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.     

Self-reported prenatal influenza vaccination and early childhood vaccine series completion

BackgroundNo studies have examined associations between prenatal vaccination and childhood vaccination. Mothers who refuse influenza vaccinations during pregnancy report similar attitudes and beliefs to those who refuse vaccinations for their children. The objective of this study was to examine the association between self-reported prenatal influenza vaccination and early childhood vaccination.MethodsA retrospective cohort study was conducted with existing surveillance data from 4022 mothers who responded to the 2009–2011 Minnesota Pregnancy Risk Assessment Monitoring System survey and child vaccination records from the Minnesota Immunization Information Connection database. The childhood vaccine series outcome included the following vaccines: diphtheria, tetanus, and pertussis; poliovirus; measles, mumps, and rubella; Haemophilus influenzae type b (Hib); hepatitis B; varicella; and pneumococcal conjugate. To evaluate the association between self-reported prenatal influenza vaccination and early childhood vaccination, unadjusted and adjusted logistic regression was used to estimate log odds for childhood vaccination status, while margins post-estimation commands were used to obtain predicted probabilities and risk differences.ResultsVaccine series completion was 10.86% higher (95% confidence interval (CI) 7.33%–14.40%, adjusted and weighted model) in children of mothers who had a prenatal influenza vaccine compared to those who did not. For individual vaccines in the recommended series, risk differences ranged from 7.83% (95% CI 5.37%, 10.30%) for the Hib vaccine to 10.06% (95% CI 7.29%, 12.83%) for the hepatitis B vaccine.ConclusionSelf-reported prenatal influenza vaccination was associated with increased early childhood vaccination. More research is needed to confirm these results and identify potential intervention strategies.     

Vaccines and the risk of Guillain-Barré syndrome

The role of vaccination in the development of Guillain-Barré syndrome (GBS) is controversial, although cases of GBS have been reported following a wide range of vaccines. A nested case–control study was conducted between January 2011 and December 2015 in three Chinese cities. Four controls were matched to a case by gender, age, address and index date. An independent expert committee validated the diagnoses of cases and controls according to the Brighton Collaboration GBS case definition. Data on vaccinations were obtained from computerized vaccination records. Causal relations were assessed by conditional logistic regression. 1056 cases of GBS and 4312 controls were included in the analyses. Among paediatric and adult population, adjusted ORs for GBS occurrence within 180 days following vaccination were 0.94 (95% CI 0.54–1.62) and 1.09 (95% CI 0.88–1.32), respectively. No increased risk of GBS was detected for vaccination against hepatitis B, influenza, hepatitis A, varicella, rabies, polio(live), diphtheria, pertuss(acellular), tetanusis, measles, mumps, rubella, Japanese Encephalitis, and meningitis vaccines. Adjusted ORs for the recurrence of GBS after vaccination among paediatric and adult population were 0.85 (95% CI 0.07–9.50) and 1.18 (95% CI 0.49–2.65), respectively. In this large retrospective study, we did not find evidence of an increased risk of GBS and its recurrence among either paediatric (≤ 18 years) or adult (> 18 years) individuals within the 180 days following vaccinations of any kind, including influenza vaccination.     

Dementia risk following influenza vaccination in a large veteran cohort

BackgroundTwo Taiwan based studies indicated influenza vaccinations are associated with lower risk for dementia in patient cohorts with chronic disease. We determined if such associations exist in a large, nationally distributed sample of U.S. patients not selected for chronic disease.MethodsData was obtained from Veterans Health Administration medical records (9/1/2009 – 8/31/19). Eligible patients were ≥65 years of age and free of dementia for two years prior to enrollment through the end of the first influenza season (9/1/2009 to 3/1/2012). Competing risk models estimated the risk of dementia in those with influenza vaccination (n = 66,822) compared to those without vaccination (n = 56,925). Propensity scores and inverse probability of treatment weighting controlled for confounding.ResultsOn average, patients were 75.5 (±7.3) years of age, 3.8% were female and 91.6% were white race. After controlling for confounding, patients with influenza vaccination were significantly less likely to develop dementia compared to patients without vaccination (HR = 0.86; 95 %CI:0.83–0.88). Patients with 1, 2 or 3–5 vaccines vs. none had similar risks for dementia and patients with ≥ 6 influenza vaccines vs. none had a significant lower risk for dementia (HR = 0.88, 95 %CI: 0.83–0.94).ConclusionsRepeated receipt of influenza vaccinations, compared to remaining unvaccinated, is associated with lower risk for dementia. This is consistent with the hypotheses that vaccinations may reduce risk of dementia by training the immune system and not by preventing specific infectious disease. If vaccines are identified as causative factors in reducing incident dementia, they offer an inexpensive, low-risk intervention with effects greater than any existing preventive measure.     

Beneficiary characteristics and vaccinations in the end-stage renal disease Medicare beneficiary population,an analysis of claims data 2006–2015

BackgroundThe Advisory Committee on Immunization Practices (ACIP) routinely recommends three vaccines – influenza, hepatitis B, and pneumococcal vaccines – for End-Stage Renal Disease (ESRD) dialysis patients.MethodsWe sought to assess vaccination coverage among fee-for-service (FFS) Medicare beneficiaries with ESRD who received Part B dialysis services at any point from January 1, 2006 through December 31, 2015 (through June 30, 2016 for influenza). To assess influenza vaccination rates in a given influenza season, we restricted the population to beneficiaries who were continuously enrolled in Medicare Parts A and B throughout all twelve months of that season. To assess hepatitis B and pneumococcal vaccine coverage following dialysis initiation, we developed a Kaplan-Meier curve for all patients who began dialysis between 2006 and 2015.ResultsFor influenza vaccination, we identified an average of approximately 325,000 ESRD dialysis beneficiaries enrolled through each influenza season from 2006–2015. Seasonal influenza vaccination rates steadily increased during the 10-year period, from 52% in 2006–2007 to 71% in 2015–2016. The greatest increases in influenza vaccination appear in non-white beneficiaries with overall utilization in non-whites higher than in whites (p < .001). For the hepatitis B and pneumococcal vaccinations, we identified over 350,000 ESRD dialysis beneficiaries who began dialysis over the 10-year study window. The probability of receiving a hepatitis B vaccine within the first three years of entering into the ESRD program was higher (77%) than the probability of receiving any pneumococcal vaccine (53%). 45% of ESRD patients completed at least one dose of the two hepatitis B series (three-dose or four-dose) at any time during the study period.ConclusionsOpportunities exist at regional and facility levels to improve vaccination coverage. Compliance to ACIP recommendations may directly affect risk for ESRD dialysis patients for complications from diseases that can be mitigated by vaccination.     

Predictors of hepatitis B vaccination completion among people who use drugs participating in a national program of targeted vaccination

BackgroundTargeted vaccination strategies are necessary to prevent people who use drugs (PWUD) becoming infected with hepatitis B virus (HBV). The aims of this study were to provide an overview of the activities for PWUD in a decentralised vaccination program in the Netherlands and to explore the determinants associated with completing a standard hepatitis B vaccination series.MethodsWe used data for behavioural risk groups from the register of the national vaccination program. The data concerned PWUD who were immunised against hepatitis B in the Netherlands between 2002 and 2011. A standard series of three vaccinations (at 0, 1, and 6 months) was offered at inclusion and was continued if serological markers for past or chronic HBV infection were absent. Completion of a vaccination series (at least three vaccinations, irrespective of timing) was a dependent variable in our logistic regression analysis.ResultsThe program reached 18,054 PWUD. Of the 15,746 participants eligible for vaccination (i.e. they were neither carriers of hepatitis B nor immune to hepatitis B), 9089 (58%) completed a series of three hepatitis B vaccinations. Factors associated with a higher completion rate of a vaccination series (p < 0.01) were: starting vaccination in the earlier years of the program, older age of PWUD, intravenous drug use, vaccine administration by addiction care centres, and flexibility in location of vaccine delivery.ConclusionDespite using a standard HBV vaccination schedule and no financial incentives, vaccination completion among PWUD was relatively high. Our results suggest that flexibility of vaccination location and administration of vaccines by healthcare workers with sustainable contact with PWUD could improve vaccination programs for this risk group.     

Safety surveillance of varicella vaccine using tree-temporal scan analysis

ImportancePassive surveillance systems are susceptible to the under-reporting of adverse events (AE) and a lack of information pertaining to vaccinated populations. Conventional active surveillance focuses on predefined AEs. Advanced data mining tools could be used to identify unusual clusters of potential AEs after vaccination.ObjectiveTo assess the feasibility of a novel tree-based statistical approach to the identification of AE clustering following the implementation of a varicella vaccination program among one-year-olds.Setting and participantsThis nationwide safety surveillance was based on data from the Taiwan National Health Insurance database and National Immunization Information System for the period 2004 through 2014. The study population was children aged 12–35 months who received the varicella vaccine.ExposureFirst-dose varicella vaccine.Outcomes and measuresAll incident ICD-9-CM diagnoses (emergency or inpatient departments) occurring 1–56 days after the varicella vaccination were classified within a hierarchical system of diagnosis categories using Multi-Level Clinical Classifications Software. A self-controlled tree-temporal data mining tool was then used to explore the incidence of AE clustering with a variety of potential risk intervals. The comparison interval consisted of days in the 56-day follow-up period that fell outside the risk interval.ResultsAmong 1,194,189 varicella vaccinees with no other same-day vaccinations, nine diagnoses with clustering features were categorized into four safety signals: fever on days 1–6 (attributable risk [AR] 38.5 per 100,000, p < 0.001), gastritis and duodenitis on days 1–2 (AR 5.9 per 100,000, p < 0.001), acute upper respiratory infection on days 1–5 (AR 11.0 per 100,000, p = 0.006), and varicella infection on days 1–9 (AR 2.7 per 100,000, p < 0.001). These safety profiles and their corresponding risk intervals have been identified in previous safety surveillance studies.ConclusionsUnexpected clusters of AEs were not detected after the mass administration of childhood varicella vaccines in Taiwan. The tree-temporal statistical method is a feasible approach to the safety surveillance of vaccines in populations of young children.     

Estimating vaccination coverage for routinely recommended vaccines among children aged 24 months and adolescents aged 13 through 17 years using data from immunization information systems in the United States

ObjectiveTo use a model-based approach to estimate vaccination coverage of routinely recommended childhood and adolescent vaccines for the United States.MethodsWe used a hierarchical model with retrospective cohort data from eleven IIS jurisdictions, which contains vaccination records submitted by providers. Numerators included data from 2014 to 2019 at the county level for 2.4 million children at age 24 months and 14.4 million adolescents aged 13–17. Age-appropriate Census populations were used as denominators. Covariates associated with childhood and adolescent vaccinations were included in the model. Model-based estimates for each county were generated and aggregated to the national level to produce national vaccination coverage estimates and compared to National Immunization Survey (NIS) estimates of vaccination coverage. Trends of estimated vaccination coverage were compared between the model-based approach and NIS.ResultsFrom 2014 to 18, model-based national vaccination coverage estimates were within ten percentage points of NIS-Child vaccination coverage estimates for most vaccines among children at age 24 months. One notable difference was higher model-based vaccination coverage estimates for hepatitis B birth dose compared to NIS-Child coverage estimates. From 2014 to 19, model-based national vaccination coverage estimates were within ten percentage points of NIS-Teen vaccination coverage estimates for most vaccines among adolescents aged 13–17 years. Model-based vaccination coverage estimates were notably lower for varicella, MMR, and Hepatitis B compared to NIS-Teen coverage estimates among adolescents. Trends in estimates of national vaccination coverage were similar between model-based estimates for children and adolescents as compared to NIS-Child and NIS-Teen, respectively.ConclusionsA hierarchical model applied to data from IIS may be used to estimate coverage for routinely recommended vaccines among children and adolescents and allows for timely analyses of childhood and adolescent vaccines to quickly assess trends in vaccination coverage across the United States. Monitoring real-time vaccination coverage can help promote immunizations to protect children and adolescents against vaccine-preventable diseases.     

Autoimmune diseases after hepatitis B immunization in adults: Literature review and meta-analysis,with reference to ‘autoimmune/autoinflammatory syndrome induced by adjuvants’ (ASIA)

BackgroundTo assess if hepatitis B vaccination in adults is causally associated with autoimmune diseases. Such causation has been claimed based mainly on case reports and uncontrolled studies, and a syndrome ‘Autoimmune/autoinflammatory Disorder Induced by Adjuvants’ (ASIA) has been claimed to be linked to immunization, particularly hepatitis B vaccination.MethodsReview of peer-reviewed literature from January 1990 to March 2017 identifying controlled studies with documented incidence of autoimmune diseases occurring after hepatitis B vaccinations in adults. From 1297 studies identified, 259 were further assessed and 49 reviewed further; 19 relevant papers reporting 21 results are reviewed here, and 14 results included in a meta-analysis.ResultsOverall no association between hepatitis B vaccination and the onset of autoimmune diseases was seen. The overall odds ratio was 1.06, with 95% confidence limits of 0.93–1.21, with non-significant heterogeneity. Only one study showed a significant excess risk between hepatitis B immunisation and autoimmune disease.ConclusionsDespite multiple case reports, there is no reliable scientific evidence of autoimmune diseases being caused by hepatitis B vaccinations.     

Concomitant HPV and MenACWY vaccination among sixth and seventh graders receiving Tdap

ObjectiveTo describe use of human papilloma virus (HPV) and meningococcal (MenACWY) vaccines among sixth and seventh grade Kansas children receiving their school-required tetanus, diphtheria, and acellular pertussis (Tdap) booster.MethodsWe used Medicaid and commercial claims data in Kansas from 2013, 2014, and 2015 to identify HPV and MenACWY vaccinations among sixth and seventh graders receiving a Tdap booster. Rates of concomitant vaccinations were calculated at the state and county level, and logistic regression was used to identify predictors of concomitant vaccination.ResultsOf sixth and seventh graders in Kansas receiving their required Tdap booster, 53–82% failed to receive a concomitant HPV vaccine and 36–47% failed to receive a concomitant MenACWY vaccine from 2013 to 2015. Rates of concomitant vaccinations varied more than four-fold across counties. Female gender, younger age, and Medicaid (versus commercial insurance) were positively associated with concomitant vaccination; concomitant vaccination rates increased from 2013 to 2015 (p < 0.001). Of children continuously enrolled in Medicaid from 2013 to 2015, who did not receive concomitant vaccination in 2013, 72.3% and 68.6% remained unvaccinated against HPV and MenACWY, respectively by the end of 2015.ConclusionsFailure to get a concomitant vaccination at the time of their Tdap booster identifies children at high risk of not getting immunized in the ensuing 2–3 years. ‘Back to school’ programs focusing only on school-required vaccinations could have negative impacts on overall vaccination rates. Tracking rates of concomitant vaccination might be useful in supporting quality assessment and improvement efforts.Clinical trial registrationThis study was not a clinical trial.     

Meningococcal B vaccination coverage among older adolescents in the United States

BackgroundSerogroup B meningococcal (MenB) vaccination recommendations for adolescents in the United States (US) include routine vaccination for all individuals at increased risk and vaccination for individuals not at increased risk aged 16–23 years (preferred age 16–18 years) based on shared clinical decision-making. The two licensed MenB vaccines require administration of ≥2 doses.MethodsThis cross-sectional study analyzed 2017–2018 National Immunization Survey-Teen (NIS-Teen) data to evaluate ≥1 dose and ≥2 dose MenB vaccination coverage among adolescents aged 17 years. Multivariable logistic regression was used to further evaluate determinants of MenB vaccination.ResultsNationally, MenB vaccination coverage among 17-year-olds increased from 14.5% in 2017 to 17.2% in 2018 for ≥1 dose and from 6.3% to 8.4% for ≥2 doses. MenB vaccination coverage (2017–2018) was the lowest in the South (≥1 dose: 14.6%; ≥2 doses: 6.3%) and highest in the Northeast region (18.3% and 9.3%), with variation observed by census division. Adolescents were more likely to have received ≥1 dose of MenB vaccine if they had any Medicaid insurance (odds ratio [OR], 1.77; 95% confidence interval [CI], 1.32–2.39) or had received human papillomavirus (OR, 1.94; 95% CI, 1.41–2.67) or meningococcal A, C, W, and Y (OR, 4.03; 95% CI, 2.92–5.56) vaccinations.ConclusionsMenB first-dose coverage in the US is low, and even lower for a second dose, with regional variation. Being up to date with other routinely administered vaccines increased the likelihood of receiving MenB vaccination.     

Vaccine safety in HIV-infected adults within the Vaccine Safety Datalink Project

ObjectivesWe evaluate safety of routine vaccination among adults infected with human immunodeficiency virus (HIV) in five healthcare organizations in the United States.MethodsWe conducted a retrospective cohort study of HIV-infected adults who received inactivated influenza vaccines, hepatitis B vaccines, pneumococcal vaccines, or tetanus, diphtheria, and acellular pertussis vaccines between 2002 and 2013. We conducted self-controlled case series analysis to estimate the relative risk (RR) for 11 pre-specified adverse events (AEs) requiring medical attention.ResultsAmong 20,417 HIV-infected adults (90.2% male), a total of 137,674 vaccine doses were administered. Based on ICD-9 codes, we detected an increased risk of cellulitis and infection (RR: 1.18, 95% CI: 1.03–1.35) among all patients, and an increased risk of stroke/cerebrovascular diseases among patients with an HIV viral load >10,000 copies/ml (adjusted RR: 3.94, 95% CI: 1.32–11.72). Further analyses on chart confirmed cases of stroke/cerebrovascular diseases indicated no statistically significant increased risk (adjusted RR: 1.72, 95% CI: 0.41–7.24). There was no evidence of increased risk for other AEs following routine vaccination in HIV-infected adults.ConclusionsRoutinely administered vaccines are generally safe for HIV-infected adults.     

Infant antibody levels following 10-valent pneumococcal-protein D conjugate and DTaP-Hib vaccinations in the first year of life after maternal Tdap vaccination: An open-label,parallel, randomised controlled trial

BackgroundMaternal antibody levels after Tdap vaccination during pregnancy may affect infant primary antibody responses to pertussis, Tetanus toxoid (TT), Diphtheria toxoid (DT) vaccinations and pneumococcal vaccines with diphtheria toxin mutants like CRM197 as carrier protein.MethodsMothers were recruited in an open label randomised parallel controlled trial in 2014–2016 through midwifes. They received Tdap [Boostrix] at 30–32 weeks of pregnancy (n = 58) or within 48 h after delivery (n = 60). Infants received DTaP-IPV-Hib-HepB [Infanrix Hexa] and 10-valent protein D conjugated pneumococcal conjugate vaccine (PHiD-CV10 [Synflorix]) at age 3, 5 and 11 months. We now report on infant specific IgG levels towards DT, TT, Haemophilus influenzae type b polyribosylribitol phosphate (Hib PRP) and PHiD-CV10 before and after primary- and booster vaccination as secondary study endpoints; pertussis antibodies were the primary endpoint of the study. This trial is registered in clinicaltrialsregister.eu (EudraCT 2012–004006-9) and trialregister.nl (NTR number NTR4314).FindingsPost primary vaccinations, antibody levels to DT, but not TT, were significantly lower after Tdap vaccination during pregnancy compared to controls (GMC ratio 0.4, 95% CI 0.3–0.6 and 0.9, 95% CI 0.6–1.2, respectively). Antibodies to serotype 19F were significantly lower in the maternal Tdap group, whereas there were no differences in antibody levels to Hib PRP and the other 9 pneumococcal serotypes. Post booster vaccinations, no significant differences were observed, except for DT.InterpretationMaternal Tdap vaccination results in significant interference with infants responses not only to DT but also to conjugated pneumococcal vaccines containing DT mutants as carrier proteins. These interactions after maternal Tdap vaccination need to be taken into account when designing infants’ national immunization schedules and choice of vaccines.FundingThe Dutch Ministry of Health, Welfare and Sport.     

Vaccination of active component US military personnel against Salmonella Typhi

IntroductionVaccination against Salmonella Typhi is one of the leading public health interventions reducing the risk of typhoid fever. There are two available licensed vaccines, Vivotif, oral live-attenuated, and Typhim Vi, intramuscular Vi capsular polysaccharide. The US military is a high risk travel population commonly vaccinated for S. Typhi. We describe the use of S. Typhi vaccination in this population and the acute reactogenicity profile of these vaccines.MethodsData were obtained from the Defense Medical Surveillance System and vaccination identified between 1998 and 2011 from vaccination codes. Clinical outcomes were assessed for four weeks post vaccination. Adverse event rates and odds ratios were estimated across the two vaccine types.ResultsA total of 1.9 million predominately male military personnel received 3.6 million S. Typhi vaccinations with 94.3% of vaccinees receiving the Vi capsule vaccine though variability in the vaccine administered was observed. Receipt of other vaccinations in the 6 months surrounding the S. Typhi vaccine was common. Rates of nausea (195 per 100,000 vaccinations), headache (13 per 100,000 vaccinations) and fever (40 per 100,000 vaccinations) were significantly higher following Vi capsule vaccination compared to receipt of Vivotif (130, 2, 10 per 100,000 vaccinations, respectively). In contrast the rates of rash and non-infectious diarrhea (186 and 426 per 100,000 vaccinations, respectively) were increased in those receiving Vivotif compared to the Vi capsule vaccine.DiscussionThe US military is a major consumer of S. Typhi vaccines. The parenterally administered vaccine appears to be more amenable, though we were limited in our ability to assess the reasons for its higher usage. While we observed a higher rate of several adverse events in subjects receiving the intramuscular vaccination, the overall rate of these events was low. Future studies assessing more long-term health outcomes are warranted.     

Are providers’ recommendation and knowledge associated with uptake of optional vaccinations among children? A multilevel analysis in three provinces of China

BackgroundImmunization services providers play a crucial role in the successful implementation of immunization, particularly for new vaccines. Several childhood vaccinations that are important for public health are not included in the National Immunization Programme in China, although they are available as optional and self-paid vaccines. Their coverage remains low.ObjectiveTo examine the association between providers’ knowledge and recommendations of optional vaccines, as well as other supply- and demand-side factors, and their uptake among children.MethodsA cross-sectional study, that included an in-person questionnaire survey for parents of children under-3 years and a self-administrative questionnaire survey for their vaccination services providers, was conducted in 36 townships or sub-districts in three provinces of China in 2013. Using a sample of 1791 household from 30 townships or sub-districts, we applied multilevel logistic analyses to examine the factors associated with the uptake of optional vaccines based on a hierarchal framework that combined demand-side and supply-side factors.ResultsCoverage of optional childhood vaccinations varied across small areas. Supply- and demand-side factors were both associated with the uptake of these vaccines. Immunization services providers’ recommendations and their knowledge about optional vaccination were positively and significantly associated with uptake. Children were more likely to receive the vaccines if they lived in communities with higher immunization worker density or larger immunization clinics. Several demand-side psychological factors about childhood vaccination were also associated with optional vaccinations.ConclusionsPromoting immunization services providers to conduct evidence-based recommendations about some important childhood optional vaccinations and enhancing their knowledge regarding optional vaccinations and communication skills are useful strategies to increase the coverage of these vaccinations.     

No significant increase in Guillain-Barré syndrome after COVID-19 vaccination in adults: A vaccine adverse event reporting system study

ObjectiveTo investigate the association between Guillain-Barré syndrome (GBS) and COVID-19 vaccination.BackgroundOn July 13, 2021, the US Food and Drug Administration (FDA) released a new warning that Johnson & Johnson COVID-19 vaccine could increase the risk of developing GBS.MethodsThe reporting rate of adult GBS after COVID-19 vaccination, ascertained with Brighton criteria, was compared with the reporting rate after other vaccinations during the same time period, and also compared with the reporting rate during control periods. Statistical methods such as proportion tests, and Pearson’s chi-squared test were utilized to identify significant relationships. Self-controlled and case centered analyses were conducted. A machine learning model was utilized to identify the factors associated with a worse outcome defined as emergency room (ER) or doctor visits, hospitalizations, and deaths.ResultsThe reporting rate of GBS after COVID-19 vaccination was significantly higher than after influenza and other vaccinations (49.7, 0.19, 0.16 per 10 million, p < 0.0001). However, the reporting rate was within the incidence range of GBS in the general population. Using self-controlled and case centered analyses, there was a significant difference in the reporting rate of GBS after COVID-19 vaccination between the risk period and control period (p < 0.0001). There was an estimated 0.7–1.7 per million excess reports of GBS within 6 weeks of COVID-19 vaccination. Machine learning model demonstrated that female gender and age between 18 and 44 are associated with worse outcome. No association was found between the onset interval of GBS and its prognosis.ConclusionsAlthough the reporting rate of GBS after COVID-19 vaccination was not statistically different than that of the general population, the increased reporting of GBS within the first 6 weeks after COVID-19 vaccination, more so than with other vaccinations, suggests that some cases of GBS are temporally associated with COVID-19 vaccination. However, there is a reduction in the reporting rate of GBS after other vaccines, compared to reporting rates pre-COVID-19, highlighting limitations inherent in any passive surveillance system. These findings warrant continuous analysis of GBS after COVID-19 vaccination. Further improvement of the machine learning model is needed for clinical use.     

Vaccinations in early life are not associated with development of islet autoimmunity in type 1 diabetes high-risk children: Results from prospective cohort data

Aims/hypothesisVaccinations in early childhood potentially stimulate the immune system and may thus be relevant for the pathogenesis of autoimmune diseases such as type 1 diabetes (T1D). We determined the association of vaccination burden with T1D-associated islet autoimmunity in children with high familial risk followed prospectively from birth.MethodsA total of 20,570 certified vaccination records from 1918 children were correlated with time to onset of T1D-associated islet autoimmunity using Cox regression, considering multiple time periods up until age two years and vaccination types, and adjusting for HLA genotype, sex, delivery mode, season of birth, preterm delivery and maternal T1D status. Additionally, prospective claims data of 295,420 subjects were used to validate associations for the tick-borne encephalitis (TBE) vaccination.ResultsMost vaccinations were not associated with a significantly increased hazard ratio (HR) for islet autoimmunity (e.g. HR [95% confidence interval]: 1.08 [0.96–1.21] per additional vaccination against measles, mumps and rubella at age 0–24 months). TBE vaccinations within the first two years of life were nominally associated with a significantly increased autoimmunity risk (HR: 1.44 [1.06–1.96] per additional vaccination at age 0–24 months), but this could not be confirmed with respect to outcome T1D in the validation cohort (HR: 1.02 [0.90–1.16]).ConclusionsWe found no evidence that early vaccinations increase the risk of T1D-associated islet autoimmunity development. The potential association with early TBE vaccinations could not be confirmed in an independent cohort and appears to be a false positive finding.     

Promotion of healthcare personnel vaccinations among newly employed doctors and nurses: Evidence-guided strategy

ObjectiveHealthcare personnel vaccinations are important to prevent vaccine-preventable diseases in hospitals. We evaluated the seroprevalence, vaccination rates, and barriers to vaccination among newly employed nurses and doctors.MethodsA cross-sectional study was conducted at a university hospital in the Republic of Korea from 2017 to 2020. The immune status for hepatitis B virus (HBV), varicella zoster virus (VZV), and hepatitis A virus (HAV) was tested. HBV, VZV, measles, mumps, and rubella (MMR) vaccinations were mandatory. HAV and tetanus-diphtheria-pertussis (Tdap) vaccinations were also recommended by specialists. A web-based survey on factors affecting vaccination completion was conducted.ResultsFor the 668 participants, the mean age was 26 ± 2 (±SD) years. Seroprevalence was 86% for HBV, 93% for VZV, and 59% for HAV. Vaccine completion rates were 40% for HBV, 70% for VZV, 65% for MMR, 42% for HAV, and 70% for Tdap. Overall compliance for mandatory vaccines was 54%. A total of 402 subjects who had worked for over one year were surveyed, with a 22% response rate. More than 50% of respondents gave the following reasons for not receiving recommend vaccines: 1) they were busy (77%), 2) vaccination process was complicated (68%), and 3) they simply forgot about vaccination (55%). Healthcare personnel agreed to be frequently informed of immunization requirements and for monitoring of vaccination rates.ConclusionVaccination compliance among newly employed doctors and nurses was 54%. Active interventions such as simplifying the vaccination process and frequent notifications are needed to achieve optimal immunization rates.     

Do selective immunisation against tuberculosis and hepatitis B reach the targeted populations? A nationwide register-based study evaluating the recommendations in the Norwegian Childhood Immunisation Programme

BackgroundSelective immunisation is an alternative to universal vaccination if children at increased risk of disease can be identified. Within the Norwegian Childhood Immunisation Programme, BCG vaccine against tuberculosis and vaccine against hepatitis B virus (HBV) are offered only to children with parents from countries with high burden of the respective disease. We wanted to study whether this selective immunisation policy reaches the targeted groups.MethodsThe study population was identified through the Norwegian Central Population Registry and consisted of all children born in Norway 2007–2010 and residing in Norway until their second birthday, in total 240,484 children. Information on vaccinations from the Norwegian Immunisation Registry, and on parental country of birth from Statistics Norway, was linked to the population registry by personal identifiers. The coverage of BCG and HBV vaccine was compared with the coverage of vaccines in the universal programme.ResultsAmong the study population, 16.1% and 15.9% belonged to the target groups for BCG and HBV vaccine, respectively. Among children in the BCG target group the BCG vaccine coverage was lower than the coverage of pertussis and measles vaccine (83.6% vs. 98.6% and 92.3%, respectively). Likewise, the HBV vaccine coverage was lower than the coverage of pertussis and measles vaccine in the HBV target group (90.0% vs. 98.6% and 92.3%, respectively). The coverage of the targeted vaccines was highest among children with parents from South Asia and Sub-Saharan Africa. The coverage of vaccines in the universal programme was similar in targeted and non-targeted groups.ConclusionsChildren targeted by selective vaccination had lower coverage of the target vaccines than of vaccines in the universal programme, indicating that selective vaccination is challenging. Improved routines for identifying eligible children and delivering the target vaccines are needed. Universal vaccination of all children with these vaccines could be considered.     

Smallpox and BCG vaccination in childhood and cutaneous malignant melanoma in Danish adults followed from 18 to 49 years

BackgroundEarly smallpox and Bacillus Calmette-Guérin (BCG) vaccinations have been associated with reduced risk of cutaneous malignant melanoma (CMM). We assessed the association between pre-school smallpox vaccination and early-school BCG vaccination and CMM in a young Danish population.MethodsWe conducted a register-based case-cohort study of individuals growing up during the phase-out period of smallpox and BCG vaccination in Denmark (born 1965–1976) utilising the decrease in vaccination during this period. Information on childhood vaccinations and potential confounders from Copenhagen school health records were linked with nationwide registers on cancer (CMM diagnoses), migrations and deaths by personal identification numbers.ResultsThe individuals were followed from age 18 until 31/12/2014 (maximum age at end of follow-up, 49 years). 188 cases of CMM occurred in the background population of 46,239 individuals; 172 CMM cases (91%) had full information and were analysed. The adjusted hazard ratio (HR) for CMM by BCG and/or smallpox vaccination compared with neither vaccine was 1.29 (95% confidence interval (CI) 0.72–2.31). For smallpox vaccination only, HR = 1.23 (95% CI 0.53–2.86) for BCG vaccination only, HR = 1.13 (95% CI 0.61–2.09) and for both smallpox and BCG vaccination, HR = 1.75 (95% CI 0.87–3.48) compared with none of these. Vaccination below the age of one year gave similar results.ConclusionsWe found no strong beneficial effect of smallpox and BCG vaccination against CMM among young adult Danes and with broad confidence intervals our data alone could be compatible with both modest preventive effects, no effects, and modest harmful effects. Our estimates do not contradict a potential modest beneficial effect of neonatal vaccination.