Japanese encephalitis vaccination in pregnancy among U.S. active duty military women

IntroductionJapanese encephalitis (JE) vaccine is an inactivated vaccine that has shown no risks in pregnancy in animal models, but epidemiologic studies are lacking. U.S. military service members located in JE endemic regions are required to be vaccinated; understanding the potential adverse events (AEs), including AEs that may occur in pregnancy, is needed. Here, we assessed pregnancy and infant health outcomes in association with JE vaccination in pregnancy.MethodsThe study population consisted of 192,570 pregnancies to active duty women (2003–2014), captured in the Department of Defense Birth and Infant Health Research program. JE vaccine in pregnancy, vaccine count, formulation, trimester, and whether first career dose coincided with pregnancy were compared with unexposed pregnancies to assess risk of pregnancy and infant health outcomes. Adjusted risk estimates and 95% confidence intervals (CIs) were calculated by multivariable models.ResultsOf the 192,570 identifed pregnancies, 513 were exposed to the JE vaccine; 474 exposures occurred in the first trimester. For all outcomes, elevated risk estimates ranging from 1.53 to 1.70, were observed with receipt of >1 JE vaccine in pregnancy, though 95% CIs were wide and encompassed the null. First dose of JE vaccination in pregnancy was associated with a 1.87 (95% CI: 1.12–3.13) times increased risk of low birthweight (LBW) when excluding pregnancies exposed to other non-routinely recommended vaccinations in pregnancy. All other associations were null in both main and subset analyses.ConclusionsThe overall results of these analyses provide reassuring findings for the safety of JE vaccination in pregnancy. Higher counts of JE vaccine received in pregnancy yielded large yet non-statistically significant risk estimates for all outcomes, though likely driven by lack of pregnancy awareness. An association was observed with LBW in subset analyses, but it was limited to women receiving their first JE vaccine and not observed in the larger main analyses.     

Race/ethnic inequities in conjoint monitoring and screening for U.S. children 3 and under

BackgroundNon-White children with developmental disabilities are frequently identified later than White children and therefore miss out on opportunities for early intervention (EI). Recent research indicates that conjoint monitoring and screening is more strongly associated with EI receipt than monitoring or screening alone.ObjectiveTo determine if there are racial/ethnic inequities in the conjoint receipt of monitoring and screening.MethodA series of survey weighted and stratified logistic regression analyses were conducted on National Surveys of Children's Health (2016–2018) data with conjoint monitoring and screening, screening alone, monitoring alone, and non-receipt as outcomes for children aged 9–23 months of age. The primary predictor was child race/ethnicity (Black, Hispanic, Other, and White). Additional co-variates included child (e.g., Age), caretaker/family (e.g., poverty level), healthcare (e.g., usual source of healthcare), state EI policies, and city metropolitan status.ResultsBivariate analyses indicated significant variation in conjoint monitoring and screening across racial/ethnic groups and covariates. Bivariate analyses showed that Black and Hispanic children had significantly lower odds of conjoint monitoring and screening receipt than White children. Multivariate analyses showed that this relationship was better accounted by co-variates. The health service variable, usual source of healthcare, had the strongest relationship with receipt of conjoint monitoring and screening.ConclusionsBlack and Hispanic children are less likely to receive conjoint monitoring and screening than White children. Analyses investigating the role of usual source of healthcare seem particularly promising for understanding the sources of inequities in monitoring and screening receipt.     

Surveillance for Guillain-Barré syndrome after influenza vaccination among U.S. Medicare beneficiaries during the 2017–2018 season

BackgroundThe U.S. Food and Drug Administration and the Centers for Medicare & Medicaid Services have been actively monitoring the risk of Guillain-Barré syndrome (GBS) following influenza vaccination among Fee-for-Service (FFS) Medicare beneficiaries every season since 2008. We present our evaluation of the GBS risk following influenza vaccinations during the 2017–2018 season.MethodsWe implemented a multilayered approach to active safety surveillance that included near real-time surveillance early in the season, comparing GBS rates post-vaccination during the 2017–2018 season with rates from five prior seasons using the Updating Sequential Probability Ratio Test (USPRT), and end-of-season self-controlled risk interval (SCRI) analyses.ResultsWe identified approximately 16 million influenza vaccinations. The near real-time surveillance did not signal for a potential 2.5-fold increased GBS risk either in days 8–21 or 1–42 post-influenza vaccination. In the SCRI analyses, we did not detect statistically significant increased GBS risks among influenza-vaccinated Medicare beneficiaries ≥65 years for either the 8–21 or 1–42-day risk windows for all seasonal vaccines combined, high-dose vaccine, or standard-dose vaccines; we did detect an increased GBS risk in days 8–21 post-vaccination for individuals vaccinated with the adjuvanted vaccine (OR: 3.75; 95% CI: 1.01, 13.96), although this finding was not statistically significant after multiplicity adjustment (p = 0.146).ConclusionsOur multilayered surveillance approach—which allows for early detection of elevated GBS risk and provides reliable end-of-season SCRI estimates of effect size—did not identify an increased GBS risk following 2017–2018 influenza vaccinations. The slightly increased GBS risk with the adjuvanted vaccine, which was not statistically significant following multiplicity adjustment, is consistent with the package inserts of all U.S.-licensed influenza vaccines, which warn of a potential low increased GBS risk. The benefits of influenza vaccines in preventing morbidity and mortality heavily outweigh this potential risk.     

Pneumococcal vaccination coverage among adults newly diagnosed with underlying medical conditions and regional variation in the U.S.

BackgroundThe Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices recommends pneumococcal vaccination for adults with chronic or immunocompromising conditions to prevent pneumococcal disease, yet vaccination rates are low and have limited information on regional variation. This study examines factors associated with pneumococcal vaccination in adults with underlying conditions and describes regional variation in vaccination across the U.S.MethodsUsing IBM MarketScan Commercial Database and Medicare Supplemental Database, this retrospective cohort study included adults ages 19–64 newly diagnosed with chronic (i.e. diabetes, chronic heart, lung, or liver disease, alcohol or tobacco dependence) or immunocompromising (i.e. cancer, chronic renal disease, organ transplant, HIV/AIDS, and asplenia) conditions in 2013. Adults were followed up until the time of pneumococcal vaccination, death, or December 31, 2019, whichever came first. Cox proportional hazards model was used to examine factors associated with vaccination. Vaccination rate was calculated by metropolitan statistical area (MSA) and visually represented on a U.S. map.Results255,330 adults were included. Vaccination rate increased from 6.0% to 21.1% among adults with one year and five years of follow-up, respectively. It took 2.4 years on average for adults to receive vaccination after initial diagnosis. Adults ages 50–64, 35–49 (relative to 19–34) or receiving influenza vaccination were more likely to receive pneumococcal vaccinations. Adults with HIV/AIDS were more likely and those with other conditions were less likely to be vaccinated than those with diabetes. Adults being diagnosed by other providers were less likely to be vaccinated than those diagnosed by primary care providers. Vaccination rate varied largely across MSAs, ranging from 0.0% (Ames, IA; Cheyenne, WY) to 34.0% (Ann Arbor, MI).ConclusionPneumococcal vaccination remains low and most adults with underlying conditions are unvaccinated. Insights into factors associated with vaccination, including regional variability, can help to increase pneumococcal vaccination.     

Vaccine timeliness and prevalence of undervaccination patterns in children ages 0–19 months,U.S., National Immunization Survey-Child 2017

ObjectivesTypically, early childhood vaccination coverage in the U.S. is measured as the proportion of children by age 24 months who completed recommended vaccine series. However, these measures do not reflect whether vaccine doses were received at the ages recommended by the U.S. Advisory Committee on Immunization Practices, or whether children received vaccines concomitantly, per the ACIP recommended schedule. This study’s objective was to quantify vaccine timeliness and prevalence of specific patterns of undervaccination in U.S. children ages 0–19 months.MethodsUsing 2017 National Immunization Survey-Child data, we calculated days undervaccinated for the combined 7-vaccine series and distinguished undervaccination patterns indicative of parental vaccine hesitancy, such as spreading out vaccines across visits (“shot-limiting”) or starting some but not all recommended vaccine series (“selective vaccination”), from other non-hesitancy patterns, such as missing final vaccine doses or receiving all doses, with some or all late. We measured associations between demographic, socioeconomic and other characteristics with undervaccination patterns using multivariable log-linked binomial regression. Analyses accounted for the complex survey design.ResultsAmong n = 15,333 U.S. children, only 41.2% received all recommended vaccine doses on-time by age 19 months. Approximately 20.9% of children had an undervaccination pattern suggestive of parental vaccine hesitancy, and 36.2% had other undervaccination non-hesitancy patterns. Uninsured children and those with lower levels of maternal education were more likely to exhibit undervaccination patterns suggestive of parental hesitancy. Lower levels of maternal education were also associated with other non-hesitancy undervaccination patterns.ConclusionsMore than half of children in the U.S. are undervaccinated at some point by 19 months of age. Ongoing assessment of vaccine timeliness and immunization schedule adherence could facilitate timely and targeted public health interventions in populations with high levels of undervaccination.     

Real-world evidence on adherence and completion of the two-dose recombinant zoster vaccine and associated factors in U.S. adults, 2017–2021

IntroductionPoor compliance with adult vaccination recommendations contributes to substantial disease burden. Evidence on adherence, completion, and completion timeliness for the 2-dose recombinant herpes zoster vaccine (RZV) and factors associated with these outcomes is limited and not readily generalizable for the entire U.S.MethodsThis retrospective, observational study examined adherence, completion, and the impact of sociodemographic, clinical and geographical factors among U.S. adults ≥ 50 years receiving RZV (4/20/2017 to 3/31/2021), using a large, geographically representative administrative claims database. Continuous enrollment in a medical benefit plan for six months prior to and following the index date (first observed vaccine dose) was required. Adherence was defined as receipt of the 2nd dose within 2–6 months, per label recommendation. Completion (receipt of all doses) was assessed at 6, 12, 18, and 24 months.ResultsAmong 726,352 adults included, the adherence rate was 71.8%. Among 208,311 adults with 24–month follow-up, the completion rate was 72.3% after 6 months and 86.2% after 24 months. Logistic regression showed low adherence/completion was associated with younger age, Black or Hispanic race/ethnicity, lower income, lower educational attainment, and possessing commercial rather than Medicare healthcare insurance. Recipients identified using pharmacy claims had much higher adherence (74.0%) than those identified using medical claims (48.0%).ConclusionsAdherence and completion rates for RZV are suboptimal, especially for adults aged 50–64, racial/ethnic minorities, individuals with lower socio-economic status and those without Medicare insurance. More research and public health efforts are needed to understand and address potential barriers to RZV uptake, adherence and completion.     

Barriers and activities to implementing or expanding influenza vaccination programs in low- and middle-income countries: A global survey

IntroductionDespite considerable global burden of influenza, few low- and middle-income countries (LMICs) have national influenza vaccination programs. This report provides a systematic assessment of barriers to and activities that support initiating or expanding influenza vaccination programs from the perspective of in-country public health officials.MethodsPublic health officials in LMICs were sent a web-based survey to provide information on barriers and activities to initiating, expanding, or maintaining national influenza vaccination programs. The survey primarily included Likert-scale questions asking respondents to rank barriers and activities in five categories.ResultsOf 109 eligible countries, 62% participated. Barriers to influenza vaccination programs included lack of data on cost-effectiveness of influenza vaccination programs (87%) and on influenza disease burden (84%), competing health priorities (80%), lack of public perceived risk from influenza (79%), need for better risk communication tools (77%), lack of financial support for influenza vaccine programs (75%), a requirement to use only WHO-prequalified vaccines (62%), and young children require two vaccine doses (60%). Activities for advancing influenza vaccination programs included educating healthcare workers (97%) and decision-makers (91%) on the benefits of influenza vaccination, better estimates of influenza disease burden (91%) and cost of influenza vaccination programs (89%), simplifying vaccine introduction by focusing on selected high-risk groups (82%), developing tools to prioritize target populations (80%), improving availability of influenza diagnostic testing (79%), and developing collaborations with neighboring countries for vaccine procurement (74%) and regulatory approval (73%). Responses varied by country region and income status.ConclusionsLocal governments and key international stakeholders can use the results of this survey to improve influenza vaccination programs in LMICs, which is a critical component of global pandemic preparedness for influenza and other pathogens such as coronaviruses. Additionally, strategies to improve global influenza vaccination coverage should be tailored to country income level and geographic location.     

Cost-effectiveness of sub-national geographically targeted vaccination programs: A systematic review

Immunization is an essential component of national health plans. However, the growing number of new vaccine introductions, vaccination campaigns and increasing administrative costs create logistic and financial challenges, especially in resource-limited settings. Sub-national geographic targeting of vaccination programs is a potential strategy for governments to reduce the impact of infectious disease outbreaks while optimizing resource allocation and reducing costs, promoting sustainability of critically important national immunization plans. We conducted a systematic review of peer-reviewed literature to identify studies that investigated the cost-effectiveness of geographically targeted sub-national vaccination programs, either through routine immunization or supplementary immunization activities. A total of 16 studies were included in our review, covering nine diseases of interest: cholera, dengue, enterotoxigenic Escherichia coli (ETEC), hepatitis A, Japanese encephalitis, measles, rotavirus, Shigella and typhoid fever. All studies modelled cost-effectiveness of geographically targeted vaccination. Despite the variation in study design, disease focus and country context, studies generally found that in countries where a heterogenous burden of disease exists, sub-national geographic targeting of vaccination programs in areas of high disease burden was more cost-effective than a non-targeted strategy. Sensitivity analysis revealed that cost-effectiveness was most sensitive to variations in vaccine price, vaccine efficacy, mortality rate, administrative and operational costs, discount rate, and treatment costs. This systematic review identified several key characteristics related to geographic targeting of vaccination, including the vaccination strategy used, variations in modelling parameters and their impact on cost-effectiveness. Additional research and guidance is needed to support the appropriateness and feasibility of geographically targeted vaccination and to determine what country context would make this a viable complement to routine immunization programs.     

WHO preferred product characteristics for monoclonal antibodies for passive immunization against respiratory syncytial virus (RSV) disease in infants – Key considerations for global use

World Health Organization (WHO) preferred product characteristics describe preferences for product attributes that would help optimize value and use to address global public health needs, with a particular focus on low- and middle-income countries. Having previously published preferred product characteristics for both maternal and paediatric respiratory syncytial virus (RSV) vaccines, WHO recently published preferred product characteristics for monoclonal antibodies to prevent severe RSV disease in infants. This article summarizes the key attributes from the preferred product characteristics and discusses key considerations for future access and use of preventive RSV monoclonal antibodies.     

Immunisation with the BCG and DTPw vaccines induces different programs of trained immunity in mice

In addition to providing pathogen-specific immunity, vaccines can also confer nonspecific effects (NSEs) on mortality and morbidity unrelated to the targeted disease. Immunisation with live vaccines, such as the BCG vaccine, has generally been associated with significantly reduced all-cause infant mortality. In contrast, some inactivated vaccines, such as the diphtheria, tetanus, whole-cell pertussis (DTPw) vaccine, have been controversially associated with increased all-cause mortality especially in female infants in high-mortality settings. The NSEs associated with BCG have been attributed, in part, to the induction of trained immunity, an epigenetic and metabolic reprograming of innate immune cells, increasing their responsiveness to subsequent microbial encounters. Whether non-live vaccines such as DTPw induce trained immunity is currently poorly understood. Here, we report that immunisation of mice with DTPw induced a unique program of trained immunity in comparison to BCG immunised mice. Altered monocyte and DC cytokine responses were evident in DTPw immunised mice even months after vaccination. Furthermore, splenic cDCs from DTPw immunised mice had altered chromatin accessibility at loci involved in immunity and metabolism, suggesting that these changes were epigenetically mediated. Interestingly, changing the order in which the BCG and DTPw vaccines were co-administered to mice altered subsequent trained immune responses. Given these differences in trained immunity, we also assessed whether administration of these vaccines altered susceptibility to sepsis in two different mouse models. Immunisation with either BCG or a DTPw-containing vaccine prior to the induction of sepsis did not significantly alter survival. Further studies are now needed to more fully investigate the potential consequences of DTPw induced trained immunity in different contexts and to assess whether other non-live vaccines also induce similar changes.     

Association between vaccination status,symptom identification and healthcare use: Implications for test negative design observational studies

AimTo test the internal validity of the test-negative design (TND) by investigating associations between maternal influenza vaccination, and new virus detection episodes (VDEs), acute respiratory illness, and healthcare visits in their children.MethodsEighty-five children from a birth cohort provided daily symptoms, weekly nasal swabs, and healthcare use data until age 2-years. Effect estimates are summarised as incidence rate ratios (IRR).ResultsThere was no association between maternal vaccination and VDEs in children (IRR = 1.1; 95 %CI = 0.9–1.2). Influenza-vaccinated mothers were more likely than unvaccinated mothers to both report, and seek healthcare for, acute lower respiratory illness in their children, IRR = 2.4; 95 %CI = 1.2–4.8 and IRR = 2.2; 95 %CI = 1.1–4.3, respectively.ConclusionA key assumption of the TND, that healthcare seeking behaviour for conditions of the same severity is not associated with vaccine receipt, did not hold. Further studies of the performance of the TND in different populations are required to confirm its validity.     

One or two doses of hepatitis A vaccine in universal vaccination programs in children in 2020: A systematic review

BackgroundHepatitis A virus (HAV) is a global health concern as outbreaks continue to occur. Since 1999, several countries have introduced universal vaccination (UV) of children against HAV according to approved two-dose schedules. Other countries have implemented one-dose UV programs since 2005; the long-term impact of this schedule is not yet known.MethodsWe conducted a systematic literature search in four electronic databases for data published between January 2000 and July 2019 to assess evidence for one-dose and two-dose UV of children with non-live HAV vaccines and describe their global impact on incidence, mortality, and severity of hepatitis A, vaccine effectiveness, vaccine efficacy, and antibody persistence.ResultsOf 3739 records screened, 33 peer-reviewed articles and one conference abstract were included. Rapid declines in incidence of hepatitis A and related outcomes were observed in all age groups post-introduction of UV programs, which persisted for at least 14 years for two-dose and six years for one-dose programs according to respective study durations. Vaccine effectiveness was ≥95% over 3–5 years for two-dose programs. Vaccine efficacy was >98% over 0.1–7.5 years for one-dose vaccination. Antibody persistence in vaccinated individuals was documented for up to 15 years (≥90%) and ten years (≥74%) for two-dose and one-dose schedules, respectively.ConclusionExperience with two-dose UV of children against HAV is extensive, demonstrating an impact on the incidence of hepatitis A and antibody persistence for at least 15 years in many countries globally. Because evidence is more limited for one-dose UV, we were unable to draw conclusions on immune response persistence beyond ten years or the need for booster doses later in life. Ongoing epidemiological monitoring is essential in countries implementing one-dose UV against HAV. Based on current evidence, two doses of non-live HAV vaccines are needed to ensure long-term protection.     

Associations between physical activity and mental health and behaviour in early adolescence

BackgroundWe examined associations between objectively-measured physical activity, depressive-symptoms, and emotional and behavioural difficulties in adolescents from a UK cohort.MethodData from 4755 participants (45% male) from the Avon Longitudinal Study of Parents and Children (ALSPAC) with physical activity assessed by accelerometry at age 11 was analysed. Indication of depressive symptoms (Short Moods and Feelings questionnaire) were obtained from parental reports at age 11 and self-reports at age 13. Behavioural and emotional problems were assessed by parents and teachers at age 11 and 13 using the Strengths and Difficulties Questionnaire (SDQ).ResultsAt age 11, males averaged 29 minutes (SD = 17) of daily moderate-to-vigorous physical activity (MVPA) compared with 18 minutes (SD = 12) among females. Higher MVPA at age 11 was associated with decreased depressive-symptoms in females at age 11 after adjusting for confounders. Among males, a positive change in MVPA between the ages of 11 and 13 was associated with a reduction in depressive symptoms. Negative associations were also found between MVPA at age 11 and the emotional symptoms scale of the SDQ at age 11 and age 13 in females. Higher MVPA predicted a decreased score on the hyperactivity subscale of the SDQ at 11 and 13 for both sexes. All effect sizes were small.ConclusionsHigher MVPA was associated with reduced depressive symptoms, behavioural and emotional-difficulties in early adolescence, however the magnitude of effects was small. Efforts to support MVPA in this age group are therefore warranted.     

Social cognitive correlates of device-measured and self-reported physical activity in Black and White individuals with multiple sclerosis

BackgroundThere is increasing research interest regarding physical activity behavior among persons with multiple sclerosis (MS), yet there is little known about physical activity and its correlates in Black persons with MS.ObjectiveThis cross-sectional study assessed associations among social cognitive theory (SCT) variables and device-measured and self-reported physical activity in samples of Black and White persons with MS.MethodsParticipants included 67 Black and 141 White persons with MS who wore an ActiGraph accelerometer on a belt around the waist measuring moderate-to-vigorous physical activity (MVPA) for seven days and completed a battery of questionnaires. Questionnaires included demographic and clinical characteristics, leisure-time exercise, exercise self-efficacy, overcoming barriers self-efficacy, function, social support, exercise outcome expectations, and goal setting and planning.ResultsBlack participants with MS engaged in significantly less MVPA, but not sedentary behavior or light physical activity, than the White participants with MS. Black participants further had significantly lower levels of exercise self-efficacy and outcome expectations than the White sample. All SCT correlates were significantly correlated with self-reported physical activity, but only exercise and barriers self-efficacy, perceived function, and exercise goal setting were associated with device-measured MVPA. The difference in physical activity between Black and White participants with MS was accounted for by differences in exercise self-efficacy and outcome expectations.ConclusionsResearchers should consider developing behavioral interventions that target exercise self-efficacy and outcome expectations as SCT variables for increasing physical activity in Black persons with MS.     

Durable antibody responses elicited by 1 dose of Ad26.COV2.S and substantial increase after boosting: 2 randomized clinical trials

BackgroundAd26.COV2.S is a well-tolerated and effective vaccine against COVID-19. We evaluated durability of anti-SARS-CoV-2 antibodies elicited by single-dose Ad26.COV2.S and the impact of boosting.MethodsIn randomized, double-blind, placebo-controlled, phase 1/2a and phase 2 trials, participants received single-dose Ad26.COV2.S (5 × 10¹⁰ viral particles [vp]) followed by booster doses of 5 × 10¹⁰ vp or 1.25 × 10¹⁰ vp. Neutralizing antibody levels were determined by a virus neutralization assay (VNA) approximately 8–9 months after dose 1. Binding and neutralizing antibody levels were evaluated by an enzyme-linked immunosorbent assay and pseudotyped VNA 6 months after dose 1 and 7 and 28 days after boosting.ResultsData were analyzed from phase 1/2a participants enrolled from 22 July–18 December 2020 (Cohort 1a, 18–55 years [y], N = 25; Cohort 2a, 18–55y, N = 17; Cohort 3, ≥65y, N = 22), and phase 2 participants from 14 to 22 September 2020 (18–55y and ≥ 65y, N = 73). Single-dose Ad26.COV2.S elicited stable neutralizing antibodies for at least 8–9 months and stable binding antibodies for at least 6 months, irrespective of age. A 5 × 10¹⁰ vp 2-month booster dose increased binding antibodies by 4.9- to 6.2-fold 14 days post-boost versus 28 days after initial immunization. A 6-month booster elicited a steep and robust 9-fold increase in binding antibody levels 7 days post-boost. A 5.0-fold increase in neutralizing antibodies was observed by 28 days post-boost for the Beta variant. A 1.25 × 10¹⁰ vp 6-month booster elicited a 3.6-fold increase in binding antibody levels at 7 days post-boost versus pre-boost, with a similar magnitude of post-boost responses in both age groups.ConclusionsSingle-dose Ad26.COV2.S elicited durable antibody responses for at least 8 months and elicited immune memory. Booster-elicited binding and neutralizing antibody responses were rapid and robust, even with a quarter vaccine dose, and stronger with a longer interval since primary vaccination.Trial Registration: ClinicalTrials.gov Identifier: NCT04436276, NCT04535453.