Adverse Event Surveillance System Research Articles

Safety Monitoring of Pfizer-BioNTech COVID-19 Vaccine Booster Doses Among Children Aged 5-11 Years - United States, May 17-July 31, 2022.

On May 17, 2022, the Food and Drug Administration (FDA) amended the Emergency Use Authorization (EUA) for BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine to authorize a homologous* booster dose for children aged 5-11 years ≥5 months after receipt of the second primary series dose† (1) based on findings from a clinical trial conducted among 401 children aged 5-11 years (2). To further characterize the safety of booster vaccination in this age group, CDC reviewed adverse events and health impact assessments after receipt of a Pfizer-BioNTech third dose reported to v-safe, a voluntary smartphone-based safety surveillance system for adverse events occurring after COVID-19 vaccination, and adverse events reported to the Vaccine Adverse Event Reporting System (VAERS), a passive vaccine safety surveillance system comanaged by CDC and FDA. During May 17-July 31, 2022, approximately 657,302 U.S. children aged 5-11 years received a third Pfizer-BioNTech dose (either a third primary series dose administered to immunocompromised children or a booster dose administered to immunocompetent children)§; 3,249 Pfizer-BioNTech third doses were reported to v-safe for children in this age group. Local and systemic reactions were reported to v-safe after a second dose and a third dose with similar frequency; some reactions (e.g., pain) were reported to be moderate or severe more frequently after a third dose. VAERS received 581 reports of adverse events after receipt of a Pfizer-BioNTech third dose by children aged 5-11 years; 578 (99.5%) reports were considered nonserious, and the most common events reported were vaccine administration errors. Three (0.5%) reports were considered serious; no reports of myocarditis or death were received. Local and systemic reactions were common among children after Pfizer-BioNTech third dose vaccination, but reports of serious adverse events were rare. Initial safety findings are consistent with those of the clinical trial (2).

Safety Monitoring of COVID-19 mRNA Vaccine First Booster Doses Among Persons Aged ≥12 Years with Presumed Immunocompromise Status - United States, January 12, 2022-March 28, 2022.

Persons with moderate to severe immunocompromising conditions are at risk for severe COVID-19, and their immune response to COVID-19 vaccination might not be as robust as the response in persons who are not immunocompromised* (1). The Advisory Committee on Immunization Practices (ACIP) recommends that immunocompromised persons aged ≥12 years complete a 3-dose primary mRNA COVID-19 vaccination series followed by a first booster dose (dose 4) ≥3 months after dose 3 and a second booster dose (dose 5) ≥4 months after dose 4.† To characterize the safety of first booster doses among immunocompromised persons aged ≥12 years during January 12, 2022-March 28, 2022, CDC reviewed adverse events and health impact assessments reported to v-safe and the Vaccine Adverse Event Reporting System (VAERS) during the week after receipt of an mRNA COVID-19 first booster dose. V-safe is a voluntary smartphone-based safety surveillance system for adverse events after COVID-19 vaccination. VAERS is a passive surveillance system for all vaccine-associated adverse events co-managed by CDC and the Food and Drug Administration (FDA). A fourth mRNA dose reported to v-safe or VAERS during January 12, 2022-March 28, 2022, was presumed to be an mRNA COVID-19 vaccine booster dose administered to an immunocompromised person because no other population was authorized to receive a fourth dose during that period (2,3). In the United States, during January 12, 2022-March 28, 2022, approximately 518,113 persons aged ≥12 years received a fourth dose. Among 4,015 v-safe registrants who received a fourth dose, local and systemic reactions were less frequently reported than were those following dose 3 of their primary series. VAERS received 145 reports after fourth doses; 128 (88.3%) were nonserious and 17 (11.7%) were serious. Health care providers, immunocompromised persons, and parents of immunocompromised children should be aware that local and systemic reactions are expected after a first booster mRNA COVID-19 vaccine dose, serious adverse events are rare, and safety findings were consistent with those previously described among nonimmunocompromised persons (4,5).

Safety Monitoring of COVID-19 Vaccine Booster Doses Among Adults - United States, September 22, 2021-February 6, 2022.

During September 22, 2021-February 6, 2022, approximately 82.6 million U.S. residents aged ≥18 years received a COVID-19 vaccine booster dose.* The Food and Drug Administration (FDA) has authorized a booster dose of either the same product administered for the primary series (homologous) or a booster dose that differs from the product administered for the primary series (heterologous). These booster authorizations apply to all three COVID-19 vaccines used in the United States (1-3).† The Advisory Committee on Immunization Practices (ACIP) recommended preferential use of an mRNA COVID-19 vaccine (mRNA-1273 [Moderna] or BNT162b2 [Pfizer-BioNTech]) for a booster, even for persons who received the Ad26.COV2.S (Janssen [Johnson & Johnson]) COVID-19 vaccine for their single-dose primary series.§ To characterize the safety of COVID-19 vaccine boosters among persons aged ≥18 years during September 22, 2021-February 6, 2022, CDC reviewed adverse events and health impact assessments following receipt of a booster that were reported to v-safe, a voluntary smartphone-based safety surveillance system for adverse events after COVID-19 vaccination, and adverse events reported to the Vaccine Adverse Event Reporting System (VAERS), a passive vaccine safety surveillance system managed by CDC and FDA. Among 721,562 v-safe registrants aged ≥18 years who reported receiving a booster, 88.8% received homologous COVID-19 mRNA vaccination. Among registrants who reported a homologous COVID-19 mRNA booster dose, systemic reactions were less frequent following the booster (58.4% [Pfizer-BioNTech] and 64.4% [Moderna], respectively) than were those following dose 2 (66.7% and 78.4%, respectively). The adjusted odds of reporting a systemic reaction were higher following a Moderna COVID-19 vaccine booster, irrespective of the vaccine received for the primary series. VAERS has received 39,286 reports of adverse events after a COVID-19 mRNA booster vaccination for adults aged ≥18 years, including 36,282 (92.4%) nonserious and 3,004 (7.6%) serious events. Vaccination providers should educate patients that local and systemic reactions are expected following a homologous COVID-19 mRNA vaccine booster; however, these reactions appear less common than those following dose 2 of an mRNA-based vaccine. CDC and FDA will continue to monitor vaccine safety and provide data to guide vaccine recommendations and protect public health.

COVID-19 Vaccine Safety in Children Aged 5-11 Years - United States, November 3-December 19, 2021.

On October 29, 2021, the Food and Drug Administration (FDA) amended the Emergency Use Authorization (EUA) for Pfizer-BioNTech COVID-19 (BNT162b2) mRNA vaccine to expand its use to children aged 5-11 years, administered as 2 doses (10 μg, 0.2mL each) 3 weeks apart (1). As of December 19, 2021, only the Pfizer-BioNTech COVID-19 vaccine is authorized for administration to children aged 5-17 years (2,3). In preauthorization clinical trials, Pfizer-BioNTech COVID-19 vaccine was administered to 3,109 children aged 5-11 years; most adverse events were mild to moderate, and no serious adverse events related to vaccination were reported (4). To further characterize safety of the vaccine in children aged 5-11 years, CDC reviewed adverse events after receipt of Pfizer-BioNTech COVID-19 vaccine reported to the Vaccine Adverse Event Reporting System (VAERS), a passive vaccine safety surveillance system co-managed by CDC and FDA, and adverse events and health impact assessments reported to v-safe, a voluntary smartphone-based safety surveillance system for adverse events after COVID-19 vaccination,* during November 3-December 19, 2021. Approximately 8.7 million doses of Pfizer-BioNTech COVID-19 vaccine were administered to children aged 5-11 years† during this period; VAERS received 4,249 reports of adverse events after vaccination with Pfizer-BioNTech COVID-19 vaccine in this age group, 4,149 (97.6%) of which were not serious. Approximately 42,504 children aged 5-11 years were enrolled in v-safe after vaccination with Pfizer-BioNTech COVID-19 vaccine; after dose 2, a total of 17,180 (57.5%) local and 12,223 systemic (40.9%) reactions (including injection-site pain, fatigue, or headache) were reported. The preliminary safety findings are similar to those from preauthorization clinical trials (4,5). The Advisory Committee on Immunization Practices (ACIP) recommends the Pfizer-BioNTech COVID-19 vaccine for children aged 5-11 years for the prevention of COVID-19 (6). Parents and guardians of children aged 5-11 years vaccinated with Pfizer-BioNTech COVID-19 vaccine should be advised that local and systemic reactions are expected after vaccination. Vaccination is the most effective way to prevent COVID-19. CDC and FDA will continue to monitor vaccine safety and will provide updates as needed to guide COVID-19 vaccination recommendations.

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.

Assessment of the surveillance system for adverse events following immunisation in the Gaza Strip: a cross-sectional study

BackgroundIn the occupied Palestinian territory, the expanded programme on immunisation (EPI) has successfully targeted 13 diseases through vaccination and achieved high population coverage. However, surveillance of adverse events following immunisation (AEFI) is inadequate in the Gaza Strip, as only post-BCG lymphadenitis is reported. This study assessed the adherence of health-care workers (HCWs) to the AEFI surveillance system in the Gaza Strip. MethodsData were collected by four methods: 105 HCWs answered a questionnaire; 24 health facilities completed a checklist enquiry; 17 medical health officers and information system managers from Ministry of Health (MOH) and UNRWA health centres and hospitals underwent in-depth interviews; and a focus group was held with 22 epidemiologists, stakeholders, consultants, and managers of the EPI. The 24 health facilities comprised seven MOH primary health-care centres (PHCs) providing vaccination, five MOH PHCs not providing vaccination, seven UNRWA PHCs, and the five hospitals of the Gaza Strip with paediatric departments. Data collected from June, 2015, to August, 2015, were analysed with SPSS version 19. Relationships among variables were assessed by independent t tests, chi squared tests and one-way ANOVA. Verbal informed consent was obtained from all participants, and written approval for the study was obtained from MOH and UNWRA directorates. FindingsAEFI are reported infrequently; approximately half of the 105 HCWs (51%; 53) report AEFI, but there were conflicting views as to whom they should report. 65% (68) thought that they should report all AEFI. Participants’ educational background, participation in workshops, and number of years of employment affected AEFI recognition and reporting. The majority (74%; 78) participate in immunisation workshops. There is an ineffective structure in MOH centres, and the UNRWA has a well-established internal system for reporting AEFI but a poor system for external reporting to the MOH epidemiology department. A lack of HCW awareness of responsibilities may also have a role. The majority of HCWs (95%; 100) reported a need for further training, and all reported a lack of cooperation or coordination between hospitals and PHCs regarding AEFI notification. All individuals (17) who were interviewed knew that they must report AEFI. A majority (65%; 11) stated no difficulties, whereas some (35%; six) reported difficulties due to absence of guidelines, protocols, or notification forms, and to fear of punishment. Focus group participants felt that all AEFI should be reported. They agreed that HCWs face obstacles such as fear of consequences, lack of knowledge and training, high workloads, not considering AEFI as related to immunisation, and absence or shortage of notification forms, protocols, and guidelines. Some felt that certain AEFI should be reported only to treating doctors, but all agreed that there is no cooperation or coordination among PHCs and between hospitals and PHCs regarding AEFI reporting. InterpretationCommon themes may explain poor adherence of HCWs to AEFI surveillance. The system is ineffective in MOH centres, and UNRWA PHCs have well-established internal but poor external reporting systems. Absence of monitoring may have a role, and a lack of guidelines, protocols, and forms for reporting were mentioned by HCWs, medical health officers and information system managers, and the focus group. Some HCWs may not know their responsibilities (eg, to whom AEFI should be reported). Many other obstacles face HCWs, including fear of punishment and accountability. Therefore, HCWs must be encouraged to report adverse events without fear of penalty. In addition, lack of education on AEFI and lack of experience in identifying AEFI may affect reporting. Training of HCWs, development of guidelines and protocols, database construction and design, and monitoring of the AEFI surveillance system are highly recommended. FundingWHO EMRO.

Implementation of Adverse event surveillance system in a Tunisian tertiary care hospital (2018-2019)

Abstract Background We found a high incidence of Adverse Events (AEs) following a survey conducted at Sahloul Hospital. Therefore, a surveillance system of AEs was implemented as a part of the implementation of the quality and risk management approach at Sahloul hospital, since April 2018. The aim of this study was to describe results of this system between May 2018 and April 2019. Methods It is a descriptive longitudinal study conducted at the Sahloul Hospital for a period of one year from May 1st, 2018 to April 30, 2019. Each service is provided with a data sheet that allows staff to report each adverse event they have witnessed. This does not include AEs that are part of alertness, blood exposure accidents or occupational accidents, or nosocomial infections which are assessed by specific circuits already in place. Results During the follow-up period, 93 AEs were reported. These AEs predominate in the sterilization unit followed by medical resuscitation and nephrology department with respective rates of 17.2%, 12.9% and 11.8%. The most frequent AEs were for maintenance (21.5%), medical device disinfection (20.5%), material resources (16.1%), and human resources (8.6%). According to criticality, the majority of AEs are tolerable under control (41.9%), unacceptable in 33.3% of cases and acceptable in 24.7% of cases. Conclusions In order to ensure proper functioning of the AEs surveillance and reporting system, the awareness of health professionals and their training would be essential. Quality of the information to be reported represents a challenge to be met to enable the planning, implementation and evaluation of improvement actions. Experience feedback would be with considerable benefit to improve the quality of professional practices. Key messages Surveillance and reporting system data analysis allow to identify mecanisms of the occurence of adverse events. Experience feedback is with considerable benefit to improve the quality of professional practices.

Active Surveillance of Adverse Events Following Human Papillomavirus Vaccination: Feasibility Pilot Study Based on the Regional Health Care Information Platform in the City of Ningbo, China.

BackgroundComprehensive safety data for vaccines from post-licensure surveillance, especially active surveillance, could guide administrations and individuals to make reasonable decisions on vaccination. Therefore, we designed a pilot study to assess the capability of a regional health care information platform to actively monitor the safety of a newly licensed vaccine.ObjectiveThis study aimed to conduct active surveillance of human papillomavirus (HPV) vaccine safety based on this information platform.MethodsIn 2017, one of China’s most mature information platforms with superior data linkage was selected. A structured questionnaire and open-ended interview guidelines were developed to investigate the feasibility of active surveillance following HPV vaccination using the regional health care information platform in Ningbo. The questionnaire was sent to participants via email, and a face-to-face interview was conducted to confirm details or resolve discrepancies.ResultsFive databases that could be considered essential to active surveillance of vaccine safety were integrated into the platform starting in 2015. Except for residents' health records, which had a coverage rate of 87%, the data sources covered more than 95% of the records that were documented in Ningbo. All the data could be inherently linked using the national identity card. There were 19,328 women who received the HPV vaccine, and 37,988 doses were administered in 2017 and 2018. Women aged 30-40 years accounted for the largest proportion. Quadrivalent vaccination accounted for 73.1% of total vaccination, a much higher proportion than that of bivalent vaccination. Of the first doses, 60 (60/19,328, 0.31%) occurred outside Ningbo. There were no missing data for vaccination-relevant variables, such as identity card, vaccine name, vaccination doses, vaccination date, and manufacturer. ICD-10 coding could be used to identify 9,180 cases using a predefined list of the outcomes of interest, and 1.88% of these cases were missing the identity card. During the 90 days following HPV vaccination, 4 incident cases were found through the linked vaccination history and electronic medical records. The combined incident rate of rheumatoid arthritis, optic neuritis, and Henoch-Schonlein purpura was 8.84/100,000 doses of bivalent HPV, and the incidence rate of rheumatoid arthritis was 3.75/100,000 doses of quadrivalent HPV.ConclusionsThis study presents an available approach to initiate an active surveillance system for adverse events following HPV vaccination, based on a regional health care information platform in China. An extended observation period or the inclusion of additional functional sites is warranted to conduct future hypothesis-generating and hypothesis-confirming studies for vaccine safety concerns.

Study of a multisite prospective adverse event surveillance system

BackgroundWe have designed a prospective adverse event (AE) surveillance method. We performed this study to evaluate this method’s performance in several hospitals simultaneously.ObjectivesTo compare AE rates obtained by prospective AE...

Evaluation of a Broad-Spectrum Partially Automated Adverse Event Surveillance System: A Potential Tool for Patient Safety Improvement in Hospitals With Limited Resources.

The aim of the study was to evaluate the sensitivity and resource efficiency of a partially automated adverse event (AE) surveillance system for routine patient safety efforts in hospitals with limited resources. Twenty-eight automated triggers from the hospital information system's clinical and administrative databases identified cases that were then filtered by exclusion criteria per trigger and then reviewed by an interdisciplinary team. The system, developed and implemented using in-house resources, was applied for 45 days of surveillance, for all hospital inpatient admissions (N = 1107). Each trigger was evaluated for its positive predictive value (PPV). Furthermore, the sensitivity of the surveillance system (overall and by AE category) was estimated relative to incidence ranges in the literature. The surveillance system identified a total of 123 AEs among 283 reviewed medical records, yielding an overall PPV of 52%. The tool showed variable levels of sensitivity across and within AE categories when compared with the literature, with a relatively low overall sensitivity estimated between 21% and 44%. Adverse events were detected in 23 of the 36 AE categories defined by an established harm classification system. Furthermore, none of the detected AEs were voluntarily reported. The surveillance system showed variable sensitivity levels across a broad range of AE categories with an acceptable PPV, overcoming certain limitations associated with other harm detection methods. The number of cases captured was substantial, and none had been previously detected or voluntarily reported. For hospitals with limited resources, this methodology provides valuable safety information from which interventions for quality improvement can be formulated.

Vaccination errors reported to the Vaccine Adverse Event Reporting System, (VAERS) United States, 2000–2013

ImportanceVaccination errors are preventable events. Errors can have impacts including inadequate immunological protection, possible injury, cost, inconvenience, and reduced confidence in the healthcare delivery system. ObjectivesTo describe vaccination error reports submitted to the Vaccine Adverse Event Reporting System (VAERS) and identify opportunities for prevention. MethodsWe conducted descriptive analyses using data from VAERS, the U.S. spontaneous surveillance system for adverse events following immunization. The VAERS database was searched from 2000 through 2013 for U.S. reports describing vaccination errors and reports were categorized into 11 error groups. We analyzed numbers and types of vaccination error reports, vaccines involved, reporting trends over time, and descriptions of errors for selected reports. ResultsWe identified 20,585 vaccination error reports documenting 21,843 errors. Annual reports increased from 10 in 2000 to 4324 in 2013. The most common error group was “Inappropriate Schedule” (5947; 27%); human papillomavirus (quadrivalent) (1516) and rotavirus (880) vaccines were most frequently involved. “Storage and Dispensing” errors (4983; 23%) included mostly expired vaccine administered (2746) and incorrect storage of vaccine (2202). “Wrong Vaccine Administered” errors (3372; 15%) included mix-ups between vaccines with similar antigens such as varicella/herpes zoster (shingles), DTaP/Tdap, and pneumococcal conjugate/polysaccharide. For error reports with an adverse health event (5204; 25% of total), 92% were classified as non-serious. We also identified 936 vaccination error clusters (i.e., same error, multiple patients, in a common setting) involving over 6141 patients. The most common error in clusters was incorrect storage of vaccine (582 clusters and more than 1715 patients). ConclusionsVaccination error reports to VAERS have increased substantially. Contributing factors might include changes in reporting practices, increasing complexity of the immunization schedule, availability of products with similar sounding names or acronyms, and increased attention to storage and temperature lapses. Prevention strategies should be considered.

Adverse events in patients with return emergency department visits

ObjectivesThis study describes the proportion of emergency department (ED) returns within 7 days due to adverse events, defined as adverse outcomes related to healthcare received.DesignProspective cohort study.SettingWe used an electronically...

Barriers and success factors to the implementation of a multi-site prospective adverse event surveillance system.

To determine the feasibility of implementing a clinical observation method for adverse event detection. Prospective adverse event surveillance was conducted from February to April 2012. We implemented this adverse event prospective surveillance system on the general internal medicine units of five sites within two teaching institutions and one community hospital. Following surveillance, we assembled provider and decision-maker focus groups to understand the barriers and success factors related to our implementation. We used a structured interview guide with facilitated discussion. We performed six focus group interviews in June and July 2012. In total, 31 individual participated including senior executives (15), managers (7) and care providers (9). We identified the following success factors: the overall design of the system including the clinical observer and clinical reviewer functions; the credibility of the data and the opportunity to make changes to practice in 'real-time'. We identified the following opportunities for improvement: the need for clear guidelines on the type of information to collect for each event trigger, and for an action plan to ensure accountability and follow through on improvement efforts once the adverse event data have been analyzed. This work supports a conclusion that prospective surveillance is viewed as beneficial and acceptable. For this reason, healthcare organizations should consider adopting prospective adverse event surveillance to support their local quality improvement methods.

How can we improve tracking of transplanted tissue in the United States?

Currently an estimated two million tissues are distributed for transplantation annually. With increasing use of recovered tissue, clusters of transplant-transmitted infection have shown the difficulty of tracking tissues from an infected donor to the recipient. The challenge of tissue tracking to multiple transplant recipients was illustrated in a recent investigation of transmission of hepatitis C virus infection from a donor of organs and tissues. When a tissue bank issued a recall of the donated tissue, the Centers for Disease Control and Prevention was notified to assist public health authorities; the mean time to locate and notify the physicians who had transplanted the tissue was 13 days, while the mean time to notify, inform, and test the patients was 29 days. Lack of common coding and nomenclature was one of the key challenges in tracking tissue to the recipient. Some changes that could improve timeliness in the event of a recall includes: (1) standardized tissue nomenclature and coding through unique donor identifiers; (2) tissue traceability requirements using systems similar to that used for blood products; (3) a surveillance system for adverse events that provides feedback at the provider level.

Investigation of an outbreak of hypersensitivity-type reactions during the 2004 national measles-mumps-rubella vaccination campaign in Brazil

IntroductionDuring Brazil's national measles, mumps, and rubella (MMR) vaccination campaign in August 2004, an unexpectedly high rate of hypersensitivity-type adverse events (HAEs) was reported. Materials and methodsWe reviewed information about children with suspected HAEs reported by clinicians to Brazil's national passive surveillance system for adverse events following immunization (AEFI), compared attack rate of HAE by manufacturer of MMR vaccine used in the campaign, and conducted a case–control study to determine possible risk factors for HAEs. ResultsDuring the 2004 national campaign, the rate of HAEs following MMR vaccination was one log higher for manufacturer A (15.2/100,000 doses administered) compared to the other two manufacturers (1.2 and 0.6/100,000 doses; p<0.0001); a similar pattern was observed retrospectively in analysis of the 2000–2003 AEFI surveillance (0.95 vs. 0.07 per 100,000 doses administered; p<0.0001). In the case–control study, among the 49 case-patients with HAEs identified, reported symptoms included conjunctival injection (60%), urticaria (55%), fever (54%), and facial edema (53%); no deaths occurred. The median time interval between vaccination and symptom onset was 42min (range: 5min–24h). We did not identify any differences in the proportion of case-patients and control children with a history of known allergy to food (including egg, egg-containing products or gelatin), drugs, or environmental antigens. DiscussionOur study highlights the importance of a well-functioning routine AEFI surveillance system linked with mass vaccination campaigns. Such a system in Brazil permitted timely detection of HAEs and validation of a safety signal associated with one vaccine manufacturer. Unlike earlier publications, this outbreak linked to a single manufacturer of MMR showed no association with a prior allergic history to eggs or other foods, including gelatin; subsequent studies implicate the dextran stabilizer in MMR from manufacturer A as the likely cause of HAEs.

Vaccine-Related Adverse Events in Cuban Children, 1999–2008

INTRODUCTION Cuba has implemented an effective National Immunization Program since 1962. The schedule, administered primarily to children, comprises 11 vaccines (8 domestically produced) protecting against 13 diseases. In 1999 Cuba launched a national vaccine adverse event surveillance system to monitor and assess the safety of the immunization program, its vaccination procedures and the products administered. OBJECTIVES Describe adverse events following vaccination reported in children aged <16 years in Cuba from 1999 through 2008. METHODS A retrospective descriptive study was conducted of adverse events following vaccination reported from January 1999 through December 2008. Variables used: year, number of adverse events, province, type of vaccine, type and severity of adverse events (common minor, rare, severe), vaccination program errors, number of deaths, and final results of investigations of severe events. Percentages and rates per dose administered were calculated. Adverse event rates were calculated per 100,000 doses administered and by percentages of individual effects among events reported. RESULTS A total of 45,237,532 vaccine doses were administered, and 26,159 vaccine-associated adverse events were reported (overall rate: 57.8 per 100,000 doses). The group aged 0-5 years reported the highest rate of vaccine-associated adverse events (82/100,000 doses). The DTwP vaccine exhibited the highest rate of adverse events. Common minor events were: fever (17,538), reactions at injection site (4470) and systemic side effects (2422). Rare events (by WHO definition) reported were: persistent crying (2666), hypotonic-hyporesponsive episodes (3), encephalopathy (2) and febrile seizures (112). Severe events included: anaphylaxis (2), respiratory distress (1), multiple organ failure (1), sudden death (1), vaccine-associated paralytic poliomyelitis (2), toxic shock syndrome (3), and sepsis (1). The 10 deaths and 3 cases of disability were investigated by an expert commission, which concluded that 8 of the 13 severe events were vaccination-related. CONCLUSIONS Low rates of severe vaccine-associated adverse events observed in this study underline the low risk of vaccination relative to its demonstrated benefits in Cuba. Decision-making for the continued success of the National Immunization Program is supported by reliable information from comprehensive national surveillance with standarized reporting, along with multidisciplinary expert analysis of rare and severe adverse events and program errors. KEYWORDS Immunization; immunization programs; vaccines; vaccination; product surveillance, postmarketing; adverse drug event; communicable disease control; Cuba.

Sistema de vigilancia continua de eventos adversos en los servicios quirúrgicos de Cantabria

Objective To design a continuous surveillance system for adverse events (AEs) in surgical services in the Autonomous Community of Cantabria. Through homogeneous methodology, this system will provide the information needed to prevent and control AEs and avoid their recurrence. Material and methods We performed a prospective study of the population undergoing inpatient surgery in our service. The methodology used was an adapted version of the IDEA (Identification of Adverse Events) project. Surgeons had access to an intranet website and introduced the data by using a personal login. A web application allowed feedback through report-generation. Results During the pilot phase, limited collection of variables requiring calculations and of those related to location and causality was observed. Assessment of the system indicated the need for simplification to obtain valid and useful information, as well as the need to provide help windows. The system was redesigned with two data input screens and currently allows for automatic report generation of registered AEs. Information was gathered on 70% of the patients and an incidence of 11.2 AEs/100 admissions was found. Of these, 47% were defined as surgical complications. Conclusions Establishing a continuous surveillance system for AEs is feasible if professionals participate in the process, data input is easy and feedback from the system is rapid and useful for implementing corrective measures. This system can be considered highly useful for obtaining information on AEs and consequently on the potential areas of improvement in surgical activity in Spanish hospitals.

Immune Globulin for Patients with Primary Immune Deficiency: An Evidence Based Practice Guideline

Background: The original use of immune globulin (IG) was for replacement in patients with primary immune deficiency (PID). The evidence supporting this stems from the 19650s; however there have not been any rigorously developed evidence based clinical practice guidelines (CPGs) for the use of IG for PID. In 2007, Canadian Blood Services and the National Advisory Committee on Blood and Blood Products in Canada convened a panel of Canadian immunologists and a methodologist to develop a CPG for the use of IG in patients with PID. The objectives of this guideline areto examine the evidence for the use of IG in patients who have PID andto provide guidance for practitioners involved in the care of PID patients and transfusion medicine specialists on the use of IG.Methods: The panel identified key clinical questions and a systematic, expert and bibliography literature search up to July 2008 was conducted to ensure all relevant publications were included. The panel generated recommendations based on the evidence. The levels of evidence and grading of recommendations were adapted from the Canadian Task Force on Preventative Health Care. To validate conclusions and recommendations, the practice guideline will be sent to immunologists internationally and to a patient representative in September 2008. The guideline will be disseminated to all immunologists, internists and pediatricians in Canada to aid implementation of the guideline. The National Advisory Committee of Blood and Blood Products in Canada will assess the performance of the guideline and will renew the guideline at timely intervals.Results and Conclusions: The panel identified the following key clinical questions:what is the prevalence of the PIDs that require IG;does treatment with IG improve morbidity and mortality; andwhat criteria should be used to monitor the effectiveness of IVIG.The literature search was conducted in August 2007 and updated to July 2008. 1087 citations were reviewed. 101 reports, 1 systematic review and 3 consensus documents/guidelines were included. Current estimates suggest PID is under-diagnosed. Although more than 75% of patients require IG at some point in their treatment, the actual incidence of requiring IG is unknown. There is ample evidence that IG reduces infections, hospitalization and days lost from work/school. There is some evidence to suggest that IG may ameliorate chronic illnesses in patients with PID however, there is no data of the effect of IG on malignancy and insufficient data on the effect of IG on autoimmune disease in this patient population to make a recommendation. Quality of life (QoL) has not been adequately assessed in the literature; however the reduction in infections and hospitalizations likely translates to an improved QoL. Although, there is no evidence to suggest clinical superiority of one IVIG formulation over another, for patients with autoimmune manifestations and PID, there is insufficient evidence that subcutaneous IG is equivalent to IVIG. The vaccination of these patients is an evolving field. Due to the complex nature of the management of patients with PID, the panel recommended assessment by an immunologist prior to the initiation of IG and monitoring by a comprehensive care clinic. Clinical outcomes such as frequency of infections, hospitalization, days missed from school/work should be used to monitor the effectiveness of IVIG. Specific recommendations for dosing and interval of IG therapy were made within the guideline based on the literature The development of a national registry for patients with primary immune deficiency, and the development of a surveillance system for adverse events from IG particularly infections were considered priorities for future development.

Reprocessing and Reuse of Single-Use Medical Devices Used During Hemodynamic Procedures in Brazil: A Widespread and Largely Overlooked Problem

Several medical devices used during hemodynamic procedures, particularly angiographic diagnostic and therapeutic cardiac catheters, are manufactured for single use only. However, reprocessing and reuse of these devices has been reported, to determine the frequency of reuse and reprocessing of single-use medical devices used during hemodynamic procedures in Brazil and to evaluate how reprocessing is performed. National survey, conducted from December 1999 to July 2001. Most of the institutions affiliated with the Brazilian Society of Hemodynamic and Interventional Cardiology were surveyed by use of a questionnaire sent in the mail. The questionnaire response rate was 50% (119 of 240 institutions). Of the 119 institutions that responded, 116 (97%) reported reuse of single-use devices used during hemodynamic procedures, and only 26 (22%) reported use of a standardized reprocessing protocol. Cleaning, flushing, rinsing, drying, sterilizing and packaging methods varied greatly and were mostly inadequate. Criteria for discarding reused devices varied widely. Of the 119 institutions that responded, 80 (67%) reported having a surveillance system for adverse events associated with the reuse of medical devices, although most of these institutions did not routinely review the data, and only 38 (32%) described a training program for the personnel who reprocessed single-use devices. The reuse of single-use devices used during hemodynamic procedures was very frequent in hospitals in Brazil. Basic guidance on how to reuse and reprocess single-use medical devices is urgently needed, because, despite the lack of studies to support reusing and reprocessing single-use medical devices, such devices are necessary in limited-resource areas in which these practices are current.

Improving Global Monitoring of Vaccine Safety

The WHO Programme for International Drug Monitoring (PIDM) was established in 1968 following the thalidomide disaster. The PIDM has had considerable success in analyzing drug-related adverse event reports, but more limited progress has been made in analyzing vaccine-related reports. In June 2005, the Global Advisory Committee on Vaccine Safety, acknowledging these limitations, called for a global consultation to address the need for improved monitoring and analysis of vaccine-related adverse event reports on an international level. In preparation for this consultation and as part of a larger study designed to evaluate the PIDM, a survey of the National Pharmacovigilance Centres of all 76 countries participating in the PIDM at the time the survey was conducted. Thirty-six countries (47%) responded. Of the 36 responding countries, 16 (44%) reported having a separate surveillance system for adverse events following immunizations (AEFIs) and 30 (83%) reported forwarding AEFI reports to the PIDM. Seven of the 36 countries (19%) indicated that one or more population subgroups are systematically excluded from their country's AEFI surveillance system. Five of the seven countries exclude reports concerning recipients of travellers' vaccines; three exclude recipients of vaccines administered by private physicians outside the national immunization programme and supply scheme; and five exclude reports from the military sector. Only half of the respondents knew of the Brighton Collaboration, a major international initiative aimed at the standardization of AEFI definitions. The survey identified critical elements that should be addressed quickly to improve global vaccine safety monitoring. Communication between national adverse drug reaction and AEFI surveillance authorities, ability to pay for advancing technology in developing countries, and proper use of services and terminologies are issues of concern.