Herpes zoster diagnosis and treatment in relation to incident dementia: A population-based retrospective matched cohort study.

BACKGROUND: Evidence suggests that some infectious diseases, such as herpes zoster (HZ), are associated with elevated risk of subsequent dementia, while certain anti-viral medications are associated with lower risk. We sought to evaluate associations between HZ diagnosis and treatment with incident dementia in a large, retrospective matched cohort. METHODS: Using ICD-9 and ICD-10 diagnosis codes in electronic medical records, we identified members of Kaiser Permanente Northwest age 50 and older from 2000-2019 with a HZ diagnosis during this period. A comparison group without HZ diagnosis was individually matched 3:1 on age at HZ diagnosis date (index date), sex, and membership length prior to index date. We excluded subjects with dementia diagnosed before the index date. Antiherpetic medication was identified using pharmacy fills 1 month before to 12 months after the index date. We employed survival analysis to examine the associations between dementia and HZ diagnosis and antiherpetic medication, adjusting multivariable models for demographic and clinical factors. We stratified on age and sex and conducted a sensitivity analysis with a 5-year lag period. RESULT: The study included 101,328 persons, 25,332 with HZ. Over a median follow-up of 4.8 years, 6,000 developed dementia. HZ diagnosis was not associated with higher hazard of dementia (hazard ratio (HR) = 0.99, 95% CI 0.93-1.05) in the primary analysis. Among persons with HZ diagnoses, the HR for receipt of any antiherpetic medication was 0.79 (95% CI 0.70-0.90) in univariate analysis and 0.88 (95% CI 0.77-1.00) after adjustment for demographic and clinical factors. Dementia was not associated with trends in duration of medication use or cumulative dose. CONCLUSIONS: We found little evidence for an association between HZ diagnosis and dementia overall. Antiherpetic medication prescribed around the time of HZ diagnosis was statistically associated with lower risk of subsequent dementia in some but not all analyses and subgroups.

Incidence of herpes zoster among varicella-vaccinated children, by number of vaccine doses and simultaneous administration of measles, mumps, and rubella vaccine.

INTRODUCTION: Children may receive measles-mumps-rubella (MMR) and varicella (VAR) vaccines separately or as measles-mumps-rubella-varicella (MMRV). We examined whether pediatric herpes zoster (HZ) incidence varied by pattern of varicella vaccine administration. METHODS: In six integrated health systems, we examined HZ incidence among children turning 12 months old during 2003-2008. All received varicella and MMR vaccines on recommended schedules. Cases were identified through 2014 using ICD-9 codes. Incidence was examined by number of varicella vaccine doses and same-day MMR. RESULTS: Among 199,797 children, overall HZ incidence was 18.6/100,000 person-years in the first-dose MMR + VAR group, 17.9/100,000 person-years in the MMRV group, and 7.5/100,000 person-years in the VAR-alone group. HZ incidence was lower following the second dose than before the second dose in all first-dose groups. CONCLUSIONS: HZ incidence was not meaningfully different between the MMRV and MMR + VAR first-dose groups. Overall and within first-dose groups, HZ incidence was lower among children receiving two varicella vaccine doses.

Uptake and safety of hepatitis A vaccination during pregnancy: A Vaccine Safety Datalink study.

INTRODUCTION: Infection with hepatitis A virus (HAV) during pregnancy, although uncommon, is associated with gestational complications and pre-term labor. Hepatitis A vaccine (HepA) is recommended for anyone at increased risk for contracting hepatitis A, including women at risk who are also pregnant. Limited data are available on the safety of maternal HepA vaccination. OBJECTIVES: Assess the frequency of maternal HepA receipt and evaluate the potential association between maternal vaccination and pre-specified maternal and infant safety outcomes. METHODS: A retrospective cohort of pregnancies in the Vaccine Safety Datalink (VSD) resulting in live births from 2004 through 2015 was included. Pregnancies with HepA exposure were compared to those with other vaccine exposures, and to those with no vaccine exposures. Risk factors for contracting hepatitis A were identified up to one-year prior to or during the pregnancy using ICD-9 codes. Maternal and fetal adverse events were evaluated according to maternal HepA exposure status. Adjusted odds ratio (OR) were used to describe the association. RESULTS: Among 666,233 pregnancies in the study period, HepA was administered at a rate of 1.7 per 1000 (n = 1140), most commonly within the first six weeks of pregnancy. Less than 3% of those exposed to HepA during pregnancy had an ICD-confirmed risk factor. There were no significant associations between HepA exposure during pregnancy and gestational hypertension, gestational diabetes, pre-eclampsia/eclampsia, cesarean delivery, pre-term delivery, and low birthweight. There was a statistically significant association between HepA exposure during pregnancy and small-for-gestational age (SGA) infants (aOR 1.32, [95% CI 1.09, 1.60], p = 0.004). CONCLUSIONS: The rate of maternal HepA vaccination was low and rarely due to documented risk factors for vaccination. HepA vaccination during pregnancy was not associated with an increased risk for a range of adverse events examined among pregnancies resulting in live births, but an identified association between maternal HepA and SGA infant outcomes, while likely due to unmeasured confounding, warrants further exploration.

Incidence of Herpes Zoster Among Children: 2003-2014.

BACKGROUND AND OBJECTIVES: After the 1996 introduction of routine varicella vaccination in the United States, most studies evaluating pediatric herpes zoster (HZ) incidence reported lower incidence over time, with varying degrees of decline. Using the combined databases of 6 integrated health care organizations, we examined HZ incidence in children over a 12-year period in the varicella vaccine era. METHODS: This study included children aged 0 through 17 years from 2003 through 2014. Using electronic medical records, we identified HZ cases through International Classification of Diseases, Ninth Revision diagnosis code 053. We calculated HZ incidence rates per 100 000 person years of health plan membership for all children and among children who were vaccinated versus unvaccinated. We calculated rates for the 12-year period and examined temporal trends. Among children who were vaccinated, we compared HZ rates by month and year of age at vaccination. RESULTS: The study included 6 372 067 children with ≥1 month of health plan membership. For the 12-year period, the crude HZ incidence rate for all subjects was 74 per 100 000 person years, and the rate among children who were vaccinated was 38 per 100 000 person years, which was 78% lower than that among children who were unvaccinated (170 per 100 000 person years; P < .0001). Overall HZ incidence declined by 72% (P < .0001) from 2003 through 2014. Annual rates in children who were vaccinated were consistently lower than in children who were unvaccinated. CONCLUSIONS: With this population-based study, we confirm the decline in pediatric HZ incidence and the significantly lower incidence among children who are vaccinated, reinforcing the benefit of routine varicella vaccination to prevent pediatric HZ.

Uptake and safety of Hepatitis B vaccination during pregnancy: A Vaccine Safety Datalink study.

INTRODUCTION: Hepatitis B virus (HBV) infection acquired during pregnancy can pose a risk to the infant at birth that can lead to significant and lifelong morbidity. Hepatitis B vaccine (HepB) is recommended for anyone at increased risk for contracting HBV infection, including pregnant women. Limited data are available on the safety of HepB administration during pregnancy. OBJECTIVES: To assess the frequency of maternal HepB receipt among pregnant women and evaluate the potential association between maternal vaccination and pre-specified maternal and infant safety outcomes. METHODS: We examined a retrospective cohort of pregnancies in the Vaccine Safety Datalink (VSD) resulting in live birth outcomes from 2004 through 2015. Eligible pregnancies in women aged 12-55 years who were continuously enrolled from 6 months pre-pregnancy to 6 weeks postpartum in VSD integrated health systems were included. We compared pregnancies with HepB exposure to those with other vaccine exposures, and to those with no vaccine exposures. High-risk conditions for contracting HBV infection were identified up to one-year prior to or during the pregnancy using ICD-9 codes. Maternal and fetal adverse events were also evaluated according to maternal HepB exposure status. RESULTS: Among over 650,000 pregnancies in the study period, HepB was administered at a rate of 2.1 per 1000 pregnancies (n = 1399), commonly within the first 5 weeks of pregnancy. Less than 3% of the HepB-exposed group had a high-risk ICD-9 code indicating need for HepB; this was similar to the rate among HepB unvaccinated groups. There were no significant associations between HepB exposure during pregnancy and gestational hypertension, gestational diabetes, pre-eclampsia/eclampsia, cesarean delivery, pre-term delivery, low birthweight or small for gestational age infants. CONCLUSIONS: Most women who received maternal HepB did not have high-risk indications for vaccination. No increased risk for the adverse events that were examined were observed among women who received maternal HepB or their offspring.

Influenza Vaccination During Pregnancy: Influenza Seasons 2002-2012, Vaccine Safety Datalink.

INTRODUCTION: Pregnant women are at risk for influenza-related complications and have been recommended for vaccination by the Advisory Committee on Immunization Practices (ACIP) since 1990. Annual rates of influenza coverage of pregnant women have been consistently low. The Vaccine Safety Datalink was used to assess influenza vaccine coverage over 10 consecutive years (2002-2012); assess patterns related to changes in ACIP recommendations; identify predictors of vaccination; and compare the results with those published by national U.S. surveys. METHODS: Retrospective cohort study of 721,898 pregnancies conducted in 2014. Coverage rates were assessed for all pregnancies and for live births only. Multivariate regression analysis identified predictors associated with vaccination. RESULTS: Coverage increased from 8.8% to 50.9% in 2002-2012. Seasonal coverage rates increased slowly following the 2004 ACIP influenza vaccine recommendation (to remove the first trimester restriction), but spiked significantly during the 2009 H1N1 influenza pandemic. Significant predictors of vaccination during pregnancy included older age; vaccination in a previous season; high-risk conditions in addition to pregnancy; pregnancy during either the 2004-2005 or 2009-2010 seasons; entering the influenza season after the first trimester of pregnancy; and a pregnancy with longer overlap with the influenza season (p<0.001 for each). CONCLUSIONS: Influenza vaccination coverage among pregnant women increased between the 2002-2003 and 2011-2012 seasons, although it was still below the developmental Healthy People 2020 goal of 80%. The 2004 ACIP language change positively impacted first-trimester vaccination uptake. Vaccine Safety Datalink data estimates were consistent with U.S. estimates.