Assessing the impact of the routine childhood hepatitis B immunization program and the need for hepatitis B vaccine birth dose in Sierra Leone, 2018.

Sierra Leone is highly endemic for hepatitis B virus (HBV) infection and thus recommends three doses of hepatitis B vaccine (HepB3) from 6 weeks of age but does not recommend a birth dose (HepB-BD) to prevent mother-to-child transmission (MTCT). We evaluated impact of the existing HepB3 schedule and risk for MTCT of HBV. We conducted a community-based serosurvey among 4-30-month-olds, their mothers, and 5-9-year-olds in three districts in Sierra Leone. Participants had an HBV surface antigen (HBsAg) rapid test; all HBsAg-positive and one HBsAg-negative mother per cluster were tested for HBV markers. We collected children's HepB3 vaccination history. Among 1889 children aged 4-30 months, HepB3 coverage was 85% and 20 (1·3% [95% CI 0·8-2·0]) were HBsAg-positive, of whom 70% had received HepB3. Among 2025 children aged 5-9 years, HepB3 coverage was 77% and 32 (1·6% [1·1-2·3]) were HBsAg-positive, of whom 56% had received HepB3. Of 1776 mothers, 169 (9·8% [8·1-11·7]) were HBsAg-positive. HBsAg prevalence was 5·9% among children of HBsAg-positive mothers compared to 0·7% among children of HBsAg-negative mothers (adjusted OR = 10·6 [2·8-40·8]). HBsAg positivity in children was associated with maternal HBsAg (p = 0·026), HBV e antigen (p < 0·001), and HBV DNA levels ≥ 200 000 IU/mL (p < 0·001). HBsAg prevalence was lower among children than mothers, for whom HepB was not available, suggesting routine infant HepB vaccination has lowered HBV burden. Since HBsAg positivity in children was strongly associated with maternal HBV infection and most of the HBsAg-positive children in the survey received HepB3, HepB-BD may prevent MTCT and chronic HBV infection.

Diphtheria and tetanus seroepidemiology among children in Ukraine, 2017.

BACKGROUND: The drastic decline of Ukraine's immunization coverage since 2009 led to concerns about potential resurgence diphtheria and tetanus, along with other vaccine-preventable diseases. METHODS: To assess population immunity against diphtheria and tetanus, we tested specimens from the serosurvey conducted in 2017 among children born in 2006-2015, the birth cohorts targeted by the nationwide outbreak response immunization following a circulating vaccine-derived poliovirus type 1 outbreak in Zakarpattya province in 2015. We surveyed four regions of Ukraine, using cluster sampling in Zakarpattya, Sumy, and Odessa provinces and simple random sampling in Kyiv City. We tested serum specimens for IgG antibodies against diphtheria and tetanus, using microbead assays (MBA). We estimated seroprevalence and calculated 95% confidence intervals. We also obtained information on the immunization status of surveyed children. RESULTS: Seroprevalence of ≥0.1 IU/mL diphtheria antibodies was <80% in all survey sites (50.0%-79.2%). Seroprevalence of ≥0.1 IU/mL tetanus antibodies was ≥80% in Sumy, Kyiv City, and Odessa (80.2%-89.1%) and 61.6% in Zakarpattya. Across the sites, the proportion of children vaccinated age-appropriately with diphtheria-tetanus-containing vaccines (DTCV) was 28.5%-57.4% among children born in 2006-2010 and 34.1%-54.3% among children born in 2011-2015. The proportion of recipients of <3 DTCV doses increased from 7.1%-16.7% among children born in 2006-2010 to 19.8%-38.6% among children born in 2011-2015, as did the proportion of recipients of zero DTCV doses (2.6%-8.8% versus 8.0%-14.0%, respectively). CONCLUSIONS: Protection against diphtheria among children born in 2006-2015 was suboptimal (<80%), particularly in Zakarpattya. Protection against tetanus was adequate (≥80%) except in Zakarpattya. Diphtheria-tetanus immunization status was suboptimal across all sites. Catch-up vaccination of unvaccinated/under-vaccinated children and other efforts to increase immunization coverage would close these immunity gaps and prevent the resurgence of diphtheria and tetanus in Ukraine, particularly in Zakarpattya.

Risk factors for measles deaths among children during a Nationwide measles outbreak - Romania, 2016-2018.

BACKGROUND: Case fatality ratio (CFR) among all age groups during the 2016-2018 measles outbreak in Romania was increased compared with previous outbreaks. To identify risk factors for measles death, we conducted a case-control study among infants and children hospitalized for measles. METHODS: National surveillance data were used to identify hospitalized cases of laboratory-confirmed or epidemiologically linked measles in infants and children aged < 59 months with rash onset from January 2016 to July 2018. We abstracted medical records of 50 fatal cases ("cases") and 250 non-fatal cases ("controls") matched by age, sex, district of residence, and urban/rural place of residence. We calculated univariable and multivariable matched odds ratios (OR) and 95% confidence intervals (CIs) for risk factors. RESULTS: Ninety-three percent of case-patients and controls had not received a valid dose of a measles-containing vaccine; only 5 % received Vitamin A supplementation once diagnosed with measles. In the univariable analysis, cases were more likely than controls to have had a healthcare-related exposure to measles manifesting as inpatient admission for pneumonia during the 7 to 21 day measles incubation period (OR: 3.0; 95% CI [1.2, 7.2]), to have had a history of malnutrition (OR: 3.4; 95% CI [1.1, 9.9]), and to have had pneumonia as a complication of measles (OR:7.1; 95% CI [2.0-24.8]). In the multivariable analysis, pneumonia as a measles complication remained a risk for death (OR: 7.1; 95% CI [1.4-35.3]). CONCLUSIONS: Implementing infection prevention and control practices, ensuring immunization of healthcare workers, and hospitalizing only severe measles cases may minimize the risk of nosocomial measles transmission. Implementing World Health Organization (WHO) recommendations for Vitamin A supplementation, improving immunization of children to prevent influenza, pneumococcal, and other bacterial respiratory diseases may decrease complications and deaths due to measles in Romania.

Cost of Tuberculosis Therapy Directly Observed on Video for Health Departments and Patients in New York City; San Francisco, California; and Rhode Island (2017-2018).

Objectives. To assess costs of video and traditional in-person directly observed therapy (DOT) for tuberculosis (TB) treatment to health departments and patients in New York City, Rhode Island, and San Francisco, California.Methods. We collected health department costs for video DOT (VDOT; live and recorded), and in-person DOT (field- and clinic-based). Time-motion surveys estimated provider time and cost. A separate survey collected patient costs. We used a regression model to estimate cost by DOT type.Results. Between August 2017 and June 2018, 343 DOT sessions were captured from 225 patients; 87 completed a survey. Patient costs were lowest for VDOT live ($1.01) and highest for clinic DOT ($34.53). The societal (health department + patient) costs of VDOT live and recorded ($6.65 and $12.64, respectively) were less than field and clinic DOT ($21.40 and $46.11, respectively). VDOT recorded health department cost was not statistically different from field DOT cost in Rhode Island.Conclusions. Among the 4 different modalities, both types of VDOT were associated with lower societal costs when compared with traditional forms of DOT.Public Health Implications. VDOT was associated with lower costs from the societal perspective and may reduce public health costs when TB incidence is high.

A Bayesian approach to sequential analysis in post-licensure vaccine safety surveillance.

With rapid development of computing technology, Bayesian statistics have increasingly gained more attention in various areas of public health. However, the full potential of Bayesian sequential methods applied to vaccine safety surveillance has not yet been realized, despite acknowledged practical benefits and philosophical advantages of Bayesian statistics. In this paper, we describe how sequential analysis can be performed in a Bayesian paradigm in the field of vaccine safety. We compared the performance of the frequentist sequential method, specifically, Maximized Sequential Probability Ratio Test (MaxSPRT), and a Bayesian sequential method using simulations and a real world vaccine safety example. The performance is evaluated using three metrics: false positive rate, false negative rate, and average earliest time to signal. Depending on the background rate of adverse events, the Bayesian sequential method could significantly improve the false negative rate and decrease the earliest time to signal. We consider the proposed Bayesian sequential approach to be a promising alternative for vaccine safety surveillance.

Safety of bivalent human papillomavirus vaccine in the US vaccine adverse event reporting system (VAERS), 2009-2017.

AIMS: Human papillomavirus (HPV) vaccines prevent infection with oncogenic virus types. We analysed reports to the US Vaccine Adverse Event Reporting System (VAERS) of adverse events (AE) following bivalent HPV vaccine (2vHPV). METHODS: We conducted descriptive analysis of 2vHPV reports, reviewed individual reports, calculated crude AE reporting rates and conducted empirical Bayesian data mining. RESULTS: Of 241 2vHPV reports, 158 were in females, 64 in males (2vHPV is approved for females only) and 19 with unknown sex; 95.8% were classified as nonserious. Dizziness, headache, nausea and injection site reactions were the most common symptoms. Crude AE reporting rates were 33.3 reports per 100 000 doses distributed overall, and 1.4 per 100 000 for serious reports. Empirical Bayesian data mining identified disproportional reporting for three types of medical errors; assessment indicated findings that were probably driven by inadvertent 2vHPV use in males. CONCLUSIONS: We did not identify any new or unexpected safety concerns in our review of 2vHPV reports to VAERS.

Post-licensure safety monitoring of quadrivalent human papillomavirus vaccine in the Vaccine Adverse Event Reporting System (VAERS), 2009-2015.

BACKGROUND: The Food and Drug Administration (FDA) approved quadrivalent human papillomavirus vaccine (4vHPV) for use in females and males aged 9-26 years, since 2006 and 2009 respectively. We characterized reports to the Vaccine Adverse Event Reporting System (VAERS), a US spontaneous reporting system, in females and males who received 4vHPV vaccination. METHODS: We searched VAERS for US reports of adverse events (AEs) following 4vHPV from January 2009 through December 2015. Signs and symptoms were coded using Medical Dictionary for Regulatory Activities (MedDRA). We calculated reporting rates and conducted empirical Bayesian data mining to identify disproportional reports. Clinicians reviewed available information, including medical records, and reports of selected pre-specified conditions. FINDINGS: VAERS received 19,760 reports following 4vHPV; 60.2% in females, 17.2% in males, and in 22.6% sex was missing. Overall, 94.2% of reports were non-serious; dizziness, syncope and injection site reactions were commonly reported in both males and females. Headache, fatigue and nausea were commonly reported serious AEs. More than 60 million 4vHPV doses were distributed during the study period. Crude AE reporting rates were 327 reports per million 4vHPV doses distributed for all reports, and 19 per million for serious reports. Among 29 verified reports of death, there was no pattern of clustering of deaths by diagnosis, co-morbidities, age, or interval from vaccination to death. INTERPRETATION: No new or unexpected safety concerns or reporting patterns of 4vHPV with clinically important AEs were detected. Safety profile of 4vHPV is consistent with data from pre-licensure trials and postmarketing safety data.

Safety of currently licensed hepatitis B surface antigen vaccines in the United States, Vaccine Adverse Event Reporting System (VAERS), 2005-2015.

INTRODUCTION: Currently four recombinant hepatitis B (HepB) vaccines are in use in the United States. HepB vaccines are recommended for infants, children and adults. We assessed adverse events (AEs) following HepB vaccines reported to the Vaccine Adverse Event Reporting System (VAERS), a national spontaneous reporting system. METHODS: We searched VAERS for reports of AEs following single antigen HepB vaccine and HepB-containing vaccines (either given alone or with other vaccines), from January 2005 - December 2015. We conducted descriptive analyses and performed empirical Bayesian data mining to assess disproportionate reporting. We reviewed serious reports including reports of special interest. RESULTS: VAERS received 20,231 reports following HepB or HepB-containing vaccines: 10,291 (51%) in persons <2 years of age; 2588 (13%) in persons 2-18 years and 5867 (29%) in persons >18 years; for 1485 (7.3%) age was missing. Dizziness and nausea (8.4% each) were the most frequently reported AEs following a single antigen HepB vaccine: fever (23%) and injection site erythema (11%) were most frequent following Hep-containing vaccines. Of the 4444 (22%) reports after single antigen HepB vaccine, 303 (6.8%) were serious, including 45 deaths. Most commonly reported cause of death was Sudden Infant Death Syndrome (197). Most common non-death serious reports following single antigen HepB vaccines among infants aged <1 month, were nervous system disorders (15) among children aged 1-23 months; infections and infestation (8) among persons age 2-18 years blood and lymphatic systemic disorders; and general disorders and administration site conditions among persons age >18 years. Most common vaccination error following single antigen HepB was incorrect product storage. CONCLUSIONS: Review current U.S.-licensed HepB vaccines administered alone or in combination with other vaccines did not reveal new or unexpected safety concerns. Vaccination errors were identified which indicate the need for training and education of providers on HepB vaccine indications and recommendations.

High Rate of Treatment Completion in Program Settings With 12-Dose Weekly Isoniazid and Rifapentine for Latent Mycobacterium tuberculosis Infection.

Background: Randomized controlled trials have demonstrated that the newest latent tuberculosis (LTBI) regimen, 12 weekly doses of directly observed isoniazid and rifapentine (3HP), is as efficacious as 9 months of isoniazid, with a greater completion rate (82% vs 69%); however, 3HP has not been assessed in routine healthcare settings. Methods: Observational cohort of LTBI patients receiving 3HP through 16 US programs was used to assess treatment completion, adverse drug reactions, and factors associated with treatment discontinuation. Results: Of 3288 patients eligible to complete 3HP, 2867 (87.2%) completed treatment. Children aged 2-17 years had the highest completion rate (94.5% [155/164]). Patients reporting homelessness had a completion rate of 81.2% (147/181). In univariable analyses, discontinuation was lowest among children (relative risk [RR], 0.44 [95% confidence interval {CI}, .23-.85]; P = .014), and highest in persons aged ≥65 years (RR, 1.72 [95% CI, 1.25-2.35]; P < .001). In multivariable analyses, discontinuation was lowest among contacts of patients with tuberculosis (TB) disease (adjusted RR [ARR], 0.68 [95% CI, .52-.89]; P = .005) and students (ARR, 0.45 [95% CI, .21-.98]; P = .044), and highest with incarceration (ARR, 1.43 [95% CI, 1.08-1.89]; P = .013) and homelessness (ARR, 1.72 [95% CI, 1.25-2.39]; P = .001). Adverse drug reactions were reported by 1174 (35.7%) patients, of whom 891 (76.0%) completed treatment. Conclusions: Completion of 3HP in routine healthcare settings was greater overall than rates reported from clinical trials, and greater than historically observed using other regimens among reportedly nonadherent populations. Widespread use of 3HP for LTBI treatment could accelerate elimination of TB disease in the United States.

Post licensure surveillance of influenza vaccines in the Vaccine Safety Datalink in the 2013-2014 and 2014-2015 seasons.

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. Copyright © 2016 John Wiley & Sons, Ltd.

Evaluating efficiency and statistical power of self-controlled case series and self-controlled risk interval designs in vaccine safety.

The self-controlled case series (SCCS) and self-controlled risk interval (SCRI) designs have recently become widely used in the field of post-licensure vaccine safety monitoring to detect potential elevated risks of adverse events following vaccinations. The SCRI design can be viewed as a subset of the SCCS method in that a reduced comparison time window is used for the analysis. Compared to the SCCS method, the SCRI design has less statistical power due to fewer events occurring in the shorter control interval. In this study, we derived the asymptotic relative efficiency (ARE) between these two methods to quantify this loss in power in the SCRI design. The equation is formulated as [Formula: see text] (a: control window-length ratio between SCRI and SCCS designs; b: ratio of risk window length and control window length in the SCCS design; and [Formula: see text]: relative risk of exposed window to control window). According to this equation, the relative efficiency declines as the ratio of control-period length between SCRI and SCCS methods decreases, or with an increase in the relative risk [Formula: see text]. We provide an example utilizing data from the Vaccine Safety Datalink (VSD) to study the potential elevated risk of febrile seizure following seasonal influenza vaccine in the 2010-2011 season.

Post-licensure surveillance of quadrivalent live attenuated influenza vaccine United States, Vaccine Adverse Event Reporting System (VAERS), July 2013-June 2014.

BACKGROUND: Quadrivalent live attenuated influenza vaccine (LAIV4) was approved in 2012 for healthy persons aged 2-49 years. Beginning with the 2013-2014 influenza season, LAIV4 replaced trivalent live attenuated influenza vaccine (LAIV3). METHODS: We analyzed LAIV4 reports to VAERS, a national spontaneous reporting system. LAIV4 reports in 2013-2014 were compared to LAIV3 reports from the previous three influenza seasons. Medical records were reviewed for non-manufacturer serious reports (i.e., death, hospitalization, prolonged hospitalization, life-threatening illness, permanent disability) and reports of selected conditions of interest. We conducted Empirical Bayesian data mining to identify disproportional reporting for LAIV4. RESULTS: In 2013-2014, 12.7 million doses of LAIV4 were distributed and VAERS received 779 reports in individuals aged 2-49 years; 95% were non-serious. Expired drug administered (42%), fever (13%) and cough (8%) were most commonly reported in children aged 2-17 years when LAIV4 was administered alone, while headache (18%), expired drug administered (15%) and exposure during pregnancy (12%) were most common in adults aged 18-49 years. We identified one death report in a child who died from complications of cerebellar vascular tumors. Among non-death serious reports, neurologic conditions were common in children and adults. In children, seizures (3) and Guillain-Barré syndrome (2) were the most common serious neurologic outcomes. We identified three serious reports of asthma/wheezing following LAIV4 in children. Data mining detected disproportional reporting for vaccine administration errors and for influenza illness in children. CONCLUSIONS: Our analysis of VAERS reports for LAIV4 did not identify any concerning patterns. The data mining finding for reports of influenza illness is consistent with low LAIV4 vaccine effectiveness observed for influenza A disease in children in 2013-2014. Reports of LAIV4 administration to persons in whom the vaccine is not recommended (e.g., pregnant women) indicate the need for education, training and screening regarding indications.

Adverse events following Haemophilus influenzae type b vaccines in the Vaccine Adverse Event Reporting System, 1990-2013.

OBJECTIVE: To characterize adverse events (AEs) after Haemophilus influenzae type b (Hib) vaccines reported to the US Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting surveillance system. STUDY DESIGN: We searched VAERS for US reports after Hib vaccines among reports received from January 1, 1990, to December 1, 2013. We reviewed a random sample of reports and accompanying medical records for reports classified as serious. All reports of death were reviewed. Physicians assigned a primary clinical category to each reviewed report. We used empirical Bayesian data mining to identify AEs that were disproportionally reported after Hib vaccines. RESULTS: VAERS received 29,747 reports after Hib vaccines; 5179 (17%) were serious, including 896 reports of deaths. Median age was 6 months (range 0-1022 months). Sudden infant death syndrome was the stated cause of death in 384 (51%) of 749 death reports with autopsy/death certificate records. The most common nondeath serious AE categories were neurologic (80; 37%), other noninfectious (46; 22%) (comprising mainly constitutional signs and symptoms); and gastrointestinal (39; 18%) conditions. No new safety concerns were identified after clinical review of reports of AEs that exceeded the data mining statistical threshold. CONCLUSION: Review of VAERS reports did not identify any new or unexpected safety concerns for Hib vaccines.

Continuous sequential boundaries for vaccine safety surveillance.

Various recently developed sequential methods have been used to detect signals for post-marketing surveillance in drug and vaccine safety. Among these, the maximized sequential probability ratio test (MaxSPRT) has been used to detect elevated risks of adverse events following vaccination using large healthcare databases. However, a limitation of MaxSPRT is that it only provides a time-invariant flat boundary. In this study, we propose the use of time-varying boundaries for controlling how type I error is distributed throughout the surveillance period. This is especially useful in two scenarios: (i) when we desire generally larger sample sizes before a signal is generated, for example, when early adopters are not representative of the larger population; and (ii) when it is desired for a signal to be generated as early as possible, for example, when the adverse event is considered rare but serious. We consider four specific time-varying boundaries (which we call critical value functions), and we study their statistical power and average time to signal detection. The methodology we present here can be viewed as a generalization or flexible extension of MaxSPRT.

Cumulative risk of Guillain-Barré syndrome among vaccinated and unvaccinated populations during the 2009 H1N1 influenza pandemic.

OBJECTIVES: We sought to assess risk of Guillain-Barré syndrome (GBS) among influenza A (H1N1) 2009 monovalent (pH1N1) vaccinated and unvaccinated populations at the end of the 2009 pandemic. METHODS: We applied GBS surveillance data from a US population catchment area of 45 million from October 15, 2009, through May 31, 2010. GBS cases meeting Brighton Collaboration criteria were included. We calculated the incidence density ratio (IDR) among pH1N1 vaccinated and unvaccinated populations. We also estimated cumulative GBS risk using life table analysis. Additionally, we used vaccine coverage data and census population estimates to calculate denominators. RESULTS: There were 392 GBS cases; 64 (16%) occurred after pH1N1vaccination. The vaccinated population had lower average risk (IDR = 0.83, 95% confidence interval = 0.63, 1.08) and lower cumulative risk (6.6 vs 9.2 cases per million persons, P = .012) of GBS. CONCLUSIONS: Our findings suggest that at the end of the influenza season cumulative GBS risk was less among the pH1N1vaccinated than the unvaccinated population, suggesting the benefit of vaccination as it relates to GBS. The observed potential protective effect on GBS attributed to vaccination warrants further study.

Assessing agreement of repeated binary measurements with an application to the CDC's anthrax vaccine clinical trial.

Cohen's kappa coefficient, which was introduced in 1960, serves as the most widely employed coefficient to assess inter-observer agreement for categorical outcomes. However, the original kappa can only be applied to cross-sectional binary measurements and, therefore, cannot be applied in the practical situation when the observers evaluate the same subjects at repeated time intervals. This study summarizes six methods of assessing agreement of repeated binary outcomes under different assumptions and discusses under which condition we should use the most appropriate method in practice. These approaches are illustrated using data from the CDC anthrax vaccine adsorbed (AVA) human clinical trial comparing the agreement for two solicited adverse events after AVA between the 1-3 day in-clinic medical record and the patient's diary on the same day. We hope this article can inspire researchers to choose the most appropriate method to assess agreement for their own study with longitudinal binary data.

Health-related quality of life in the CDC Anthrax Vaccine Adsorbed Human Clinical Trial.

BACKGROUND: After the Department of Defense implemented a mandatory anthrax vaccination program in 1998 concerns were raised about potential long-term safety effects of the current anthrax vaccine. The CDC multicenter, randomized, double-blind, placebo-controlled Anthrax Vaccine Adsorbed (AVA) Human Clinical Trial to evaluate route change and dose reduction collected data on participants' quality of life. Our objective is to assess the association between receipt of AVA and changes in health-related quality of life, as measured by the SF-36 health survey (Medical Outcomes Trust, Boston, MA), over 42 months after vaccination. METHODS: 1562 trial participants completed SF-36v2 health surveys at 0, 12, 18, 30 and 42 months. Physical and mental summary scores were obtained from the survey results. We used Generalized Estimating Equations (GEE) analyses to assess the association between physical and mental score difference from baseline and seven study groups receiving either AVA at each dose, saline placebo at each dose, or a reduced AVA schedule substituting saline placebo for some doses. RESULTS: Overall, mean physical and mental scores tended to decrease after baseline. However, we found no evidence that the score difference from baseline changed significantly differently between the seven study groups. CONCLUSIONS: These results do not favor an association between receipt of AVA and an altered health-related quality of life over a 42-month period.

A cluster of nonspecific adverse events in a military reserve unit following pandemic influenza A (H1N1) 2009 vaccination-possible stimulated reporting?

BACKGROUND: On February 20, 2010, a 23 year old male Army Reservist (index case) with symptom onset 4 h after receiving inactivated monovalent pandemic 2009 (H1N1) vaccine (MIV) was hospitalized with possible Guillain-Barré syndrome (GBS). Within 1-2 days, 13 reservists from the same unit presented to the emergency department and 14 filed Vaccine Adverse Event Reporting System (VAERS) reports of nonspecific symptoms following MIV. OBJECTIVES: To describe the spectrum of adverse events (AE) among reservists in the unit after MIV and to identify factors contributing to this cluster of reports. METHODS: We reviewed the reservists' VAERS reports and hospital records for demographics, influenza vaccination status, diagnostic results and outcome. All VAERS reports after vaccination from the same MIV lot were also screened. We conducted a survey of unit reservists to identify contributing factors for this cluster. RESULTS: The presumptive diagnosis of GBS in the index case was not confirmed. All other reservists demonstrated normal exam findings and laboratory investigations. VAERS reports following vaccination from the same MIV lot revealed no consistent pattern. Our survey of factors contributing to the cluster was returned by 55 reservists (response rate 28%). AEs following MIV were significantly more often reported by female and black reservists. There was a tendency for concern about the safety of the 2010-2011 seasonal influenza vaccine to be higher for reservists that reported an AE to MIV (p=0.13) or that sought medical attention for their symptoms (p=0.08). CONCLUSIONS: This cluster represents possible stimulated reporting following receipt of inactivated pandemic 2009 (H1N1) vaccine among service personnel.

Health-related quality of life in the Anthrax Vaccination Program for workers in the Laboratory Response Network.

BACKGROUND: In 2002 CDC initiated the Anthrax Vaccination Program (AVP) to provide voluntary pre-exposure vaccination with Anthrax Vaccine Adsorbed (AVA) for persons at high risk of exposure to Bacillus anthracis spores. There has been concern that AVA could be associated with long term impairment of physical and/or mental health. OBJECTIVES: To ascertain whether physical and mental functional status, as measured by the SF-36v2 health survey (Medical Outcomes Trust, Boston, MA), of AVA recipients and controls changed differently over time. METHODS: We enrolled 437 exposed (received AVA) and 139 control subjects. The exposed group received AVA under then-current Advisory Committee on Immunization Practices (ACIP) recommendations. SF-36v2 surveys were completed at 0, 12, and 30 months. SF-36v2 physical and mental scores both range from 0 to 100 with an estimated national average of 50 points. RESULTS: For physical scores, the average change from baseline was -0.53 for exposed vs. -0.67 for controls at 12 months (p=0.80) and -1.09 for exposed vs. -1.97 for controls at 30 months (p=0.23). For mental scores, the average change from baseline was -1.50 for exposed vs. -1.64 for controls at 12 months (p=0.86) and -2.11 for exposed vs. -0.24 for controls at 30 months (p=0.06). In multivariable analysis, the difference in mental score change between exposed vs. controls at 30 months was less pronounced (p=0.37) but other findings were similar to univariate analyses. CONCLUSIONS: These results do not favor an association between receipt of AVA and an altered health related quality of life over a 30-month period.