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Evidence indicates that mRNA COVID-19 vaccination is associated with risk of myocarditis and possibly pericarditis, especially in young males. It is not clear if risk differs between mRNA-1273 versus BNT162b2. We assessed if risk differs using comprehensive health records on a diverse population.Members 18-39 years of age at eight integrated healthcare-delivery systems were monitored using data updated weekly and supplemented with medical record review of myocarditis and pericarditis cases. Incidence of myocarditis and pericarditis events that occurred among vaccine recipients 0 to 7 days after either dose 1 or 2 of a messenger RNA (mRNA) vaccine was compared with that of vaccinated concurrent comparators who, on the same calendar day, had received their most recent dose 22 to 42 days earlier. Rate ratios (RRs) were estimated by conditional Poisson regression, adjusted for age, sex, race and ethnicity, health plan, and calendar day. Head-to-head comparison directly assessed risk following mRNA-1273 versus BNT162b2 during 0-7 days post-vaccination.From December 14, 2020 - January 15, 2022 there were 41 cases after 2,891,498 doses of BNT162b2 and 38 cases after 1,803,267 doses of mRNA-1273. Cases had similar demographic and clinical characteristics. Most were hospitalized for ≤1 day; none required intensive care. During days 0-7 after dose 2 of BNT162b2, the incidence was 14.3 (CI: 6.5-34.9) times higher than the comparison interval, amounting to 22.4 excess cases per million doses; after mRNA-1273 the incidence was 18.8 (CI: 6.7-64.9) times higher than the comparison interval, amounting to 31.2 excess cases per million doses. In head-to-head comparisons 0-7 days after either dose, risk was moderately higher after mRNA-1273 than after BNT162b2 (RR: 1.61, CI 1.02-2.54).Both vaccines were associated with increased risk of myocarditis and pericarditis in 18-39-year-olds. Risk estimates were modestly higher after mRNA-1273 than after BNT162b2.

COVID-19 vaccination is critical to ending the COVID-19 pandemic. Members of minority racial and ethnic groups have experienced disproportionate COVID-19-associated morbidity and mortality (1); however, COVID-19 vaccination coverage is lower in these groups (2). CDC used data from CDC's Vaccine Safety Datalink (VSD)* to assess disparities in vaccination coverage among persons aged ≥16 years by race and ethnicity during December 14, 2020-May 15, 2021. Measures of coverage included receipt of ≥1 COVID-19 vaccine dose (i.e., receipt of the first dose of the Pfizer-BioNTech or Moderna COVID-19 vaccines or 1 dose of the Janssen COVID-19 vaccine [Johnson & Johnson]) and full vaccination (receipt of 2 doses of the Pfizer-BioNTech or Moderna COVID-19 vaccines or 1 dose of Janssen COVID-19 vaccine). Among 9.6 million persons aged ≥16 years enrolled in VSD during December 14, 2020-May 15, 2021, ≥1-dose coverage was 48.3%, and 38.3% were fully vaccinated. As of May 15, 2021, coverage with ≥1 dose was lower among non-Hispanic Black (Black) and Hispanic persons (40.7% and 41.1%, respectively) than it was among non-Hispanic White (White) persons (54.6%). Coverage was highest among non-Hispanic Asian (Asian) persons (57.4%). Coverage with ≥1 dose was higher among persons with certain medical conditions that place them at higher risk for severe COVID-19 (high-risk conditions) (63.8%) than it was among persons without such conditions (41.5%) and was higher among persons who had not had COVID-19 (48.8%) than it was among those who had (42.4%). Persons aged 18-24 years had the lowest ≥1-dose coverage (28.7%) among all age groups. Continued monitoring of vaccination coverage and efforts to improve equity in coverage are critical, especially among populations disproportionately affected by COVID-19.

The COVID-19 pandemic has affected routine vaccine delivery in the US and globally. The magnitude of these disruptions and their association with childhood vaccination coverage are unclear.To compare trends in pediatric vaccination before and during the pandemic and to evaluate the proportion of children up to date (UTD) with vaccinations by age, race, and ethnicity.This surveillance study used a prepandemic-postpandemic control design with data from 8 health systems in California, Oregon, Washington, Colorado, Minnesota, and Wisconsin in the Vaccine Safety Datalink. Children from age groups younger than 24 months and 4 to 6, 11 to 13, and 16 to 18 years were included if they had at least 1 week of health system enrollment from January 5, 2020, through October 3, 2020, over periods before the US COVID-19 pandemic (January 5, 2020, through March 14, 2020), during age-limited preventive care (March 15, 2020, through May 16, 2020), and during expanded primary care (May 17, 2020, through October 3, 2020). These individuals were compared with those enrolled during analogous weeks in 2019.This study evaluated UTD status among children reaching specific ages in February, May, and September 2020, compared with those reaching these ages in 2019.Weekly vaccination rates for routine age-specific vaccines and the proportion of children UTD for all age-specific recommended vaccines.Of 1 399 708 children in 2019 and 1 402 227 in 2020, 1 371 718 were female (49.0%) and 1 429 979 were male (51.0%); 334 216 Asian individuals (11.9%), 900 226 were Hispanic individuals (32.1%), and 201 619 non-Hispanic Black individuals (7.2%). Compared with the prepandemic period and 2019, the age-limited preventive care period was associated with lower weekly vaccination rates, with ratios of rate ratios of 0.82 (95% CI, 0.80-0.85) among those younger than 24 months, 0.18 (95% CI, 0.16-0.20) among those aged 4 to 6 years, 0.16 (95% CI, 0.14-0.17) among those aged 11 to 13 years, and 0.10 (95% CI, 0.08-0.13) among those aged 16 to 18 years. Vaccination rates during expanded primary care remained lower for most ages (ratios of rate ratios:24 months, 0.96 [95% CI, 0.93-0.98]; 11-13 years, 0.81 [95% CI, 0.76-0.86]; 16-18 years, 0.57 [95% CI, 0.51-0.63]). In September 2020, 74% (95% CI, 73%-76%) of infants aged 7 months and 57% (95% CI, 56%-58%) of infants aged 18 months were UTD vs 81% (95% CI, 80%-82%) and 61% (95% CI, 60%-62%), respectively, in September 2019. The proportion UTD was lowest in non-Hispanic Black children across most age groups, both during and prior to the COVID-19 pandemic (eg, in May 2019, 70% [95% CI, 64%-75%] of non-Hispanic Black infants aged 7 months were UTD vs 82% [95% CI, 81%-83%] in all infants aged 7 months combined).As of September 2020, childhood vaccination rates and the proportion who were UTD remained lower than 2019 levels. Interventions are needed to promote catch-up vaccination, particularly in populations at risk for underimmunization.

Background Between May 2005 and March 2007, three vaccines were recommended by the Advisory Committee on Immunization Practices for routine use in adolescents in the United States: quadrivalent meningococcal conjugate vaccine (MenACWY), tetanus, diphtheria and acellular pertussis vaccine (Tdap), and human papillomavirus vaccine (HPV). Understanding historical adolescent vaccination patterns may inform future vaccination coverage efforts for these and emerging adolescent vaccines, including COVID-19 vaccines. Methods This was a descriptive, retrospective cohort study. All vaccines administered to adolescents aged 11 through 18 years in the Vaccine Safety Datalink population between January 1, 2007 and December 31, 2016 were examined. Vaccination coverage was assessed by study year for ≥1 dose Tdap or Td, ≥1 dose Tdap, ≥1 dose MenACWY, ≥1 dose HPV, and ≥3 dose HPV. The proportion of vaccine visits with concurrent vaccination (≥2 vaccines administered at the same visit) was calculated by sex and study year. The most common vaccine combinations administered in the study population were described by sex for two time periods: 2007–2010 and 2011–2016. Results The number of 11–18-year-olds in the study population averaged 522,565 males and 503,112 females per study year. Between January 2007 and December 2016 there were 4,884,553 vaccine visits in this population (45% among males). The overall proportion of concurrent vaccine visits among males was 43% (33–61% by study year). Among females, 39% of all vaccine visits included concurrent vaccination (32–48% by study year). Vaccine coverage for Tdap, MenACWY, and 1- and 3-dose HPV increased across the study period. A wide variety of vaccine combinations were administered among both sexes and in both time periods. Conclusions The high vaccine uptake and multitude of vaccine combinations administered concurrently in the adolescent population of the Vaccine Safety Datalink provide historical patterns with which to compare future adolescent vaccination campaigns.

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.Retrospective cohort study among children who were36months 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 χAmong 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 had3 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).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 AND OBJECTIVES: Human papillomavirus is the most common sexually transmitted infection in the United States and causes certain anogenital and oropharyngeal cancers. The 9-valent human papillomavirus vaccine (9vHPV) provides protection against additional types not included in the quadrivalent vaccine. We conducted near real-time vaccine safety surveillance for 24 months after the vaccine became available in the Vaccine Safety Datalink. METHODS: Immunizations and adverse events were extracted weekly from October 2015 to October 2017 from standardized data files for persons 9 to 26 years old at 6 Vaccine Safety Datalink sites. Prespecified adverse events included anaphylaxis, allergic reaction, appendicitis, Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, injection site reaction, pancreatitis, seizure, stroke, syncope, and venous thromboembolism. The observed and expected numbers of events after 9vHPV were compared weekly by using sequential methods. Both historical and concurrent comparison groups were used to identify statistical signals for adverse events. Unexpected signals were investigated by medical record review and/or additional analyses. RESULTS: During 105 weeks of surveillance, 838 991 doses of 9vHPV were administered. We identified unexpected statistical signals for 4 adverse events: appendicitis among boys 9 to 17 years old after dose 3; pancreatitis among men 18 to 26 years old; and allergic reactions among girls 9 to 17 years old and women 18 to 26 years old after dose 2. On further evaluation, which included medical record review, temporal scan analysis, and additional epidemiological analyses, we did not confirm signals for any adverse events. CONCLUSIONS: After 2 years of near real-time surveillance of 9vHPV and several prespecified adverse events, no new safety concerns were identified.

In light of waning immunity to pertussis following receipt of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine, maintaining protection may require repeated Tdap vaccination. We evaluated the safety of repeated doses of tetanus-containing vaccine in 68 915 nonpregnant adolescents and adults in the Vaccine Safety Datalink population who had received an initial dose of Tdap. Compared with 7521 subjects who received a subsequent dose of tetanus toxoid, reduced diphtheria (Td) vaccine, the 61 394 subjects who received a subsequent dose of Tdap did not have significantly elevated risk of medical visits for seizure, cranial nerve disorders, limb swelling, pain in limb, cellulitis, paralytic syndromes, or encephalopathy/encephalitis/meningitis. These results suggest that repeated Tdap vaccination has acceptable safety relative to Tdap vaccination followed by Td vaccination.

Objective To determine the risks associated with zoster vaccine when administered to patients taking immunosuppressant medications. Patients and Methods Patients enrolled in 1 of 7 managed care organizations affiliated with the Vaccine Safety Datalink between January 1, 2006, and December 31, 2009, were eligible. The exposure of interest was zoster vaccination in patients with current or remote immunosuppressant drug use. The primary outcomes were disseminated varicella zoster virus (VZV) and herpes zoster in the 42 days after vaccination. Automated data were collected on immunosuppressant drugs and baseline medical conditions. A logistic regression model using inverse probability treatment weights was used to estimate the odds of developing VZV or herpes zoster. Results A total of 14,554 individuals had an immunosuppressant medication dispensed around the time of vaccination, including 4826 with current use and 9728 with remote use. Most patients were taking low-dose corticosteroids. No cases of disseminated VZV were found in the current or remote users. The risk of herpes zoster was elevated in the 42 days after vaccination in current vs remote users (adjusted odds ratio, 2.99; 95% CI, 1.58-5.70). Conclusion We found that patients taking immunosuppressant medications at the time of vaccination had a modest increased risk of herpes zoster in the 42 days after vaccination. The development of herpes zoster within 42 days after vaccination suggests that this is more likely due to reactivation of latent zoster virus than dissemination of the vaccine-derived varicella virus. These findings support the current zoster vaccination guidelines.

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.

Although no increased risk was detected for serious adverse events in the prelicensure trials for the 13-valent pneumococcal vaccine, Prevnar 13(®) (PCV13), continued monitoring of rare but serious adverse events is necessary. A surveillance system using cohort study design was set up to monitor safety of PCV13 immediately after it was included in the childhood immunization program in the United States. The exposed population included children of 1 month to 2 years old who received PCV13 from April, 2010 to January, 2012 from the eight managed care organizations participating in the Vaccine Safety Datalink Project in the United States. The historical unexposed population was children of the same age who received the 7-valent pneumococcal conjugate vaccine Prevnar 7(®) (PCV7) in 2007 (or 2005 depending on the outcome of interest) to 2009. The risk of pre-specified adverse events in the risk window following PCV13 was repeatedly compared to that in the historical comparison group. The number of doses included in the study was 599,229. No increased risk was found for febrile seizures, urticaria or angioneurotic edema, asthma, thrombocytopenia, or anaphylaxis. An increased risk for encephalopathy was not confirmed following the medical record review. The relative risk for Kawasaki disease in 0-28 days following vaccination was 1.94 (95% confidence interval: 0.79-4.86), comparing PCV13 to PCV7. Comparing to PCV7 vaccine, we identified no significant increased risk of pre-specified adverse events in the Vaccine Safety Datalink study cohort. The possible association between PCV13 and Kawasaki disease may deserve further investigation.

OBJECTIVE: Our objective was to assess whether the occurrence of medically attended local reactions to intramuscularly administered vaccines varies by injection site (arm versus thigh) in children 1 to 6 years of age. METHODS: This is a retrospective cohort study of children in the Vaccine Safety Datalink population from 2002 to 2009. Site of injection and the outcome of medically attended local reactions were identified from administrative data. RESULTS: The study cohort of 1.4 million children received 6.0 million intramuscular (IM) vaccines during the study period. The primary analyses evaluated the IM vaccines most commonly administered alone, which included inactivated influenza, hepatitis A, and diphtheria-tetanus-acellular pertussis (DTaP) vaccines. For inactivated influenza and hepatitis A vaccines, local reactions were relatively uncommon, and there was no difference in risk of these events with arm versus thigh injections. The rate of local reactions after DTaP vaccines was higher, and vaccination in the arm was associated with a significantly greater risk of this outcome compared with vaccination in the thigh, both for children 12 to 35 months (relative risk: 1.88 [95% confidence interval: 1.34–2.65]) and 3 to 6 years of age (relative risk: 1.41 [95% confidence interval: 0.84–2.34]), although this difference was not statistically significant in the older age group. CONCLUSIONS: Injection in the thigh is associated with a significantly lower risk of a medically attended local reaction to a DTaP vaccination among children 12 to 35 months of age, supporting current recommendations to administer IM vaccinations in the thigh for children younger than 3 years of age.

SUMMARYWe conducted prospective, community-wide surveillance for acute respiratory illnesses (ARIs) in Rochester, NY and Marshfield, WI during a 3-month period in winter 2011. We estimated the incidence of ARIs in each community, tested for viruses, and determined the proportion of ARIs associated with healthcare visits. We used a rolling cross-sectional design to sample participants, conducted telephone interviews to assess ARI symptoms (defined as a current illness with feverishness or cough within the past 7 days), collected nasal/throat swabs to identify viruses, and extracted healthcare utilization from outpatient/inpatient records. Of 6492 individuals, 321 reported an ARI within 7 days (4·9% total, 5·7% in Rochester, 4·4% in Marshfield); swabs were collected from 208 subjects. The cumulative ARI incidence for the entire 3-month period was 52% in Rochester [95% confidence interval (CI) 42–63] and 35% in Marshfield (95% CI 28–42). A specific virus was identified in 39% of specimens: human coronavirus (13% of samples), rhinovirus (12%), RSV (7%), influenza virus (4%), human metapneumovirus (4%), and adenovirus (1%). Only 39/200 (20%) had a healthcare visit (2/9 individuals with influenza). ARI incidence was ~5% per week during winter.

During the 2007-08 influenza season, we reported an interim vaccine effectiveness (VE) estimate of 44% for preventing medically attended influenza. In this analysis we report results for the entire season and compare them with the interim estimate.Patients with feverishness, chills, or cough8 days duration were prospectively recruited over 10 weeks and tested for influenza by real-time reverse transcriptase PCR (rRT-PCR). Case-control analyses were performed using data from patients with rRT-PCR confirmed influenza (cases) and ill patients without influenza (test-negative controls). VE was estimated as 100×(1-adjusted odds ratio) in a logistic regression model adjusting for age, week, and high risk medical condition. A sample of influenza isolates was antigenically characterized.Influenza was detected by rRT-PCR in 865 (44%) of 1972 patients; 73% were type A and 27% were type B. VE was 37% (95% CI, 22-49%) overall and 44% (95% CI, 27-58%) among participants tested 0-3 days after illness onset. VE was 39% (95% CI, 2-62%) in children 6-59 months old and 37% (95% CI, -2% to 61%) in adults ≥50 years old. VE was 41% (95% CI, 24-53%) for influenza A and 31% (95% CI, 3-51%) for influenza B. All 24 characterized influenza A viruses were antigenically matched to the H3N2 vaccine strain, although 14 viruses exhibited mild antigenic drift. There was a lineage mismatch with the vaccine strain for all 39 characterized influenza B viruses.The 2007-08 influenza vaccine provided modest protection against medically attended influenza in this population. The interim estimate of VE after 17 days closely approximated the final season VE, supporting the potential use of interim VE estimates while influenza seasons are still in progress.

Mass vaccination campaigns during which new vaccines may be administered to many millions of people in a short period of time call for timely and accurate post-licensure surveillance to monitor vaccine safety. To address the need for timely H1N1 influenza vaccine safety information during the 2009-2010 H1N1 influenza pandemic, the Vaccine Safety Datalink (VSD) project assessed the feasibility and potential mechanisms for utilizing data from state and local immunization registries to capture vaccinations that would not otherwise be captured by the data systems of the participating VSD managed care organizations (MCOs). Three of the eight VSD sites were able to capture H1N1 immunization data electronically from the state and local registries, and one site was able to capture the immunizations through a paper-based system; however, the remaining four sites encountered various obstacles that prevented capture of such data. Additional work will be required at these sites to overcome the barriers, which included privacy and confidentiality laws, time constraints brought on by the pandemic, as well as data quality concerns.

Objectives. We performed a case–control study to determine if participants with herpes zoster had fewer contacts with persons with varicella or zoster, and with young children, to explore the hypothesis that exposure to persons with varicella zoster virus (VZV) results in “immune boosting.” Methods. Participants were patients of the multispecialty Marshfield Clinic in Wisconsin. We identified patients aged 40 to 79 years with a new diagnosis of zoster from August 2000 to July 2005. We frequency matched control participants to case participants for age. We confirmed diagnoses by chart review and assessed exposures by interview. Results. Interviews were completed by 633 of 902 eligible case participants (70.2%) and 655 of 1149 control participants (57.0%). The number of varicella contacts was not associated with zoster; there was no trend even at the highest exposure level (3 or more contacts). Similarly, there was no association with exposure to persons with zoster or to children, or with workplace exposures. Conclusions. Although exposure to VZV in our study was relatively low, the absence of a relationship with zoster reflects the uncertain influence of varicella circulation on zoster epidemiology.

Importance In recent years, rates of vaccination have been declining. Whether this phenomenon disproportionately affects children with autism spectrum disorder (ASD) or their younger siblings is unknown. Objectives To investigate if children after receiving an ASD diagnosis obtain their remaining scheduled vaccines according to the Advisory Committee on Immunization Practices (ACIP) recommendations and to compare the vaccination patterns of younger siblings of children with ASD with the vaccination patterns of younger siblings of children without ASD. Design, Setting, and Participants This investigation was a retrospective matched cohort study. The setting was 6 integrated health care delivery systems across the United States within the Vaccine Safety Datalink. Participants were children born between January 1, 1995, and September 30, 2010, and their younger siblings born between January 1, 1997, and September 30, 2014. The end of follow-up was September 30, 2015. Exposures Recommended childhood vaccines between ages 1 month and 12 years. Main Outcome and Measure The proportion of children who received all of their vaccine doses according to ACIP recommendations. Results The study included 3729 children with ASD (676 [18.1%] female), 592 907 children without ASD, and their respective younger siblings. Among children without ASD, 250 193 (42.2%) were female. For vaccines recommended between ages 4 and 6 years, children with ASD were significantly less likely to be fully vaccinated compared with children without ASD (adjusted rate ratio, 0.87; 95% CI, 0.85-0.88). Within each age category, vaccination rates were significantly lower among younger siblings of children with ASD compared with younger siblings of children without ASD. The adjusted rate ratios varied from 0.86 for siblings younger than 1 year to 0.96 for those 11 to 12 years old. Parents who had a child with ASD were more likely to refuse at least 1 recommended vaccine for that child’s younger sibling and to limit the number of vaccines administered during the younger sibling’s first year of life. Conclusions and Relevance Children with ASD and their younger siblings were undervaccinated compared with the general population. The results of this study suggest that children with ASD and their younger siblings are at increased risk of vaccine-preventable diseases.

Several case reports have described immune hemolytic anemia (IHA) following vaccination in children. We examined the risk of IHA in the 42 days following vaccination exposure using a self-controlled case series study design. In our population-based cohort of nearly 4.5 million children in the Vaccine Safety Datalink, we identified 55 confirmed cases of new-onset IHA from 1991 through 2000. We found no association between IHA and diphtheria-pertussis-tetanus vaccination (incidence rate ratio (IRR)=0.65, 95% CI: 0.19-2.24), hepatitis B vaccination (IRR=1.73, 95% CI: 0.59-5.01), or any vaccination (IRR=1.04, 95% CI: 0.46-2.32).

We evaluated influenza vaccination status as determined by self-report and a regional, real-time immunization registry during two influenza seasons when subjects were enrolled in a study to estimate vaccine effectiveness. We enrolled 2907 patients during the two consecutive seasons. The sensitivity and specificity of self-reported influenza vaccination when compared to immunization registry records were 95% and 90%, respectively. The positive predictive value of self-reported vaccination was 89% and negative predictive value was 96%. In our study population, self-reported influenza vaccine status was a sensitive and fairly specific indicator of actual vaccine status. Misclassification was more common among young children.

Adamantane-resistant influenza A is an emerging problem, but infections caused by resistant and susceptible viruses have not been compared. We identified adamantane resistance in 47% of 152 influenza A virus (H3N2) isolates collected during 2005. Resistant and susceptible viruses caused similar symptoms and illness duration. The prevalence of resistance was highest in children.

To investigate concerns about a potential association between quadrivalent human papillomavirus vaccination (HPV4) and venous thromboembolism (VTE), we conducted a self-controlled case series study in adolescents and young adults 9-26 years of age in the Vaccine Safety Datalink.We identified potential VTE cases diagnosed in 2008 through 2011 who had also received at least one HPV4 dose during that period. We confirmed each presumptive diagnosis by medical record review. We calculated incidence rate ratios (IRRs) and 95% confidence intervals (CI) to estimate the risk in the 1-60 day period following HPV4 exposure and in subsets of that period. IRRs were stratified by age, gender, hormonal contraceptive use, and recent surgery or trauma.We identified 313 potential cases of VTE among HPV4 vaccinees, and 291 (93%) had sufficient medical records for review. Of these, we confirmed 156 (54%) cases. VTE was uncommon among males (n=3) and 9-12 year olds (n=4). Nearly all confirmed cases (97%) had at least one known risk factor for VTE, including hormonal contraceptive use, obesity, and hypercoagulability. Sixteen (10%) confirmed cases occurred in the 1-60 days following HPV4 exposure. The risk of VTE varied from 1.47 (95% CI: 0.47-4.64) in the 1-7 days following HPV4 exposure to 0.92 (95% CI: 0.54-1.57) in the 1-60 days following vaccination. It was not possible to calculate a stratified IRR for males due to small sample size; the other risk factors evaluated did not significantly affect the risk of VTE after HPV4 exposure.The risk of developing VTE among 9- to 26-year-olds was not elevated following HPV4 exposure. Sample size limited our ability to rigorously evaluate potential effect modifiers, such as gender, through stratified analysis.

Objective—To identify factors significantly associated with an epidemic of fibrinous pericarditis during spring 2001 among horses in central Kentucky. Design—Case-control study. Animals—38 horses with fibrinous pericarditis and 30 control horses examined for other reasons. Procedure—A questionnaire was developed to solicit information regarding a wide range of management practices and environmental exposures from farm owners or managers. Results—The following factors were found in bivariate analyses to be significantly associated with an increased risk of pericarditis: being from a farm with mares and foals affected by mare reproductive loss syndrome, exposure to Eastern tent caterpillars in or around horse pastures, younger age, shorter duration of residence in Kentucky and at the farm of current residence, being fed hay grown outside Kentucky, a lack of access to pond water, access to orchard grass for grazing, and a lack of direct contact with cattle. In multivariate logistic regression analyses, only variables related to caterpillar exposure and age were significantly associated with fibrinous pericarditis. Conclusions and Clinical Relevance—Results suggest that fibrinous pericarditis in horses may be associated with mare reproductive loss syndrome. Exposure to Eastern tent caterpillars was the greatest risk factor for development of fibrinous pericarditis. The distribution of times of diagnosis of fibrinous pericarditis was consistent with a point-source epidemic. (J Am Vet Med Assoc 2003;223:832–838)

The automated health plan data and data from medical chart abstractions from eight large health maintenance organizations were used to evaluate the positive predictive values (PPVs) of the International Classification of Diseases, 9th revision (ICD-9) codes for cases of peptic ulcers and upper gastrointestinal bleeding. Overall, 207 of 884 cases of peptic ulcers and upper gastrointestinal bleeding (23%) were confirmed by surgery, endoscopy, X-ray, or autopsy. The PPVs were 66% for hospitalizations with codes for duodenal ulcer (ICD-9-CM 532), 61% for gastric/gastrojejunal ulcer (ICD-9-CM 531, 534), 1% for peptic ulcer (ICD-9-CM 533), and 9% for gastrointestinal hemorrhage (ICD-9-CM578). The overall and diagnostic category-specific PPVs were generally similar for the various HMOs. This study, using data from a large number of health plans located in different geographical regions, underscores the importance of evaluating the accuracy of the diagnoses from automated health plan databases.

Introduction Observational studies of influenza vaccine effectiveness often study persons seeking medical care for acute respiratory infection (ARI). We conducted a pilot study to determine if vaccine effectiveness could be estimated in the general population with a novel rolling cross-sectional survey sampling design and laboratory confirmation of influenza. Methods Cross-sectional samples were selected weekly from defined populations in Marshfield, Wisconsin and Monroe County, New York from January through April, 2011 (12 weeks). Persons were telephoned and asked about the occurrence of ARI in the past week. Nasal and throat swabs were obtained from consenting individuals with ARI and tested by real-time reverse transcription polymerase chain reaction (RT-PCR). Vaccine effectiveness (VE) was defined as (100 × [1 − OR]) for vaccination in a logistic regression model that adjusted for age, calendar week, and site. The comparison group included all study participants without RT-PCR confirmed influenza, including those who were not ill. Results Study personnel contacted 9537 (62%) of 15,303 persons sampled; the primary analysis included 5678 subjects. Of these, 193 (3%) reported an ARI and agreed to be tested for influenza; 13 (7%) were influenza positive. The adjusted effectiveness of the influenza vaccine was 1% (95% confidence limits −239–70%). Conclusions The rolling cross-sectional design is methodologically feasible and may be useful as a complement to clinic-based VE studies. This pilot study did not have sufficient power to detect significant vaccine effectiveness during a mild influenza season, but this approach may facilitate rapid estimation of VE in a pandemic setting when normal patterns of health care utilization are disrupted.

The automated records of over 250,000 members of a health maintenance organization were analyzed to assess the epidemiology of varicella and its complications between 1 July 1990 and 30 June 1992. All complications were verified by review of full-text medical records. The incidence rates of varicella in persons15 years of age were 20%-50% lower than published figures, probably reflecting underreporting. The rates in thoseor = 15 years old, however, were greater than those reported for 1972-1978 (607 vs. 291/10(5) years, 15-19 years old; 175 vs. 33/10(5) years,or = 20 years old). The rates of hospitalization for uncomplicated varicella, skin superinfections, and pneumonia in children were, respectively, 15, 11, and 4 times higher than previous estimates. Hospitalization rates for adults with pneumonia and uncomplicated varicella were5 times higher than prior figures. Thus, varicella in adults and varicella complications in general may be more frequent than previously estimated.

Epidemiological and pathological findings of 433 late-term abortions associated with the mare reproductive loss syndrome (MRLS) in central Kentucky were identified by reviewing the records of the University of Kentucky Livestock Diseases Diagnostic Center. The distribution of dates of abortion was clustered during a brief period of time, presumably from a simultaneous environmental exposure. The most common pathological findings were microscopic pulmonary lesions consisting of squamous epithelial cells present in alveoli with or without concurrent infiltration of inflammatory cells (neutrophils, macrophages, or monocytes) in the interstitium or within alveoli. Isolation of a non–β-hemolytic Streptococcus (52% of fetuses) or an Actinobacillus sp. (19% of fetuses) was common. Placentitis or funisitis was identified in 44% of fetuses. No single pathological finding, however, was pathognomonic for MRLS-associated late-term abortion. This report describes the pathological findings characterizing the MRLS-associated abortion. A cause of MRLS could not be determined from necropsy findings.

Large observational vaccine safety studies often use automated diagnoses extracted from medical care databases to identify pre-specified potential adverse events following immunization (AEFI). We assessed the secular trends and variability in the number of diagnoses per encounter regardless of immunization status referred as diagnostic code density, by healthcare setting, age, and pre-specified condition in eight large health care systems of the Vaccine Safety Datalink project during 2001–2009. An increasing trend in diagnostic code density was observed in all healthcare settings and age groups, with variations across the sites. Sudden increases in diagnostic code density were observed at certain sites when changes in coding policies or data inclusion criteria took place. When vaccine safety studies use an historical comparator, the increased diagnostic code density over time may generate low expected rates (based on historical data) and high observed rates (based on current data), suggesting a false positive association between a vaccine and AEFI. The ongoing monitoring of the diagnostic code density can provide guidance on study design and choice of appropriate comparison groups. It can also be used to ensure data quality and allow timely correction of errors in an active safety surveillance system.

Objectives. We studied compliance with multiple-dose vaccine schedules, assessed factors associated with noncompliance, and examined timeliness of series completion among older children, adolescents, and adults. Methods. We conducted a large, multisite, retrospective cohort study of older children, adolescents, and adults in the Vaccine Safety Datalink population from 1996 through 2004. We quantified the rates of completion of all required doses for varicella, hepatitis A, and hepatitis B vaccines according to their recommended schedules. Results. Among those who received a first dose of varicella (n = 16 075), hepatitis A (n = 594 917), and hepatitis B (n = 590 445) vaccine, relatively few completed the series (55%–65% for hepatitis B vaccine and 40%–50% for hepatitis A and varicella vaccines in most age groups). Compliance was lowest among adolescents (35.9%) and Medicaid recipients (29.7%) who received varicella vaccine and among younger adult age groups who received hepatitis A vaccine (25%–35% across those age groups). Even among series completers, there was a relatively long interval of undervaccination between the first and last doses. Conclusions. Compliance with multiple-dose vaccine series among older children, adolescents, and adults is suboptimal. Further evaluations of strategies to improve compliance in these populations are needed.

BACKGROUND. Ischemic stroke is a known complication of varicella disease. Although there have been case reports of ischemic stroke after varicella vaccination, the existence and magnitude of any vaccine-associated risk has not been determined. OBJECTIVE. The purpose of this work was to determine whether varicella vaccination is associated with an increased risk of ischemic stroke and encephalitis in children within 12 months after vaccination. PATIENTS AND METHODS. We conducted a retrospective cohort study based on computerized data from children 11 months through 17 years old enrolled for ≥12 months in the Vaccine Safety DataLink from 1991 through 2004. International Classification of Disease codes identified cases of ischemic stroke (433–436, 437.1, 437.4, 437.6, 437.8–437.9) and encephalitis (052.0, 323.5, 323.8–9). Cox regression was used to model the risk in the 12 months after vaccination relative to all other person-time. Covariates included calendar time, gender, and stroke risk factors (eg, sickle cell disease). RESULTS. Varicella vaccine was administered to 35.3% of the 3.2 million children in the cohort. There were 203 new inpatient ischemic stroke diagnoses, including 8 that occurred within 12 months after vaccination; there was no temporal clustering. The adjusted stroke hazard ratio was not elevated during any of the time periods in the 12 months after vaccination. Stroke was strongly associated with known risk factors such as sickle cell disease and cardiac disease. None of the 243 encephalitis cases occurred during the first 30 days after vaccination, and there was no association between encephalitis and varicella vaccination at any time in the 12 months after vaccination. CONCLUSION. Our retrospective cohort study of >3 million children found no association between varicella vaccine and ischemic stroke.

In order to define the risk factors for infection with hepatitis C virus, the authors determined the prevalence and incidence of antibodies to hepatitis C in three cohorts in Baltimore, Maryland, enrolled in prospective studies of human immunodeficiency virus (HIV-1) infection. Among 500 multi-transfused patients who underwent cardiac surgery in 1985 and 1986, 12 (2.4%) were hepatitis C seropositive before surgery while 19 (3.9%) developed antibodies in the 8-12 months after surgery. The seroprevalence of hepatitis C virus among 225 intravenous drug users followed since 1988 was 85%, which did not vary by HIV-1 status. Longer duration of intravenous drug use was significantly associated with hepatitis C seropositivity. Among 926 homosexual/bisexual men followed since 1984, 15 (1.6%) were hepatitis C seropositive; only intravenous drug use and a history of hepatitis A were marginally associated with hepatitis C in this population. No association was found between hepatitis C virus and HIV-1 or sexual behavior variables in this population. These data suggest that hepatitis C is readily transmitted by blood exposure, but is transmitted inefficiently by sexual means.

Purpose The Food and Drug Administration currently requires the labeling of HMG-CoA reductase inhibitors to recommend liver function tests (LFTs) before the start of therapy and at various intervals during therapy, depending on the specific agent. We sought to determine the frequency and patterns of LFT screening in patients receiving HMG-CoA reductase inhibitors. Methods A retrospective study was conducted at a staff-model health maintenance organization among 4178 new users of HMG-CoA reductase inhibitors during the period 1 January 1991 through 31 December 1996. The number and proportions of HMG-CoA reductase inhibitor therapy courses with baseline LFTs (within 180 days prior to dispensing), follow-up LFTs and LFT abnormalities were calculated. Results For the initial HMG-CoA reductase inhibitor dispensed, 1947 patients (47%) had at least one screening LFT at baseline and 3063 (73%) had at least one follow-up LFT. Twenty-seven (0.9%) patients with at least one follow-up LFT performed had a level greater than 3 times the upper limit of normal. In a random sample of 100 discontinued patients, none discontinued due to elevated LFTs or liver disease. Conclusions A large proportion of patients dispensed HMG-CoA reductase inhibitors in this managed care setting did not have baseline and follow-up LFTs performed. Modest LFT abnormalities were common among users of HMG-CoA reductase inhibitors; however, in this population, serious abnormalities were rare. Copyright © 2003 John Wiley & Sons, Ltd.

Background Isolated case reports of gastric ulcers after alendronate sodium use raised concern about the gastroduodenal safety of daily alendronate. This study was conducted to estimate the excess risk of hospitalizations for gastric or duodenal perforations, ulcers, and bleeding associated with alendronate use. Participants and Methods Study subjects were 6432 men and women, 35 years or older. The subjects were members of 8 health maintenance organizations who were dispensed alendronate from October 1995 through September 1997. There was also a group of 33 176 age-, sex-, and health maintenance organization–matched unexposed persons. Because of concerns that osteoporosis might confound the association between alendronate use and perforation, ulcer, or bleeding, a second comparison group of 9776 women, 60 years or older, who had osteoporotic fractures was assembled. Hospitalizations for gastroduodenal events were identified by discharge diagnosis codes in automated claims records, and confirmed by manual record review. Results Based on the 14 confirmed events in the alendronate group and 35 in the unexposed group, the crude incidence rate ratio of gastroduodenal perforation, ulcer, or bleeding for the alendronate cohort was 3.0. The incidence rate ratio was 1.8 (95% confidence interval, 0.8-3.9) after control for prior hospitalizations, comorbidity, and recent exposure to prescription nonsteroidal anti-inflammatory drugs and oral corticosteroids. The crude incidence ratio rate for the age, sex, and health maintenance organizations–restricted cohort of alendronate users relative to the fracture cohort was 1.1 and the adjusted incidence rate ratio was 1.1 (95% confidence interval, 0.6-2.2). Conclusions Osteoporosis and related factors appear to play an important role in the relationship between alendronate use and confirmed gastroduodenal perforation, ulcer, or bleeding; a substantial fraction of the increased risk we observed for alendronate users in the unadjusted analysis was the result of confounding.

Objective To compare ambulatory visit patterns, rates of medication use, and emergency department and hospital utilization for children with asthma covered under Medicaid and commercial payers within the same health maintenance organization (HMO). Design Retrospective cohort study. Setting Eleven staff-model pediatric departments of an HMO. Patients A total of 1928 Medicaid and 11,007 non-Medicaid children aged 2 to 18 years with at least 1 encounter with a diagnosis of asthma between October 1, 1991, and September 30, 1996. Methods We linked patient-level data from the HMO's automated medical record system for ambulatory encounters, a claims system for emergency department and hospital care, and an automated pharmacy dispensing database. Medicaid and non-Medicaid patients were compared for all encounter types and for prescribing and dispensing of β-agonist and controller medications (inhaled corticosteroids and cromolyn sodium). Incidence rate ratios were calculated from Poisson regression models to control for age, sex, and, when appropriate, β-agonist dispensing rate. The number of refills authorized on each prescription and the fraction of medications dispensed as refills compared with new prescriptions were compared for Medicaid and non-Medicaid patients. Results Medicaid-insured children in the HMO were 1.4 times (95% confidence interval, 1.2-1.5) more likely to receive care in emergency departments and 1.3 times (95% confidence interval, 1.1-1.5) more likely to be hospitalized for their asthma compared with non-Medicaid members. Medicaid and non-Medicaid enrollees had similar yearly rates of nonurgent (1.32 vs 1.17) and urgent (0.38 vs 0.31) ambulatory visits. β-Agonists were dispensed roughly equally to Medicaid and non-Medicaid members. Although Medicaid patients were less likely to have controller medications dispensed (relative risk, 0.72; 95% confidence interval, 0.69-0.74), they were equally likely to have them prescribed. Conclusions Differences in ambulatory contact for Medicaid members do not explain the higher rates of emergency department visits and hospitalization in this population. Reasons for lower rates of dispensing of controller medications should continue to be investigated as one cause of increased morbidity for low-income children with asthma.

Background Allergic rhinitis and asthma are important sources of morbidity among adults and children. Although immunotherapy is sometimes used to treat these conditions, there is little information on its use, adherence, or cost in the general population. Objective We sought to characterize the recipients of immunotherapy for allergic rhinitis and/or asthma with respect to their immunotherapy and utilization of health care services. Methods A combination of automated and manually extracted data was used to identify HMO members with diagnoses of allergic rhinitis or asthma who were treated with immunotherapy. Costs associated with immunotherapy and related care were examined by linear regression. Proportional hazards and Kaplan-Meier plots were used to evaluate duration of therapy. Results Of the 122,196 persons with a diagnosis of asthma or rhinitis, 2,667 were also treated with immunotherapy. Eligibility criteria were satisfied by 603 individuals who had 28,266 encounters for immunotherapy (median 48). Most patients (>80%) were treated with multiple allergens; ragweed was the most common single allergen administered. Thirty-three percent of patients with sufficient observation time completed the intended course of 61 immunotherapy treatments. Females and younger patients had shorter durations of immunotherapy. The most common reason for discontinuation of therapy was patient's decision (54%). Immunotherapy costs were related most strongly to costs for care of rhinitis and asthma. Prescription drugs accounted for more than 50% of the non-immunotherapy costs; hospitalizations accounted for less than 20%. Conclusions Approximately 2% of HMO members with an asthma or rhinitis diagnosis received immunotherapy. Although screened to optimize compliance, most patients did not complete immunotherapy. Costs of non-immunotherapy care were higher for individuals who completed immunotherapy which is consistent with more severe disease in this group.

PURPOSE: To investigate the possible association between ibuprofen use and dermatologic superinfections among children with recent varicella infection. METHODS: A retrospective cohort study of children in Harvard Pilgrim Health Care, a health maintenance organization in New England, was conducted. Outcomes and exposures of interest were identified from automated medical and pharmacy records. Exposure was defined by dispensing of ibuprofen before varicella to avoid potential confounding by indication. RESULTS: Between July 1, 1990 and September 30, 1994, 89 superinfections developed among 7,013 cases of varicella. The 30-day risk of superinfection was 7.2/10 3 cases (95% CI = 5.8 – 8.8/10 3 cases). Four of 169 children dispensed ibuprofen within 180 days of varicella developed superinfection. Relative to children without prior use, children with ibuprofen dispensed in the month prior to varicella were 3.1 times more likely to be diagnosed with a superinfection (95% CI = 0.1–19.7; P -value: 0.31). Restriction of outcomes to superinfections treated with systemic antibiotics increased the odds ratio to 5.1 (95% CI = 0.1–32.5; P -value: 0.22). CONCLUSIONS: The results of this study are consistent with a broad range of effects including no association and suggest that further study is needed.

OBJECTIVE To evaluate the effectiveness of serologic testing of blood donors for human immunodeficiency virus type 1 (HIV-1) and human T-cell lymphotropic virus types I and II (HTLV-I/II) infections and to estimate the risk for transmission of HIV-1 and HTLV-I/II by transfusion of seronegative blood from screened donors. DESIGN A prospective multicenter cohort study of cardiac surgery patients who received multiple transfusions between 1985 and 1991. SETTING Cardiac surgery services of three large tertiary care hospitals. PATIENTS The study included 11,532 patients in three hospitals who had cardiovascular surgery. MEASUREMENTS Incident HIV-1 and HTLV-I or HTLV-II infection. RESULTS We detected two new HIV-1 infections among patients transfused with 120,312 units of blood components from seronegative donors. In each case a donor was detected on follow-up who had seroconverted since the donation. The HIV-1 infection rate was 0.0017% with an upper limit of the 95% CI of 0.0053%. Before donor screening for HTLV-I, transfusion of 51,026 units resulted in two HTLV-I infections (0.0039%) and four HTLV-II infections (0.0078%). After HTLV-I screening was instituted, one recipient was infected with HTLV-II among participants exposed to 69,272 units, a rate of 0.0014%. A corresponding HTLV-I/II-infected donor was found for this patient. CONCLUSION Serologic screening of donors for antibodies to HIV-1 and HTLV-I coupled with exclusion of donors from groups having a relatively high risk for infection has led to a low incidence of transfusion-transmitted HIV-1 and HTLV-I/II infection in the United States. A small risk remains, however, despite these measures. We estimate the residual risk for HIV-1 and HTLV-II infection from transfusion of screened blood during the time of this study to be about 1 in 60,000 units.

We determined the rates of seroconversion to human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus Type I (HTLV-I) in a cohort of patients receiving transfusions of blood components screened for antibody to HIV-1. Preoperative and postoperative serum samples were collected from 4163 adults undergoing cardiac surgery who received 36,282 transfusions of blood components. The postoperative samples from all patients were tested for serologic evidence of HIV-1 infection, and those that were positive were compared with the corresponding preoperative samples. One case of HIV-1 transmission by transfusion of screened blood components was identified; two preexisting HIV-1 infections were found. Samples from 2749 patients were tested similarly for serologic evidence of HTLV-I infection; these patients received 20,963 units of blood components. Five new cases and two preexisting cases of HTLV-I infection were detected. The observed risk of HIV-1 transmission by transfusion was 0.003 percent per unit; the risk of HTLV-I transmission was 0.024 percent per unit. We conclude that there is a very small risk of HTLV-I infection from transfused blood products that have been screened for antibodies to HIV-1, but that it is nearly 10-fold higher than the risk of HIV-1 infection.

The system used by the National Nosocomial Infection Surveillance (NNIS) program to measure risk of surgical site infection uses a score of 3 on the American Society of Anesthesiologists (ASA)-physical status scale as a measure of underlying illness. The chronic disease score measures health status as a function of age, sex, and 29 chronic diseases, inferred from dispensing of prescription drugs. We studied the relationship between the chronic disease score and surgical site infection and whether the score can supplement the NNIS risk index. In a retrospective comparison of 191 patients with surgical site infection and 378 uninfected controls, the chronic disease score and ASA score were highly correlated. The chronic disease score improved prediction of infection by the NNIS risk index and augmented the ASA score for risk adjustment.