BACKGROUND: In 2019, there were an estimated 1.2 million persons with HIV (PWH) and 35,100 new infections in the United States. The HIV care continuum has a large influence on transmission dynamics. METHODS: We updated Progression and Transmission of HIV 3.0, an agent-based simulation model, to estimate 2019 HIV transmission rates and distribution of transmissions by the HIV care continuum, race/ethnicity, transmission group, and age group. RESULTS: In 2019, the estimated transmission rate in the United States was 2.94 new infections per 100 person-years (inf /100p-y). Transmission rates decreased along the HIV care continuum; the highest transmission rate was associated with persons with acute HIV infection and unaware of their HIV status at 16.35 inf /100p-y, followed by persons with HIV (non-acute) and unaware of their HIV status (9.52), persons aware of their HIV status and not in care (5.96), persons receiving HIV care (on antiretroviral therapy) but not virally suppressed (4.53), and persons virally suppressed (0). The highest transmission rate by transmission group was among men who have sex with men at 3.68 inf /100p-y. Transmission rates decreased as age increased and are similar by race/ethnicity, after accounting for the HIV care continuum. CONCLUSION: Our results support a continued emphasis on helping PWH move along the care continuum through early diagnosis, linkage to care, and adherence to ART, resulting in viral suppression to reduce HIV transmissions. Further, efforts should focus on reducing disparities in the provision of HIV prevention and care services, particularly for populations disproportionally affected by HIV.

BACKGROUND: The World Health Organization (WHO) recommends that HIV treatment scale-up is accompanied by a robust assessment of drug resistance emergence and transmission. The WHO HIV Drug Resistance (HIVDR) monitoring and surveillance strategy includes HIVDR testing in adults both initiating and receiving antiretroviral therapy (ART). Due to limited information about HIVDR in Mozambique, we conducted two nationally representative surveys of adults initiating and receiving first-line ART regimes to better inform the HIV program. METHODS: We carried out a cross-sectional study between March 2017 and December 2019. Adults (older than 15 years) living with HIV (PLHIV) initiating ART or receiving first-line ART for between 9-15 months at 25 health facilities across all eleven provinces in Mozambique were included. Genotypic HIVDR was assessed on dried blood spots (DBS) when viral loads were  ≥ 1000 copies/ml. Genotypic resistance for non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) was determined using the Stanford HIV database algorithm 9.5 and calibrated population resistance tool 8.1. RESULTS: Of 828 participants -enrolled, viral load (VL) testing was performed on 408 initiators and 409 ART experienced. Unsuppressed VL was found in 68.1% 419 initiators and 18.8% (77/409) of the ART experienced. Of the 278 initiators and 70 ART experienced who underwent sequencing, 51.7% (144/278) and 75.7% (53/70) were sequenced successfully. Among the new initiators, pretreatment drug resistance (PDR) for NNRTI and PI was found in 16.0% (23/144) and 1.4% (2/144) of the participants, respectively. Acquired drug resistance (ADR) was found in 56.5% (30/53) of the ART-experienced participants of whom 24.5% (13/53) were resistant to both NRTI and NNRTI. CONCLUSION: High rates of PDR and ADR for NNRTI and ADR for NRTI were observed in our study. These findings support the replacement of NNRTIs with dolutegravir (DTG) but high levels of NRTI resistance in highly treatment-experienced individuals still require attention when transitioning to new regimens. Moreover, the study underlines the need for routine VL testing and HIVDR surveillance to improve treatment management strategies.

Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. In 2020, the COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized hundreds of thousands of specific predictions from more than 50 different academic, industry, and independent research groups. This manuscript systematically evaluates 23 models that regularly submitted forecasts of reported weekly incident COVID-19 mortality counts in the US at the state and national level. One of these models was a multi-model ensemble that combined all available forecasts each week. The performance of individual models showed high variability across time, geospatial units, and forecast horizons. Half of the models evaluated showed better accuracy than a naïve baseline model. In combining the forecasts from all teams, the ensemble showed the best overall probabilistic accuracy of any model. Forecast accuracy degraded as models made predictions farther into the future, with probabilistic accuracy at a 20-week horizon more than 5 times worse than when predicting at a 1-week horizon. This project underscores the role that collaboration and active coordination between governmental public health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks.Competing Interest StatementAV, MC, and APP report grants from Metabiota Inc outside the submitted work.Funding StatementFor teams that reported receiving funding for their work, we report the sources and disclosures below. CMU-TimeSeries: CDC Center of Excellence, gifts from Google and Facebook. CU-select: NSF DMS-2027369 and a gift from the Morris-Singer Foundation. COVIDhub: This work has been supported by the US Centers for Disease Control and Prevention (1U01IP001122) and the National Institutes of General Medical Sciences (R35GM119582). The content is solely the responsibility of the authors and does not necessarily represent the official views of CDC, NIGMS or the National Institutes of Health. Johannes Bracher was supported by the Helmholtz Foundation via the SIMCARD Information& Data Science Pilot Project. Tilmann Gneiting gratefully acknowledges support by the Klaus Tschira Foundation. DDS-NBDS: NSF III-1812699. EPIFORECASTS-ENSEMBLE1: Wellcome Trust (210758/Z/18/Z) GT_CHHS-COVID19: William W. George Endowment, Virginia C. and Joseph C. Mello Endowments, NSF DGE-1650044, NSF MRI 1828187, research cyberinfrastructure resources and services provided by the Partnership for an Advanced Computing Environment (PACE) at Georgia Tech, and the following benefactors at Georgia Tech: Andrea Laliberte, Joseph C. Mello, Richard Rick E. & Charlene Zalesky, and Claudia & Paul Raines GT-DeepCOVID: CDC MInD-Healthcare U01CK000531-Supplement. NSF (Expeditions CCF-1918770, CAREER IIS-2028586, RAPID IIS-2027862, Medium IIS-1955883, NRT DGE-1545362), CDC MInD program, ORNL and funds/computing resources from Georgia Tech and GTRI. IHME: This work was supported by the Bill & Melinda Gates Foundation, as well as funding from the state of Washington and the National Science Foundation (award no. FAIN: 2031096). IowaStateLW-STEM: Iowa State University Plant Sciences Institute Scholars Program, NSF DMS-1916204, NSF CCF-1934884, Laurence H. Baker Center for Bioinformatics and Biological Statistics. JHU_IDD-CovidSP: State of California, US Dept of Health and Human Services, US Dept of Homeland Security, US Office of Foreign Disaster Assistance, Johns Hopkins Health System, Office of the Dean at Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University Modeling and Policy Hub, Centers fo Disease Control and Prevention (5U01CK000538-03), University of Utah Immunology, Inflammation, & Infectious Disease Initiative (26798 Seed Grant). LANL-GrowthRate: LANL LDRD 20200700ER. MOBS-GLEAM_COVID: COVID Supplement CDC-HHS-6U01IP001137-01. NotreDame-mobility and NotreDame-FRED: NSF RAPID DEB 2027718 UA-EpiCovDA: NSF RAPID Grant # 2028401. UCSB-ACTS: NSF RAPID IIS 2029626. UCSD-NEU: Google Faculty Award, DARPA W31P4Q-21-C-0014, COVID Supplement CDC-HHS-6U01IP001137-01. UMass-MechBayes: NIGMS R35GM119582, NSF 1749854. UMich-RidgeTfReg: The University of Michigan Physics Department and the University of Michigan Office of Research.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:UMass-Amherst IRBAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll data and code referred to in the manuscript are publicly available. https://github.com/reichlab/covid19-forecast-hub/ https://github.com/reichlab/covidEnsembles https://zoltardata.com/project/44

We examined parents' COVID-19 vaccination intentions for their children, reasons for not vaccinating, and the potential impact of a school/daycare vaccination requirement or pediatrician's recommendation on vaccination intentions. Two online surveys were conducted in June-July and September-October 2021, before pediatric COVID-19 vaccines were authorized for emergency use in children age < 12 years, with an internet-based, non-probability sample of U.S. adults. Respondents with children (age < 18 years) in the household were asked about their intention (likelihood) of vaccinating these children against COVID-19. Weighted Chi-square tests using a Rao-Scott correction were performed. Vaccinated (45.7 %) versus unvaccinated (6.9 %) parents were almost seven times more likely to have vaccinated their 12-17-year-old children against COVID-19. Approximately 58.4 % of respondents with unvaccinated children ages 2-11 years and 42.4 % of those with children < 2 years said they are "very" or "extremely likely" to vaccinate these children against COVID-19. Female parents were significantly more likely (p < .01 to p < .001) to express lower levels of COVID-19 vaccine intentions. Across all age groups of children unvaccinated against COVID-19, parental vaccine intentions increased with increased household income and education levels. COVID-19 vaccine side effects and safety concerns were primary reasons for not vaccinating children. Strategies including school vaccination requirements and recommendations from pediatricians were shown to increase parental COVID-19 vaccination intentions for some. More research is needed on factors that increase/hinder COVID-19 pediatric vaccine uptake.

The benefits of physical activity to health and obesity prevention are well established. However, attributes of the built environment influence participation in physical activity. The purpose of this study is to assess differences in perceptions of neighborhood walkability across demographic characteristics and social environment factors among rural residents. In a telephone survey, adult respondents (N = 448) across nine rural counties in a southeastern state answered questions about perceived neighborhood walkability, demographic characteristics, and their neighborhood social environment. Study recruitment for a convenience sample occurred through collaborations with local community organizations. Prevalence of destinations and barriers were estimated according to demographic and neighborhood social environment characteristics. Multiple logistic regression models assessed the association of demographic and neighborhood social environment characteristics with neighborhood walkability and calculated adjusted prevalence. Relaxing places to walk were the most often reported destinations (62.0%), followed by retail destinations (45.7%), and communal destinations (42.6%). Traffic was the most reported barrier to safe walking (40.4%), followed by animals (37.5%), and crime (30.5%). Perceptions of retail and communal destinations varied by age and race. Perceptions of traffic and crime as barriers varied by race, weight status, and income. Community belonging and social cohesion were associated with lower perceptions of barriers. Study findings present demographic characteristics and social environment attributes as key factors that shape perceived neighborhood walkability. Findings can help inform programmatic efforts and environmental change strategies to improve walking in rural areas.

OBJECTIVES: We examined COVID-19 vaccination status, intention, and hesitancy and the effects of five strategies to increase the willingness of unvaccinated adults (≥18 years) to get a COVID vaccine. METHODS: Online surveys were conducted between October 1-17, 2020 (N = 14,946), December 4-16, 2020 (N = 15,229), April 8-22, 2021 (N = 14,557), June 17-July 6, 2021 (N = 30,857), and September 3-October 4, 2021 (N = 33,088) with an internet-based, non-probability opt-in sample of U.S. adults matching demographic quotas. Respondents were asked about current COVID-19 vaccination status, intention and hesitancy to get vaccinated, and reasons for vaccine hesitancy. Unvaccinated respondents were assigned to treatment groups to test the effect of five strategies (endorsements, changing social restrictions, financial incentives, vaccine requirements for certain activities, and vaccine requirements for work). Chi-square tests of independence were performed to detect differences in the response distributions. RESULTS: Willingness to be vaccinated (defined as being vaccinated or planning to be) increased over time from 47.6 % in October 2020 to 81.1 % in October 2021. By October 2021, across most demographic groups, over 75 % of survey respondents had been or planned to be vaccinated. In terms of strategies: (1) endorsements had no positive effect, (2) relaxing the need for masks and social distancing increased Intention to Get Vaccinated (IGV) by 6.4 % (p < 0.01), (3) offering financial incentives increased the IGV between 12.3 and 18.9 % (p <.001), (4) vaccine requirements for attending sporting events or traveling increased IGV by 7.8 % and 9.1 %, respectively (p = 0.02), and vaccine requirement for work increased IGV by 35.4 %. The leading causes (not mutually exclusive) for hesitancy were concerns regarding vaccine safety (52.5 %) or side effects (51.6 %), trust in the government's motives (41.0 %), and concerns about vaccine effectiveness (37.6 %). CONCLUSIONS: These findings suggest that multiple strategies may be effective and needed to increase COVID-19 vaccination among hesitant adults during the pandemic.

SignificanceThis paper compares the probabilistic accuracy of short-term forecasts of reported deaths due to COVID-19 during the first year and a half of the pandemic in the United States. Results show high variation in accuracy between and within stand-alone models and more consistent accuracy from an ensemble model that combined forecasts from all eligible models. This demonstrates that an ensemble model provided a reliable and comparatively accurate means of forecasting deaths during the COVID-19 pandemic that exceeded the performance of all of the models that contributed to it. This work strengthens the evidence base for synthesizing multiple models to support public-health action.

Importance: In Africa, the persistently high HIV incidence rate among young women is the major obstacle to achieving the goal of epidemic control. Objective: To determine trends in coverage of HIV prevention and treatment programs and HIV incidence. Design, Setting, and Participants: This cohort study consisted of 2 sequential, community-based longitudinal studies performed in the Vulindlela and Greater Edendale area in KwaZulu-Natal, South Africa. Participants enrolled from June 11, 2014, to June 22, 2015 (2014 survey), with a single follow-up visit from June 24, 2016, to April 3, 2017 (2016 cohort), or enrolled from July 8, 2015, to June 7, 2016 (2015 survey), with a single follow-up visit from November 7, 2016, to August 30, 2017 (2017 cohort). Men and women aged 15 to 49 years were enrolled in the 2014 and 2015 surveys, and HIV-seronegative participants aged 15 to 35 years were followed up in the 2016 and 2017 cohorts. Analysis was conducted from January 1 through December 31, 2018. Exposures: HIV prevention and treatment programs in a real-world, nontrial setting. Main Outcomes and Measures: Trends in sex- and age-specific HIV incidence rates, condom use, voluntary medical male circumcision, knowledge of HIV-seropositive status, uptake of antiretroviral therapy, and viral suppression. Results: A total of 9812 participants (6265 women [63.9%]; median age, 27 years [interquartile range, 20-36 years]) from 11 289 households were enrolled in the 2014 survey, and 10 236 participants (6341 women [61.9%]; median age, 27 years [interquartile range, 20-36 years]) from 12 247 households were enrolled in the 2015 survey. Of these, 3536 of 4539 (annual retention rate of 86.7%) completed follow-up in the 2016 cohort, and 3907 of 5307 (annual retention rate of 81.4%) completed follow-up in the 2017 cohort. From 2014 to 2015, condom use with last sex partner decreased by 10% from 24.0% (n = 644 of 3547) to 21.6% (n = 728 of 3895; P = .12) in men and by 17% from 19.6% (n = 1039 of 6265) to 16.2% (n = 871 of 6341; P = .002) in women. Voluntary medical male circumcision increased by 13% from 31.9% (1102 of 3547) to 36.1% (n = 1472 of 3895); P = .007) in men, and the proportion of women reporting that their partner was circumcised increased by 35% from 35.7% (n = 1695 of 4766) to 48.2% (n = 2519 of 5207; P < .001). Knowledge of HIV-seropositive status increased by 21% from 51.8% (n = 504 of 3547) to 62.9% (n = 570 of 3895; P < .001) in men and by 14% from 64.6% (n = 1833 of 6265) to 73.4% (n = 2182 of 6341; P < .001) in women. Use of antiretroviral therapy increased by 32% from 36.7% (n = 341 of 3547) to 48.6% (n = 432 of 3895; P < .001) in men and by 29% from 45.6% (n = 1251 of 6265) to 58.8% (n = 1743 of 6341; P < .001) in women; HIV viral suppression increased by 20% from 41.9% (n = 401 of 3547) to 50.3% (n = 456 of 3895; P = .005) in men and by 13% from 54.8% (n = 1547 of 6265) to 61.9% (n = 1828 of 6341; P < .001) in women. Incidence of HIV declined in women aged 15 to 19 years from 4.63 (95% CI, 3.29-6.52) to 2.74 (95% CI, 1.84-4.09) per 100 person-years (P = .04) but declined marginally or remained unchanged among men and women in other age groups. Conclusions and Relevance: This study showed a significant decline in HIV incidence in young women; however, to further reduce HIV incidence, HIV prevention and treatment program coverage must be intensified and scaled up.

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.

INTRODUCTION: Despite minimal evidence, public concerns that the human papillomavirus (HPV) vaccine can cause autoimmune diseases (AD) persist. We evaluated whether HPV vaccine is associated with a long-term increased risk of diabetes mellitus type 1 (DM1). METHODS: This was a retrospective cohort study in which we identified all potential DM1 cases from Kaiser Permanente Northern California (KPNC) members who were between 11 and 26years old any time after June 2006 through December 2015. We chart reviewed a random sample of 100 DM1 cases to confirm diagnosis and to develop a computer algorithm that reliably determined symptom onset date. Our DM1 Analysis Population comprised all individuals who met membership criteria and who were age and sex eligible to have received HPV vaccine. We adjusted for age, sex, race, Medicaid, and years of prior KPNC membership by stratification using a Cox multiplicative hazards model with a calendar timeline. RESULTS: Our DM1 analysis included 911,648 individuals. Of 2613 DM1 cases identified, 338 remained in the analysis after applying our algorithm, HPV vaccine eligibility and membership criteria. Over the 10years of the study period, comparing vaccinated with unvaccinated persons, we did not find an increased risk of DM1 associated with HPV vaccine receipt (hazard ratio 1.21, 95% Confidence Interval 0.94, 1.57). CONCLUSIONS: We found no increased risk for development of DM1 following HPV vaccination. Our study provides reassurance that during the 10-year time period after HPV vaccine was introduced, there was no substantial increased risk for DM1 following HPV vaccination.

BACKGROUND: Population-based estimates of influenza-associated outpatient visits including both pandemic and inter-pandemic seasons are uncommon. Comparisons of such estimates with laboratory-confirmed rates of outpatient influenza are rare. OBJECTIVE: To estimate influenza-associated outpatient visits in six US integrated health care delivery organizations enrolling ~7.7 million persons. METHODS: Using negative-binomial regression methods, we modeled rates of influenza-associated visits with ICD-9-CM-coded pneumonia or acute respiratory outpatient visits during 2001-10. These estimated counts were added to visits coded specifically for influenza to derive estimated rates. We compared these rates with those observed in two contemporaneous studies recording RT-PCR-confirmed influenza outpatient visits. RESULTS: Outpatient rates estimated with pneumonia visits were 39 (95% confidence interval [CI], 30-70) and 203 (95% CI, 180-240) per 10,000 person-years, respectively, for inter-pandemic and pandemic seasons. Corresponding rates estimated with respiratory visits were 185 (95% CI, 161-255) and 542 (95% CI, 441-823) per 10,000 person-years. During the pandemic, children aged 2-17 years had the largest increase in rates (when estimated with pneumonia visits, from 64 [95% CI, 50-121] to 381 [95% CI, 366-481]). Rates estimated with pneumonia visits were consistent with rates of RT-PCR-confirmed influenza visits during 4 of 5 seasons in one comparison study. In another, rates estimated with pneumonia visits during the pandemic for children and adults were consistent in timing, peak, and magnitude. CONCLUSIONS: Estimated rates of influenza-associated outpatient visits were higher in children than adults during pre-pandemic and pandemic seasons. Rates estimated with pneumonia visits plus influenza-coded visits were similar to rates from studies using RT-PCR-confirmed influenza. This article is protected by copyright. All rights reserved.

BACKGROUND: Following the H1N1 influenza pandemic in 2009, pregnant women were recommended to receive both seasonal (TIV) and H1N1 influenza vaccines. This study presents incidence of adverse birth and pregnancy outcomes among a population of pregnant women immunized with TIV and H1N1 vaccines at Kaiser Permanente Northern California during 2009-2010. METHODS: We telephone surveyed pregnant Kaiser Permanente Northern California members to assess non-medically-attended reactions following H1N1, TIV or both vaccines during 2009-2010 (n=5365) in a separate study. Here we assessed preterm birth (<37weeks), very preterm birth (<32weeks), low birth weight (<2500 g, LBW), very low birth weight (<1500g), small for gestational age, spontaneous abortions, stillbirths and congenital anomalies among this cohort by comparing incidence and 95% confidence intervals between the following immunization groups: TIV only, H1N1 only, H1N1 prior to TIV immunization, TIV prior to H1N1 and both immunizations given at the same time. RESULTS: Results did not vary significantly between groups. Comparing H1N1 with TIV, incidence were similar for preterm births (6.37vs 6.28/100 births), very preterm births (5.30vs 8.29/1000 births), LBW (4.19vs 2.90/100 births), very LBW (4.54vs 5.52/1000 births), small for gestational age (9.99vs 9.24/1000 births), spontaneous abortion (7.10vs 6.83/1000 pregnancies), stillbirths (7.10vs 4.57/1000 pregnancies), and congenital anomalies (2.67vs 2.43/100 births). CONCLUSIONS: Although constrained by small sample size, complex vaccine groups, and differential vaccine availability during 2009-2010, this study found no difference in adverse birth outcomes between H1N1 vaccine and TIV.

OBJECTIVE: To investigate whether there is a difference in the risk of asthma exacerbations between children with pre-existing asthma who receive live attenuated influenza vaccine (LAIV) compared with inactivated influenza vaccine (IIV). MATERIAL AND METHODS: We identified IIV and LAIV immunizations occurring between July 1, 2007 and March 31, 2014 among Kaiser Permanente Northern California members aged 2 to <18years with a history of asthma, and subsequent asthma exacerbations seen in the inpatient or Emergency Department (ED) setting. We calculated the ratio of the odds (OR) of an exacerbation being in the risk interval (1-14days) versus the comparison interval (29-42days) following immunization, separately for LAIV and IIV, and then examined whether the OR differed between children receiving LAIV and those receiving IIV ("difference-in-differences"). RESULTS: Among 387,633 immunizations, 85% were IIV and 15% were LAIV. Children getting LAIV vs. IIV were less likely to have "current or recent, persistent" asthma (25% vs. 47%), and more likely to have "remote history" of asthma (47% vs. 25%). Among IIV-vaccinated asthmatic children, the OR of an inpatient/ED asthma exacerbation was 0.97 (95% CI: 0.82-1.15). Among LAIV-vaccinated asthmatic children the OR was 0.38 (95% CI: 0.17-0.90). In the difference-in-differences analysis, the odds of asthma exacerbation following LAIV were less than IIV (Ratio of ORs: 0.40, CI: 0.17-0.95, p value: 0.04). CONCLUSION: Among children ≥2years old with asthma, we found no increased risk of asthma exacerbation following LAIV or IIV, and a decreased risk following LAIV compared to IIV.

BACKGROUND: Live attenuated influenza vaccine (LAIV) might increase the risk of wheezing in persons with asthma or children younger than 5 years with a history of recurrent wheezing. OBJECTIVE: To describe the use and assess the safety of LAIV in persons with asthma in the Vaccine Safety Datalink population. METHODS: We identified persons with asthma using diagnosis codes and medication records in 7 health care organizations over 3 influenza seasons (2008-2009 through 2010-2011) and determined their influenza vaccination rates. Using the self-controlled risk interval method, we calculated the incidence rate ratio of medically attended respiratory events in the 14 days after LAIV compared with 29 to 42 days after vaccination in persons 2 through 49 years old. RESULTS: In our population of 6.3 million, asthma prevalence was 5.9%. Of persons with asthma, approximately 50% received any influenza vaccine but less than 1% received LAIV. The safety study included 12,354 LAIV doses (75% in children; 93% in those with intermittent or mild persistent asthma). The incidence rate ratio for inpatient and emergency department visits for lower respiratory events (including asthma exacerbation and wheezing) was 0.98 (95% confidence interval 0.63-1.51) and the incidence rate ratio for upper respiratory events was 0.94 (95% confidence interval 0.48-1.86). The risk of lower respiratory events was similar for intermittent and mild persistent asthma, across age groups, and for seasonal trivalent LAIV and 2009 H1N1 pandemic monovalent LAIV. CONCLUSION: LAIV use in asthma was mostly in persons with intermittent or mild persistent asthma. LAIV was not associated with an increased risk of medically attended respiratory adverse events.

BACKGROUND: Seven to ten days after a first dose of a measles-containing vaccine (MCV; i.e., MMR or MMRV), children have elevated fever risk which can be associated with febrile seizures. This study investigated individual and familial factors associated with fever 7-10days after MCV. METHODS: Retrospective cohort study among children who were <36months of age at receipt of MCV in six sites of the Vaccine Safety Datalink from 1/1/2000 to 12/31/2012. We evaluated medically-attended clinic or emergency department visits with a code for fever 7-10days after any MCV ("MCV- associated"). We evaluated factors associated with MCV-associated fever using chi2 and multivariable logistic regression analyses. RESULTS: Among 946,806 children vaccinated with MCV, we identified 7480 (0.8%) MCV-associated fever visits. Compared with children without fever after MCV, children with MCV-associated fever were more likely to have received MMRV than MMR (OR 1.3 95% CI 1.2, 1.5), have had medically attended fever both following previous vaccines (OR 1.3 95% CI 1.1, 1.6) and at any other previous time (OR 1.7 95% CI 1.6, 1.8), have had at least 1 prior seizure (OR 2.2 95% CI 1.7, 2.7), and have had >3 medical visits within the 6months before MCV (OR 1.7 95% CI 1.6, 1.8). In families with multiple MCV-immunized children, after adjusting for healthcare seeking behavior care for fever, those whose siblings had MCV-associated fever were more likely to also have MCV-associated fever (OR 3.5 95% CI 2.5, 4.8). DISCUSSION: Children who received MMRV vaccine or who had prior medically-attended fevers and seizures during the first year of life had increased risk of fever after a first dose of measles vaccine. After adjusting for familial propensity to seek care, MCV-associated fever still clustered within families, suggesting a possible genetic basis for susceptibility to developing fever due to measles vaccines.

BACKGROUND: Case reports have suggested that vaccines may trigger transverse myelitis (TM) or acute disseminated encephalomyelitis (ADEM), but the evidence for a causal association is inconclusive. We analyzed the association of immunization and subsequent development of TM or ADEM. METHODS: We identified all cases of TM and ADEM in the Vaccine Safety Datalink (VSD) population. Using a case centered method, we compared vaccination of each case to vaccination of all matched persons in the study population, who received the same type of vaccine, with respect to whether or not their vaccination occurred during a pre-determined exposure interval. We calculated a risk difference (excess risk) of TM and ADEM for each vaccine. RESULTS: Following nearly 64 million vaccine doses, only 7 cases of TM and 8 cases of ADEM were vaccinated during the primary exposure window 5-28 days prior to onset. For TM, there was no statistically significant increased risk of immunization. For ADEM, there was no statistically significant increased risk following any vaccine except for Tdap (adolescent and adult tetanus, reduced diphtheria, acellular pertussis) vaccine. Based on 2 exposed cases, the OR for Tdap exposure 5-28 days prior to ADEM onset was 15.8 (95% CI 1.2-471.6, p=0.04) and the estimated excess risk was 0.385 (-0.04-1.16) cases per million doses. CONCLUSIONS: We found no association between TM and prior immunization. There was a possible association of ADEM with Tdap vaccine, but the excess risk is not likely to be more than 1.16 cases of ADEM per million vaccines administered.

We evaluated the risk of optic neuritis (ON) after vaccines, using a case-centered analysis, comparing the time since vaccination for the patients with ON with that for all similar vaccinees in a large integrated health plan population. We did not detect any association between ON and receipt of any type of vaccine.

There is a high incidence of cardiovascular disease and certain cancers in firefighters that may be related to their occupational exposure to hazardous substances. Exposure may result from contaminated personal protective gear, as well as from direct exposure at fire scenes. This study characterized flame retardant contamination on firefighter personal protective clothing to assess exposure of firefighters to these chemicals. Samples from used and unused firefighter protective clothing, including gloves, hoods and a coat wristlet, were extracted with methylene chloride and analyzed by EPA method 8270D Specific Ion Method (SIM) for polybrominated diphenyl ethers (PBDEs). Until recently PBDEs were some of the most common flame retardant chemicals used in the US. Fifteen of the seventeen PBDEs for which analysis was performed were found on at least one clothing swatch. Every clothing sample, including an unused hood and all three layers of an unused glove, held a detectable concentration of at least one PBDE. These findings, along with previous research, suggest that firefighters are exposed to PBDE flame retardants at levels much higher than the general public. PBDEs are found widely dispersed in the environment and still persist in existing domestic materials such as clothing and furnishings. Firefighter exposure to flame retardants therefore merits further study.

PURPOSE: The changes in each year in influenza vaccine antigenic components as well as vaccine administration patterns may pose new risks of adverse events following immunization (AEs). To evaluate the safety of influenza vaccines annually administered to people ≥ 6 months, we conducted weekly post licensure surveillance for seven pre-specified adverse events following receipt of influenza vaccines during the 2013-2014 and 2014-2015 seasons in the Vaccine Safety Datalink (VSD). METHODS: We used both a historically-controlled cohort design with the Poisson-based maximized sequential probability ratio test (maxSPRT) and a self-controlled risk interval (SCRI) design with the binomial-based maxSPRT. For each adverse event outcome, we defined the risk interval on the basis of biologic plausibility and prior literature. For the historical cohort design, numbers of expected adverse events were calculated from the prior seven seasons, adjusted for age and site. For the SCRI design, a comparison window was defined either before vaccination or after vaccination, depending on each specific outcome. RESULTS: An elevated risk of febrile seizures 0-1 days following trivalent inactivated influenza vaccine (IIV3) was identified in children aged 6-23 months during the 2014-2015 season using the SCRI design. We found the relative risk (RR) of febrile seizures following concomitant administration of IIV3 and PCV13 was 5.3 with a 95% CI 1.87-14.75. Without concomitant PCV 13 administration, the estimated risk decreased and was no longer statistically significant (RR: 1.4; CI: 0.54 - 3.61). CONCLUSION: No increased risks, other than for febrile seizures, were identified in influenza vaccine safety surveillance during 2013-2014 and 2014-2015 seasons in the VSD.

OBJECTIVE: Case reports of sudden sensorineural hearing loss (SSHL) following vaccines have led to concerns that vaccines may rarely cause hearing loss. Because of this concern, we analyzed for an association between SSHL and vaccinations. STUDY DESIGN: We used a case-centered method, equivalent to a case control design using immunization dates from all matched members of the population to calculate exposure to vaccines, rather than sampling. SETTING: Kaiser Permanente Northern California (KPNC), 2007 to 2013. SUBJECTS AND METHODS: We searched KPNC databases from 2007 to 2013 for all first-time diagnoses of SSHL. We used the date of any hearing- or ear-related visit in the 60 days prior to the first SSHL diagnosis as the onset date. Using only SSHL cases immunized in the prior 9 months, we compared the vaccine exposure in several risk intervals prior to onset with the exposure to the same vaccine during the same time period in all KPNC membership, matched to sex and age. RESULTS: During the study period, >20 million vaccines were administered at KPNC. In all risk intervals prior to onset of SSHL, we found no evidence of increased risk of immunization compared with matched controls. The odds ratios for vaccination 1 week prior to SSHL were 0.965 (95% confidence interval, 0.61-1.50) for trivalent inactivated influenza vaccine (TIV); 0.842 (0.39-1.62) for tetanus, reduced diphtheria, and reduced acellular pertussis; and 0.454 (0.08-1.53) for zoster vaccine. CONCLUSION: A large-scale analysis applying a case-centered method did not detect any association between SSHL and previous receipt of TIV or other vaccines.

OBJECTIVE: This study evaluates the potential association of vaccination and death in the Vaccine Safety Datalink (VSD). METHODS: The study cohort included individuals ages 9 to 26 years with deaths between January 1, 2005, and December 31, 2011. We implemented a case-centered method to estimate a relative risk (RR) for death in days 0 to 30 after vaccination.Deaths due to external causes (accidents, homicides, and suicides) were excluded from the primary analysis. In a secondary analysis, we included all deaths regardless of cause. A team of physicians reviewed available medical records and coroner's reports to confirm cause of death and assess the causal relationship between death and vaccination. RESULTS: Of the 1100 deaths identified during the study period, 76 (7%) occurred 0 to 30 days after vaccination. The relative risks for deaths after any vaccination and influenza vaccination were significantly lower for deaths due to nonexternal causes (RR 0.57, 95% confidence interval [CI] 0.38-0.83, and RR 0.44, 95% CI 0.24-0.80, respectively) and deaths due to all causes (RR 0.72, 95% CI 0.56-0.91, and RR 0.44, 95% CI 0.28-0.65). No other individual vaccines were significantly associated with death. Among deaths reviewed, 1 cause of death was unknown, 25 deaths were due to nonexternal causes, and 34 deaths were due to external causes. The causality assessment found no evidence of a causal association between vaccination and death. CONCLUSIONS: Risk of death was not increased during the 30 days after vaccination, and no deaths were found to be causally associated with vaccination.

BACKGROUND: In addition to antigens, vaccines contain small amounts of preservatives, adjuvants, and residual substances from the manufacturing process. Some parents have concerns about the safety of these ingredients, yet no large epidemiological studies have specifically examined associations between health outcomes and vaccine ingredients, other than thimerosal. This study examined the extent to which the Vaccine Safety Datalink (VSD) could be used to study vaccine ingredient safety in children. METHODS: Children born 2004-2011 were identified in VSD data. Using immunization records, two cohorts were identified: children who were up-to-date and children who were undervaccinated before age 2 years. A database was also created linking vaccine type and manufacturer with ingredient amounts documented in vaccine package inserts. Thirty-four ingredients in two or more infant vaccines were identified. However, only amounts (in mg) for aluminum were consistently documented and commonly contained in infant vaccines. Analyses compared vaccine aluminum exposure across cohorts and determined the statistical power for studying associations between aluminum exposure and hypothetical vaccine adverse events. RESULTS: Among 408,608 children, mean cumulative vaccine aluminum exposure increased from 1.11 to 4.00mg between ages 92-730 days. Up-to-date children were exposed to 11-26% more aluminum from vaccines than undervaccinated children. Power analyses demonstrated that safety studies of aluminum could detect relative risks ranging from 1.1 to 5.8 for a range of adverse event incidence. CONCLUSIONS: The safety of vaccine aluminum exposure can be feasibly studied in the VSD. However, possible biological mechanisms and confounding variables would need to be considered before conducting any studies.

INTRODUCTION: Pan American Health Organization's (PAHO) ProVac Initiative aims to strengthen countries' technical capacity to make evidence-based immunization policy. With financial support from the Bill and Melinda Gates Foundation, PAHO established the ProVac International Working Group (IWG), a platform created for two years to transfer the ProVac Initiative's tools and methods to support decisions in non-PAHO regions. METHODS: In 2011, WHO Regional Offices and partner agencies established the IWG to transfer the ProVac framework for new vaccine decision support, including tools and trainings to other regions of the world. During the two year period, PAHO served as the coordinating secretariat and partner agencies played implementing or advisory roles. RESULTS: Fifty nine national professionals from 17 countries received training on the use of economic evaluations to aid vaccine policy making through regional workshops. The IWG provided direct technical support to nine countries to develop cost-effectiveness analyses to inform decisions. All nine countries introduced the new vaccine evaluated or their NITAGs have made a recommendation to the Ministry of Health to introduce the new vaccine. DISCUSSION: Developing countries around the world are increasingly interested in weighing the potential health impact due to new vaccine introduction against the investments required. During the two years, the ProVac approach proved valuable and timely to aid the national decision making processes, even despite the different challenges and idiosyncrasies encountered in each region. The results of this work suggest that: (1) there is great need and demand for technical support and for capacity building around economic evaluations; and (2) the ProVac method of supporting country-owned analyses is as effective in other regions as it has been in the PAHO region. CONCLUSION: Decision support for new vaccine introduction in low- and middle-income countries is critical to guiding the efficient use of resources and prioritizing high impact vaccination programs.

INTRODUCTION: Pneumonia is one of the most important causes of morbidity and mortality in children under 5 in Egypt, and the Ministry of Health of Egypt is considering introducing pneumococcal conjugate vaccine (PCV) in its national immunization program. We performed an economic analysis to evaluate the cost-effectiveness of this vaccine in Egypt and to provide the decision-makers with needed evidence. METHODS: The analysis was done using the TRIVAC model. Data included demographic characteristics, burden of disease, coverage and efficacy of the vaccine, health resource utilization, and costs of pneumococcal disease vaccination and treatment. Whenever possible, we used national or regional data. Two alternatives were compared: (1) general vaccination of children younger than 5 years with the 13-valent pneumococcal conjugate vaccine (PCV13), using a three-dose schedule without booster, and (2) no vaccination. Outcomes of 10 cohorts from birth to 5 years were analyzed. The study was performed from the governmental perspective and selected public health providers. RESULTS: In comparison to no vaccine, the introduction of PCV13 would be cost-effective, with an incremental cost-effectiveness ratio of US$ 3916 per disability-adjusted life-year (DALY) averted (government perspective). The total incremental cost of the PCV vaccination program (10 cohorts) would be approximately US$ 1.09 billion. Over the 10 cohorts, the program would avert 8583 pneumococcal deaths - 42% of all pneumococcal-related deaths. CONCLUSION: The introduction of PCV13 would be a good value for money from the government perspective. It would represent a high-impact public health intervention for Egypt and respond to the National Immunization Technical Advisory Group (NITAG) resolution on reducing pneumonia burden and overall child mortality. Strengthening surveillance will be critical to generating high-quality national data, improving future economic analyses that support evidence-based decisions for introducing vaccines and public health interventions, and to monitoring their impact.

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.

The Vaccine Safety Datalink (VSD) is a collaborative project between the Centers for Disease Control and Prevention (CDC) and 9 health care organizations. Established in 1990, VSD is a vital resource informing policy makers and the public about the safety of vaccines used in the United States. Large linked databases are used to identify and evaluate adverse events in over 9 million individuals annually. VSD generates rapid, important safety assessments for both routine vaccinations and emergency vaccination campaigns. VSD monitors safety of seasonal influenza vaccines in near-real time, and provided essential information on the safety of monovalent H1N1 vaccine during the 2009 pandemic. VSD investigators have published important studies demonstrating that childhood vaccines are not associated with autism or other developmental disabilities. VSD prioritizes evaluation of new vaccines; searches for possible unusual health events after vaccination; monitors vaccine safety in pregnant women; and has pioneered development of biostatistical research methods.

PURPOSE: We conducted weekly surveillance for pre-specified adverse events following receipt of the 2012-2013 influenza vaccines in the Vaccine Safety Datalink (VSD). METHODS: For each outcome, risk intervals (i.e., period after vaccination with a potentially increased risk) were defined on the basis of biologic plausibility and prior literature. Seizures following inactivated influenza vaccine (IIV) were monitored in children in three age groups (6-23 months, 24-59 months, and 5-17 years) using a self-controlled risk interval design. We also monitored for Guillain-Barre syndrome, encephalitis, and anaphylaxis following IIV in patients ≥6 months of age using a cohort design with historical controls. In the risk intervals following live attenuated influenza vaccine (LAIV), we collected weekly counts of Guillain-Barre syndrome, encephalitis, and anaphylaxis in patients ages 2-49. Among LAIV vaccinees, numbers of expected events based on rates in historical controls were calculated, adjusted for age and site. RESULTS: At the end of surveillance, approximately 3.6 million first doses of IIV and 250 000 first doses of LAIV had been administered in the VSD. No elevated risks were identified in risk intervals following 2012-2013 IIV, as compared with a self-matched control interval or to historical controls. For each outcome, fewer than three events occurred in the risk interval following 2012-2013 LAIV, and we thus were unable to estimate measures of relative risks. CONCLUSIONS: No increased risk was identified for any of the pre-specified outcomes following 2012-2013 influenza vaccinations in the VSD. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

IMPORTANCE: The first dose of live attenuated measles-containing vaccines is associated with an increased risk of febrile seizures 7 to 10 days following immunization among 12- to 23-month-old children. The combination measles, mumps, rubella, and varicella vaccine is associated with a 2-fold increased risk of febrile seizures 7 to 10 days following immunization compared with the separately administered measles, mumps, and rubella and varicella vaccines. It is unknown whether the magnitude of these increased risks depends on age at immunization. OBJECTIVE: To examine the potential modifying effect of age on the risk of fever and seizures following immunization with measles-containing vaccines. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study at 8 Vaccine Safety Datalink sites of a total of 840 348 children 12 to 23 months of age who had received a measles-containing vaccine from 2001 through 2011. EXPOSURES: Any measles-containing vaccines and measles-containing vaccines by type. MAIN OUTCOMES AND MEASURES: Fever and seizure events occurring during a 42-day postimmunization observation period. RESULTS: In the analysis of any measles-containing vaccines, the increased risk of seizures during the 7- to 10-day risk interval, using the remainder of the observation period as the control interval, was significantly greater among older children (relative risk, 6.5; 95% CI, 5.3-8.1; attributable risk, 9.5 excess cases per 10 000 doses; 95% CI, 7.6-11.5) than among younger children (relative risk, 3.4; 95% CI, 3.0-3.9; attributable risk = 4.0 excess cases per 10 000 doses; 95% CI, 3.4-4.6). The relative risk of postimmunization fever was significantly greater among older children than among younger children; however, its attributable risk was not. In the analysis of vaccine type, measles, mumps, rubella, and varicella vaccine was associated with a 1.4-fold increase in the risk of fever and 2-fold increase in the risk of seizures compared with measles, mumps, and rubella vaccine administered with or without varicella vaccine in both younger and older children. CONCLUSIONS AND RELEVANCE: Measles-containing vaccines are associated with a lower increased risk of seizures when administered at 12 to 15 months of age. Findings of this study that focused on safety outcomes highlight the importance of timely immunization of children with the first dose of measles-containing vaccines.

BACKGROUND: Non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant mutants have been shown to emerge after interruption of suppressive NNRTI-based antiretroviral therapy (ART) using routine testing. The aim of this study was to quantify the risk of resistance by sensitive testing and correlate the detection of resistance with NNRTI concentrations after treatment interruption and virologic responses after treatment resumption. METHODS: Resistance-associated mutations (RAMs) and NNRTI concentrations were studied in plasma from 132 patients who interrupted suppressive ART within SMART. RAMs were detected by Sanger sequencing, allele-specific PCR, and ultra-deep sequencing. NNRTI concentrations were measured by sensitive high-performance liquid chromatography. RESULTS: Four weeks after NNRTI interruption, 19/31 (61.3%) and 34/39 (87.2%) patients showed measurable nevirapine (>0.25 ng/ml) or efavirenz (>5 ng/ml) concentrations, respectively. Median eight weeks after interruption, 22/131 (16.8%) patients showed ≥1 NNRTI-RAM, including eight patients with NNRTI-RAMs detected only by sensitive testing. The adjusted odds ratio (OR) of NNRTI-RAM detection was 7.62 (95% confidence interval [CI] 1.52, 38.30; p = 0.01) with nevirapine or efavirenz concentrations above vs. below the median measured in the study population. Staggered interruption, whereby nucleos(t)ide reverse transcriptase inhibitors (NRTIs) were continued for median nine days after NNRTI interruption, did not prevent NNRTI-RAMs, but increased detection of NRTI-RAMs (OR 4.25; 95% CI 1.02, 17.77; p = 0.03). After restarting NNRTI-based ART (n = 90), virologic suppression rates <400 copies/ml were 8/13 (61.5%) with NNRTI-RAMs, 7/11 (63.6%) with NRTI-RAMs only, and 51/59 (86.4%) without RAMs. The ORs of re-suppression were 0.18 (95% CI 0.03, 0.89) and 0.17 (95% CI 0.03, 1.15) for patients with NNRTI-RAMs or NRTI-RAMs only respectively vs. those without RAMs (p = 0.04). CONCLUSIONS: Detection of resistant mutants in the rebound viremia after interruption of efavirenz- or nevirapine-based ART affects outcomes once these drugs are restarted. Further studies are needed to determine RAM persistence in untreated patients and impact on newer NNRTIs.

BACKGROUND: Determining the baseline mortality rate in a vaccinated population is necessary to be able to identify any unusual increases in deaths following vaccine administration. Background rates are particularly useful during mass immunization campaigns and in the evaluation of new vaccines. PURPOSE: Provide background mortality rates and describe causes of death following vaccination in the Vaccine Safety Datalink (VSD). METHODS: Analyses were conducted in 2012. Mortality rates were calculated at 0-1 day, 0-7 days, 0-30 days, and 0-60 days following vaccination for deaths occurring between January 1, 2005, and December 31, 2008. Analyses were stratified by age and gender. Causes of death were examined, and findings were compared to National Center for Health Statistics (NCHS) data. RESULTS: Among 13,033,274 vaccinated people, 15,455 deaths occurred between 0 and 60 days following vaccination. The mortality rate within 60 days of a vaccination visit was 442.5 deaths per 100,000 person-years. Rates were highest in the group aged ≥85 years, and increased from the 0-1-day to the 0-60-day interval following vaccination. Eleven of the 15 leading causes of death in the VSD and NCHS overlap in both systems, and the top four causes of death were the same in both systems. CONCLUSIONS: VSD mortality rates demonstrate a healthy vaccinee effect, with rates lowest in the days immediately following vaccination, most apparent in the older age groups. The VSD mortality rate is lower than that in the general U.S. population, and the causes of death are similar.