Post-licensure surveillance of trivalent adjuvanted influenza vaccine (aIIV3; Fluad), Vaccine Adverse Event Reporting System (VAERS), United States, July 2016-June 2018.

BACKGROUND: Trivalent adjuvanted influenza vaccine (aIIV3; Fluad®) was approved in the United States (U.S.) in 2015 for adults aged ≥65 years and has been in use since the 2016-17 influenza season. METHODS: We analyzed U.S. reports for aIIV3 submitted from July 1, 2016 through June 30, 2018 to the Vaccine Adverse Event Reporting System (VAERS), a national spontaneous reporting system. Medical records were reviewed for serious reports. Among individuals ≥65 years of age, the relative frequency of the most commonly reported adverse events (AEs) after aIIV3 were compared with non-adjuvanted inactivated influenza vaccines given to adults aged ≥65 years, high-dose trivalent influenza vaccine (IIV3-HD) and trivalent or quadrivalent vaccines (IIV3/IIV4). Data mining analyses were undertaken to identify whether AEs for aIIV3 occurred disproportionately more than expected compared to all influenza vaccines. RESULTS: VAERS received 630 reports after aIIV3, of which 521 (83%) were in adults aged ≥65 years; 79 (13%) in persons <65 years and in 30 (5%) reports age was missing; 19 (3%) reports were serious, including two deaths (0.4%) related to myocardial infarction and Sjogren's syndrome. The most common AEs reported in adults aged ≥65 years were injection site pain (21%) and erythema (18%), with similar proportions reported for IIV3-HD (17% and 19%, respectively) and for IIV3/IIV4 (15%, each). Except for reports related to vaccination of inappropriate age (n = 79) and syringe malfunction (n = 6), data mining did not identify other disproportionately reported AEs. CONCLUSIONS: Although our review of aIIV3 in VAERS did not identify any unexpected health conditions of concern, we observed more than twice the expected number of reports with administration of the vaccine to persons outside of the age range for which the vaccine is approved in the U.S. Health care providers should be educated on the age groups for whom aIIV3 is recommended.

Postlicensure Safety Surveillance of Recombinant Zoster Vaccine (Shingrix) - United States, October 2017-June 2018.

Recombinant zoster vaccine (RZV; Shingrix), an adjuvanted glycoprotein vaccine, was licensed by the Food and Drug Administration (FDA) and recommended by the Advisory Committee on Immunization Practices for adults aged ≥50 years in October 2017 (1). The previously licensed live-attenuated zoster vaccine (ZVL; Zostavax) is recommended for adults aged ≥60 years. RZV is administered intramuscularly as a 2-dose series, with an interval of 2-6 months between doses. In prelicensure clinical trials, 85% of 6,773 vaccinated study participants reported local or systemic reactions after receiving RZV, with approximately 17% experiencing a grade 3 reaction (erythema or induration >3.5 inches or systemic symptoms that interfere with normal activity). However, rates of serious adverse events (i.e., hospitalization, prolongation of existing hospitalization, life-threatening illness, permanent disability, congenital anomaly or birth defect, or death) were similar in the RZV and placebo groups (2). After licensure, CDC and FDA began safety monitoring of RZV in the Vaccine Adverse Event Reporting System (VAERS) (3). During the first 8 months of use, when approximately 3.2 million RZV doses were distributed (GlaxoSmithKline, personal communication, 2018), VAERS received a total of 4,381 reports of adverse events, 130 (3.0%) of which were classified as serious. Commonly reported signs and symptoms included pyrexia (fever) (1,034; 23.6%), injection site pain (985; 22.5%), and injection site erythema (880; 20.1%). No unexpected patterns were detected in reports of adverse events or serious adverse events. Findings from early monitoring of RZV are consistent with the safety profile observed in prelicensure clinical trials.

Safety of 9-valent human papillomavirus vaccine administration among pregnant women: Adverse event reports in the Vaccine Adverse Event Reporting System (VAERS), 2014-2017.

INTRODUCTION: 9-valent human papillomavirus vaccine (9vHPV) was approved by the Food and Drug Administration (FDA) in December 2014. 9vHPV is not recommended during pregnancy, but some women of childbearing age may be inadvertently exposed. This study aims to evaluate reports submitted to the Vaccine Adverse Event Reporting System (VAERS) of pregnant women exposed to 9vHPV. METHODS: We searched the VAERS database, a national post-licensure vaccine safety surveillance system, for reports of pregnant women vaccinated with 9vHPV in the United States between December 10, 2014 and December 31, 2017. Disproportionate reporting of adverse events (AEs) was assessed using proportional reporting ratios (PRRs). RESULTS: A total of 82 pregnancy reports were identified. Sixty reports (73.2%) did not describe an AE and were submitted only to report the vaccine exposure during pregnancy. The most frequently reported pregnancy-specific AE was spontaneous abortion (n = 3; 3.7%), followed by vaginal bleeding (n = 2; 2.4%). Among non-pregnancy-specific AEs, injection site reaction (n = 3; 3.7%) was most common. No disproportionate reporting of any AE was found. DISCUSSION: No unexpected AEs were observed among these pregnancy reports.

Anaphylaxis after vaccination reported to the Vaccine Adverse Event Reporting System, 1990-2016.

BACKGROUND: Anaphylaxis, a rare and potentially life-threatening hypersensitivity reaction, can occur after vaccination. OBJECTIVE: We sought to describe reports of anaphylaxis after vaccination made to the Vaccine Adverse Event Reporting System (VAERS) during 1990-2016. METHODS: We identified domestic reports of anaphylaxis within VAERS using a combination of Medical Dictionary for Regulatory Activity queries and Preferred Terms. We performed a descriptive analysis, including history of hypersensitivity (anaphylaxis, respiratory allergies, and drug allergies) and vaccines given. We reviewed all serious reports and all nonserious reports with available medical records to determine if they met the Brighton Collaboration case definition for anaphylaxis or received a physician's diagnosis. RESULTS: During the analytic period, VAERS received 467,960 total reports; 828 met the Brighton Collaboration case definition or received a physician's diagnosis of anaphylaxis: 654 (79%) were classified as serious, and 669 (81%) had medical records available. Of 478 reports in children aged less than 19 years, 65% were male; childhood vaccines were most commonly reported. Of 350 reports in persons aged 19 years or greater, 80% were female, and influenza vaccines were most frequently reported. Overall, 41% of reports described persons with no history of hypersensitivity. We identified 8 deaths, 4 among persons with no history of hypersensitivity. CONCLUSION: Anaphylaxis after vaccination is rare in the United States and can occur among persons with no history of hypersensitivity. Most persons recover fully with treatment, but serious complications, including death, can occur.

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

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

Safety Surveillance of Diphtheria and Tetanus Toxoids and Acellular Pertussis (DTaP) Vaccines.

OBJECTIVE: To assess the safety of currently licensed diphtheria-tetanus-acellular pertussis (DTaP) vaccines in the United States by using data from the Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting surveillance system. METHODS: We searched VAERS for US reports of DTaP vaccinations occurring from January 1, 1991, through December 31, 2016, and received by March 17, 2017. We reviewed available medical records for all death reports and a random sample of reports classified as nondeath serious. We used Empirical Bayesian data mining to identify adverse events that were disproportionally reported after DTaP vaccination. RESULTS: VAERS received 50 157 reports after DTaP vaccination; 43 984 (87.7%) of them reported concomitant administration of other vaccines, and 5627 (11.2%) were serious. Median age at vaccination was 19 months (interquartile range 35 months). The most frequently reported events were injection site erythema (12 695; 25.3%), pyrexia (9913; 19.8%), injection site swelling (7542; 15.0%), erythema (5599; 11.2%), and injection site warmth (4793; 9.6%). For 3 of the DTaP vaccines, we identified elevated values for vaccination errors using Empirical Bayesian data mining. CONCLUSIONS: No new or unexpected adverse events were detected. The observed disproportionate reporting for some nonserious vaccination errors calls for better education of vaccine providers on the specific indications for each of the DTaP vaccines.

Adverse events after vaccination among HIV-positive persons, 1990-2016.

Human immunodeficiency virus (HIV) causes immune dysregulation, potentially affecting response to vaccines in infected persons. We investigated if unexpected adverse events (AEs) or unusual patterns of AEs after vaccination were reported among HIV-positive persons. We searched for domestic reports among HIV-positive persons to the Vaccine Adverse Event Reporting System (VAERS) during 1990-2016. We analyzed reports by age group (<19 and ≥19 years), sex, serious or non-serious status, live vaccine type (live versus inactivated), AEs reported, and CD4 counts. Of 532,235 reports received, 353 (0.07%) described HIV-positive persons, of whom 67% were aged ≥19 years, and 57% were male; most reports (75%) were non-serious. The most commonly reported inactivated vaccines were pneumococcal polysaccharide (27%) and inactivated influenza (27%); the mostly reported common live virus vaccines were combination measles, mumps, and rubella (8%) and varicella (6%). Injection site reactions were commonly reported (39%). Of 67 reports with CD4 counts available, 41 (61%) described persons immunocompromised at time of vaccination (CD4 count <500 cells/mm3), and differed from overall reports only in that varicella was the most common live virus vaccine (4 reports). Of 22 reports describing failure to protect against infection, 6 described persons immunocompromised at time of vaccination, among whom varicella vaccine was most common (3 reports). Of 66 reports describing live virus vaccines, 7 described persons with disseminated infection: 6 had disseminated varicella, 3 of whom had vaccine strain varicella-zoster virus. Of 18 reported deaths, 7 resulted from disseminated infection: 6 were among immunocompromised persons, 1 of whom had vaccine strain varicella-zoster virus. We identified no unexpected or unusual patterns of AEs among HIV-positive persons. These data reinforce current vaccine recommendations for this risk group. However, healthcare providers should know their HIV-positive patients' immune status because immunocompromising conditions can potentially increase the risk of rare, but severe, AEs following vaccination with live virus vaccines.

Post-licensure safety surveillance of zoster vaccine live (Zostavax®) in the United States, Vaccine Adverse Event Reporting System (VAERS), 2006-2015.

BACKGROUND: Herpes zoster (HZ), or shingles, is caused by reactivation of varicella-zoster virus in latently infected individuals. Live-attenuated HZ vaccine (zoster vaccine live, ZVL) is approved in the United States for persons aged ≥50 years and recommended by the CDC for persons ≥60 years. METHODS: We analyzed U.S. reports of adverse events (AEs) following ZVL submitted to the Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting system to monitor vaccine safety, for persons vaccinated May 1, 2006, through January 31, 2015. We conducted descriptive analysis, clinical reviews of reports with selected pre-specified conditions, and empirical Bayesian data mining. RESULTS: VAERS received 23,092 reports following ZVL, of which 22,120 (96%) were classified as non-serious. Of reports where age was documented (n = 18,817), 83% were in persons aged ≥60 years. Reporting rates of AEs were 106 and 4.4 per 100,000 ZVL doses distributed for all reports and serious reports, respectively. When ZVL was administered alone among persons aged ≥50 years, injection site erythema (27%), HZ (17%), injection site swelling (17%), and rash (14%) were the most commonly reported symptoms among non-serious reports; HZ (29%), pain (18%), and rash (16%) were the most commonly reported symptoms among serious reports. Six reports included laboratory evidence of vaccine-strain varicella-zoster virus (Oka/Merck strain) infection; AEs included HZ, HZ- or varicella-like illness, and local reaction with vesicles. In our review of reports of death with sufficient information to determine cause (n = 46, median age 75 years), the most common causes were heart disease (n = 28), sepsis (n = 4), and stroke (n = 3). Empirical Bayesian data mining did not detect new or unexpected safety signals. CONCLUSIONS: Findings from our safety review of ZVL are consistent with those from pre-licensure clinical trials and other post-licensure assessments. Transient injection-site reactions, HZ, and rashes were most frequently reported to VAERS following ZVL. Overall, our results are reassuring regarding the safety of ZVL.

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

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

Safety of vaccines that have been kept outside of recommended temperatures: Reports to the Vaccine Adverse Event Reporting System (VAERS), 2008-2012.

BACKGROUND: Vaccines should be stored and handled according to manufacturer specifications. Inadequate cold chain management can affect potency; but, limited data exist on adverse events (AE) following administration of vaccines kept outside of recommended temperatures. OBJECTIVE: To describe reports to the Vaccine Adverse Event Reporting System (VAERS) involving vaccines inappropriately stored outside of recommended temperatures and/or exposed to temperatures outside of manufacturer specifications for inappropriate amounts of time. METHODS: We searched the VAERS database (analytic period 2008-2012) for reports describing vaccines kept outside of recommended temperatures. We analyzed reports by vaccine type, length outside of recommended temperature and type of temperature excursion, AE following receipt of potentially compromised vaccine, and reasons for cold chain breakdown. RESULTS: We identified 476 reports of vaccines kept outside of recommended temperatures; 77% described cluster incidents involving multiple patients. The most commonly reported vaccines were quadrivalent human papillomavirus (n = 146, 30%), 23-valent pneumococcal polysaccharide (n = 51, 11%), and measles, mumps, and rubella (n = 45, 9%). Length of time vaccines were kept outside of recommended temperatures ranged from 15 mins to 6 months (median 51 h). Most (n = 458, 96%) reports involved patients who were administered potentially compromised vaccines; AE were reported in 32 (7%), with local reactions (n = 21) most frequent. Two reports described multiple patients contracting diseases they were vaccinated against, indicating possible influenza vaccine failure. Lack of vigilance, inadequate training, and equipment failure were reasons cited for cold chain management breakdowns. CONCLUSIONS: Our review does not indicate any substantial direct health risk from administration of vaccines kept outside of recommended temperatures. However, there are potential costs and risks, including vaccine wastage, possible decreased protection, and patient and parent inconvenience related to revaccination. Maintaining high vigilance, proper staff training, regular equipment maintenance, and having adequate auxiliary power are important components of comprehensive vaccine cold chain management.

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

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

Assessing the safety of hepatitis B vaccination during pregnancy in the Vaccine Adverse Event Reporting System (VAERS), 1990-2016.

BACKGROUND: The safety of hepatitis B vaccination during pregnancy has not been well studied. OBJECTIVE: We characterized adverse events (AEs) after hepatitis B vaccination of pregnant women reported to the Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting surveillance system. METHODS: We searched VAERS for AEs reports involving pregnant women who received hepatitis B vaccine from January 1, 1990-June 30, 2016. All reports and available medical records were reviewed by physicians. Observed AEs were compared to expected AEs and known rates of pregnancy outcomes to assess for any unexpected safety concern. RESULTS: We found 192 reports involving pregnant women following hepatitis B vaccination of which 110 (57.3%) described AEs; 12 (6.3%) were classified as serious; one newborn death was identified in a severely premature delivery, and there were no maternal deaths. Eighty-two (42.7%) reports did not describe any AEs. Among pregnancies for which gestational age was reported, most women were vaccinated during the first trimester, 86/115 (74.7%). Among reports describing an AE, the most common pregnancy-specific outcomes included spontaneous abortion in 23 reports, preterm delivery in 7 reports, and elective termination in 5 reports. The most common non-pregnancy specific outcomes were general disorders and administration site conditions, such as injection site and systemic reactions, in 21 reports. Among 22 reports describing an AE among infants born to women vaccinated during pregnancy, 5 described major birth defects each affecting different organ systems. CONCLUSION: Our analysis of VAERS reports involving hepatitis B vaccination during pregnancy did not identify any new or unexpected safety concerns.

A multi-site feasibility study to assess fever and wheezing in children after influenza vaccines using text messaging.

BACKGROUND: Using text messaging for vaccine safety monitoring, particularly for non-medically attended events, would be valuable for pandemic influenza and emergency vaccination program preparedness. We assessed the feasibility and acceptability of text messaging to evaluate fever and wheezing post-influenza vaccination in a prospective, observational, multi-site pediatric study. METHODS: Children aged 2-11 years old, with an emphasis on children with asthma, were recruited during the 2014-2015 influenza season from three community-based clinics in New York City, and during the 2014-2015 and 2015-2016 seasons from a private practice in Fall River, Massachusetts. Parents of enrolled children receiving quadrivalent live attenuated (LAIV4) or inactivated influenza vaccine (IIV4) replied to text messages assessing respiratory symptoms (day 3 and 7, then weekly through day 42), and temperature on the night of vaccination and the next seven nights (day 0-7). Missing data were collected via diary (day 0-7 only) and phone. Phone confirmation was obtained for both presence and absence of respiratory symptoms. Reporting rates, fever (T≥100.4 °F) frequency, proportion of wheezing and/or chest tightness reports captured via text message versus all sources (text, phone, diary, electronic health record) and parental satisfaction were assessed. RESULTS: Across both seasons, 266 children were analyzed; 49.2% with asthma. Parental text message response rates were high (>70%) across sites. Overall, fever frequency was low (day 0-2: 4.1% [95% confidence interval (CI) 2.3-7.4%]; d3-7: 6.7% [95% CI 4.1-10.8%]). A third (39.2%) of parents reported a respiratory problem in their child, primarily cough. Most (88.2%) of the 52 wheezing and/or chest tightness reports were by text message. Most (88.1%) participants preferred text messaging over paper reporting. CONCLUSIONS: Text messaging can provide information about pediatric post-vaccination fever and wheezing and was viewed positively by parents. It could be a helpful tool for rapid vaccine safety monitoring during a pandemic or other emergency vaccination program. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02295007.

Reports of Postural Orthostatic Tachycardia Syndrome After Human Papillomavirus Vaccination in the Vaccine Adverse Event Reporting System.

PURPOSE: Human papillomavirus (HPV) vaccination prevents infections with HPV strains that cause certain cancers. Reports of postural orthostatic tachycardia syndrome (POTS) following HPV vaccination have raised safety concerns. We reviewed POTS reports submitted to the Vaccine Adverse Event Reporting System (VAERS). METHODS: We searched the VAERS database for reports of POTS following any type of HPV vaccination (bivalent, quadrivalent, or nonavalent) from June 2006 to August 2015. We reviewed reports and applied established POTS diagnostic criteria. We calculated unadjusted POTS case reporting rates based on HPV vaccine doses distributed and conducted empirical Bayesian data mining to screen for disproportional reporting of POTS following HPV vaccination. RESULTS: Among 40,735 VAERS reports following HPV vaccination, we identified 29 POTS reports that fully met diagnostic criteria. Of these, 27 (93.1%) were in females and mean age was 14 years (range 12-32). Median time from vaccination to start of symptoms was 43 days (range 0-407); most (18, 75.0%) had onset between 0 and 90 days. Symptoms frequently reported concomitantly included headache (22, 75.9%) and dizziness (21, 72.4%). Twenty (68.9%) reports documented a history of pre-existing medical conditions, of which chronic fatigue (5, 17.2%), asthma (4, 13.8%), and chronic headache (3, 10.3%) were most common. Approximately one POTS case is reported for every 6.5 million HPV vaccine doses distributed in the United States. No empirical Bayesian data mining safety signals for POTS and HPV vaccination were detected. CONCLUSIONS: POTS is rarely reported following HPV vaccination. Our review did not detect any unusual or unexpected reporting patterns that would suggest a safety problem.

Major Birth Defects after Vaccination Reported to the Vaccine Adverse Event Reporting System (VAERS), 1990 to 2014.

BACKGROUND: Major birth defects are important infant outcomes that have not been well studied in the postmarketing surveillance of vaccines given to pregnant women. We assessed the presence of major birth defects following vaccination in the Vaccine Adverse Event Reporting System (VAERS), a national spontaneous reporting system used to monitor the safety of vaccines in the United States. METHODS: We searched VAERS for reports of major birth defects during January 1, 1990, through December 31, 2014. We excluded birth defects from vaccines that had been studied in pregnancy registries or other epidemiological studies (e.g., human papilloma virus, varicella, measles/mumps/rubella, and anthrax vaccines). Birth defects were categorized into trimester of vaccination and classified based on the organs and/or systems affected. If several birth defects affecting different systems were described, we classified those as multiple body systems. Empirical Bayesian data mining was used to assess for disproportionate reporting. RESULTS: We identified 50 reports of major birth defects; in 28 reports, the vaccine was given during the first trimester; 25 were reports with single vaccines administered. Birth defects accounted for 0.03% of all reports received by VAERS during the study period and 3.2% of pregnancy reports; reported defects affected predominately the musculoskeletal (N = 10) or nervous (N = 10) systems. No unusual clusters or specific birth defects were identified. CONCLUSION: This review of the VAERS database found that major birth defects were infrequently reported, with no particular condition reported disproportionally. Birth defects after routine maternal vaccination will continue to be monitored in VAERS for signals to prompt future studies. Birth Defects Research 109:1057-1062, 2017. © 2017 Wiley Periodicals, Inc.

Feasibility of Text Message Influenza Vaccine Safety Monitoring During Pregnancy.

INTRODUCTION: The feasibility and accuracy of text messaging to monitor events after influenza vaccination throughout pregnancy and the neonatal period has not been studied, but may be important for seasonal and pandemic influenza vaccines and future maternal vaccines. METHODS: This prospective observational study was conducted during 2013-2014 and analyzed in 2015-2016. Enrolled pregnant women receiving inactivated influenza vaccination at a gestational age <20 weeks were sent text messages intermittently through participant-reported pregnancy end to request fever, health events, and neonatal outcomes. Text message response rates, Day 0-2 fever (≥100.4°F), health events, and birth/neonatal outcomes were assessed. RESULTS: Most (80.2%, n=166) eligible women enrolled. Median gestational age was 8.9 (SD=3.9) weeks at vaccination. Response rates remained high (80.0%-95.2%). Only one Day 0-2 fever was reported. Women reported via text both pregnancy- and non-pregnancy-specific health events, not all associated with medical visits. Most pregnancy-specific events in the electronic medical record (EMR) were reported via text message. Of all enrollees, 84.9% completed the study (131 reported live birth, ten reported pregnancy loss). Two losses reported via text were not medically attended; there was one additional EMR-identified loss. Gestational age and weight at birth were similar between text message-reported and EMR-abstracted data and 95% CIs were overlapping for proportions of prematurity, low birth weight, small for gestational age, and major birth defects, as identified by text message-reported versus EMR-abstracted plus text message-reported versus EMR-abstracted data only. CONCLUSIONS: This study demonstrated the feasibility of text messaging for influenza vaccine safety surveillance sustained throughout pregnancy. In these women receiving inactivated influenza vaccination during pregnancy, post-vaccination fever was infrequent and a typical pattern of maternal and neonatal health outcomes was observed.

Adverse events following quadrivalent meningococcal CRM-conjugate vaccine (Menveo®) reported to the Vaccine Adverse Event Reporting system (VAERS), 2010-2015.

BACKGROUND: Limited data are available describing the post-licensure safety of meningococcal vaccines, including Menveo®. We reviewed reports of adverse events (AEs) to the Vaccine Adverse Event Reporting System (VAERS) to assess safety in all age groups. METHODS: VAERS is a national spontaneous vaccine safety surveillance system co-administered by the Centers for Disease Control and Prevention and the US Food and Drug Administration. We searched the VAERS database for US reports of adverse events in persons who received Menveo from 1 January 2010 through 31 December 2015. We clinically reviewed reports and available medical records for serious AEs, selected pre-specified outcomes, and vaccination during pregnancy. We used empirical Bayesian data mining to identify AEs that were disproportionately reported after receipt of Menveo. RESULTS: During the study period, VAERS received 2614 US reports after receipt of Menveo. Of these, 67 were classified as serious, including 1 report of death. Adolescents (aged 11-18years) accounted for 74% of reports. Most of the reported AEs were non-serious and described AEs consistent with data from pre-licensure studies. Anaphylaxis and syncope were the two most common events in the serious reports. We did not identify any new safety concerns after review of AEs that exceeded the data mining threshold, although we did observe disproportionate reporting for terms that were not associated with an adverse event (e.g., "incorrect drug dosage form administered", "wrong technique in drug usage process"). Although reports were limited, we did not find any evidence for concern regarding the use of Menveo during pregnancy. CONCLUSIONS: In our review of VAERS reports, findings of AEs were consistent with the data from pre-licensure studies. Vaccine providers should continue to emphasize and adhere to proper administration of the vaccine.

Safety of Second-Dose Single-Antigen Varicella Vaccine.

BACKGROUND AND OBJECTIVE: In 2006, routine 2-dose varicella vaccination for children was recommended to improve control of varicella. We assessed the safety of second-dose varicella vaccination. METHODS: We identified second-dose single-antigen varicella vaccine reports in the Vaccine Adverse Event Reporting System during 2006 to 2014 among children aged 4 to 18 years. We analyzed reports by age group (4-6 and 7-18 years), sex, serious or nonserious status, most common adverse events (AEs), and whether other vaccines were administered concomitantly with varicella vaccine. We reviewed serious reports of selected AEs and conducted empirical Bayesian data mining to detect disproportional reporting of AEs. RESULTS: We identified 14 641 Vaccine Adverse Event Reporting System reports after second-dose varicella vaccination, with 494 (3%) classified as serious. Among nonserious reports, injection site reactions were most common (48% of children aged 4-6 years, 38% of children aged 7-18 years). The most common AEs among serious reports were pyrexia (31%) for children aged 4 to 6 years and headache (28%) and vomiting (27%) for children aged 7 to 18 years. Serious reports of selected AEs included anaphylaxis (83), meningitis (5), encephalitis (16), cellulitis (52), varicella (6), herpes zoster (6), and deaths (7). One immunosuppressed adolescent was reported with vaccine-strain herpes zoster. Only previously known AEs were reported more frequently after second-dose varicella vaccination compared with other vaccines. CONCLUSIONS: We identified no new or unexpected safety concerns for second-dose varicella vaccination. Robust safety monitoring remains an important component of the national varicella vaccination program.

Assessing Fever Frequency After Pediatric Live Attenuated Versus Inactivated Influenza Vaccination.

BACKGROUND: Some studies have found a higher frequency of fever with trivalent live attenuated influenza vaccine (LAIV) than with inactivated influenza vaccine (IIV), but quadrivalent LAIV has not been assessed. Understanding fever is important for safety reviews and for parents and providers. In addition, there have been only a limited number of studies in which text messaging was used for vaccine adverse-event (AE) surveillance. METHODS: We conducted a prospective observational study in 3 community clinics in New York City to assess post-influenza vaccination fever in 24- to 59-month-olds during the 2013-2014 season. Enrolled families of children who received quadrivalent LAIV (LAIV4) or IIV (trivalent IIV3 or quadrivalent IIV4) replied to text messages that assessed their temperature on vaccination night and the next 10 nights (days 0 to 10); missing data were collected via telephone and a diary. We compared frequencies of fever (temperature ≥ 100.4°F) according to vaccine group on days 0 to 2 and 3 to 10 by using χ2 and multivariate log-binomial regression adjusted for age, previous influenza vaccination, and vaccine coadministration. We also assessed outcomes using all sources versus only text messages. RESULTS: Most (84.1% [n = 540]) eligible parents enrolled. Fever frequencies on days 0 to 2 did not differ between LAIV4 and any IIV (3.8% vs 5.7%, respectively; adjusted relative risk [aRR] [95% confidence interval], 0.60 [0.25-1.46]), between LAIV4 and IIV4 (4.2% vs 7.1%, respectively; aRR, 0.58 [0.19-1.72]), or between IIV4 and IIV3 (7.1% vs 6.0%, respectively; aRR, 1.02 [0.30-3.46]). The findings were similar when all data sources versus text-message data alone were used. There were no significant differences on days 3 to 10. CONCLUSIONS: Postvaccination fever frequencies were low overall and did not differ according to influenza vaccine type during the 2013-2014 influenza season. The similarity of results when data were limited to text messages lends support to its use for surveillance of vaccine adverse events.