Safety of influenza vaccination during pregnancy.
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Adverse Drug Reaction Reporting Systems↗
Biomedical subjects
John Iskander
Publications and source records attributed to John Iskander.
Data mining in the US using the Vaccine Adverse Event Reporting System.
The US Vaccine Adverse Event Reporting System (VAERS), which is charged with vigilance for detecting vaccine-related safety issues, faces an increasingly complex immunisation environment. Since 1990, steady increases in vaccine licensing and distribution have resulted in increasing numbers of reports to VAERS. Prominent features of current reports include more routine vaccine co-administration and frequent reports of new postvaccination clinical syndromes. Data-mining methods, based on disproportionality analyses, are one strategy being pursued by VAERS researchers to increase the utility of its complex database. The types of analyses used include proportional reporting ratios, association rule discovery, and various 'historic limits' methods that compare observed versus expected event counts. The use of such strategies in VAERS has been primarily supplemental and retrospective. Signals for inactivated influenza, typhoid and tetanus toxoid-containing vaccines have been successfully identified. Concerns flagged through data mining should always be subject to clinical case review as a first evaluation step. Persistent issues should be subject to formal hypothesis testing in large linked databases or other controlled-study settings. Automated data-mining techniques for prospective use are currently undergoing development and evaluation within VAERS. Their use (as one signal-detection tool among many) by trained medical evaluators who are aware of system limitations is one legitimate approach to improving the ability of VAERS to generate vaccine-safety hypotheses. Such approaches are needed as more new vaccines continue to be licensed.
Adverse Drug Reaction Reporting Systems↗
Adverse events reported following live, cold-adapted, intranasal influenza vaccine.
CONTEXT: In June 2003, the US Food and Drug Administration licensed a trivalent live, attenuated influenza vaccine (LAIV-T) for intranasal administration to healthy persons 5 to 49 years of age. Although prelicensure testing involved 20 228 vaccinees, clinical trials were not of sufficient size to detect rare adverse events reliably. OBJECTIVE: To identify adverse events reported following LAIV-T administration after licensure. DESIGN, SETTING, AND PARTICIPANTS: All adverse events reported to the US Vaccine Adverse Event Reporting System (VAERS) during the 2003-2004 and the 2004-2005 influenza seasons. MAIN OUTCOME MEASURES: Numbers and proportions of reported adverse events and reporting rates of adverse events per 100,000 vaccinees. RESULTS: Approximately 2,500,000 persons received LAIV-T during the first 2 postlicensure seasons. As of August 16, 2005, VAERS received 460 adverse event reports for vaccinations received from August 2003 through July 2005. No fatalities were reported. There were 7 reports of possible anaphylaxis, 2 reports of Guillain-Barré syndrome, 1 report of Bell palsy, and 8 reports of asthma exacerbation among individuals with a prior asthma history. Events in individuals for whom the vaccine was not indicated accounted for 73 reports (16%). CONCLUSIONS: Reports to VAERS in the first 2 seasons of LAIV-T use did not identify any unexpected serious risks with this vaccine when used according to approved indications. Like many vaccines and other medical products, LAIV-T may rarely cause anaphylaxis. Secondary transmission of the vaccine virus merits further investigation. Reports of asthma exacerbations in vaccinees with prior asthma history highlight the risks of vaccine use inconsistent with approved labeling.
Administration, Intranasal↗
Neurologic adverse events associated with smallpox vaccination in the United States, 2002-2004.
CONTEXT: Neurologic illness is an infrequent but severe adverse event associated with smallpox vaccination. The reinstatement of smallpox vaccination in the United States in response to possible bioterrorism renewed concerns about vaccine-related adverse neurologic events. OBJECTIVE: To determine rates and describe the clinical features of neurologic events associated with smallpox vaccination. DESIGN AND SETTING: We assessed reports of adverse events obtained through active case reporting and review of data reported to the Vaccine Adverse Event Reporting System among 665,000 persons vaccinated against smallpox by the Departments of Defense (n = 625,400 [corrected]) and Health and Human Services (n = 39,400 [corrected]) during the 2002-2004 US Smallpox Vaccination Program. MAIN OUTCOME MEASURE: Adverse neurologic events temporally associated with smallpox vaccination. RESULTS: Between December 16, 2002, and March 11, 2004, 214 neurologic adverse events temporally associated with smallpox vaccination were reported; 111 reports involved Department of Health and Human Services and 103 involved Department of Defense vaccinees. Fifty-four percent of these events occurred within 1 week of vaccination, and 53% were among primary vaccinees. The most common neurologic adverse event was headache (95 cases), followed by nonserious limb paresthesias (n = 17) or pain (n = 13) and dizziness or vertigo (n = 13). Serious neurologic adverse events included 13 cases of suspected meningitis, 3 cases of suspected encephalitis or myelitis, 11 cases of Bell palsy, 8 seizures (including 1 death), and 3 cases of Guillain-Barré syndrome. Among these 39 events, 27 (69%) occurred in primary vaccinees and all but 2 occurred within 12 days of vaccination. CONCLUSIONS: During the 2002-2004 smallpox vaccination campaign, reported neurologic events were generally mild and self-limited, and no neurologic syndrome was identified at a rate above baseline estimates. Serious neurologic adverse events, such as postvaccinal encephalitis, Bell palsy, and Guillain-Barré syndrome, occurred in accordance with expected ranges.
Adverse Drug Reaction Reporting Systems↗
Vaccination of yeast sensitive individuals: review of safety data in the US vaccine adverse event reporting system (VAERS).
The preparation of recombinant hepatitis B vaccines involves using cellular cultures of Saccharomyces cerevisiae, otherwise known as baker's yeast. Prior to vaccine licensure, clinical trials were performed to address whether residual yeast proteins in the vaccines could induce anaphylaxis, including testing for IgE anti-yeast antibody levels. 1-2% of subjects had anti-yeast IgE antibodies before immunization, but demonstrated no significant rise in IgE after HBV. We searched reports in the Vaccine Adverse Event Reporting System (VAERS) for those that mentioned a history of allergy to yeast and then reviewed the adverse events described in these reports for potential anaphylactic reactions. Probable anaphylaxis was defined as the presence of one or more dermatologic symptoms and one or more respiratory, gastrointestinal, or cardiovascular symptoms with onset within 4 h of Hepatitis B vaccination. Possible anaphylaxis was defined in one of two ways: (1) cases that described dermatologic or respiratory symptoms (but not both) occurring within 4h of vaccination; or (2) cases that described one or more dermatologic and/or respiratory symptoms occurring 4-12 h post vaccination. Among the 107 reports of pre-existing "yeast allergies," 11 reports described probable or possible anaphylaxis after HBV. Four additional cases were described after other vaccines. The majority of vaccinees who met the case definitions and had a history of yeast allergies were female, ages ranged from 10 to 64, and symptom onset ranged from 15 min to 5 h after vaccination. No deaths were reported. The small number of reports to VAERS may be partly due to health care professionals observing current contraindications by not vaccinating yeast sensitive individuals. Nevertheless, yeast associated anaphylaxis after HBV in sensitized patients appears to be a rare event.
Adverse Drug Reaction Reporting Systems↗
Tracking vaccine lot lifecycles using reports to the vaccine adverse event reporting system (VAERS).
PURPOSE: There is currently no systematically available information available on how rapidly a specific lot of vaccine is used once distributed. We used data from reports to the Vaccine Adverse Event Reporting System (VAERS) to develop a proxy means of surveillance for the lifecycle of selected vaccine lots. METHODS: A convenience sample, consisting of selected lots of: diphtheria, tetanus, and acellular pertussis (DTaP), Haemophilus influenzae type b (Hib), Hepatitis B, and varicella vaccines, was selected for lifecycle analysis. Assuming that circulation of a vaccine lot is proportional to vaccine-specific adverse event (AE) reporting for that vaccine type, we constructed Gamma distributed usage models and compared them with lot-specific VAERS reports to estimate the actual lifecycle of lots in the system. RESULTS: Evidence of lot circulation was detected within 1-2 months, and a peak was observed 3-4 months after the vaccine release date for most of the study vaccines. Ninety percent of the vaccine doses in each lot were estimated to be used within 5-9 months of distribution. The length of time a vaccine lot was in use ranged from 5 to 17 months from earliest vaccination date. CONCLUSIONS: Our modeled and inferred administration of the selected lots of different vaccines were concordant. This method may be useful for spatial and temporal tracking of vaccine lot utilization.
Models, Theoretical↗
Severe headaches following smallpox vaccination.
Headaches are common following smallpox vaccination; the re-introduction of civilian vaccination necessitates better understanding of the clinical features and outcome of postvaccination headache. We identified patients reporting headache following vaccination from among those reported to the U.S. Vaccine Adverse Events Reporting System to characterize demographic and clinical features. One-hundred and eight reports were obtained from among 627 smallpox vaccine-related reports, including 15 hospitalized persons. None had neurologic dysfunction or acute laboratory abnormalities; headache resolved in all except 2 hospitalized patients within 3 months. Severe headache following smallpox vaccination is generally transient, but debilitating headache may occur and further characterization is needed.
Adult↗
Adverse events after inactivated influenza vaccination among children less than 2 years of age: analysis of reports from the vaccine adverse event reporting system, 1990-2003.
BACKGROUND: In April 2002, the Advisory Committee on Immunization Practices (ACIP) encouraged providers to vaccinate healthy 6- to 23-month-old infants and children with trivalent influenza vaccine (TIV). OBJECTIVES: To describe adverse events (AEs) reported to the Vaccine Adverse Event Reporting System (VAERS) after TIV vaccination among children <2 years of age and to compare reports before the ACIP guideline (January 1990 to June 2002) and after the ACIP guideline (July 2002 to June 2003). METHODS: VAERS is a passive vaccine safety surveillance system begun by the Food and Drug Administration and the Centers for Disease Control and Prevention in 1990. We reviewed reports to VAERS for children <2 years of age who received TIV, alone or in combination with other vaccines. Influenza seasons were defined as the period from July 1 of one year to June 30 of the following year. RESULTS: Between 1990 and 2003, VAERS received 166 TIV reports for children <2 years of age. There were 62 reports (37%) after administration of TIV alone and 104 reports (63%) after administration of TIV and > or =1 other vaccine. Approximately one third of reports (N = 61) were in the post-ACIP guideline period. The 4 most frequent AE coding terms were fever (N = 59, 35%), unspecified or urticarial rash (42, 25%), seizure (28, 17%), and injection site reaction (28, 17%). The median number of days from vaccination to symptom onset, the percentage of reports that represented serious AEs, and the gender distribution were similar in the pre-ACIP guideline and post-ACIP guideline periods. The percentage of reports describing an underlying medical condition for the subject decreased from 58% before the ACIP guideline to 37% after the ACIP guideline. Nineteen of 28 seizure reports (68%) described fever with the seizure within 2 days after vaccination. Seizure was the most frequent coding term (N = 10, 7 with fever) among 23 serious reports. The annual number of TIV-related VAERS reports for children <2 years of age increased in the post-ACIP guideline period, probably at least in part because of an increase in the number of vaccinees after the ACIP announcement. The safety profiles in the pre-ACIP guideline and post-ACIP guideline periods were similar. CONCLUSIONS: In October 2003, the ACIP recommended that all healthy children 6 to 23 months of age be vaccinated with TIV, starting in the 2004-2005 influenza season. This study provides generally reassuring, although limited, data regarding the safety of TIV among children in this age range. Continued surveillance for seizures and other clinically significant AEs is warranted and will continue.
Adverse Drug Reaction Reporting Systems↗
Monitoring vaccine safety during an influenza pandemic.
In the event that a vaccine is available during an influenza pandemic, vaccine safety monitoring will occur as part of comprehensive public health surveillance of the vaccination campaign. Though inactivated influenza vaccines have been widely used in the United States and much is known about their safety profile, attention will need to be paid to both common self-limited adverse reactions and rarer, more serious events that may or may not be causally related to vaccination. The primary surveillance systems used to generate and test hypotheses about vaccine safety concerns are the Vaccine Adverse Event Reporting System (VAERS) and the Vaccine Safety Datalink (VSD), respectively. Examples of recent use of these systems to investigate influenza vaccine safety and enhancements planned for use during a pandemic are presented. Ethical issues that will need to be addressed as part of an overall vaccine safety response include risk communication and injury compensation. Advance planning and the use of available technologic solutions are needed to respond to the scientific and logistic challenges involved in safely implementing mass vaccination during a pandemic.
Adverse Drug Reaction Reporting Systems↗
Guillain-Barré syndrome following influenza vaccination.
CONTEXT: An unexplained increase in the risk of Guillain-Barre syndrome (GBS) occurred among recipients of the swine influenza vaccine in 1976-1977. Guillain-Barre syndrome remains the most frequent neurological condition reported after influenza vaccination to the Vaccine Adverse Events Reporting System (VAERS) since its inception in 1990. OBJECTIVE: To evaluate trends of reports to VAERS of GBS following influenza vaccination in adults. DESIGN, SETTING, AND PARTICIPANTS: VAERS is the US national spontaneous reporting system for adverse events following vaccination. Reports of GBS in persons 18 years or older following influenza vaccination were evaluated for each influenza season from July 1, 1990, through June 30, 2003. The number of people vaccinated was estimated from the National Health Interview Survey and US census data. Beginning in 1994, active follow-up was conducted to verify GBS diagnosis and obtain other clinical details. MAIN OUTCOME MEASURE: Reporting rates of GBS following influenza vaccination over time. RESULTS: From July 1990 through June 2003, VAERS received 501 reports of GBS following influenza vaccination in adults. The median onset interval (13 days) was longer than that of non-GBS reports of adverse events after influenza vaccine (1 day) (P<.001). The annual reporting rate decreased 4-fold from a high of 0.17 per 100,000 vaccinees in 1993-1994 to 0.04 in 2002-2003 (P<.001). A GBS diagnosis was confirmed in 82% of reports. Preceding illness within 4 weeks of vaccination was identified in 24% of reported cases. CONCLUSIONS: From 1990 to 2003, VAERS reporting rates of GBS after influenza vaccination decreased. The long onset interval and low prevalence of other preexisting illnesses are consistent with a possible causal association between GBS and influenza vaccine. These findings require additional research, which can lead to a fuller understanding of the causes of GBS and its possible relationship with influenza vaccine.
Adult↗
Postlicensure safety surveillance for 7-valent pneumococcal conjugate vaccine.
CONTEXT: Clinical trials evaluate a vaccine's safety before approval, but some risks may escape detection or adequate characterization until larger population exposures occur after licensure. OBJECTIVE: To summarize reports of events occurring after vaccination with 7-valent pneumococcal conjugate vaccine (PCV), including those that may warrant further investigation to assess possible causation by PCV. DESIGN: Descriptive epidemiology of reports submitted to the Vaccine Adverse Event Reporting System (VAERS), a national passive surveillance database. SETTING AND PATIENTS: United States during first 2 years after licensure of PCV (February 2000 through February 2002). Reports studied were for children younger than 18 years and vaccinated with PCV. MAIN OUTCOME MEASURES: Numbers and proportional distributions of reports. RESULTS: A total of 4154 reports of events following PCV were submitted to VAERS, for a rate of 13.2 reports per 100,000 doses distributed. Multiple vaccines were given in 74.3% of reports. The most frequently reported symptoms and signs included fever, injection site reactions, fussiness, rashes, and urticaria. Serious events were described in 14.6% of reports. There were 117 deaths, 23 reports of positive rechallenges, and 34 cases of invasive pneumococcal infections possibly representing vaccine failure. Immune-mediated events occurred in 31.3% of reports. All 14 patients with anaphylactic or anaphylactoid reactions survived. Thrombocytopenia developed in 14 patients and serum sickness in 6 others. Neurologic symptoms occurred in 38% of reports. Seizures described in 393 reports included 94 febrile seizures. CONCLUSIONS: The majority of reports to VAERS in the first 2 years after licensure of PCV described generally minor adverse events previously identified in clinical trials. The proportion of reports portraying serious events was similar to that for other vaccines. Although there are important limitations in passive surveillance data, and caution in their interpretation is necessary, symptoms experienced by a few children more than once after successive PCV doses, including allergic reactions, prolonged or abnormal crying, fussiness, dyspnea, and gastrointestinal distress, warrant continued surveillance, as do reports of rare but potentially serious events, such as seizures, anaphylactic or anaphylactoid reactions, serum sickness, and thrombocytopenia.
Adolescent↗
Understanding vaccine safety information from the Vaccine Adverse Event Reporting System.
The Vaccine Adverse Event Reporting System (VAERS) is administered by the Food and Drug Administration and CDC and is a key component of postlicensure vaccine safety surveillance. Its primary function is to detect early warning signals and generate hypotheses about possible new vaccine adverse events or changes in frequency of known ones. VAERS is a passive surveillance system that relies on physicians and others to voluntarily submit reports of illness after vaccination. Manufacturers are required to report all adverse events of which they become aware. There are a number of well-described limitations of such reporting systems. These include, for example, variability in report quality, biased reporting, underreporting and the inability to determine whether a vaccine caused the adverse event in any individual report. Strengths of VAERS are that it is national in scope and timely. The information in VAERS reports is not necessarily complete nor is it verified systematically. Reports are classified as serious or nonserious based on regulatory criteria. Reports are coded by VAERS in a uniform way with a limited number of terms using a terminology called COSTART. Coding is useful for search purposes but is necessarily imprecise. VAERS is useful in detecting adverse events related to vaccines and most recently was used for enhanced reporting of adverse events in the national smallpox immunization campaign. VAERS data have always been publicly available. However, it is essential for users of VAERS data to be fully aware of the strengths and weaknesses of the system. VAERS data contain strong biases. Incidence rates and relative risks of specific adverse events cannot be calculated. Statistical significance tests and confidence intervals should be used with great caution and not routinely. Signals detected in VAERS should be subjected to further clinical and descriptive epidemiologic analysis. Confirmation in a controlled study is usually required. An understanding of the system's defined objectives and inherent drawbacks is vital to the effective use of VAERS data in vaccine safety investigations.
Adverse Drug Reaction Reporting Systems↗