Immunogenicity of adjuvanted versus high-dose inactivated influenza vaccines in older adults: a randomized clinical trial.

BACKGROUND: Adjuvanted inactivated influenza vaccine (aIIV) and high-dose inactivated influenza vaccine (HD-IIV) are U.S.-licensed for adults aged ≥ 65 years. This study compared serum hemagglutination inhibition (HAI) antibody titers for the A(H3N2) and A(H1N1)pdm09 and B strains after trivalent aIIV3 and trivalent HD-IIV3 in an older adult population. RESULTS: The immunogenicity population included 342 participants who received aIIV3 and 338 participants who received HD-IIV3. The proportion of participants that seroconverted to A(H3N2) vaccine strains after allV3 (112 participants [32.8%]) was inferior to the proportion of participants that seroconverted after HD-IIV3 (130 participants [38.5%]) at day 29 after vaccination (difference, - 5.8%; 95%CI, - 12.9% to 1.4%). There were no significant differences between the vaccine groups in percent seroconversion to A(H1N1)pdm09 or B vaccine strains, in percent seropositivity for any of the strains, or in post-vaccination GMT for the A(H1N1)pdm09 strain. The GMTs for the post-vaccination A(H3N2) and B strains were higher after HD-IIV than after aIIV3. CONCLUSIONS: Overall immune responses were similar after aIIV3 and HD-IIV3. For the primary outcome, the aIIV3 seroconversion rate for H3N2 did not meet noninferiority criteria compared with HD-IIV3, but the HD-IIV3 seroconversion rate was not statistically superior to the aIIV3 seroconversion rate. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03183908.

Surveillance for Multisystem Inflammatory Syndrome in US Children Aged 5-11 Years Who Received Pfizer-BioNTech COVID-19 Vaccine, November 2021 through March 2022.

Multisystem inflammatory syndrome in children (MIS-C) is a complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; in the United States, reporting of MIS-C after coronavirus disease 2019 (COVID-19) vaccination is required for vaccine safety monitoring. Pfizer-BioNTech COVID-19 vaccine was authorized for children aged 5-11 years on 29 October 2021. Covering a period when approximately 7 million children received vaccine, surveillance for MIS-C ≤ 90 days postvaccination using passive systems identified 58 children with MIS-C and laboratory evidence of past/recent SARS-CoV-2 infection, and 4 without evidence. During a period with extensive SARS-CoV-2 circulation, MIS-C illness in children after COVID-19 vaccination who lacked evidence of SARS-CoV-2 infection was rare (<1 per million vaccinated children).

Safety of Live Attenuated Influenza Vaccine in Children With Asthma.

BACKGROUND AND OBJECTIVES: Asthma is considered a precaution for use of quadrivalent live attenuated influenza vaccine (LAIV4) in persons aged ≥5 years because of concerns for wheezing events. We evaluated the safety of LAIV4 in children with asthma, comparing the proportion of children with asthma exacerbations after LAIV4 or quadrivalent inactivated influenza vaccine (IIV4). METHODS: We enrolled 151 children with asthma, aged 5 to 17 years, during 2 influenza seasons. Participants were randomly assigned 1:1 to receive IIV4 or LAIV4 and monitored for asthma symptoms, exacerbations, changes in peak expiratory flow rate (PEFR), and changes in the asthma control test for 42 days after vaccination. RESULTS: We included 142 participants in the per-protocol analysis. Within 42 days postvaccination, 18 of 142 (13%) experienced an asthma exacerbation: 8 of 74 (11%) in the LAIV4 group versus 10 of 68 (15%) in the IIV4 group (LAIV4-IIV4 = -0.0390 [90% confidence interval -0.1453 to 0.0674]), meeting the bounds for noninferiority. When adjusted for asthma severity, LAIV4 remained noninferior to IIV4. There were no significant differences in the frequency of asthma symptoms, change in PEFR, or childhood asthma control test/asthma control test scores in the 14 days postvaccination between LAIV4 and IIV4 recipients. Vaccine reactogenicity was similar between groups, although sore throat (P = .051) and myalgia (P <.001) were more common in the IIV4 group. CONCLUSIONS: LAIV4 was not associated with increased frequency of asthma exacerbations, an increase in asthma-related symptoms, or a decrease in PEFR compared with IIV4 among children aged 5 to 17 years with asthma.

U.S. Population-Based background incidence rates of medical conditions for use in safety assessment of COVID-19 vaccines.

The Coronavirus Disease 2019 (COVID-19) pandemic has had a devastating impact on global health, and has resulted in an unprecedented, international collaborative effort to develop vaccines to control the outbreak, protect human lives, and avoid further social and economic disruption. Mass vaccination campaigns are underway in multiple countries and are expected worldwide once more vaccine becomes available. Some early candidate vaccines use novel platforms, such as mRNA encapsulated in lipid nanoparticles, and relatively new platforms, such as replication-deficient viral vectors. While these new vaccine platforms hold promise, limited safety data in humans are available. Serious health outcomes linked to vaccinations are rare, and some outcomes may occur incidentally in the vaccinated population. Knowledge of background incidence rates of these medical conditions is a critical component of vaccine safety monitoring to aid in the assessment of adverse events temporally associated with vaccination and to put these events into context with what would be expected due to chance alone. A list of 22 potential adverse events of special interest (AESI), including neurologic, autoimmune, and cardiovascular disorders, was compiled by subject matter experts at the U.S. Food and Drug Administration and the Centers for Disease Control and Prevention. The most recently available U.S. background rates for these medical conditions, overall and by age, sex, and race/ethnicity (when available), were sourced from reported statistics (data published by medical panels/ associations or federal government reports), and literature reviews in PubMed. This review provides estimates of background incidence rates for medical conditions that may be monitored or studied as AESI during safety surveillance and research for COVID-19 vaccines and other new vaccines.

US Case Reports of Cerebral Venous Sinus Thrombosis With Thrombocytopenia After Ad26.COV2.S Vaccination, March 2 to April 21, 2021.

Importance: Cerebral venous sinus thrombosis (CVST) with thrombocytopenia, a rare and serious condition, has been described in Europe following receipt of the ChAdOx1 nCoV-19 vaccine (Oxford/AstraZeneca), which uses a chimpanzee adenoviral vector. A mechanism similar to autoimmune heparin-induced thrombocytopenia (HIT) has been proposed. In the US, the Ad26.COV2.S COVID-19 vaccine (Janssen/Johnson & Johnson), which uses a human adenoviral vector, received Emergency Use Authorization (EUA) on February 27, 2021. By April 12, 2021, approximately 7 million Ad26.COV2.S vaccine doses had been given in the US, and 6 cases of CVST with thrombocytopenia had been identified among the recipients, resulting in a temporary national pause in vaccination with this product on April 13, 2021. Objective: To describe reports of CVST with thrombocytopenia following Ad26.COV2.S vaccine receipt. Design, Setting, and Participants: Case series of 12 US patients with CVST and thrombocytopenia following use of Ad26.COV2.S vaccine under EUA reported to the Vaccine Adverse Event Reporting System (VAERS) from March 2 to April 21, 2021 (with follow-up reported through April 21, 2021). Exposures: Receipt of Ad26.COV2.S vaccine. Main Outcomes and Measures: Clinical course, imaging, laboratory tests, and outcomes after CVST diagnosis obtained from VAERS reports, medical record review, and discussion with clinicians. Results: Patients' ages ranged from 18 to younger than 60 years; all were White women, reported from 11 states. Seven patients had at least 1 CVST risk factor, including obesity (n = 6), hypothyroidism (n = 1), and oral contraceptive use (n = 1); none had documented prior heparin exposure. Time from Ad26.COV2.S vaccination to symptom onset ranged from 6 to 15 days. Eleven patients initially presented with headache; 1 patient initially presented with back pain and later developed headache. Of the 12 patients with CVST, 7 also had intracerebral hemorrhage; 8 had non-CVST thromboses. After diagnosis of CVST, 6 patients initially received heparin treatment. Platelet nadir ranged from 9 ×103/µL to 127 ×103/µL. All 11 patients tested for the heparin-platelet factor 4 HIT antibody by enzyme-linked immunosorbent assay (ELISA) screening had positive results. All patients were hospitalized (10 in an intensive care unit [ICU]). As of April 21, 2021, outcomes were death (n = 3), continued ICU care (n = 3), continued non-ICU hospitalization (n = 2), and discharged home (n = 4). Conclusions and Relevance: The initial 12 US cases of CVST with thrombocytopenia after Ad26.COV2.S vaccination represent serious events. This case series may inform clinical guidance as Ad26.COV2.S vaccination resumes in the US as well as investigations into the potential relationship between Ad26.COV2.S vaccine and CVST with thrombocytopenia.

Safety, Reactogenicity, and Health-Related Quality of Life After Trivalent Adjuvanted vs Trivalent High-Dose Inactivated Influenza Vaccines in Older Adults: A Randomized Clinical Trial.

Importance: Trivalent adjuvanted inactivated influenza vaccine (aIIV3) and trivalent high-dose inactivated influenza vaccine (HD-IIV3) are US-licensed for adults aged 65 years and older. Data are needed on the comparative safety, reactogenicity, and health-related quality of life (HRQOL) effects of these vaccines. Objective: To compare safety, reactogenicity, and changes in HRQOL scores after aIIV3 vs HD-IIV3. Design, Setting, and Participants: This randomized blinded clinical trial was a multicenter US study conducted during the 2017 to 2018 and 2018 to 2019 influenza seasons. Among 778 community-dwelling adults aged at least 65 years and assessed for eligibility, 13 were ineligible and 8 withdrew before randomization. Statistical analysis was performed from August 2019 to August 2020. Interventions: Intramuscular administration of aIIV3 or HD-IIV3 after age-stratification (65-79 years; ≥80 years) and randomization. Main Outcomes and Measures: Proportions of participants with moderate-to-severe injection-site pain and 14 other solicited reactions during days 1 to 8, using a noninferiority test (5% noninferiority margin), and serious adverse events (SAE) and adverse events of clinical interest (AECI), including new-onset immune-mediated conditions, during days 1 to 43. Changes in HRQOL scores before and after vaccination (days 1, 3) were also compared between study groups. Results: A total of 757 adults were randomized, 378 to receive aIIV3 and 379 to receive HD-IIV3. Of these participants, there were 420 women (55%) and 589 White individuals (78%) with a median (range) age of 72 (65-97) years. The proportion reporting moderate-to-severe injection-site pain, limiting or preventing activity, after aIIV3 (12 participants [3.2%]) (primary outcome) was noninferior compared with HD-IIV3 (22 participants [5.8%]) (difference -2.7%; 95% CI, -5.8 to 0.4). Ten reactions met noninferiority criteria for aIIV3; 4 (moderate-to-severe injection-site tenderness, arthralgia, fatigue, malaise) did not. It was inconclusive whether these 4 reactions occurred in higher proportions of participants after aIIV3. No participant sought medical care for a vaccine reaction. No AECI was observed. Nine participants had at least SAE after aIIV3 (2.4%; 95% CI,1.1% to 4.5%); 3 had at least 1 SAE after HD-IIV3 (0.8%; 95% CI, 0.2% to 2.2%). No SAE was associated with vaccination. Changes in prevaccination and postvaccination HRQOL scores were not clinically meaningful and not different between the groups. Conclusions and Relevance: Overall safety and HRQOL findings were similar after aIIV3 and HD-IIV3, and consistent with prelicensure data. From a safety standpoint, this study's results support using either vaccine to prevent influenza in older adults. Trial Registration: ClinicalTrials.gov Identifier: NCT03183908.

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.

Drinking Water to Prevent Postvaccination Presyncope in Adolescents: A Randomized Trial.

BACKGROUND AND OBJECTIVES: Postvaccination syncope can cause injury. Drinking water prephlebotomy increases peripheral vascular tone, decreasing risk of blood-donation presyncope and syncope. This study evaluated whether drinking water prevaccination reduces postvaccination presyncope, a potential syncope precursor. METHODS: We conducted a randomized trial of subjects aged 11 to 21 years receiving ≥1 intramuscular vaccine in primary care clinics. Intervention subjects were encouraged to drink 500 mL of water, with vaccination recommended 10 to 60 minutes later. Control subjects received usual care. Presyncope symptoms were assessed with a 12-item survey during the 20-minutes postvaccination. Symptoms were classified with a primary cutoff sensitive for presyncope, and a secondary, more restrictive cutoff requiring greater symptoms. Results were adjusted for clustering by recruitment center. RESULTS: There were 906 subjects randomly assigned to the control group and 901 subjects randomly assigned to the intervention group. None had syncope. Presyncope occurred in 36.2% of subjects by using the primary definition, and in 8.0% of subjects by using the restrictive definition. There were no significant differences in presyncope by intervention group for the primary (1-sided test, P = .24) or restrictive outcome (1-sided test, P = .17). Among intervention subjects vaccinated within 10 to 60 minutes after drinking all 500 mL of water (n = 519), no reduction in presyncope was observed for the primary or restrictive outcome (1-sided tests, P = .13, P = .17). In multivariable regression analysis, presyncope was associated with younger age, history of passing out or nearly passing out after a shot or blood draw, prevaccination anxiety, receiving >1 injected vaccine, and greater postvaccination pain. CONCLUSIONS: Drinking water before vaccination did not prevent postvaccination presyncope. Predictors of postvaccination presyncope suggest opportunities for presyncope and syncope prevention interventions.

Live attenuated influenza vaccine use and safety in children and adults with asthma.

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.

Arm Paralysis After Routine Childhood Vaccinations: Application of Advanced Molecular Methods to the Causality Assessment of an Adverse Event After Immunization.

Post-licensure surveillance for adverse events following immunizations (AEFI) can identify rare complications of vaccinations and rigorous vaccine adverse event causality assessments can help to identify possible causal relationships. We report the development of arm paralysis after varicella vaccination in a 1-year-old child. Paralysis was initially presumed to be due to vOka because of the temporal relationship between vaccination and onset of arm weakness; however, molecular studies identified wild-type varicella zoster virus VZV (WT-VZV) in the CSF, leading the authors to conclude that WT-VZV was the probable cause. This case illustrates the complexity of assessing AEFI causality, and the importance of careful and complete evaluations when determining the most likely cause of an AEFI.

Sudden-Onset Sensorineural Hearing Loss after Immunization: A Case-Centered Analysis.

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.

Absence of venous thromboembolism risk following quadrivalent human papillomavirus vaccination, Vaccine Safety Datalink, 2008-2011.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Chorioamnionitis following vaccination in the Vaccine Adverse Event Reporting System.

BACKGROUND: In October 2012, the Advisory Committee on Immunization Practices (ACIP) recommended a dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) during each pregnancy, irrespective of the woman's prior history of receiving Tdap. A retrospective cohort study to assess the safety of Tdap vaccination in pregnant women in two Vaccine Safety Datalink (VSD) sites during 2010-2012 found a small but statistically significant increased risk of chorioamnionitis. OBJECTIVE: We conducted a review of the VAERS database to describe reports of chorioamnionitis following receipt of any vaccines. METHODS: We searched the VAERS database for reports of chorioamnionitis after any vaccine in the United States during the period from July 1, 1990 through February 2, 2014. RESULTS: VAERS received 31 reports of chorioamnionitis out of 3389 pregnancy reports in 24 years. The three most common vaccines in these reports were 2009 H1N1 inactivated influenza, quadrivalent human papillomavirus (HPV4), and Tdap vaccines in 32%, 29% and 26% of reports, respectively. Fifty-eight percent of reports had at least one reported risk factor for chorioamnionitis. Chorioamnionitis was identified in 3 reports of spontaneous abortions and 6 stillbirths, 6 reports of preterm birth (two of whom died) and 16 reports of term birth; maternal outcomes included two reports of postpartum hemorrhage and one report of maternal admission to the intensive care unit. No maternal deaths were reported. CONCLUSION: Chorioamnionitis was found to be uncommonly reported, representing 1% of pregnancy reports to VAERS. A majority of reports had at least one risk factor for chorioamnionitis.

Adverse events after Fluzone ® Intradermal vaccine reported to the Vaccine Adverse Event Reporting System (VAERS), 2011-2013.

BACKGROUND: In May 2011, the first trivalent inactivated influenza vaccine exclusively for intradermal administration (TIV-ID) was licensed in the US for adults aged 18-64 years. OBJECTIVE: To characterize adverse events (AEs) after TIV-ID reported to the US Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting surveillance system. METHODS: We searched VAERS for US reports after TIV-ID among persons vaccinated from July 1, 2011-February 28, 2013. Medical records were requested for reports coded as serious (death, hospitalization, prolonged hospitalization, disability, life-threatening-illness), and those suggesting anaphylaxis. Clinicians reviewed available information and assigned a primary clinical category to each report. Empirical Bayesian data mining was used to identify disproportional AE reporting following TIV-ID. Causality was not assessed. RESULTS: VAERS received 466 reports after TIV-ID; 9 (1.9%) were serious, including one reported fatality in an 88-year-old vaccinee. Median age was 43 years (range 4-88 years). The most common AE categories were: 218 (46.8%) injection site reactions; 89 (19.1%) other non-infectious (comprised mainly of constitutional signs and symptoms); and 74 (15.9%) allergy. Eight reports (1.7%) of anaphylaxis were verified by the Brighton criteria or a documented physician diagnosis. Disproportional reporting was identified for three AEs: 'injection site nodule', 'injection site pruritus', and 'drug administered to patient of inappropriate age'. The findings for the first two AEs were expected. Twenty-four reports of vaccinees <18 years or ≥ 65 years were reported, and 14 of 24 were coded with the AE 'drug administered to patient of inappropriate age'. CONCLUSIONS: Review of VAERS reports did not identify any new or unexpected safety concerns after TIV-ID. Injection site reactions were the most commonly reported AEs, similar to the pre-licensure clinical trials. Use of TIV-ID in younger and older individuals outside the approved age range highlights the need for education of healthcare providers regarding approved TIV-ID use.

Asthma incidence among children and adults: findings from the Behavioral Risk Factor Surveillance system asthma call-back survey--United States, 2006-2008.

BACKGROUND: Asthma, a chronic respiratory condition affecting 8.2% of the US population (2009), causes significant societal and economic burden, resulting in missed school/work days, activity limitations, and increased healthcare utilization. Annual asthma prevalence estimates are available from national surveys, but these surveys have not routinely collected asthma incidence data that are important for identifying risk factors and trends in rates of disease onset. The Asthma Call-back Survey (ACBS), implemented in 2006, provides detailed asthma data that supplement Behavioral Risk Factor Surveillance System (BRFSS) data. We analyzed BRFSS and ACBS data to estimate annual asthma incidence and to determine whether these rates differed by age group, sex, and race/ethnicity. METHODS: BRFSS and ACBS data from the participating states during 2006-2008 (24 states and District of Columbia [DC] in 2006; 34 states and DC in 2007 and 2008) were analyzed to calculate 12-month incidence rates. Incident cases of asthma were defined as people diagnosed with asthma by a healthcare provider within 12 months prior to survey participation. RESULTS: Estimated asthma incidence among at-risk adults was 3.8/1000, whereas that among at-risk children was 12.5/1000. Incidence among children aged 0-4 years was 23.4/1000, more than five times greater than that among youth aged 12-17 years (4.4/1000). Adult females had 1.8 times greater asthma incidence than adult males (4.9/1000 vs. 2.8/1000, respectively). Incidence among non-Hispanic (NH) White adults was 3.9/1000, among NH non-White adults was 3.2/1000, and among Hispanic adults was 4.0/1000. CONCLUSIONS: This is the first successful application of the BRFSS-ACBS during 2006-2008 to estimate asthma incidence rates from participating states and DC. As with known patterns in asthma prevalence, we found that asthma incidence was higher in children than adults, higher in younger children than older children and adolescents, and higher in adult females than adult males. However, we were unable to identify statistically significant differences in asthma incidence among most race/ethnic groups. As additional data on asthma incidence become available from the ACBS, these rates, coupled with ACBS data on symptoms, asthma self-management practices, and healthcare utilization, may help asthma control programs identify risk factors for disease development and target asthma prevention and control measures to populations most affected.

Knowledge and adoption of community mitigation efforts in Mexico during the 2009 H1N1 pandemic.

BACKGROUND: The public's ability and willingness to adopt community mitigation efforts during a pandemic are debated in the literature. PURPOSE: Awareness and adoption of community mitigation efforts in Mexico during the 2009 pandemic influenza A (H1N1) (pH1N1) outbreak were measured to evaluate if the population received, understood, and acted on public health messages. METHODS: A cross-sectional representative household survey in Mexico City; San Luis Potosi (high case ratio); and Queretaro (low case ratio) was conducted in May and June 2009. Accounting for the complex survey design, percentages and 95% CI for answers to all questions were generated and compared based on living inside or outside Mexico City, high versus low prevalence of infection in the community, and perceived severity and knowledge of the virus. RESULTS: Greater than 90% of respondents received community mitigation messages and adopted one or more community mitigation efforts. There were few differences among cities. Respondents reported high cost of masks, soaps, and gels as barriers to community mitigation-effort adoption. Nearly one fifth of respondents, disproportionally from the lower socioeconomic tertile, found some messages confusing. Half of all households reported a negative economic impact resulting from the outbreak. CONCLUSIONS: Mexico's community mitigation campaign reached the majority of the population in three surveyed cities. Confusion regarding messages and economic barriers to community mitigation-effort adoption were sometimes reported.

Epidemiology of extrapulmonary tuberculosis in the United States, 1993-2006.

BACKGROUND: Almost one-fifth of United States tuberculosis cases are extrapulmonary; unexplained slower annual case count decreases have occurred in extrapulmonary tuberculosis (EPTB), compared with annual case count decreases in pulmonary tuberculosis (PTB) cases. We describe the epidemiology of EPTB by means of US national tuberculosis surveillance data. METHODS: US tuberculosis cases reported from 1993 to 2006 were classified as either EPTB or PTB. EPTB encompassed lymphatic, pleural, bone and/or joint, genitourinary, meningeal, peritoneal, and unclassified EPTB cases. We excluded cases with concurrent extrapulmonary-pulmonary tuberculosis and cases of disseminated (miliary) tuberculosis. Demographic characteristics, drug susceptibility test results, and risk factors, including human immunodeficiency virus (HIV) status, were compared for EPTB and PTB cases. RESULTS: Among 253,299 cases, 73.6% were PTB and 18.7% were EPTB, including lymphatic (40.4%), pleural (19.8%), bone and/or joint (11.3%), genitourinary (6.5%), meningeal (5.4%), peritoneal (4.9%), and unclassified EPTB (11.8%) cases. Compared with PTB, EPTB was associated with female sex (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.7-1.8) and foreign birth (OR, 1.5; CI, 1.5-1.6), almost equally associated with HIV status (OR, 1.1; CI, 1.1-1.1), and negatively associated with multidrug resistance (OR, 0.6; CI, 0.5-0.6) and several tuberculosis risk factors, especially homelessness (OR, 0.3; CI, 0.3-0.3) and excess alcohol use (OR, 0.3; CI, 0.3-0.3). Slower annual decreases in EPTB case counts, compared with annual decreases in PTB case counts, from 1993 through 2006 have caused EPTB to increase from 15.7% of tuberculosis cases in 1993 to 21.0% in 2006. CONCLUSIONS: EPTB epidemiology and risk factors differ from those of PTB, and the proportion of EPTB has increased from 1993 through 2006. Further study is needed to identify causes of the proportional increase in EPTB.

Multidrug-resistant tuberculosis outbreak among US-bound Hmong refugees, Thailand, 2005.

In January 2005, tuberculosis (TB), including multidrug-resistant TB (MDR TB), was reported among Hmong refugees who were living in or had recently immigrated to the United States from a camp in Thailand. We investigated TB and drug resistance, enhanced TB screenings, and expanded treatment capacity in the camp. In February 2005, 272 patients with TB (24 MDR TB) remained in the camp. Among 17 MDR TB patients interviewed, 13 were found to be linked socially. Of 23 MDR TB isolates genotyped, 20 were similar according to 3 molecular typing methods. Before enhanced screening was implemented, 46 TB cases (6 MDR TB) were diagnosed in the United States among 9,455 resettled refugees. After enhanced screening had begun, only 4 TB cases (1 MDR TB), were found among 5,705 resettled refugees. An MDR TB outbreak among US-bound refugees led to importation of disease; enhanced pre-immigration TB screening and treatment decreased subsequent importation.

Isoniazid-monoresistant tuberculosis in the United States, 1993 to 2003.

BACKGROUND: Seven percent of tuberculosis (TB) cases reported to the US National Tuberculosis Surveillance System in 2005 had Mycobacterium tuberculosis isolates with resistance to at least isoniazid. METHODS: We undertook this study to describe demographic characteristics, risk factor information, and treatment outcomes for persons with isoniazid-monoresistant (resistant to isoniazid and susceptible to rifampin, pyrazinamide, and ethambutol hydrochloride) TB compared with persons with TB susceptible to all first-line anti-TB drugs. RESULTS: The numbers of isoniazid-monoresistant TB cases increased from 303 (4.1%) in 1993 to 351 (4.2%) in 2005. In our multivariate analysis of all TB cases reported from 1993 to 2003, the races/ethnicities of patients with isoniazid-monoresistant TB were significantly more likely to be US-born Asian/Pacific Islander (adjusted odds ratio [aOR], 1.9; 95% confidence interval [CI], 1.4-2.6), foreign-born Asian/Pacific Islander (1.8; 1.4-2.1), foreign-born black non-Hispanic (1.4; 1.1-1.7), or US-born Hispanic (1.3; 1.1-1.5). Isoniazid monoresistance was also associated with failure to complete therapy within 1 year (aOR, 1.7; 95% CI, 1.5-1.8), a history of TB (1.5; 1.3-1.7), and correctional facility residence (1.5; 1.2-1.7). CONCLUSIONS: Isoniazid-monoresistant TB did not decline from January 1, 1993, through December 31, 2005, despite national downward trends observed in overall TB cases and in multidrug-resistant TB cases. Physicians must ensure completion of treatment for patients taking isoniazid as part of their TB or latent TB infection therapy. In addition, physicians should maintain heightened vigilance for isoniazid resistance when evaluating certain at-risk populations for TB and latent TB infection.

Investigation of Mycobacterium tuberculosis transmission aboard the U.S.S. Ronald Reagan, 2006.

Pulmonary tuberculosis (TB) was diagnosed in a sailor aboard the U.S.S. Ronald Reagan; an investigation was conducted to determine a screening strategy for 1,172 civilian passengers who were aboard during a temporary guest rider program. Sailors were screened for latent TB infection (LTBI) and TB disease. A case-control study was conducted among sailors to determine factors associated with new LTBI. No secondary TB disease was identified; 13% of close contacts had new LTBI. Factors associated with new LTBI among sailors were having been born outside the United States (adjusted odds ratio = 2.80; 95% confidence interval, 1.55--5.07) and being a carrier air wing member (adjusted odds ratio = 2.89; 95% confidence interval, 1.83--4.58). Among 38 civilian passengers berthed near the patient, 1 (3%) had LTBI. The investigation results indicated that Mycobacterium tuberculosis transmission was minimal and eliminated unnecessary TB screening for 1,134 civilians which saved public health resources.