Rulin C. Hechter

Vaccines and the Risk of Multiple Sclerosis and Other Central Nervous System Demyelinating Diseases

IMPORTANCE Because vaccinations are common, even a small increased risk of multiple sclerosis (MS) or other acquired central nervous system demyelinating syndromes (CNS ADS) could have a significant effect on public health. OBJECTIVE To determine whether vaccines, particularly those for hepatitis B (HepB) and human papillomavirus (HPV), increase the risk of MS or other CNS ADS. DESIGN, SETTING, AND PARTICIPANTS A nested case-control study was conducted using data obtained from the complete electronic health records of Kaiser Permanente Southern California (KPSC) members. Cases were identified through the KPSC CNS ADS cohort between 2008 and 2011, which included extensive review of medical records by an MS specialist. Five controls per case were matched on age, sex, and zip code. EXPOSURES Vaccination of any type (particularly HepB and HPV) identified through the electronic vaccination records system. MAIN OUTCOMES AND MEASURES All forms of CNS ADS were analyzed using conditional logistic regression adjusted for race/ethnicity, health care utilization, comorbid diseases, and infectious illnesses before symptom onset. RESULTS We identified 780 incident cases of CNS ADS and 3885 controls; 92 cases and 459 controls were females aged 9 to 26 years, which is the indicated age range for HPV vaccination. There were no associations between HepB vaccination (odds ratio [OR], 1.12; 95% CI, 0.72-1.73), HPV vaccination (OR, 1.05; 95% CI, 0.62-1.78), or any vaccination (OR, 1.03; 95% CI, 0.86-1.22) and the risk of CNS ADS up to 3 years later. Vaccination of any type was associated with an increased risk of CNS ADS onset within the first 30 days after vaccination only in younger (<50 years) individuals (OR, 2.32; 95% CI, 1.18-4.57). CONCLUSIONS AND RELEVANCE We found no longer-term association of vaccines with MS or any other CNS ADS, which argues against a causal association. The short-term increase in risk suggests that vaccines may accelerate the transition from subclinical to overt autoimmunity in patients with existing disease. Our findings support clinical anecdotes of CNS ADS symptom onset shortly after vaccination but do not suggest a need for a change in vaccine policy.

Declining Effectiveness of Herpes Zoster Vaccine in Adults Aged ≥60 Years

Understanding long-term effectiveness of herpes zoster (HZ) vaccine is critical for determining vaccine policy. 176 078 members of Kaiser Permanente ≥60 years vaccinated with HZ vaccine and three matched unvaccinated members were included. Hazard ratios and 95% confidence intervals (CIs) associated with vaccination at each year following vaccination were estimated by Cox regression model. The effectiveness of HZ vaccine decreased from 68.7% (95% CI, 66.3%-70.9%) in the first year to 4.2% (95% CI, -24.0% to 25.9%) in the eighth year. This rapid decline in effectiveness of HZ vaccine suggests that a revaccination strategy may be needed, if feasible.

Second-dose varicella vaccination coverage in children and adolescents in a managed care organization in California, 2006-2009.

We assessed trends of second-dose varicella-containing vaccine coverage among children and adolescents in Kaiser Permanente Southern California health plan since the Advisory Committee on Immunization Practices recommendation of 2-dose varicella vaccination in 2006. The overall second-dose coverage increased rapidly from 42.1% in 2007 to 74.6% in 2009. The increasing trend was observed in all strata defined by age and race/ethnicity, with the highest coverage among children aged 5 to 6 years old. However, non-Hispanic White race/ethnicity and living in a neighborhood with higher education level were inversely associated with the second-dose uptake.

Safety of Measles-Containing Vaccines in 1-Year-Old Children

BACKGROUND AND OBJECTIVES: All measles-containing vaccines are associated with several types of adverse events, including seizure, fever, and immune thrombocytopenia purpura (ITP). Because the measles-mumps-rubella-varicella (MMRV) vaccine compared with the separate measles-mumps-rubella (MMR) and varicella (MMR + V) vaccine increases a toddler’s risk for febrile seizures, we investigated whether MMRV is riskier than MMR + V and whether either vaccine elevates the risk for additional safety outcomes. METHODS: Study children were aged 12 to 23 months in the Vaccine Safety Datalink from 2000 to 2012. Nine study outcomes were investigated: 7 main outcomes (anaphylaxis, ITP, ataxia, arthritis, meningitis/encephalitis, acute disseminated encephalomyelitis, and Kawasaki disease), seizure, and fever. Comparing MMRV with MMR + V, relative risk was estimated by using stratified exact binomial tests. Secondary analyses examined post-MMRV or MMR + V risk versus comparison intervals; risk and comparison intervals were then contrasted for MMRV versus MMR+V. RESULTS: We evaluated 123 200 MMRV and 584 987 MMR + V doses. Comparing MMRV with MMR + V, risks for the 7 main outcomes were not significantly different. Several outcomes had few or zero postvaccination events. Comparing risk versus comparison intervals, ITP risk was higher after MMRV (odds ratio [OR]: 11.3 [95% confidence interval (CI): 1.9 to 68.2]) and MMR + V (OR: 10 [95% CI: 4.5 to 22.5]) and ataxia risk was lower after both vaccines (MMRV OR: 0.8 [95% CI: 0.5 to 1]; MMR + V OR: 0.8 [95% CI: 0.7 to 0.9]). Compared with MMR + V, MMRV increased risk of seizure and fever 7 to 10 days after vaccination. CONCLUSIONS: This study did not identify any new safety concerns comparing MMRV with MMR + V or after either the MMRV or the MMR + V vaccine. This study provides reassurance that these outcomes are unlikely after either vaccine.

Effectiveness of Herpes Zoster Vaccine in Patients 60 Years and Older With End-stage Renal Disease

BACKGROUND Unlike in a healthy population, the protection of herpes zoster (HZ) vaccine in end-stage renal disease (ESRD) patients might be insufficient, considering data demonstrating suboptimal response to other vaccines. The study evaluates the association between HZ vaccination and the subsequent HZ risk among ESRD patients. METHODS This cohort study included ESRD patients age ≥60 years who were enrolled in Kaiser Permanente Southern California. The vaccinated cohort included 582 patients who received HZ vaccine during 01/01/2007 through 12/31/2013. Each vaccinated patient was matched to five unvaccinated patients on age, sex, and dialysis duration. Subjects were passively followed through their electronic health records to identify HZ incidence. Cox regression was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) associated with vaccination. Kaplan-Meier estimates of the cumulative incidence were generated. RESULTS The number of HZ cases was 16 in 1373 person-years (11.7 per 1000 person-years; 95% CI, 7.1-19.0) among the vaccinated and 126 in 5644 person-years (22.3 per 1000 person-years; 95% CI, 18.7-26.6) among the unvaccinated. The 36-month cumulative risk of incident HZ was 4.1% and 6.6%, respectively. HZ vaccination was associated with a reduced risk of HZ (adjusted HR = 0.49; 95% CI, .29-.85). The reduced risk seems more prominent if the vaccine is given within two years of dialysis initiation. CONCLUSIONS Among ESRD patients age ≥60 years, receipt of HZ vaccine was associated with a lower incidence of HZ. In addition, HZ vaccination soon after the initiation of dialysis may provide greater protection.

Quadrivalent Human Papillomavirus Vaccine Uptake in Adolescent Boys and Maternal Utilization of Preventive Care and History of Sexually Transmitted Infections

OBJECTIVES We examined whether maternal utilization of preventive care and history of sexually transmitted infections (STIs) predicted quadrivalent human papillomavirus vaccine (HPV4) uptake among adolescent boys 1 year following the recommendation for permissive use of HPV4 for males. METHODS We linked maternal information with electronic health records of 254 489 boys aged 9 to 17 years who enrolled in Kaiser Permanente Southern California health plan from October 21, 2009, through December 21, 2010. We used multivariable Poisson regression with robust error variance to examine whether HPV4 initiation was associated with maternal uptake of influenza vaccine, Papanicolaou (Pap) screening, and history of STIs. RESULTS We identified a modest but statistically significant association between initiation of HPV4 series and maternal receipt of influenza vaccine (rate ratio [RR] = 1.16; 95% confidence interval [CI] = 1.07, 1.26) and Pap screening (RR = 1.13; 95% CI = 1.01, 1.26). Boys whose mothers had a history of genital warts were more likely to initiate HPV4 (RR = 1.47; 95% CI = 0.93, 2.34), although the association did not reach statistical significance (P = .1). CONCLUSIONS Maternal utilization of preventive care and history of genital warts may influence HPV4 uptake among adolescent boys. The important role of maternal health characteristics and health behaviors needs be considered in intervention efforts to increase vaccine uptake among boys.

Trends and disparity in zoster vaccine uptake in a managed care population

OBJECTIVES Zoster vaccine is recommended for prevention of herpes zoster among adults aged 60 years and older. We examined the zoster vaccination rates during 2007-2011 and assessed association with age, sex, race/ethnicity, neighborhood income and education attainment in eligible adults at Kaiser Permanente Southern California, a managed care organization in the US. METHODS We calculated annual zoster vaccination rate among members ≥60 years without documented contraindications. Multivariable logistic regression was performed to examine factors associated with zoster vaccine uptake in an open cohort of 819,466 adults. RESULTS The zoster vaccination rates increased annually in all groups and the overall rate reached 21.7% in 2011 (P-trend<0.001). Coverage was highest among individuals aged 65-74 years, who were female and non-Hispanic White. In the adjusted analysis, odds of vaccination decreased by age. Females (odds ratio [OR]=1.19, 95% confidence interval [CI]=1.17-1.20) and those who lived in neighborhoods with higher education attainment were more likely to be vaccinated (>75% vs. <50% adults with some college education: OR=1.76, 95% CI=1.73-1.80). Compared to Whites, non-Hispanic Blacks and Hispanics were less likely to receive the vaccine (non-Hispanic Blacks: OR=0.56, 95% CI=0.55-0.58; Hispanics: OR=0.59, 95% CI=0.58-0.60). CONCLUSION The zoster vaccine coverage is higher in this insured population than previously reported in the US general population, but it remains low. Significant racial/ethnic disparity was observed and worsened even among individuals with relatively equal access to zoster vaccination.

The Accuracy and Trends of Smoking History Documentation in Electronic Medical Records in a Large Managed Care Organization

The accuracy of smoking history documentation in the electronic medical records was examined at a large managed care organization among 36,494 male members who self-reported smoking history in mailed surveys. The sensitivity of electronic smoking history documentation for ever-smoking status was 0.19 in years 2003–2005 (using ICD-9/CPT code only), 0.80 in 2006–2008 and 0.84 in 2009–2010 (combination of ICD-9/CPT codes and risk factor module used after 2006). The positive predictive value was 0.96, 0.90, and 0.95 in these periods, respectively. Among self-reported ever-smokers, increased healthcare utilization and smoking intensity/duration were associated with higher likelihood of having electronic smoking history documentation, while Asian race and Spanish language preference were associated with lower likelihood. These data suggest that enhanced efforts may be needed to screen for and document smoking among racial/ethnic minorities.

Clinical effectiveness of pneumococcal polysaccharide vaccine in men: California Men's Health Study

OBJECTIVE To examine the effectiveness of pneumococcal polysaccharide vaccine (PPV) among approximately 40,000 community-dwelling men aged 45 years and older in the California Mens Health Study (CMHS) cohort. METHODS All participants completed an extensive questionnaire at baseline (2002-2003) and were followed for the occurrence of invasive pneumococcal disease (IPD) or all-cause pneumonia hospitalization through the end of 2009. Immunization status and incident IPD and pneumonia cases were ascertained through electronic medical records. The associations between vaccination and IPD or pneumonia hospitalization were assessed using time-dependent Cox proportional models to account for sociodemographics, time-updated vaccination status, and comorbidities. RESULTS The median follow-up period of the 39,222 participants was 7.3 years. Among them, 11,902 (30.3%) had received at least one PPV vaccine at baseline and 7653 (19.5%) received their first PPV vaccine during the follow-up. There were 17 pneumococcal bacteremia cases, 647 hospitalized pneumonia cases, and no pneumococcal meningitis cases. The results suggested a reduced risk of pneumococcal bacteremia among men vaccinated at age ≥65 (adjusted hazard ratio [HR]: 0.35; 95% confidence interval [CI]: 0.06-1.91; p=0.22). PPV vaccination did not show a protective effect against all-cause pneumonia hospitalization (adjusted HR: 1.18; 95% CI: 1.02-1.37, p=0.03) among men vaccinated before 65 years old, but a moderate protective effect was suggested among men without chronic obstructive pulmonary diseases who were vaccinated after 65 years old (adjusted HR: 0.84; 95% CI: 0.67-1.06, p=0.15). CONCLUSIONS The findings in this large cohort of men in Southern California suggested a benefit of PPV for protection against pneumococcal bacteremia among men vaccinated at age 65 years and older. PPV might not provide adequate protection against all-cause pneumonia hospitalization among men.

Safety of Quadrivalent Meningococcal Conjugate Vaccine in 11- to 21-Year-Olds

BACKGROUND: Meningococcal conjugate vaccination is recommended in the United States. This study evaluates the safety of quadrivalent meningococcal conjugate vaccine in a cohort aged 11 to 21 years. METHODS: This cohort study with self-controlled case-series analysis was conducted at Kaiser Permanente Southern California. Individuals receiving MenACWY-CRM, a quadrivalent meningococcal conjugate vaccine, during September 30, 2011 to June 30, 2013, were included. Twenty-six prespecified events of interest (EOIs), including neurologic, rheumatologic, hematologic, endocrine, renal, pediatric, and pediatric infectious disease EOIs, were identified through electronic health records 1 year after vaccination. Of these, 16 were reviewed by case review committees. Specific risk and comparison windows after vaccination were predefined for each EOI. The relative incidence (RI) and 95% confidence intervals (CIs) were estimated through conditional Poisson regression models, adjusted for seasonality. RESULTS: This study included 48 899 vaccinated individuals. No cases were observed in the risk window for 14 of 26 EOIs. The RI for Bell’s palsy, a case review committee-reviewed EOI, was statistically significant (adjusted RI: 2.9, 95% CI: 1.1–7.5). Stratified analyses demonstrated an increased risk for Bell’s palsy in subjects receiving concomitant vaccines (RI = 5.0, 95% CI = 1.4–17.8), and no increased risk for those without concomitant vaccine (RI = 1.1, 95% CI = 0.2–5.5). CONCLUSIONS: We observed a temporal association between occurrence of Bell’s palsy and receipt of MenACWY-CRM concomitantly with other vaccines. The association needs further investigation as it could be due to chance, concomitant vaccination, or underlying medical history predisposing to Bell’s palsy.