone interviews for community cases, and conducted a cohort study among adult camp staff by administering an online questionnaire. In total, we identified 109 Y. enterocolitica cases. Consumption of Dairy A milk was known for 37 (34%); of these, Dairy A milk was consumed by 31 (84%). Dairy A had shipped 214 gallons of pasteurized milk in 5 weekly shipments to the camp by mid-July. Dairy A milk was the only shared exposure identified between the camp and community. Y. enterocolitica was isolated from Dairy A unpasteurized milk samples. Five clinical isolates from camp members, two clinical isolates from community members, and nine isolates from unpasteurized milk were indistinguishable by whole-genome sequencing. The risk for yersinosis among camp staff who drank Dairy A milk was 5.3 times the risk for those who did not (95% confidence interval: 1.6-17.3). Because Dairy A only sold pasteurized milk, pasteurized milk was considered the outbreak source. We recommend governmental agencies and small dairies conducting on-site pasteurization collaborate to develop outbreak prevention strategies.

Timing of Rotavirus Vaccine Doses and Severe Rotavirus Gastroenteritis Among Vaccinated Infants in Low- and Middle-income Countries.

BACKGROUND: Altering rotavirus vaccine schedules may improve vaccine performance in low- and middle-income countries. We analyzed data from clinical trials of the monovalent (RV1) and pentavalent (RV5) rotavirus vaccines in low- and middle-income countries to understand the association between vaccine dose timing and severe rotavirus gastroenteritis incidence. METHODS: We assessed the association between variations in rotavirus vaccine administration schedules and severe rotavirus gastroenteritis risk. We used the complement of the Kaplan-Meier survival estimator to estimate risk differences for different schedules. To adjust risk differences (RDs) for confounding, we calibrated estimates in the vaccinated arm using estimates from the placebo arm. RESULTS: There were 3,114 and 7,341 children included from the RV1 and RV5 trials, respectively. The 18-month adjusted severe rotavirus gastroenteritis risk was 4.0% (95% confidence interval [CI] = 1.1, 7.1) higher for those receiving their first RV5 dose at <6 versus ≥6 weeks. For RV1, there was a 4.0% (95% CI = 0.0, 8.2) increase in 12-month adjusted risk for a 4- versus 6-week interval between doses. Further analysis revealed those receiving their first RV5 dose at 3-4 and 5-7 weeks had 2.9% (95% CI = 0.8, 5.3) and 1.3% (95% CI = -0.3, 3.0), respectively, higher risk compared with those at 9-12 weeks. Those receiving their first dose at 8 weeks had the lowest risk (RD: -2.6% [95% CI = -5.4, -0.1]) compared with those at 9-12 weeks. CONCLUSIONS: A modest delay in rotavirus vaccination start and increase in interval between doses may be associated with lower severe rotavirus gastroenteritis risk in low- and middle-income countries.

Evaluation of U.S. Poison Center Data for Surveillance of Foodborne Disease.

INTRODUCTION: Enhancing foodborne disease (FBD) surveillance and improving the timeliness of outbreak detection have been identified as public health priorities. Consumer complaint data have become increasingly useful for FBD surveillance and the detection of outbreaks. Calls to poison centers are a potential source of consumer complaint data. A retrospective analysis of data from the National Poison Data System (NPDS) (2000-2011) was undertaken to evaluate the value of data collected through the United States poison centers for detection of large national outbreaks and recalls. METHODS: Demographic and clinical data were summarized. Prevalences of FBD calls were calculated and analyzed for time trends. Significant increases in daily call prevalences were identified, and dates of the increases were compared to the announcement of 18 national outbreaks/recalls. RESULTS: Over the 12-year period, there were 433,788 unique calls self-reporting a suspected FBD exposure in humans. Overall, daily call prevalences decreased over time. Only about half of callers reported common gastrointestinal clinical effects. Of the 42 identified significant increases in call prevalences, none occurred within 14 days before an outbreak announcement; 7 occurred within 14 days after an outbreak announcement. CONCLUSIONS: Based on this analysis, there are significant limitations to using self-reported FBD exposures to NPDS as a source of information for FBD surveillance of large national outbreaks and recalls; however, a syndromic approach may yield different results and should be explored. Improved data collection and coordination with public health agencies may improve the ability to use NPDS data to monitor FBD in near real-time, identify potential outbreaks, and improve situational awareness.

Rice consumption contributes to arsenic exposure in US women.

Emerging data indicate that rice consumption may lead to potentially harmful arsenic exposure. However, few human data are available, and virtually none exist for vulnerable periods such as pregnancy. Here we document a positive association between rice consumption and urinary arsenic excretion, a biomarker of recent arsenic exposure, in 229 pregnant women. At a 6-mo prenatal visit, we collected a urine sample and 3-d dietary record for water, fish/seafood, and rice. We also tested women's home tap water for arsenic, which we combined with tap water consumption to estimate arsenic exposure through water. Women who reported rice intake (n = 73) consumed a median of 28.3 g/d, which is ∼0.5 cup of cooked rice each day. In general linear models adjusted for age and urinary dilution, both rice consumption (g, dry mass/d) and arsenic exposure through water (µg/d) were significantly associated with natural log-transformed total urinary arsenic (ßrice = 0.009, ßwater = 0.028, both P < 0.0001), as well as inorganic arsenic, monomethylarsonic acid, and dimethylarsinic acid (each P < 0.005). Based on total arsenic, consumption of 0.56 cup/d of cooked rice was comparable to drinking 1 L/d of 10 µg As/L water, the current US maximum contaminant limit. US rice consumption varies, averaging ∼0.5 cup/d, with Asian Americans consuming an average of >2 cups/d. Rice arsenic content and speciation also vary, with some strains predominated by dimethylarsinic acid, particularly those grown in the United States. Our findings along with others indicate that rice consumption should be considered when designing arsenic reduction strategies in the United States.

Assessment of potential adverse events following the 2022-2023 seasonal influenza vaccines among U.S. adults aged 65 years and older.

BACKGROUND: While safety of influenza vaccines is well-established, some studies have suggested potential associations between influenza vaccines and certain adverse events (AEs). This study examined the safety of the 2022-2023 influenza vaccines among U.S. adults ≥ 65 years. METHODS: A self-controlled case series compared incidence rates of anaphylaxis, encephalitis/encephalomyelitis, Guillain-Barré Syndrome (GBS), and transverse myelitis following 2022-2023 seasonal influenza vaccinations (i.e., any, high-dose or adjuvanted) in risk and control intervals among Medicare beneficiaries ≥ 65 years. We used conditional Poisson regression to estimate incidence rate ratios (IRRs) and 95 % confidence intervals (CIs) adjusted for event-dependent observation time and seasonality. Analyses also accounted for uncertainty from outcome misclassification where feasible. For AEs with any statistically significant associations, we stratified results by concomitant vaccination status. RESULTS: Among 12.7 million vaccine recipients, we observed 76 anaphylaxis, 276 encephalitis/encephalomyelitis, 134 GBS and 75 transverse myelitis cases. Only rates of anaphylaxis were elevated in risk compared to control intervals. With all adjustments, an elevated, but non-statistically significant, anaphylaxis rate was observed following any (IRR: 2.40, 95% CI: 0.96-6.03), high-dose (IRR: 2.31, 95% CI: 0.67-7.91), and adjuvanted (IRR: 3.28, 95% CI: 0.71-15.08) influenza vaccination; anaphylaxis IRRs were 2.54 (95% CI: 0.49-13.05) and 1.64 (95% CI: 0.38-7.05) for persons with and without concomitant vaccination, respectively. CONCLUSIONS: Rates of encephalitis/encephalomyelitis, GBS, or transverse myelitis were not elevated following 2022-2023 seasonal influenza vaccinations among U.S. adults ≥ 65 years. There was an increased rate of anaphylaxis following influenza vaccination that may have been influenced by concomitant vaccination.

Safety of Ancestral Monovalent BNT162b2, mRNA-1273, and NVX-CoV2373 COVID-19 Vaccines in US Children Aged 6 Months to 17 Years.

Importance: Active monitoring of health outcomes after COVID-19 vaccination provides early detection of rare outcomes that may not be identified in prelicensure trials. Objective: To conduct near-real-time monitoring of health outcomes after COVID-19 vaccination in the US pediatric population. Design, Setting, and Participants: This cohort study evaluated 21 prespecified health outcomes after exposure before early 2023 to BNT162b2, mRNA-1273, or NVX-CoV2373 ancestral monovalent COVID-19 vaccines in children aged 6 months to 17 years by applying a near-real-time monitoring framework using health care data from 3 commercial claims databases in the US (Optum [through April 2023], Carelon Research [through March 2023], and CVS Health [through February 2023]). Increased rates of each outcome after vaccination were compared with annual historical rates from January 1 to December 31, 2019, and January 1 to December 31, 2020, as well as between April 1 and December 31, 2020. Exposure: Receipt of an ancestral monovalent BNT162b2, mRNA-1273, or NVX-CoV2373 COVID-19 vaccine dose identified through administrative claims data linked with Immunization Information Systems data. Main Outcomes and Measures: Twenty-one prespecified health outcomes, of which 15 underwent sequential testing and 6 were only monitored descriptively due to lack of historical rates. Results: Among 4 102 016 vaccinated enrollees aged 6 months to 17 years, 2 058 142 (50.2%) were male and 3 901 370 (95.1%) lived in an urban area. Thirteen of 15 sequentially tested outcomes did not meet the threshold for a statistical signal. Statistical signals were detected for myocarditis or pericarditis after BNT162b2 vaccination in children aged 12 to 17 years and seizure after vaccination with BNT162b2 and mRNA-1273 in children aged 2 to 4 or 5 years. However, in post hoc sensitivity analyses, a statistical signal for seizure was observed only after mRNA-1273 when 2019 background rates were selected; no statistical signal was observed when 2022 rates were selected. Conclusions and Relevance: In this cohort study of pediatric enrollees across 3 commercial health insurance databases, statistical signals detected for myocarditis or pericarditis after BNT162b2 (ages 12-17 years) were consistent with previous reports, and seizures after BNT162b2 (ages 2-4 years) and mRNA-1273 vaccinations (ages 2-5 years) should be further investigated in a robust epidemiologic study with confounding adjustment. The US Food and Drug Administration concludes that the known and potential benefits of COVID-19 vaccination outweigh the known and potential risks of COVID-19 infection.

Effectiveness of monovalent COVID-19 booster/additional vaccine doses in the United States.

Background: Monovalent booster/additional doses of COVID-19 vaccines were first authorized in August 2021 in the United States. We evaluated the real-world effectiveness of receipt of a monovalent booster/additional dose of COVID-19 vaccine compared with receiving a primary vaccine series without a booster/additional dose. Methods: Cohorts of individuals receiving a COVID-19 booster/additional dose after receipt of a complete primary vaccine series were identified in 2 administrative insurance claims databases (Optum, CVS Health) supplemented with state immunization information system data between August 2021 and March 2022. Individuals with a complete primary series but without a booster/additional dose were one-to-one matched to boosted individuals on calendar date, geography, and clinical factors. COVID-19 diagnoses were identified in any medical setting, or specifically in hospitals/emergency departments (EDs). Propensity score-weighted hazards ratios (HRs) and 95% confidence intervals (CI) were estimated with Cox proportional hazards models; vaccine effectiveness (VE) was estimated as 1 minus the HR by vaccine brand overall and within subgroups of variant-specific eras, immunocompromised status, and homologous/heterologous booster status. Results: Across both data sources, we identified 752,165 matched pairs for BNT162b2, 410,501 for mRNA-1273, and 11,398 for JNJ-7836735. For any medically diagnosed COVID-19, meta-analyzed VE estimates for BNT162b2, mRNA-1273, and JNJ-7836735, respectively, were: BNT162b2, 54% (95% CI, 53%-56%); mRNA-1273, 58% (95% CI, 56%-59%); JNJ-7836735, 34% (95% CI, 23%-44%). For hospital/ED-diagnosed COVID-19, VE estimates ranged from 70% to 76%. VE was generally lower during the Omicron era than the Delta era and for immunocompromised individuals. There was little difference observed by homologous or heterologous booster status. Conclusion: The original, monovalent booster/additional doses were reasonably effective in real-world use among the populations for which they were indicated during the study period. Additional studies may be informative in the future as new variants emerge and new vaccines become available.Registration: The study protocol was publicly posted on the BEST Initiative website (https://bestinitiative.org/wp-content/uploads/2022/03/C19-VX-Effectiveness-Protocol_2022_508.pdf).

Diet and toenail arsenic concentrations in a New Hampshire population with arsenic-containing water.

BACKGROUND: Limited data exist on the contribution of dietary sources of arsenic to an individual's total exposure, particularly in populations with exposure via drinking water. Here, the association between diet and toenail arsenic concentrations (a long-term biomarker of exposure) was evaluated for individuals with measured household tap water arsenic. Foods known to be high in arsenic, including rice and seafood, were of particular interest. METHODS: Associations between toenail arsenic and consumption of 120 individual diet items were quantified using general linear models that also accounted for household tap water arsenic and potentially confounding factors (e.g., age, caloric intake, sex, smoking) (n = 852). As part of the analysis, we assessed whether associations between log-transformed toenail arsenic and each diet item differed between subjects with household drinking water arsenic concentrations <1 µg/L versus ≥1 µg/L. RESULTS: As expected, toenail arsenic concentrations increased with household water arsenic concentrations. Among the foods known to be high in arsenic, no clear relationship between toenail arsenic and rice consumption was detected, but there was a positive association with consumption of dark meat fish, a category that includes tuna steaks, mackerel, salmon, sardines, bluefish, and swordfish. Positive associations between toenail arsenic and consumption of white wine, beer, and Brussels sprouts were also observed; these and most other associations were not modified by exposure via water. However, consumption of two foods cooked in water, beans/lentils and cooked oatmeal, was more strongly related to toenail arsenic among those with arsenic-containing drinking water (≥1 µg/L). CONCLUSIONS: This study suggests that diet can be an important contributor to total arsenic exposure in U.S. populations regardless of arsenic concentrations in drinking water. Thus, dietary exposure to arsenic in the US warrants consideration as a potential health risk.

Safety of the BNT162b2 COVID-19 Vaccine in Children Aged 5 to 17 Years.

Importance: Active monitoring of health outcomes after COVID-19 vaccination offers early detection of rare outcomes that may not be identified in prelicensure trials. Objective: To conduct near-real-time monitoring of health outcomes following BNT162b2 COVID-19 vaccination in the US pediatric population aged 5 to 17 years. Design, Setting, and Participants: This population-based study was conducted under a public health surveillance mandate from the US Food and Drug Administration. Participants aged 5 to 17 years were included if they received BNT162b2 COVID-19 vaccination through mid 2022 and had continuous enrollment in a medical health insurance plan from the start of an outcome-specific clean window until the COVID-19 vaccination. Surveillance of 20 prespecified health outcomes was conducted in near real time within a cohort of vaccinated individuals from the earliest Emergency Use Authorization date for the BNT162b2 vaccination (December 11, 2020) and was expanded as more pediatric age groups received authorization through May and June 2022. All 20 health outcomes were monitored descriptively, 13 of which additionally underwent sequential testing. For these 13 health outcomes, the increased risk of each outcome after vaccination was compared with a historical baseline with adjustments for repeated looks at the data as well as a claims processing delay. A sequential testing approach was used, which declared a safety signal when the log likelihood ratio comparing the observed rate ratio against the null hypothesis exceeded a critical value. Exposure: Exposure was defined as receipt of a BNT162b2 COVID-19 vaccine dose. The primary analysis assessed primary series doses together (dose 1 + dose 2), and dose-specific secondary analyses were conducted. Follow-up time was censored for death, disenrollment, end of the outcome-specific risk window, end of the study period, or a receipt of a subsequent vaccine dose. Main Outcomes: Twenty prespecified health outcomes: 13 were assessed using sequential testing and 7 were monitored descriptively because of a lack of historical comparator data. Results: This study included 3 017 352 enrollees aged 5 to 17 years. Of the enrollees across all 3 databases, 1 510 817 (50.1%) were males, 1 506 499 (49.9%) were females, and 2 867 436 (95.0%) lived in an urban area. In the primary sequential analyses, a safety signal was observed only for myocarditis or pericarditis after primary series vaccination with BNT162b2 in the age group 12 to 17 years across all 3 databases. No safety signals were observed for the 12 other outcomes assessed using sequential testing. Conclusions and Relevance: Among 20 health outcomes that were monitored in near real time, a safety signal was identified for only myocarditis or pericarditis. Consistent with other published reports, these results provide additional evidence that COVID-19 vaccines are safe in children.

Associations between toenail arsenic concentration and dietary factors in a New Hampshire population.

BACKGROUND: Dietary factors such as folate, vitamin B12, protein, and methionine are important for the excretion of arsenic via one-carbon metabolism in undernourished populations exposed to high levels of arsenic via drinking water. However, the effects of dietary factors on toenail arsenic concentrations in well-nourished populations exposed to relatively low levels of water arsenic are unknown. METHODS: As part of a population-based case-control study of skin and bladder cancer from the USA, we evaluated relationships between consumption of dietary factors and arsenic concentrations in toenail clippings. Consumption of each dietary factor was determined from a validated food frequency questionnaire. We used general linear models to examine the associations between toenail arsenic and each dietary factor, taking into account potentially confounding effects. RESULTS: As expected, we found an inverse association between ln-transformed toenail arsenic and consumption of vitamin B12 (excluding supplements) and animal protein. Unexpectedly, there were also inverse associations with numerous dietary lipids (e.g., total fat, total animal fat, total vegetable fat, total monounsaturated fat, total polyunsaturated fat, and total saturated fat). Finally, increased toenail arsenic concentrations were associated with increased consumption of long chain n-3 fatty acids. CONCLUSION: In a relatively well-nourished population exposed to relatively low levels of arsenic via water, consumption of certain dietary lipids may decrease toenail arsenic concentration, while long chain n-3 fatty acids may increase toenail arsenic concentration, possibly due to their association with arsenolipids in fish tissue.

Pharmacist insights into adolescent human papillomavirus vaccination provision in the United States.

HPV vaccination coverage in the United States (US) falls short of the Healthy People 2020 goal of 80% coverage among 13-15 year-old adolescents. Pharmacies are a promising alternative vaccine delivery site that may increase access to HPV vaccination. Our objective was to assess pharmacists' insights into HPV vaccination provision to adolescents. We recruited 40 licensed pharmacists in eight states with different pharmacy vaccination laws: Alabama, California, Indiana, Kentucky, Maine, Tennessee, Texas, and Washington. Eligible pharmacists either previously provided or were currently providing HPV, tetanus-diphtheria-pertussis, or meningococcal vaccines to adolescents aged 9-17 years. Pharmacists were administered a semi-structured survey to explore insights into HPV vaccination provision. Forty-five percent of surveyed pharmacies offered HPV vaccination to adolescents. Pharmacists' reported challenges to providing HPV vaccination were parental consent (28%), tracking and patient recall (17%), perceived stigma of vaccination (17%), and education about or promotion of vaccination (17%). Pharmacists offering HPV vaccination sent patient reminders for vaccines with multiple doses (89%) and utilized telephone reminders (72%). Pharmacists informed patients' primary care providers of HPV vaccination doses most commonly through fax (72%) and updating electronic medical records (22%). One-third of pharmacists reported vaccination provision using the state immunization information system (IIS). Seventy-five percent reported vaccination rates could be increased at their respective pharmacy. Pharmacies are underutilized, although highly accessible, for HPV vaccination in the US. National efforts should expand educational programs to improve public awareness of in-pharmacy HPV vaccination, and improve the utilization of state IIS for reporting immunization coverage of adolescents by pharmacists.

Rotavirus Vaccine Schedules and Vaccine Response Among Infants in Low- and Middle-Income Countries: A Systematic Review.

BACKGROUND: Rotavirus vaccine schedules may impact vaccine response among children in low- and middle-income countries (LMICs). Our objective was to review the literature evaluating the effects of monovalent (RV1) or pentavalent rotavirus vaccines schedules on vaccine response. METHODS: We searched PubMed, Web of Science, Embase, and ClinicalTrials.gov for eligible trials conducted in LMICs comparing ≥2 vaccine schedules and reporting immunologic response or efficacy. We calculated seroconversion proportion differences and geometric mean concentration (GMC) ratios with 95% confidence intervals. RESULTS: We abstracted data from 8 eligible trials of RV1. The point estimates for seroconversion proportions difference ranged from -0.25 to -0.09 for the 6/10-week schedule compared with 10/14. The range for the 6/10/14- compared with 10/14-week schedule was -0.02 to 0.10. Patterns were similar for GMC ratios and efficacy estimates. CONCLUSIONS: The commonly used 6/10-week RV1 schedule in LMICs may not be optimal. Further research on the effect of rotavirus schedules using clinical endpoints is essential.

Risk Factors for Norovirus Gastroenteritis among Nicaraguan Children.

Norovirus is a leading cause of pediatric gastroenteritis. Understanding norovirus epidemiology is essential for reducing disease burden. We conducted a case-control study to describe the distribution, clinical features, and risk factors of norovirus gastroenteritis among children < 5 years of age in León, Nicaragua. Cases were children testing positive for norovirus and controls were children living in the cases' communities. Study staff interviewed mothers of enrolled cases and controls to obtain detailed exposure information including food, water, and sanitation sources; recent exposures; household characteristics; and handwashing practices. In addition, study staff requested stool samples to be tested for norovirus from select household members. We used descriptive statistics to understand the epidemiologic and clinical features of gastroenteritis episodes. To analyze potential risk factors, we used Firth's penalized logistic regression to estimate crude and adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs). There were 102 children with gastroenteritis, 18 cases of norovirus and 31 controls. Norovirus cases occurred later in the year, corresponding to a delay in the rainy season. Cases were more likely to have a household member with norovirus in their stool as compared with controls [crude OR: 13.3 (95% CI: 2.5, 136.2) and adjusted OR: 11.5 (95% CI: 1.6, 223.2)]. In addition, alcohol-based hand sanitizer use among household members was reported for 10 (32%) of controls and but never for cases. Further research is needed to understand household transmission of norovirus in low- and middle-income countries and the potential impact of hand sanitizer use.

Pediatric norovirus GII.4 infections in Nicaragua, 1999-2015.

OBJECTIVES: Investigate clinical and epidemiological factors of pediatric GII.4 norovirus infections in children with acute gastroenteritis (AGE) in Nicaragua between 1999 and 2015. METHODS: We retrospectively analyzed laboratory and epidemiologic data from 1,790 children≤7years with AGE from 6 hospitals in Nicaragua (n=538), and 3 community clinics (n=919) and households (n=333) in León, between 1999 and 2015. Moreover, asymptomatic children from community clinics (n=162) and households (n=105) were enrolled. Norovirus was detected by real-time PCR and genotyped by sequencing the N-terminal and shell region of the capsid gene. RESULTS: Norovirus was found in 19% (n=338) and 12% (n=32) of children with and without AGE, respectively. In total, 20 genotypes including a tentatively new genotype were detected. Among children with AGE, the most common genotypes were GII.4 (53%), GII.14 (7%), GII.3 (6%) and GI.3 (6%). In contrast, only one (1.4%) GII.4 was found in asymptomatic children. The prevalence of GII.4 infections was significantly higher in children between 7 and 12months of age. The prevalence of GII.4 was lowest in households (38%), followed by community clinics (50%) and hospitals (75%). Several different GII.4 variants were detected and their emergence followed the global temporal trend. CONCLUSIONS: Overall our study found the predominance of pediatric GII.4 norovirus infections in Nicaragua mostly occurring in children between 7 and 12months of age, implicating GII.4 as the main norovirus vaccine target.

Opportunities and Challenges of Adolescent and Adult Vaccination Administration Within Pharmacies in the United States.

Pharmacies have been endorsed as alternative vaccine delivery sites to improve vaccination rates through increased access to services. Our objective was to identify challenges and facilitators to adolescent and adult vaccination provision in pharmacy settings in the United States. We recruited 40 licensed pharmacists in states with different pharmacy vaccination laws. Eligible pharmacists previously administered or were currently administering human papillomavirus (HPV); tetanus, diphtheria, and pertussis (TDAP); or meningitis (meningococcal conjugate vaccine [MCV4]) vaccines to adolescents aged 9 to 17 years. Pharmacists participated in a semistructured survey on in-pharmacy vaccine provision. Pharmacists commonly administered vaccinations to age-eligible adolescents and adults: influenza (100%, 100%), pneumococcal (35%, 98%), TDAP (80%, 98%), MCV4 (60%, 78%), and HPV (45%, 53%). Common challenges included reimbursement/insurance coverage (28%, 78%), education of patients/parents (30%, 40%), and pharmacists' time constraints (28%, 35%). Three-quarters of pharmacists reported that vaccination rates could be increased. National efforts should expand insurance coverage for vaccine administration reimbursement and improve data information systems to optimize provision within pharmacies.

Heterogeneity of Rotavirus Vaccine Efficacy Among Infants in Developing Countries.

BACKGROUND: Rotavirus is the leading cause of severe diarrhea worldwide in young children. Although rotavirus vaccine efficacy is high in developed countries, efficacy is lower in developing countries. Here, we investigated heterogeneity of rotavirus vaccine efficacy by infant characteristics in developing countries. METHODS: An exploratory, post hoc analysis was conducted using randomized controlled trial data of the pentavalent rotavirus vaccine (RV5) conducted in Africa and Asia (NCT00362648). Infants received either 3 doses of vaccine/placebo and were followed for up to 2 years. Within subgroups, vaccine efficacies and 95% confidence intervals (CIs) against rotavirus gastroenteritis (RVGE) were estimated using Poisson regression. We assessed heterogeneity of efficacy by age at first dose, gender, breastfeeding status and nutrition status. RESULTS: African children receiving the first dose at <8 weeks had lower efficacy (23.7%; 95% CI: -8.2%-46.3%) than those vaccinated at ≥8 weeks (59.1%; 95% CI: 34.0%-74.6%). Marginally statistically significant differences were observed by age at first dose, gender and underweight status in Ghana and gender in Asian countries. CONCLUSIONS: Heterogeneity of efficacy was observed for age at first dose in African countries. This was an exploratory analysis; additional studies are needed to validate these results.

Indoor and Outdoor Air Pollution and Lung Cancer in New Hampshire and Vermont.

Indoor and outdoor air pollution is known to contribute to increased lung cancer incidence. This study is the first to address the contribution of home heating fuel and geographical course particulate matter (PM10) concentrations to lung cancer rates in New Hampshire, U.S. First, Pearson correlation analysis and Geographically weighted regression were used to investigate spatial relationships between outdoor PM10 and lung cancer rates. While the aforementioned analyses did not indicate a significant contribution of PM10 to lung cancer in the state, there was a trend towards a significant association in the northern and southwestern regions of the state. Second, case-control data were used to estimate the contributions of indoor pollution and second hand smoke to risk of lung cancer with adjustment for confounders. Increased risk was found among those who used wood or coal to heat their homes for more than 10 winters before the age of 18, with a significant increase in risk per winter. Resulting data suggest that further investigation of the relationship between heating-related air pollution levels and lung cancer risk is needed.