Evaluation of the Brighton Collaboration case definition of acute intussusception during active surveillance

To evaluate the Brighton Collaboration case definition of acute intussusception, we reviewed all episodes reported to the Swiss Paediatric Surveillance Unit (SPSU) during 1 year (4/2003--3/2004). Of 96 confirmed episodes 86 (90%, 95% CI 83--96) were captured by the case definition. Of the remaining 10 episodes, 9 resolved spontaneously following presentation with clinical signs and symptoms, and ultrasound findings compatible with intussusception. Eighty-two episodes met level 1 of the definition, the highest level of diagnostic certainty. Compared to level 1, the sensitivity of level 2 (intermediate level) and level 3 (lowest level) was 65% (CI 55--74) and 30% (CI 20--40), respectively. In conclusion, the case definition was useful and applicable to assess the background rate of intussusception in the light of potential future rotavirus immunization.     

Sensorineural hearing loss (SNHL) as an adverse event following immunization (AEFI): Case definition & guidelines for data collection,analysis, and presentation of immunization safety data

This is a Brighton Collaboration case definition of the term “Sensorineural Hearing Loss” to be utilized in the evaluation of adverse events following immunization. The case definition was developed by a group of experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of vaccines for Lassa Fever and other emerging pathogens. The case definition format of the Brighton Collaboration was followed to develop a consensus definition and define levels of diagnostic certainty, after an exhaustive review of the literature and expert consultation. The document underwent peer review by the Brighton Collaboration Network.     

Thrombosis and thromboembolism: Brighton collaboration case definition and guidelines for data collection,analysis, and presentation of immunization safety data

This is a Brighton Collaboration case definition of thrombosis and thromboembolism to be used in the evaluation of adverse events following immunization, and for epidemiologic studies for the assessment of background incidence or hypothesis testing. The case definition was developed by a group of experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of SARS-CoV-2 vaccines. The case definition format of the Brighton Collaboration was followed to develop a consensus definition and defined levels of certainty, after an exhaustive review of the literature and expert consultation. The document underwent peer review by the Brighton Collaboration Network and by selected expert reviewers prior to submission.     

An algorithm developed using the Brighton Collaboration case definitions is more efficient for determining diagnostic certainty

The Brighton Collaboration is a global research network focused on vaccine safety. The Collaboration has created case definitions to determine diagnostic certainty for several adverse events. Currently nested within multi-page publications, these definitions can be cumbersome for use. We report the results of a randomized trial in which the case definition for anaphylaxis was converted into a user-friendly algorithm and compared the algorithm with the standard case definition. The primary outcomes were efficiency and accuracy. Forty medical students determined the Brighton Level of diagnostic certainty of a sample case of anaphylaxis using either the algorithm or the original case definition. Most participants in both groups selected the correct Brighton Level. Participants using the algorithm required significantly less time to review the case and determine the level of diagnostic certainty [mean difference = 107 s (95% CI: 13–200; p = 0.026)], supporting that the algorithm was more efficient without impacting accuracy.     

Anosmia: Brighton Collaboration case definition and guidelines for data collection,analysis, and presentation of immunization safety data

This is a Brighton Collaboration case definition of anosmia to be used in the evaluation of adverse events following immunization, and for epidemiologic studies for the assessment of background incidence or hypothesis testing. The case definition was developed by a group of experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of SARS-CoV-2 vaccines. The case definition format of the Brighton Collaboration was followed to develop a consensus definition and defined levels of certainty, after an exhaustive review of the literature and expert consultation. The document underwent peer review by the Brighton Collaboration Network and by two expert reviewers prior to submission.     

Vaccine-associated enhanced disease: Case definition and guidelines for data collection,analysis, and presentation of immunization safety data

This is a Brighton Collaboration Case Definition of the term “Vaccine Associated Enhanced Disease” to be utilized in the evaluation of adverse events following immunization. The Case Definition was developed by a group of experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of vaccines for SARS-CoV-2 vaccines and other emerging pathogens. The case definition format of the Brighton Collaboration was followed to develop a consensus definition and defined levels of certainty, after an exhaustive review of the literature and expert consultation. The document underwent peer review by the Brighton Collaboration Network and by selected Expert Reviewers prior to submission.     

Applicability, reliability, sensitivity, and specificity of six Brighton Collaboration standardized case definitions for adverse events following immunization

We evaluated the applicability, reliability, sensitivity, and specificity of six standardized case definitions for adverse events following immunization (AEFI) (for fever, generalized convulsive seizure, hypotonic-hyporesponsive episode, intussusception, nodule, and persistent crying) developed by the Brighton Collaboration using the U.S. Vaccine Adverse Event Reporting System (VAERS). The evaluation included: (a) the development of codified search strings using standardized coding terminology, and (b) for sensitivity and specificity analyses, the development of a "gold standard" for case determination by clinical expert reviews, and its comparison against the application of the definitions to VAERS reports by nonclinicians. Application of the case definitions in an automated approach proved to be valid, feasible, and unlikely to miss confirmed cases of the reported clinical event. The definitions had variable but generally high sensitivity and specificity compared to clinician review, which in itself yielded inconsistent case determination. The study demonstrated the need for the developed standardized definitions for AEFI and their usefulness in passive surveillance.     

Increased risk of anaphylaxis following administration of 2009 AS03-adjuvanted monovalent pandemic A/H1N1 (H1N1pdm09) vaccine

Background

Anaphylaxis after trivalent influenza vaccination is typically reported at a rate of <1 per million doses. In Quebec, Canada, anaphylaxis following administration of the monovalent AS03-adjuvanted H1N1pdm09 vaccine was reported through passive surveillance at a rate of 8 per million doses administered. This was 20 times higher than the reporting rate for non-adjuvanted trivalent vaccines administered during the six previous seasons. However, adequate estimation of the incidence of anaphylaxis is hindered by wide variations in definitions and diagnosis.

Methods

Using the Brighton collaboration case definition of anaphylaxis, all cases with allergic symptoms (AS) reported to public health were reviewed to estimate the incidence of anaphylaxis following AS03-adjuvanted H1N1pdm09 vaccine.

Results

Among 752 reports of allergic symptoms, 33 were initially reported as anaphylaxis of which 20/33 (60%) met the Brighton definition (19/20 with certainty levels 1 or 2). A total of 38 additional cases with onset within 1 h of vaccination also met the Brighton definition of anaphylaxis (27 (71%) with certainty levels 1 or 2). The 58 cases meeting Brighton Level 1 or 2 criteria for anaphylaxis represent a 75% increase over the 33 passively reported and an incidence of 13 per million doses administered.

Conclusion

A substantial number of patients with early-onset allergic symptoms met the most specific levels of the Brighton case definition but were not reported as anaphylaxis. Based on this specific case definition, the incidence of anaphylaxis after AS03-adjuvanted H1N1pdm09 vaccine substantially exceeded that reported with seasonal influenza vaccines, a signal that warrants better understanding.     

Guillain-Barré syndrome following receipt of influenza A (H1N1) 2009 monovalent vaccine in Korea with an emphasis on Brighton Collaboration case definition

Background

In 2009-2010 season, with ongoing of influenza A (H1N1), employment of mass vaccination has generated concerns in issue of adverse events following immunization (AEFI). This study investigates the clinical and laboratory data of reported cases of Guillain-Barré syndrome (GBS) and Fisher syndrome (FS) following receipt of influenza A (H1N1) 2009 monovalent vaccine to the National Vaccine Injury Compensation Program (NVICP) in Korea, with all cases reviewed under case definition developed by Brighton Collaboration GBS Working Group.

Method

Retrospective review of medical records for all suspected cases of GBS ad FS following receipt of influenza A (H1N1) monovalent vaccine reported to NVICP from December 1, 2009, through April 28, 2010 was conducted. Additional analyses were performed for identification of levels of diagnostic certainty according to Brighton Collaboration case definition.

Result

Of 29 reported cases, 22 were confirmed to meet Brighton criteria level 1, 2, or 3 for GBS (21) or FS (1). Of those, 2 (9.1%) met level 1, 9 (40.9%) met level 2, and 11 (50.0%) met level 3. The male to female ratio was 2:0 in cases with level 1, 8:1 in cases with level 2, and 3:8 in cases with level 3. The mean age was older in cases with level 1 (54.0 ± 26.9) than that of cases with level 2 (25.6 ± 22.8), and level 3 (13.6 ± 2.4, P = 0.005). The median onset interval was longer in cases with level 1 (16 days) than that of cases that met level 2 (12.44 days), and 3 (1.09 days, P = 0.019).

Conclusion

The Brighton case definition was used to improve the quality of AEFI data in Korea, and was applicable in retrospective review of medical records in cases with GBS and FS after influenza A (H1N1) vaccination. These findings suggest that standardized case definition was feasible in clarifying the AEFI data, and to further increase the understanding of possible relationship of influenza vaccine and GBS.     

COVID-19 vaccine safety monitoring in Republic of Korea from February 26, 2021 to October 31, 2021

ObjectivesThis study aimed to present data on reported adverse events following coronavirus disease 2019 (COVID-19) vaccination in Republic of Korea from February 26 to October 31, 2021, and to determine whether any significant patterns emerged from an analysis of the characteristics of suspected adverse event cases for each type of vaccine.MethodsAdverse events following COVID-19 vaccination reported by medical doctors and forensic pathologists were analyzed. Cases of suspected anaphylaxis were classified using the Brighton Collaboration definition.ResultsBy October 31, 2021, a total of 353,535 (0.45%) adverse events were reported after 78,416,802 COVID-19 vaccine doses. Of the adverse events, 96.4% were non-serious and 3.6% were serious. The most frequently reported adverse events were headache, myalgia, and dizziness. Of the 835 reported deaths after COVID-19 vaccination, 2 vaccine-related deaths were confirmed. Suspected anaphylaxis was confirmed in 454 cases using the Brighton Collaboration definition.ConclusionThe commonly reported symptoms were similar to those described in clinical trials. Most reported adverse events were non-serious, and the reporting rate of adverse events following COVID-19 vaccination was higher in women than in men (581 vs. 315 per 100,000 vaccinations). Confirmed anaphylaxis was reported in 5.8 cases per 1,000,000 vaccinations.     

Immunization in pregnancy safety surveillance in low and middle-income countries- field performance and validation of novel case definitions

BackgroundA globally standardized approach in high and low and middle-income countries (LMIC) to actively monitor the safety of vaccines for pregnant women during development and implementation phases is critical. Brighton Collaboration’s (BC) Global Alignment of Immunization Safety Assessment in Pregnancy (GAIA) project has developed globally standardized case definitions (CDs) of key obstetric and neonatal terms for the assessment of safety of vaccines in pregnancy. CDs are categorized into levels of diagnostic certainty, facilitating their use in varied settings. This study evaluates the field performance of CDs in LMIC.MethodsData from pregnant participants of RCTs for trivalent inactivated influenza vaccine conducted at Chris Hani Baragwanath Academic Hospital, South Africa (SA) between 2011 and 2013 were reviewed retrospectively for preterm birth, stillbirth and hypertension CDs and the Gestational age assessment (GA) algorithm. Data from an ongoing pneumococcal vaccine trial (conducted at MRC Unit, The Gambia) were collected prospectively for GA.ResultsFor GA, 600 mother-infant dyads from Gambia and 155 mother-infant dyads from SA were reviewed. Level 2B (unsure LMP and US in 2nd trimester) was the most common level seen in Gambia (63%) and level 3B1 (unsure LMP with physical examination) in SA (43%). Preterm deliveries had similar results in SA. The pregnancy-induced hypertension definition performed well, with 96% (54/56) of cases fulfilling ‘level 1’ for ‘preeclampsia with severe features’. 24 stillbirths were identified and 21 records were reviewed; 73.3% (11/15) of the stillbirths classified as antepartum by attending physicians and 83.3% (5/6) of the intrapartum stillbirths did not fulfil the criteria for any level of certainty.ConclusionBC CDs for neonatal and maternal outcomes (preterm and hypertension) and GA were sensitive, reliable and feasible to use in RCTs in SA and Gambia. Modifications to the stillbirth CD are required to improve its usefulness in varied settings.     

Anaphylaxis following H1N1 pandemic vaccines: safety data in perspective

We present here a detailed analysis of anaphylaxis cases reported to GlaxoSmithKline safety database following vaccination with its H1N1 pandemic influenza vaccines, Pandemrix™ and Arepanrix™. Cases were assessed according to the Brighton Collaboration Case Definition (BCCD) as either confirmed diagnosis (97/395, 24.6%), insufficient information to fulfil the minimal criteria of the case definition (117/395, 29.6%) or anaphylaxis excluded (181/395, 45.8%). There was no evidence that the rate of anaphylaxis following vaccination with Pandemrix™ or Arepanrix™ is increased with respect to the rates of anaphylaxis for other vaccines. Our analysis also highlighted the challenges of reliably determining the rate of anaphylaxis as an adverse event in the postmarketing setting following mass vaccination, as anaphylaxis was excluded in 45.8% of reported cases.     

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.     

Neonatal infections: Case definition and guidelines for data collection,analysis, and presentation of immunisation safety data

Maternal vaccination is an important area of research and requires appropriate and internationally comparable definitions and safety standards. The GAIA group, part of the Brighton Collaboration was created with the mandate of proposing standardised definitions applicable to maternal vaccine research. This study proposes international definitions for neonatal infections.The neonatal infections GAIA working group performed a literature review using Medline, EMBASE and the Cochrane collaboration and collected definitions in use in neonatal and public health networks. The common criteria derived from the extensive search formed the basis for a consensus process that resulted in three separate definitions for neonatal blood stream infections (BSI), meningitis and lower respiratory tract infections (LRTI). For each definition three levels of evidence are proposed to ensure the applicability of the definitions to different settings.Recommendations about data collection, analysis and presentation are presented and harmonized with the Brighton Collaboration and GAIA format and other existing international standards for study reporting.     

Neurologic Disease after Yellow Fever Vaccination,São Paulo,Brazil, 2017–2018

Yellow fever (YF) vaccine can cause neurologic complications. We examined YF vaccine–associated neurologic disease reported from 3 tertiary referral centers in São Paulo, Brazil, during 2017–2018 and compared the performance of criteria established by the Yellow Fever Vaccine Working Group/Centers for Disease Control and Prevention and the Brighton Collaboration. Among 50 patients who met inclusion criteria, 32 had meningoencephalitis (14 with reactive YF IgM in cerebrospinal fluid), 2 died, and 1 may have transmitted infection to an infant through breast milk. Of 7 cases of autoimmune neurologic disease after YF vaccination, 2 were acute disseminated encephalomyelitis, 2 myelitis, and 3 Guillain-Barré syndrome. Neurologic disease can follow fractional vaccine doses, and novel potential vaccine-associated syndromes include autoimmune encephalitis, opsoclonus-myoclonus-ataxia syndrome, optic neuritis, and ataxia. Although the Brighton Collaboration criteria lack direct vaccine causal assessment, they are more inclusive than the Centers for Disease Control and Prevention criteria.