Long-Term Effectiveness of the Live Zoster Vaccine in Preventing Shingles: A Cohort Study.

A live attenuated zoster vaccine was licensed in the United States in 2006 for prevention of shingles in persons aged 60 years or older; the indication was extended in 2011 to cover those aged 50-59 years. We assessed vaccine effectiveness (VE) against shingles for 8 years after immunization at Kaiser Permanente Northern California. VE was estimated by Cox regression with a calendar timeline that was stratified by birth year. We adjusted for demographics and time-varying covariates, including comorbidities and immune compromise. From 2007 to 2014, 1.4 million people entered the study when they became age eligible for vaccination; 392,677 (29%) received the zoster vaccine. During 5.8 million person-years of follow-up, 48,889 cases of shingles were observed, including 5,766 among vaccinees. VE was 49.1% (95% confidence interval (CI): 47.5, 50.6) across all follow-up. VE was 67.5% (95% CI: 65.4, 69.5) during the first year after vaccination, waned to 47.2% (95% CI: 44.1, 50.1) during the second year after vaccination, and then waned more gradually through year 8, when VE was 31.8% (95% CI: 15.1, 45.2). Unexpectedly, VE in persons vaccinated when they were aged 80 years or older was similar to VE in younger vaccinees, and VE in persons vaccinated when immune compromised was similar to VE in persons vaccinated when immune competent.

Complications of herpes zoster in cancer patients.

Cancer patients tend to have a higher incidence of herpes zoster (HZ), but little is known about their risk of HZ complications. We conducted a retrospective study of 424 newly diagnosed hematologic (HM, n = 140) and solid tumor malignancy (STM, n = 284) patients who developed HZ between January 2001 and December 2006 to measure the frequency and identify risk factors of HZ complications. Patients were adult members of Kaiser Permanente Northern California. HZ diagnosis and complications were confirmed by medical chart review. HM patients with HZ tended to have more HZ complications than STM patients (34% vs 23%, p = 0.02), largely due to more frequent non-pain complications. On multivariate analysis, older age and being male were associated with a higher risk of HZ complications in HM patients; more advanced cancer stage was associated with HZ complications in STM patients. HZ complications are frequent and can present extra disease burden in cancer patients who develop HZ.

Safety of 9-valent human papillomavirus vaccine administered to males and females in routine use.

BACKGROUND: The nine-valent human papillomavirus vaccine (HPV9, Gardasil®9) was licensed in the USA in December 2014. This study was a multiyear post-licensure study to assess HPV9 safety following routine administration. METHODS: This retrospective cohort study compared the risk of emergency department visits and hospitalizations during the interval soon after vaccination with risk during a later interval. Kaiser Permanente Northern California (KPNC) members aged ≥ 9 years who received ≥ 1 HPV9 dose between 10/1/2015-9/30/2017 were included. Outcomes were grouped into predefined diagnostic categories. We compared the odds of events in postvaccination risk intervals (days 0-14, days 1-60) with odds of events during control intervals (days 61-75, days 61-120) using conditional logistic regression. We characterized prespecified events on the day of vaccination (allergic reaction and syncope) and all deaths in the study period. RESULTS: The study included 215,965 individuals receiving ≥ 1 dose of HPV9, of whom 140,628 had no prior HPV vaccination. We observed similar numbers of males and females and racial/ethnic diversity consistent with the underlying population. At first dose median age was 12-13 years and 77% received ≥ 1 concomitant vaccine. Eighteen event categories were significantly elevated, including skin disorders (odds ratio [OR] 1.88, 95% confidence interval [CI] 1.00, 3.53) and ill-defined conditions (OR 1.36, 95% CI 1.13, 1.64; category includes abdominal pain, allergic reactions, syncope, etc.). On review, most findings were previously known, preceded vaccination, or had other causes. Allergic reactions and syncope at vaccination were infrequent but many were potentially related. No deaths (n = 37) were considered related to HPV9 and were consistent with the background rate. CONCLUSIONS: We did not identify new safety concerns related to HPV9. The results are consistent with the HPV9 safety profile as established from previous studies/surveillance. REGISTRATION: European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (EUPAS13151, protocol V503-028).

Incident autoimmune conditions among males receiving quadrivalent human papillomavirus vaccine in the United States.

BACKGROUND: The potential for vaccines to induce autoimmunity has been the subject of considerable investigation and autoimmune induction remains a common focus for vaccine safety research. This study assessed the risk of new onset autoimmune conditions among males receiving the 4-valent human papillomavirus (HPV) vaccine (4vHPV). METHODS: Within a US health insurance claims database, we formed a cohort of male 4vHPV vaccine recipients between 2009 and 2016, along with a propensity score matched cohort of males who did not receive the 4vHPV vaccine. The study outcome was new onset autoimmune conditions (20 separate conditions) within four categories (rheumatologic/hematologic, gastroenterologic, endocrinologic and neurologic/ophthalmalogic). Outcomes identified using diagnosis codes were adjudicated through medical record review. Incidence rates (per 1,000 person-years) were estimated for the vaccinated and unvaccinated groups along with rate ratios (RRs). RESULTS: There were 65,606 males receiving at least one dose of 4vHPV vaccine, and 55,670 were matched to a comparator. The matched 4vHPV vaccine cohort provided 35 confirmed cases among 39,735 person-years, for an incidence rate of 0.88 (95% CI: 0.61-1.23), while the comparator cohort provided 47 confirmed cases among 58,215 person-years, an incidence rate of 0.81 (0.59-1.07), a RR of 1.09 (0.70-1.69). The RR within categories was 0.49 (0.10-2.42) for rheumatologic/hematologic, 1.26 (0.58-2.71) for gastroenterologic, 1.11 (0.61-2.02) for endocrinologic and 1.46 (0.21-10.40) for neurologic. CONCLUSIONS: The incidence of autoimmune conditions among males receiving the 4vHPV vaccine was similar to that among unvaccinated males. These results are consistent with other studies that have assessed autoimmunity with the 4vHPV vaccine.

Effectiveness of the live zoster vaccine during the 10 years following vaccination: real world cohort study using electronic health records.

OBJECTIVES: To assess the effectiveness of live zoster vaccine during more than 10 years after vaccination; and to describe methods for ascertaining vaccine effectiveness in the context of waning. DESIGN: Real world cohort study using electronic health records. SETTING: Kaiser Permanente Northern California, an integrated healthcare delivery system in the US, 1 January 2007 to 31 December 2018. POPULATION: More than 1.5 million people aged 50 years and older followed for almost 9.4 million person years. MAIN OUTCOME MEASURE: Vaccine effectiveness in preventing herpes zoster, postherpetic neuralgia, herpes zoster ophthalmicus, and admission to hospital for herpes zoster was assessed. Change in vaccine effectiveness by time since vaccination was examined using Cox regression with a calendar timeline. Time varying indicators were specified for each interval of time since vaccination (30 days to less than one year, one to less than two years, etc) and adjusted for covariates. RESULTS: Of 1 505 647 people, 507 444 (34%) were vaccinated with live zoster vaccine. Among 75 135 incident herpes zoster cases, 4982 (7%) developed postherpetic neuralgia, 4439 (6%) had herpes zoster ophthalmicus, and 556 (0.7%) were admitted to hospital for herpes zoster. For each outcome, vaccine effectiveness was highest in the first year after vaccination and decreased substantially over time. Against herpes zoster, vaccine effectiveness waned from 67% (95% confidence interval 65% to 69%) in the first year to 15% (5% to 24%) after 10 years. Against postherpetic neuralgia, vaccine effectiveness waned from 83% (78% to 87%) to 41% (17% to 59%) after 10 years. Against herpes zoster ophthalmicus, vaccine effectiveness waned from 71% (63% to 76%) to 29% (18% to 39%) during five to less than eight years. Against admission to hospital for herpes zoster, vaccine effectiveness waned from 90% (67% to 97%) to 53% (25% to 70%) during five to less than eight years. Across all follow-up time, overall vaccine effectiveness was 46% (45% to 47%) against herpes zoster, 62% (59% to 65%) against postherpetic neuralgia, 45% (40% to 49%) against herpes zoster ophthalmicus, and 66% (55% to 74%) against admission to hospital for herpes zoster. CONCLUSIONS: Live zoster vaccine was effective initially. Vaccine effectiveness waned substantially yet some protection remained 10 years after vaccination. After 10 years, protection was low against herpes zoster but higher against postherpetic neuralgia. TRIAL REGISTRATION: ClinicalTrials.gov number NCT01600079; EU PAS register number EUPAS17502.

Safety of 4-valent human papillomavirus vaccine in males: a large observational post-marketing study.

The 4-valent human papillomavirus (HPV) vaccine (4vHPV vaccine), Gardasil®, is indicated for the prevention of several HPV-related diseases. The objective was to assess the safety of 4vHPV vaccine administered to males as part of routine care. The study used a US health insurance claims database, and included males, age 9 to 26 years, who initiated 4vHPV between October 2009 and December 2016. General safety outcomes were identified using ICD diagnosis codes associated with emergency room visits and hospitalizations in the claims database in risk periods (Days 1-60 and Days 1-14 following vaccine administration) and self-comparison periods (Days 91-150 and 91-104 for the Days 1-60 and Days 1-14 analysis, respectively). Incidence rates (IRs) and relative rates (RRs) with 95% confidence intervals (CIs) were calculated comparing the risk and self-comparison periods. In this study, 114,035 males initiated 4vHPV vaccine and received 202,737 doses. Using the 60-day time window, 5 outcomes had significantly elevated RRs after accounting for multiple comparisons: ear conditions (RR 1.28, 95% CI 1.03-1.59); otitis media and related conditions (RR 1.65, 95% CI 1.09-2.54); cellulitis and abscess of arm (RR 2.17, 95% CI 1.06-4.72); intracranial injury (RR 1.23, 95% CI 1.01-1.50); and concussion (RR 1.29, 95% CI 1.05-1.59). A higher rate of allergic reactions was noted on the day of 4vHPV vaccine receipt compared to other vaccines (21.07 events per 10,000 doses, 95% CI 18.89-23.44 versus 11.44 per 10,000 doses, 95% CI 9.84-13.22). A higher incidence rate of VTE was observed following vaccination but this association was not significant (RR 2.17, 95% CI 0.35-22.74). The 4vHPV vaccine was associated with same-day allergic reactions as well as ear infections, intracranial injury, cellulitis, and concussion within 2 months after vaccination. While allergic reaction and cellulitis are consistent with the known safety profile of 4vHPV vaccine, the association of the other outcomes were determined by an independent Safety Review Committee to be most likely a result of activities common in adolescent males that coincide with the timing of vaccination and not directly related to vaccination itself.Implications and Contributions: The study results support the general safety of routine immunization with 4vHPV vaccine among males to prevent HPV-related diseases and cancers.

Vaccine initiation and 3-dose series completion of 4vHPV vaccine among US insured males 2012-2016.

OBJECTIVE: The quadrivalent human papillomavirus vaccine (4vHPV, GARDASIL®), was approved in the US in 2009 for use in males aged 9 to 26 for the prevention of HPV-related genital warts, and in 2010 for the prevention of certain HPV-related anogenital diseases. A regimen was approved in 2016 for those who initiate the vaccine series between the ages of 9 to 14 years. We describe patterns of 4vHPV administration among US males before this modification. METHODS: The study used a US health insurance claims database, and included males, age 9 to 26 years, who initiated 4vHPV between 2012 and 2016. Time from first dose to subsequent doses was estimated. Logistic regression identified factors associated with regimen completion. RESULTS: Among 100,786 males who initiated 4vHPV (corresponding to âˆ¼ 13% of male birth cohorts), 50,573 (50.2%) and 25,763 (25.6%) received a second and third dose, respectively. Annual administration was common, with 47% of males receiving 3 doses over 3 years (1 dose per year) as compared to 12% receiving the 3-dose series in the recommended 6-month timeframe. Receipt of 4vHPV was 2.2 (range 1.5 to 2.9) times as likely to occur in summer months compared to other times of the year. Individuals aged 18 to 21 years and those living in Western states or rural regions were less likely to complete the 3-dose regimen. CONCLUSIONS: The real-world patterns of 4vHPV vaccination observed, particularly the low uptake and regimen completion, suggest that better strategies are needed for males to improve 4vHPV vaccine use in males.

Long-term effectiveness of zoster vaccine live for postherpetic neuralgia prevention.

BACKGROUND: Postherpetic neuralgia (PHN) occurs in 5-30% of individuals with herpes zoster (HZ) and is characterized by long-lasting pain. Zoster vaccine live (ZVL) is licensed for people 50 years and older to prevent HZ and PHN. This study evaluated vaccine effectiveness (VE) of ZVL against PHN. METHODS: We conducted an open cohort study within Kaiser Permanente Northern California with continuous accrual of people as they became age-eligible for ZVL. We defined PHN using a PHN diagnosis between 90 and 365 days after an incident episode of HZ. We estimated VE against PHN using Cox regression with a calendar timeline stratified by year of birth and adjusted for sex, race, influenza vaccination, outpatient visit frequency, comorbidities, and immune compromise status. RESULTS: From 2007 to 2016, 1·5 million people entered the study population and 33% received ZVL. During 7·6 million person-years of follow-up, there were 62,205 HZ cases, 4150 (6·7%) of which went on to develop PHN. Overall VE for PHN was 64·8% (95% CI 61·3, 68). VE was 82·8% (95% CI 77·6, 86·7) during the first year after vaccination, 58·3% (95% CI 50.1, 65.2) during the third year, and then waned more gradually to 48·7% (95% CI 30·2, 62·3) during the eighth year. VE in persons vaccinated when aged 80 years or older was similar to VE in younger vaccinees. VE in persons vaccinated when immune compromised was similar to VE in immune competent. CONCLUSIONS: Overall, ZVL was 65% effective against PHN. It was effective in all age groups and provided moderate protection through 8 years.

Herpes zoster and postherpetic neuralgia: optimizing management in the elderly patient.

Herpes zoster (HZ) results from reactivation of varicella-zoster virus (VZV) that has been persistent and clinically dormant in spinal ganglia or cranial sensory nerves since primary infection with VZV. The most common reason for reactivation is a decline in zoster-specific cell mediated immunity as a result of aging (immunosenescence). More than two-thirds of HZ cases occur in people >or=60 years of age. HZ incidence is higher in persons who are immunocompromised as a result of disease (e.g. malignancies such as lymphoma, HIV/AIDS, diabetes mellitus) or treatments such as chemotherapy and radiotherapy. HZ incidence is also increased by therapeutic immune suppression following organ transplantation and in patients taking high-dose corticosteroids. However, HZ may occur in otherwise healthy young people. Although serious and life-threatening complications sometimes occur, the most common complication is postherpetic neuralgia (PHN), which may persist for months or years and is significantly resistant to treatment despite substantial advances in the understanding of its pathological mechanisms. The medical and social costs of HZ and PHN are high, particularly in older patients. Prevention of PHN in patients with HZ is unsatisfactory although antiviral drugs reduce the duration of pain after HZ. A live attenuated vaccine has been shown to reduce the incidence of HZ and PHN as well as the burden of illness in subjects aged >or=60 years. In view of the increasing numbers of elderly persons in the population and the poor outcomes of PHN treatment, vaccination against HZ at approximately 60 years of age appears to be an appropriate strategy.

A population-based study of the incidence and complication rates of herpes zoster before zoster vaccine introduction.

OBJECTIVE: To establish accurate, up-to-date, baseline epidemiological data for herpes zoster (HZ) before the introduction of the recently licensed HZ vaccine. METHODS: Using data from January 1, 1996, to October 15, 2005, we conducted a population-based study of adult residents (Greater than or equal to 22 years) of Olmsted County, MN, to determine (by medical record review) the incidence of HZ and the rate of HZ-related complications. Incidence rates were determined by age and sex and adjusted to the US population. RESULTS: A total of 1669 adult residents with a confirmed diagnosis of HZ were identified between January 1, 1996, and December 31, 2001. Most (92%) of these patients were immunocompetent and 60% were women. When adjusted to the US adult population, the incidence of HZ was 3.6 per 1000 person-years (95% confidence interval, 3.4-3.7), with a temporal increase from 3.2 to 4.1 per 1000 person-years from 1996 to 2001. The incidence of HZ and the rate of HZ-associated complications increased with age, with 68% of cases occurring in those aged 50 years and older. Postherpetic neuralgia occurred in 18% of adult patients with HZ and in 33% of those aged 79 years and older. Overall, 10% of all patients with HZ experienced 1 or more nonpain complications. CONCLUSIONS: Our population-based data suggest that HZ primarily affects immunocompetent adults older than 50 years; 1 in 4 experiences some type of HZ-related complication.

The impact of acute herpes zoster pain and discomfort on functional status and quality of life in older adults.

OBJECTIVES: To describe the interference of herpes zoster (HZ) pain and discomfort with activities of daily living (ADLs) and health-related quality of life (HRQL) during the acute rash phase, and to quantify the relationship between acute HZ pain and discomfort and impaired ADLs and HRQL in older persons. METHODS: Prospective, observational study of 160 HZ outpatients age > or =60 at 4 US study sites who completed the Zoster Brief Pain Inventory (ZBPI), Zoster Impact Questionnaire (ZIQ), McGill Pain Questionnaire, EuroQol, and SF-12 questionnaires on a predetermined schedule. Patients rated interference on a 0 to 10 scale for ADL items in the ZBPI and the ZIQ. Interference scores were averaged to create summary measures for the ZBPI items (ZBPI ADLI) and ZIQ items (ZIQ ADLI). A composite pain score was used in mixed-effects models analyses of the association between pain and discomfort and ADLI and HRQL measures during the first 35 days after HZ rash onset. RESULTS: HZ pain interfered with all ADLs but interference was greatest for enjoyment of life, sleep, general activity, leisure activities, getting out of the house, and shopping. For every 1.0 point increase in pain and discomfort intensity, there was a 0.69 and 0.53 point increase in ZBPI and ZIQ interference, respectively, and a 2.81 point, 1.57 point, and 1.95 point decrease in EuroQol, SF-12 physical, and SF-12 mental scales, respectively. DISCUSSION: Acute zoster pain and discomfort has a significant negative impact on functional status and HRQL in older adults. The magnitude of interference increases with increasing pain and discomfort intensity.

Pneumococcal serotype distribution: A snapshot of recent data in pediatric and adult populations around the world.

S. pneumoniae infection remains a serious public health concern despite the availability of vaccines covering up to 23 of more than 94 known serotypes. The purpose of the present study was to monitor recent serotype distribution data. PubMed, EMBASE, Cochrane Reviews and Ingenta databases were searched. Serotype data covering invasive pneumococcal disease (IPD) and non-IPD were extracted from articles published from March 2014 to March 2015. Fifty-nine studies presented pneumococcal serotype prevalence by specific age categories. Most prevalent serotypes not covered by pneumococcal conjugate vaccines (PCV) were as follows: 15B, 22F, 15A, 23A among children under the age of 7 y with IPD; among adults with IPD: 22F, 11A, 10A, 38 in the 65 y and older age group; 12F, 9N, 8 in the 50-64 year-old age group and 12F, 8, 6C, 16F in the 15-59 age group. Geographic variations in serotype distribution highlight the importance of monitoring evolving pneumococcal serotype prevalence after pneumococcal vaccine implementation.

Herpes zoster vaccine live: A 10 year review of post-marketing safety experience.

BACKGROUND: Zoster vaccine is a single dose live, attenuated vaccine (ZVL) indicated for individuals ≥50 years-old for the prevention of herpes zoster (HZ). Safety data from clinical trials and post-licensure studies provided reassurance that ZVL is generally safe and well tolerated. The objective of this review was to provide worldwide post-marketing safety information following 10 years of use and >34 million doses distributed. METHODS: All post-marketing adverse experience (AE) reports received worldwide between 02-May-2006 and 01-May-2016 from healthcare professionals following vaccination with ZVL and submitted to the MSD AE global safety database, were analyzed. RESULTS: A total of 23,556 AE reports, 93% non-serious, were reported. Local injection site reactions (ISRs), with a median time-to-onset of 2 days, were the most frequently reported AEs followed by HZ. The majority of HZ reports were reported within 2 weeks of vaccination and considered, based on time-to-onset, pathogenesis of HZ, and data from clinical trials, to be caused by wild-type varicella-zoster virus (VZV). HZ confirmed by PCR analysis to be VZV Oka/Merck vaccine-strain was identified in an immunocompetent individual 8 months postvaccination and in 4 immunocompromised individuals. Disseminated HZ was reported very rarely (<1%) with 38% occurring in immunocompromised individuals. All reports of disseminated HZ confirmed by PCR as VZV Oka/Merck vaccine-strain were in individuals with immunosuppressive conditions and/or therapy at the time of vaccination. CONCLUSIONS: The safety profile of ZVL, following 10 years of post-marketing use, was favorable and consistent with that observed in clinical trials and post-licensure studies.

The incidence of herpes zoster in a United States administrative database.

BACKGROUND: Few recent studies have reported data on the incidence of herpes zoster (HZ) in U.S. general clinical practice. OBJECTIVE: To estimate the age- and sex-specific incidence of HZ among U.S. health plan enrollees. DESIGN: Data for the years 2000 to 2001 were obtained from the Medstat MarketScan database, containing health insurance enrollment and claims data from over 4 million U.S. individuals. Incident HZ cases were identified through HZ diagnosis codes on health care claims. The burden of HZ among high-risk individuals with recent care for cancer, HIV, or transplantation was examined in sub-analyses. Overall incidence rates were age- and sex-adjusted to the 2000 U.S. population. PARTICIPANTS: MarketScan U.S. health plan enrollees of all ages. MEASUREMENTS AND MAIN RESULTS: We identified 9,152 incident cases of HZ (3.2 per 1,000 person-years) (95% confidence interval [CI], 3.1 to 3.2 per 1,000). Annual HZ rates per 1,000 person-years were higher among females (3.8) than males (2.6) (P<.0001). HZ rates rose sharply with age, and were highest among individuals over age 80 (10.9 per 1,000 person-years) (95% CI, 10.2 to 11.6). The incidence of HZ per 1,000 person-years among patients with evidence of recent care for transplantation, HIV infection, or cancer (10.3) was greater than for individuals without recent care for these conditions (3.0) (P<.0001). CONCLUSIONS: The overall incidence of HZ reported in the present study was found to be similar to rates observed in U.S. analyses conducted 10 to 20 years earlier, after age- and sex-standardizing estimates from all studies to the 2000 U.S. population. The higher rate of HZ in females compared with males contrasts with prior U.S. studies.

Impact of vaccination on the epidemiology of varicella: 1995-2009.

BACKGROUND: When varicella vaccine was licensed in the United States in 1995, there were concerns that childhood vaccination might increase the number of adolescents susceptible to varicella and shift disease toward older age groups where it can be more severe. METHODS: We conducted a series of 5 cross-sectional studies in 1994 to 1995 (prevaccine), 2000, 2003, 2006, and 2009 in Kaiser Permanente of Northern California to assess changes in varicella epidemiology in children and adolescents, as well as changes in varicella hospitalization in people of all ages. For each study, information on varicella history and varicella occurrence during the past year was obtained by telephone survey from a sample of ∼8000 members 5 to 19 years old; varicella hospitalization rates were calculated for the entire membership. RESULTS: Between 1995 and 2009, the overall incidence of varicella in 5- to 19-year-olds decreased from 25.8 to 1.3 per 1000 person-years, a ∼90% to 95% decline in the various age categories (5-9, 10-14, and 15-19 years of age). The proportion of varicella-susceptible children and adolescents also decreased in all age groups, including in 15- to 19-year-olds (from 15.6% in 1995 to 7.6% in 2009). From 1994 to 2009, age-adjusted varicella hospitalization rates in the general member population decreased from 2.13 to 0.25 per 100,000, a ∼90% decline. CONCLUSIONS: In the 15 years after the introduction of varicella vaccine, a major reduction in varicella incidence and hospitalization was observed with no evidence of a shift in the burden of varicella to older age groups.

Long-term effectiveness of varicella vaccine: a 14-Year, prospective cohort study.

BACKGROUND: Varicella vaccine was licensed in the United States in 1995 for individuals ≥12 months of age. A second dose was recommended in the United States in June 2006. Varicella incidence and vaccine effectiveness were assessed in a 14-year prospective study conducted at Kaiser Permanente Northern California. METHODS: A total of 7585 children vaccinated with varicella vaccine in their second year of life in 1995 were followed up prospectively for breakthrough varicella and herpes zoster (HZ) through 2009. A total of 2826 of these children received a second dose in 2006-2009. Incidences of varicella and HZ were estimated and compared with prevaccine era rates. RESULTS: In this cohort of vaccinated children, the average incidence of varicella was 15.9 per 1000 person-years, nine- to tenfold lower than in the prevaccine era. Vaccine effectiveness at the end of the study period was 90%, with no indication of waning over time. Most cases of varicella were mild and occurred early after vaccination. No child developed varicella after a second dose. HZ cases were mild, and rates were lower in the cohort of vaccinated children than in unvaccinated children during the prevaccine era (relative risk: 0.61 [95% confidence interval: 0.43-0.89]). CONCLUSIONS: This study confirmed that varicella vaccine is effective at preventing chicken pox, with no waning noted over a 14-year period. One dose provided excellent protection against moderate to severe disease, and most cases occurred shortly after the cohort was vaccinated. The study data also suggest that varicella vaccination may reduce the risks of HZ in vaccinated children.

Safety of Zostavax™--a cohort study in a managed care organization.

BACKGROUND: Zostavax™ is a live, attenuated varicella-zoster virus vaccine indicated for the prevention of herpes zoster (shingles). An observational post-licensure (Phase IV) study was conducted at Kaiser Permanente Northern California (KPNC), a US managed care organization, to assess the safety of zoster vaccine in people 60 years of age or older, vaccinated in routine medical care. METHODS: We performed a cohort study, comparing rates of clinical events resulting in hospitalizations or emergency department visits in a 42-day risk time period immediately following vaccination with rates in the same cohort in a subsequent comparison time period. The study data were reviewed and interpreted by an external safety review committee of 3 independent experts. RESULTS: Approximately 29,000 people ≥ 60 years of age were vaccinated with zoster vaccine from July 2006 to November 2007. Of the 386 comparisons performed for the main analysis, 4 had an increased relative risk with a nominal p-value ≤ 0.05. After medical records review, the timing of these conditions and procedures was found to be often prior to vaccination, and no clear increase in health events was observed in the risk period following vaccination compared to later. Persons receiving zoster vaccine appeared to be in their optimal health at the time of vaccination, which led to an apparent protective effect of the vaccine for some health outcomes, due to the study design. CONCLUSIONS: There was no evidence of a safety concern for zoster vaccine.

Adaptation of a previously validated vaccination report card for use in adult vaccine clinical trials to align with the 2007 FDA Toxicity Grading Scale Guidance.

The Adult/Adolescent Vaccination Report Card (VRC) was developed and validated by Merck in 1998 for use in vaccine clinical trials to collect information from trial subjects on complaints for both local and systemic events after vaccination. This short report describes the revision to the original validated VRC in order to align with the guidelines outlined in the 2007 FDA Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. Since the VRC elicits trial subjects' self-reports of any adverse experiences (AE) occurring post vaccination, it was important that subsequent modifications of the VRC retained the original user-friendly characteristics while gathering the appropriate information to align with the FDA Guidance. A convenience sample of 15 participants (71% females, 87% white and mean (SD) age 45 (13) years was recruited to obtain feedback in order to revise the Adult/Adolescent VRC. Based on the feedback received, the following were slightly revised: ruler for the measurements of local systemic reactions, severity ratings, and general instructions. The revised VRC is currently being used in Merck vaccine clinical trials.

Work and productivity loss related to herpes zoster.

OBJECTIVE: To estimate absenteeism and presenteeism-related work loss due to herpes zoster (HZ) among working individuals of 50-64 years of age. METHODS: This telephone survey included individuals with ≥1 insurance claim for HZ in the past year in administrative claims data from five US commercial health plans. Demographic information, characteristics of the HZ episode; impact of HZ on activities of daily living (ADL), and work days loss and productivity were surveyed. RESULTS: Responses were obtained from 153 of 1654 individuals who were contacted and were eligible for the survey (9.3%). Most had moderate or severe HZ (72.6%). Close to two-thirds reported some impact of HZ on ADL such as shopping, housework/chores, and social engagement. About half (51%) reported missing work due to HZ, and about an equal percentage reported little or much worse productivity than usual due to HZ while at work. On average, age-adjusted absenteeism- and presenteeism-related work loss was estimated at 31.6 hours, and 84.4 hours, respectively, with a combined work loss of 116.0 hours per HZ episode in a working person of 50-64 years of age. Work loss tended to increase with age and the duration and severity of the HZ episode. CONCLUSIONS: The study documents a substantial societal burden of HZ-related work and productivity loss. This is important information to take into consideration, in addition to the direct medical burden, when making policy decisions around vaccine prevention of HZ. LIMITATIONS: The study may potentially be subject to selection bias due to low survey response rate and since only those cases who sought care for a HZ episode were captured. The study may also be subject to respondent recall bias. Finally, since some respondents could still be having the HZ episode at the time of survey, the study may potentially have under-estimated the work and productivity loss.

Herpes zoster recurrences more frequent than previously reported.

OBJECTIVE: To present population-based estimates of herpes zoster (HZ) recurrence rates among adults. PATIENTS AND METHODS: To identify recurrent cases of HZ, we reviewed the medical records (through December 31, 2007) of all Olmsted County, Minnesota, residents aged 22 years or older who had an incident case of HZ between January 1, 1996, and December 31, 2001. Kaplan-Meier curves and Cox regression models were used to describe recurrences by age, immune status, and presence of prolonged pain at the time of the incident HZ episode. RESULTS: Of the 1669 persons with a medically documented episode of HZ, 95 had 105 recurrences (8 persons with >1 recurrence) by December 31, 2007, an average follow-up of 7.3 years. The Kaplan-Meier estimate of the recurrence rate at 8 years was 6.2%. With a maximum follow-up of 12 years, the time between HZ episodes in the same person varied from 96 days to 10 years. Recurrences were significantly more likely in persons with zoster-associated pain of 30 days or longer at the initial episode (hazard ratio, 2.80; 95% confidence interval, 1.84-4.27; P<.001) and in immunocompromised individuals (hazard ratio, 2.35; 95% confidence interval, 1.35-4.08; P=.006). Women and anyone aged 50 years or older at the index episode also had a greater likelihood of recurrence. CONCLUSION: Rates of HZ recurrence appear to be comparable to rates of first HZ occurrence in immunocompetent individuals, suggesting that recurrence is sufficiently common to warrant investigation of vaccine prevention in this group.