Thrombocytopenia after vaccination: case reports to the US Vaccine Adverse Event Reporting System, 1990-2008

We reviewed thrombocytopenia (TP) reports to the US Vaccine Adverse Event Reporting System (VAERS). We examined TP patterns for differences in single versus multiple immunization reports, presence of a live viral vaccine, seriousness, age, and interval to symptom onset. We found 1510 reports of possible TP and after exclusions evaluated 1440 for possible causes. Most (1078; 75%) met the regulatory definition of a serious adverse event. TP was reported after inactivated and live viral vaccines. Platelet counts <10 × 10⁹/L were reported. Identified vaccines could be prioritized for hypothesis-testing studies.     

Postmarketing safety surveillance of trivalent recombinant influenza vaccine: Reports to the Vaccine Adverse Event Reporting System

On January 16, 2013, the Food and Drug Administration approved recombinant hemagglutinin influenza vaccine (RIV3) (Spodoptera frugiperda cell line; Flublok), which is the first completely egg-free flu vaccine licensed in the United States. To improve our understanding of the safety profile of this vaccine, we reviewed and summarized reports to the Vaccine Adverse Event Reporting System (VAERS) following RIV3. Through June 30, 2016, VAERS received 88 reports. Allergic reactions, including anaphylaxis, were the most common type of adverse event. Based on medical review, 10 cases met the Brighton Collaboration case definition of anaphylaxis, 21 reports described allergic reactions other than anaphylaxis, and 11 reports described signs and symptoms that suggested hypersensitivity. Other adverse events included injection site reactions, fatigue, myalgia, headache, and fever. The occurrence of anaphylaxis and other allergic reactions in some individuals may reflect an underlying predisposition to atopy that may manifest itself after an exposure to any drug or vaccine, and it does not necessarily suggest a causal relationship with the unique constituents that are specific to the vaccine product administered. Further research may elucidate the mechanism of allergic reactions following influenza vaccination: it is possible that egg proteins and influenza hemagglutinin play little or no role. Vaccination remains the single best defense against influenza and its complications. The information summarized here may enable policy makers, health officials, clinicians, and patients to make a more informed decision regarding vaccination strategies.     

Postmarketing safety surveillance of high-dose quadrivalent influenza vaccine: Reports to the Vaccine Adverse Event Reporting System

On November 4, 2019, the Food and Drug Administration approved high-dose quadrivalent influenza vaccine (Fluzone High-Dose Quadrivalent; QIV-HD) for active immunization for the prevention of influenza disease in individuals 65 years of age and older. A prelicensure randomized, active-controlled, modified double-blind trial did not reveal any major differences in adverse events following QIV-HD versus Fluzone High-Dose (trivalent). To improve our understanding of the safety profile of QIV-HD, we reviewed and summarized reports of adverse events after QIV-HD to the Vaccine Adverse Event Reporting System (VAERS). From July 30, 2020 through June 30, 2021, VAERS received 2,122 reports after QIV-HD. The vast majority (2,018; 95.1%) were non-serious and included events that had been observed in the prelicensure clinical trial, such as injection site reactions, fever, headache, and nausea. The most common serious events included Guillain-Barré syndrome, cellulitis or other local reactions, constitutional signs/symptoms (e.g., fever), and cardiovascular events. Our review did not reveal any new safety concerns. This information may enable policy makers, health officials, clinicians, and patients to make a more informed decision regarding vaccination strategies.     

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.

医疗不良事件报告系统的设计与应用

目的设计科学合理的医疗不良事件报告系统,建立全面的、统一的医疗不良事件标准分类系统和患者安全术语,使不良事件上报管理更加标准化和科学化。方法通过借鉴国内外医疗不良事件报告系统的先进经验,本系统对医疗不良事件从类型、原因、对患者的影响、事后处理、原因分析等项目均设置了大量统一、规范的预设项,报告输入时采用选择题式和简单的描述性语言即可完成不良事件的上报。结论应用医疗不良事件报告系统后,不仅简化了医务人员工作量,提高了不良事件上报率,而且便于管理者对不良事件进行不同角度和纬度的统计分析,采取改进措施,避免类似事件的再次发生。     

不良事件主动报告制度的构建与实践

探讨医院不良事件主动报告流程及策略,提出制定不良事件主动报告制度,设计电子报告流程,采用根本原因分析法调查不良事件,同时引入激励机制和保护机制促进不良事件的主动报告,对及时发现安全隐患、提高医疗质量具有重要意义。     

Safety surveillance of meningococcal group B vaccine (Bexsero®), Vaccine Adverse Event Reporting System, 2015–2018

BackgroundBexsero® (GlaxoSmithKline) is a four-component Neisseria meningitidis serogroup B vaccine (MenB-4C). It was licensed in the United States in 2015 for use among individuals ages 10–25 years. We aimed to assess the post-licensure safety profile of MenB-4C by examining reports received in the Vaccine Adverse Event Reporting System (VAERS).MethodsVAERS is a national passive surveillance system for adverse events (AEs) following immunization that uses the Medical Dictionary for Regulatory Activities to code reported AEs and the Code of Federal Regulations to classify reports by seriousness. In this case series, we analyzed U.S. reports involving MenB-4C received between January 23, 2015 through December 31, 2018. We used Empirical Bayesian data mining to identify MenB-4C/AE combinations reported at least twice as often as expected.ResultsVAERS received 1,867 reports following MenB-4C administration, representing 332 reports per million doses distributed. Most reports were for females (59%), with a median age of 17 years (interquartile range: 16–18 years); 40% of reports described simultaneous administration of other vaccines. The majority of reports were classified as non-serious (96%). The most commonly reported AEs were injection site pain (22%), pyrexia (16%), and headache (16%). Data mining identified disproportionate reporting for “injected limb mobility decreased” secondary to injection site reactions, including extensive swelling of the vaccinated limb and injection site pain.ConclusionsAnalysis of passive surveillance data from over 5.6 million doses of MenB-4C distributed in the United States did not reveal new safety concerns. The large majority of reports were classified as non-serious and the reported AEs were generally consistent with the safety experience described in clinical studies and the product’s package insert. While our results are reassuring, continued post-marketing surveillance is warranted.     

Ischemic cardiac events and other adverse events following ACAM2000 smallpox vaccine in the Vaccine Adverse Event Reporting System

Background

The Vaccine Adverse Event Reporting System (VAERS) is a passive reporting system, used for monitoring the safety of all US licensed vaccines. In March 2008, ACAM2000^® replaced Dryvax^® as the only licensed smallpox vaccine and is administered to all persons entering military service and certain civilian researchers. In 2011, routine data mining of VAERS identified a vaccine safety concern resulting in acute ischemic cardiac events (ICE) following ACAM2000^®.

Methods

During March 1, 2008 through June 30, 2013, we reviewed all serious reports received following ACAM2000^®and classified them by diagnostic category. We identified possible ICE cases by searching the Medical Dictionary for Regulatory Affairs (MedDRA^®) terms for “myocardial ischaemia,” “acute myocardial infarction,” “myocardial infarction,” and “ischaemia,” and applied standardized surveillance case definitions.

Results

VAERS received 1149 reports following ACAM2000^® administration; 169 (14.7%) were serious (resulting in permanent disability, hospitalization or prolongation of hospitalization, life-threatening illness or death), including one death. The two most frequent diagnostic categories for serious reports were cardiovascular and other infectious conditions. The MedDRA^® search found 31 reports of possible ICE after receipt of ACAM2000^® vaccine. Of a total 30 possible ICE cases with demographic information, all but one was male; the age range was 20–45 years (median 32) and median interval to onset of symptoms was 12 days. On clinical review there were 16 cases of myocarditis/pericarditis and 15 ICE cases.

Conclusions

Our review of the data mining signal did not substantiate the concerns about ICE after ACAM2000^®. Our study also suggests that with current pre-vaccination screening, cardiac morbidity in generally healthy vaccinated populations remains uncommon.     

我国医疗安全不良事件报告系统现状分析与对策探讨

医疗不良事件报告是提高医疗质量的重要措施.指出我国医疗不良事件报告系统分为强制报告系统、自愿报告系统、内部报告系统等.从宏观和微观两方面分析了报告系统存在的问题.指出：应科学界定医疗不良事件,应提高系统上报安全性和保密性,应科学改进上报系统,应建立和完善报告激励机制,应实现信息共享,应落实人员培训等.     

医疗不良事件和病人安全隐患报告系统的构建

通过介绍北京协和医院进行医疗不良事件和病人安全隐患事件报告系统工作实务,介绍了在大型综合医院如何结合具体实际情况,探索有效的病人安全实践措施,旨在对医疗机构进行医疗不良事件报告系统和制度的建立、正常运行和完善有所借鉴。     

手术室非惩罚性护理不良事件报告制度的建立

手术室护理不良事件发生率影响因素较多,建立非惩罚性护理不良事件报告制度是非常有效的控制不良事件的通过在本院手术室建立非惩罚性护理不良事件报告制度,分析上报的护理不良事件发生的根本原因并提出修正方案及预防措施,提升护理质量,完善护理流程及管理制度。     

Adverse events after anthrax vaccination reported to the Vaccine Adverse Event Reporting System (VAERS), 1990-2007

During the period March 1, 1998 to January 14, 2007, approximately 6 million doses of Anthrax vaccine adsorbed (AVA) vaccine were administered. As of January 16, 2007, 4753 reports of adverse events following receipt of AVA vaccination had been submitted to the Vaccine Adverse Event Reporting System (VAERS). Taken together, reports to VAERS did not definitively link any serious unexpected risk to this vaccine, and review of death and serious reports did not show a distinctive pattern indicative of a causal relationship to AVA vaccination. Continued monitoring of VAERS and analysis of potential associations between AVA vaccination and rare, serious events is warranted.     

Causality assessment of adverse events reported to the Vaccine Adverse Event Reporting System (VAERS)

Adverse events following immunization (AEFI) reported to the national Vaccine Adverse Event Reporting System (VAERS) represent true causally related events, as well as events that are temporally, but not necessarily causally related to vaccine.     

医疗安全不良事件主动报告系统的设计与实现

本文主要介绍医疗安全不良事件报告系统的总体设计思路、实现方法及主要功能。医疗安全不良事件报告系统的实施对于医院内部防范医疗差错、减少医疗事故提供流程化、规范化的技术手段,为提高医院管理水平、促进医疗服务质量的改善提供支持。     

Safety review of the purified chick embryo cell rabies vaccine: Data from the Vaccine Adverse Event Reporting System (VAERS), 1997-2005

On October 20, 1997, the U.S. Food and Drug Administration (FDA) licensed Purified Chick Embryo Cell (PCEC, RabAvert) vaccine against rabies in humans following clinical trials demonstrating safety and efficacy. From October 1997 through December 2005, the Vaccine Adverse Event Reporting System (VAERS) received 336 reports of adverse events (AEs) following vaccination with PCEC vaccine in the U.S.; there were no death reports. Serious events, including 20 hospitalizations and 13 neurological events, were described in 24 (7%) reports. There was no pattern among the 13 neurological AEs suggesting a plausible relationship to vaccination. A total of 20 AEs, 3 serious, were classified as possible anaphylaxis. There were 312 non-serious AEs (93%). Nineteen reports (6%) described that the vaccination series was discontinued because of non-serious AEs. Most reported AEs are non-serious and consistent with pre-licensure safety data. The rabies risk must be carefully considered before vaccine discontinuation.     

A comparative assessment of immunization records in the Defense Medical Surveillance System and the Vaccine Adverse Event Reporting System

We compared immunization data in the Defense Medical Surveillance System (DMSS) and immunization data for service members with an anthrax vaccine-associated adverse event reported to the Vaccine Adverse Event Reporting System (VAERS) during January 1998 through December 2004. Our main measure of agreement was sensitivity of the DMSS conditional on an immunization record(s) occurring in VAERS. The sensitivity of DMSS was 73% for all vaccines and 74% for the anthrax vaccine on the VAERS index immunization date. Our study is the first to quantify the agreement between immunization records in VAERS and DMSS. Our data suggest the immunization information in military VAERS reports and the DMSS is similar for anthrax and non-anthrax immunizations.     

Elective termination of pregnancy after vaccination reported to the Vaccine Adverse Event Reporting System (VAERS): 1990-2006

Generally, live-virus vaccines are contraindicated for pregnant women because of the theoretical risk of transmission of the vaccine virus to the fetus. Advisory groups recommend avoiding pregnancy in the immediate period after administration of such contraindicated vaccines (CVs) and stress benefit-to-risk evaluation for live or inactivated vaccines regarding pregnancy. Given the limited available data and theoretical risks associated particularly with live-virus vaccines, inadvertent immunization with CVs may lead to elective termination of pregnancy (ETP), despite advisory group statements that "vaccination is not ordinarily an indication to terminate the pregnancy." The Vaccine Adverse Event Reporting System (VAERS), a national passive surveillance system managed by the Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC), accepts reports of adverse events after vaccination. The objectives of this review were to describe reports of ETP in VAERS and characterize the circumstances of inadvertent administration of vaccines to pregnant women among ETP reports. We reviewed VAERS reports of ETP submitted from 1990 to 2006. Reports of ETP for reasons other than vaccination during or shortly before pregnancy, such as fetal abnormalities or deaths, were excluded. Of 80 ETP reports, 62 (78%) originated from the US; 79 (99%) were reported by manufacturers. Median age of vaccinees was 26 years (range: 13-43 years; 67 reports). Seventy-three vaccinees (91%) received a single vaccine; 65 (81%) received at least one live-virus vaccine. In 48 (60%) ETP reports, vaccinees were unaware of pregnancy at time of immunization. In 15 (19%) reports, vaccinees became pregnant within 3 months of vaccination; in 13 (16%) reports, vaccinees might have been pregnant before vaccination; in 4 (5%) reports, information was missing. All 80 reports of ETP involved vaccines for which possible effects on fetal development are unknown. However, no cases of vaccine-associated congenital rubella or varicella syndromes have been reported in the medical literature. Also, these syndromes have not been reported to varicella or rubella vaccine pregnancy registries. VAERS has the limitations of passive surveillance systems. Under-reporting of ETP in VAERS could be substantial. More attention may be needed to assess the likelihood of pregnancy when administering vaccines to women with child-bearing potential, and to inform women who learn they are pregnant shortly after being immunized of current information on risks. Quantifying the frequency of ETP related to CVs and the risk (if any) to the fetus of such vaccines can help to inform policy, practice, and individual decision making. Good quality information may be obtained from controlled observational studies.     

Adverse events after tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine administered to adults 65 years of age and older reported to the Vaccine Adverse Event Reporting System (VAERS), 2005-2010

Background

Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine was not licensed for use in adults aged ≥65 years due to lack of sufficient efficacy and safety data.

Objective

To characterize reports to the Vaccine Adverse Event Reporting System (VAERS) among adults aged ≥65 years who received Tdap vaccine ‘off-label’ to assess for potential vaccine safety concerns.

Methods

We searched VAERS for US reports of adverse events (AEs) in subjects aged ≥65 years who received Tdap vaccine from 9/1/2005 to 9/08/2010. Medical records were requested for all reports coded as serious (death, hospitalization, prolonged hospitalization, permanent disability, life-threatening-illness). Proportional reporting ratio (PRR) was used to assess for higher proportionate reporting for AEs after Tdap compared with Td reports in subjects aged ≥65 years.

Results

VAERS received 243 reports following Tdap administered to persons aged ≥65 years. Eleven (4.5%) reports were serious, including two deaths. Most common AEs were local reactions in 100 (41.2%) reports. Seventy-eight (32.1%) reports contained coding terms that denoted inappropriate administration of vaccine. ‘Cough’ was the only term associated with disproportionately higher reporting after Tdap compared with Td. Six of seven Tdap reports containing the term ‘Cough’ were non-serious. Clinical review of serious reports identified no unusual patterns of AEs.

Conclusion

Our VAERS review of the ‘off-label’ use of Tdap vaccine in adults ≥65 years did not find any safety concerns that warrant further study. These data will provide useful baseline information to assist CDC and FDA with monitoring efforts as permissive recommendations for Tdap in older persons are adopted.     

Vaccination of persons allergic to latex: a review of safety data in the Vaccine Adverse Event Reporting System (VAERS)

Vaccine products currently licensed in the US and other countries are marketed in vials and syringes that may contain natural latex allergens. Little scientific information exists regarding the safety of vaccination of latex-allergic individuals. A review of data within the Vaccine Adverse Event Reporting System (VAERS), a large registry of reported possible vaccine adverse reactions was conducted. A search of the database, which contains >160,000 vaccine adverse event reports, revealed only 28 cases of possible immediate-type hypersensitivity reactions in vaccine recipients with a history of allergy to latex. Given the large number of immunizations administered every year in the US, the reported risk of allergic reactions possibly due to latex contamination of vaccines appears to be very small.