Lina S. Sy

Herpes zoster vaccine in older adults and the risk of subsequent herpes zoster disease.

CONTEXT Approximately 1 million episodes of herpes zoster occur annually in the United States. Although prelicensure data provided evidence that herpes zoster vaccine works in a select study population under idealized circumstances, the vaccine needs to be evaluated in field conditions. OBJECTIVE To evaluate risk of herpes zoster after receipt of herpes zoster vaccine among individuals in general practice settings. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study from January 1, 2007, through December 31, 2009, of individuals enrolled in the Kaiser Permanente Southern California health plan. Participants were immunocompetent community-dwelling adults aged 60 years or older. The 75,761 members in the vaccinated cohort were age matched (1:3) to 227,283 unvaccinated members. MAIN OUTCOME MEASURE Incidence of herpes zoster. RESULTS Herpes zoster vaccine recipients were more likely to be white, women, with more outpatient visits, and fewer chronic diseases. The number of herpes zoster cases among vaccinated individuals was 828 in 130,415 person-years (6.4 per 1000 person-years; 95% confidence interval [CI], 5.9-6.8), and for unvaccinated individuals it was 4606 in 355,659 person-years (13.0 per 1000 person-years; 95% CI, 12.6-13.3). In adjusted analysis, vaccination was associated with a reduced risk of herpes zoster (hazard ratio [HR], 0.45; 95% CI, 0.42-0.48); this reduction occurred in all age strata and among individuals with chronic diseases. Risk of herpes zoster differed by vaccination status to a greater magnitude than the risk of unrelated acute medical conditions, suggesting results for herpes zoster were not due to bias. Ophthalmic herpes zoster (HR, 0.37; 95% CI, 0.23-0.61) and hospitalizations coded as herpes zoster (HR, 0.35; 95% CI, 0.24-0.51) were less likely among vaccine recipients. CONCLUSIONS Among immunocompetent community-dwelling adults aged 60 years or older, receipt of the herpes zoster vaccine was associated with a lower incidence of herpes zoster. The risk was reduced among all age strata and among individuals with chronic diseases.

Surveillance of autoimmune conditions following routine use of quadrivalent human papillomavirus vaccine.

Abstract.  Chao C, Klein NP, Velicer CM, Sy LS, Slezak JM, Takhar H, Ackerson B, Cheetham TC, Hansen J, Deosaransingh K, Emery M, Liaw K‐L, Jacobsen SJ (Kaiser Permanente Southern California, Pasadena, CA; Kaiser Permanente Vaccine Study Center, Kaiser Permanente Northern California, Oakland, CA; Merck Research Laboratories, Upper Gwynedd, PA; South Bay Medical Center, Kaiser Permanente Southern California, Los Angeles, CA; and Kaiser Permanente Southern California, Downey, CA, USA). Surveillance of autoimmune conditions following routine use of quadrivalent human papillomavirus vaccine. J Intern Med 2012; 271: 193–203.

Observational safety study of febrile convulsion following first dose MMRV vaccination in a managed care setting

BACKGROUND A combined measles, mumps, rubella, varicella live vaccine (MMRV, Merck and Co., Inc., US) was recently licensed in the US. Pre-licensure clinical trial data showed a significant increase in fever in days 5-12 following MMRV vaccination as compared to the vaccines given separately (MMR+V). This post-licensure retrospective cohort study was undertaken to assess the incidence of febrile convulsion following MMRV. METHODS Children ages 12-60 months who received a first dose of MMRV in February 2006-June 2007 in a managed care organization were included in the study. Subjects were optimally matched on age, sex, and calendar date of vaccination to children who received MMR+V concomitantly in November 2003-January 2006, before MMRV licensure. Potential cases of febrile convulsion were identified through administrative data and adjudicated by expert panel, according to pre-specified criteria. RESULTS During the 30 days post-vaccination, there were 128 and 94 potential convulsion cases among the 31,298 children in the MMRV and MMR+V cohorts, respectively. After review of available medical charts and adjudication, there were 84 cases of confirmed febrile convulsion, 44 (1.41/1000) and 40 (1.28/1000) in the MMRV and MMR+V cohorts, respectively (RR=1.10, 95% CI=0.72, 1.69). In days 5-12 following vaccination, a pre-specified period of interest, the respective numbers were 22 (0.70/1000) and 10 (0.32/1000) (RR=2.20, 95% CI=1.04, 4.65). CONCLUSION These data suggest that the risk of febrile convulsion is increased in days 5-12 following vaccination with MMRV as compared to MMR+V given separately during the same visit, when post-vaccination fever and rash are also increased in clinical trials. While there was no evidence of an increase in the overall month following vaccination, the elevated risk during this time period should be communicated and needs to be balanced with the potential benefit of a combined vaccine.

Safety of quadrivalent human papillomavirus vaccine administered routinely to females.

OBJECTIVE To assess the safety of the quadrivalent human papillomavirus vaccine (HPV4) in females following routine administration. DESIGN In a cohort of vaccinated females, we compared the risk of emergency department visits and hospitalizations during the interval soon after vaccination with risk during a comparison interval more remote from vaccination. SETTING Kaiser Permanente in California. PARTICIPANTS All females who received the HPV4 vaccine. MAIN EXPOSURE One or more doses of HPV4 between August 2006 and March 2008. MAIN OUTCOME MEASURES Outcomes were emergency department visits and hospitalizations, grouped into predefined diagnostic categories. Within diagnostic groups, we used odds ratios (ORs) to estimate whether each subject had any outcome in postvaccination risk intervals (days 1-60, days 1-14, and day 0), compared with a control interval distant in time from vaccination. RESULTS One hundred eighty-nine thousand six hundred twenty-nine females received at least 1 dose and 44 001 received 3 HPV4 doses. Fifty categories had significantly elevated ORs during at least 1 risk interval. Medical record review revealed that most diagnoses were present before vaccination or diagnostic workups were initiated at the vaccine visit. Only skin infections during days 1 to 14 (OR, 1.8; 95% CI, 1.3-2.4) and syncope on day of vaccination (OR, 6.0; 95% CI, 3.9-9.2) were noted by an independent Safety Review Committee as likely associations with HPV4. CONCLUSIONS The quadrivalent human papillomavirus vaccine was associated with same-day syncope and skin infections in the 2 weeks after vaccination. This study did not detect evidence of new safety concerns among females 9 to 26 years of age secondary to vaccination with HPV4.

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.

Pneumococcal Vaccination and Risk of Acute Myocardial Infarction and Stroke in Men

CONTEXT Multiple studies have shown that preventing influenza by vaccination reduces the risk of vascular events. However, the effect of pneumococcal polysaccharide vaccine on vascular events remains controversial. OBJECTIVE To examine the association between pneumococcal vaccination and risk of acute myocardial infarction (MI) and stroke among men. DESIGN, SETTING, AND PARTICIPANTS A prospective cohort study of Kaiser Permanente Northern and Southern California health plans with 84 170 participants aged 45 to 69 years from the California Mens Health Study who were recruited between January 2002 and December 2003, and followed up until December 31, 2007. The cohort was similar to the population of health plan members and men who responded to a general health survey in California on important demographic and clinical characteristics. Demographic and detailed lifestyle characteristics were collected from surveys. Vaccination records were obtained from the Kaiser Immunization Tracking System. MAIN OUTCOME MEASURE Incidence of acute MI and stroke during the follow-up period in men who had no history of such conditions. RESULTS During follow-up, there were 1211 first MIs in 112,837 vaccinated person-years (10.73 per 1000 person-years) compared with 1494 first MI events in 246,170 unvaccinated person-years (6.07 per 1000 person-years). For stroke, there were 651 events in 122,821 vaccinated person-years (5.30 per 1000 person-years) compared with 483 events in 254,541 unvaccinated person-years (1.90 per 1000 person-years). With propensity score adjustment, we found no evidence for an association between pneumococcal vaccination and reduced risk of acute MI (adjusted hazard ratio [HR], 1.09; 95% confidence interval [CI], 0.98-1.21) or stroke (adjusted HR, 1.14; 95% CI, 1.00-1.31). An inverse association was also not found in men of different age and risk groups. The results appeared to be consistent, because using more specific International Classification of Diseases, Ninth Revision codes for the outcome definition did not change the estimations. CONCLUSION Among a cohort of men aged 45 years or older, receipt of pneumococcal vaccine was not associated with subsequent reduced risk of acute MI and stroke.

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.

Incidence of herpes zoster among children vaccinated with varicella vaccine in a prepaid health care plan in the United States, 2002-2008.

Background: Herpes zoster (HZ), or shingles, is caused by reactivation of latent varicella-zoster virus after a primary infection with either wild-type or vaccine-type varicella-zoster virus, the latter having been introduced in 1995 for children. Since then, few population-based data about the incidence of childhood HZ are available. Methods: We identified children aged ≤12 years who were vaccinated with 1 dose of varicella vaccine between 2002 and 2008 in a prepaid health plan and followed them through their electronic health records for a diagnosis of HZ. The medical records of these children were reviewed. Persistent and chronic conditions for these children before HZ were identified. Results: There were 172,163 children vaccinated, with overall follow-up of 446,027 person-years (Incidence rate = 27.4 per 100,000 person-years, 95% confidence interval: 22.7–32.7). Children vaccinated after age 5 years had a higher but not statistically significant different rate than children vaccinated between 12 and 18 months (34.3 vs. 28.5 per 100,000 person-years). Among children vaccinated between 12 and 18 months, incidence rates gradually increased each year in the first 4 years after vaccination (P < 0.001). Among the HZ cases, there were 1 (0.7%) case of lymphoid leukemia, 1 (0.7%) case of drug abuse, 16 (11.1%) cases of asthma with 3 or more acute exacerbations, 12 (8.3%) cases of developmental disorders, and 3 (2.1%) cases of psychological or mental disorders. Conclusions: These data demonstrate that diagnosed HZ is rare among children following varicella vaccine. Despite the small numbers, the roles of delayed vaccination, severe asthma, and development disorders warrant further investigation. In the future, analyses of HZ isolates will be needed to identify the virus strains causing reactivation.

Herpes Zoster Vaccine and the Incidence of Recurrent Herpes Zoster in an Immunocompetent Elderly Population

BACKGROUND The benefit of vaccinating immunocompetent patients who have had shingles has not been examined. The study assessed the association between vaccination and the incidence of herpes zoster recurrence among persons with a recent episode of clinically diagnosed herpes zoster. METHODS This is a matched cohort study in Kaiser Permanente Southern California. Study populations were immunocompetent elderly individuals ≥ 60 years old with a recent episode of herpes zoster. Incidence of recurrent herpes zoster was compared between the vaccinated and the unvaccinated matched cohorts. RESULTS A total of 1036 vaccinated and 5180 unvaccinated members were included. On the basis of clinically confirmed cases, the incidence of recurrent herpes zoster among persons aged <70 years was 0.99 (95% confidence interval [CI], .02-5.54) and 2.20 (95% CI, 1.10-3.93) cases per 1000 person-years in the vaccinated and unvaccinated cohorts, respectively. The adjusted hazard ratio was 0.39 (95% CI, .05-4.45) among persons aged <70 years and 1.05 (95% CI, .30-3.69) among persons aged ≥ 70 years. CONCLUSIONS The risk of herpes zoster recurrence following a recent initial episode is fairly low among immunocompetent adults, regardless of vaccination status. Such a low risk suggests that one should evaluate the necessity of immediately vaccinating immunocompetent patients who had a recent herpes zoster episode.

Safety of zoster vaccine in adults from a large managed-care cohort: a Vaccine Safety Datalink study

Abstract.  Tseng HF, Liu A, Sy L, Marcy SM, Fireman B, Weintraub E, Baggs J, Weinmann S, Baxter R, Nordin J, Daley MF, Jackson L, Jacobsen SJ, for the Vaccine Safety Datalink (VSD) Team (Kaiser Permanente, Pasadena, CA; Kaiser Permanente, Oakland, CA; Centers for Disease Control and Prevention, Atlanta, GA; Kaiser Permanente, Portland, OR; HealthPartners Research Foundation, Minneapolis, MN; Kaiser Permanente, Denver, CO; and Group Health Cooperative of Puget Sound, Seattle, WA; USA). Safety of zoster vaccine in adults from a large managed‐care cohort: a Vaccine Safety Datalink study. J Intern Med 2012; 271: 510–520.