Hypotonic-hyporesponsive Episodes Research Articles

Acute adverse events following immunization with DTP-HB-Hib pentavalent vaccine in the first year of life.

Since November 2014, the pentavalent (Diptheria+Tetanus+Pertussis and Hepatitis B and Hib or DTP-HBHib) vaccine has been integrated into the Iranian national vaccination programme. We conducted a prospective study in Zahedan in the southeast of the Islamic Republic of Iran to determine the incidence of adverse events following immunization (AEFI) with the pentavalent vaccine in children aged under one year. Using cluster sampling, 1119 children aged 2-10 months at 15 public health clinics were invited, through their parents, to participate in the study. The parents were trained to register and report any AEFIs in a questionnaire. They were instructed to return the child to the clinic for further examination by a physician if they observed any complications within 3 days of vaccination. The most commonly reported AEFIs were fever (50.94%), mild (41.46%) and severe (1.70%) injection site complications, persistent crying for 3 hours or more (1.88%), hypotonic hyporesponsive episode (0.36%), vomiting (1.88%), diarrhoea (2.95%), and sterile abscess (0.62%). There were no cases of convulsion, purulent abscess or rash. The work experience of vaccinators (OR = 1.85; 95% CI: 1.4-2.46) showed a significant statistical association with the incidence of mild local complications at the injection site. Those with a history of Bacillus Calmette-Guérin (BCG) lymphadenitis (OR = 3.89; 95% CI:1.04-14.49) had a higher risk of severe local complications at the injection site. The observed incidence of serious AEFIs following pentavalent vaccine injection in the study population was within the expected range. However, some of the relationships observed in this study require further research.

Surveillance of adverse events following immunization of 13-valent pneumococcal conjugate vaccine among infants, in Zhejiang province, China

ABSTRACT Objectives To evaluate the safety of 13-valent pneumococcal conjugate vaccine (PCV13) after its licensure. Methods Review and describe the AEFI reported to national adverse event following immunization surveillance system (NAEFISS) in Zhejiang province from 2017 to 2020. Reporting rates of AEFI were calculated by age, city, severity of AEFI, categories of AEFI, and reaction categories. The data mining algorithm used in this study was reporting odds ratio (ROR). A value of ROR-1.96SE >1 (standard error [SE]) was considered as the positive signal. Results NAEFISS received 3332 AEFI cases following PCV13, with a reporting rate of 17.58/10000 doses. Of the reported AEFI, 652 were serious AEFI cases and the reporting rate was 3.44 for serious AEFI. The reporting rate of fever was the highest among all the clinical diagnosis (7.39/10000 doses). The positive signals were obtained for injection site reaction (ROR-1.96SE: 1.55), hypotonic hyporesponsive episode (HHE) (ROR-1.96SE: 1.62) and febrile seizure (ROR-1.96SE: 1.52). Conclusion The present results supported previous observations that the PCV13 administered as the four-dose schedule was generally well tolerated in Chinese infants as we did not identify any new/unexpected safety concern from the NAEFISS during a four-year time period.

Postmarketing surveillance of adverse events following meningococcal B vaccination: data from Apulia Region, 2014–19

ABSTRACT Since the multicomponent meningococcal B vaccine introduction, the Apulian Regional Health Authority implemented postmarketing surveillance program, as provided by Italian laws. From National Pharmacovigilance Network, we selected 4CMenB AEFIs reported in Apulia from 01 January 2014 to 31 December 2019, while the number of 4 cMen B doses administered per year was obtained from the regional immunization database (GIAVA). For each subject who experienced an adverse event following meningococcal B vaccine (AEFIs), a predefined form was filled in. A total of 214 AEFIs (26.5 × 100.000 doses) were reported after any dose of MenB-4 c vaccination of which 58/214 (27.1%) were classified as serious (7.2 × 100,000 doses), 145/214 (67.8%) as not serious (180 × 100,000 doses), and 11/214 (5.1%) as undefined (1.3 × 100,000 doses). The average age of subjects who experimented and AEFI was 30 months. The majority of serious AEFIs were reported in 2- to 11-month-old children (44/57; 77.2%). A total of 31/58 (3.8 × 100,000 doses; 53.4%) serious AEFIs were reported as having a ‘consistent causal association’ with vaccination. Of these, fever/hyperpyrexia was reported in 21/31 (2.6 × 100,000 doses; 67.7%); hypotonic-hyporesponsive episode was reported in 7/31 (0.9 × 100,000 doses [add %-age]) and was the most frequent adverse event with neurological symptoms. A total of 13/31 (41.9%) serious AEFIs classified as ‘consistent causal association’ were reported after the first dose of 4cMenB, of these 5/13 (38.5%) children did not complete the vaccination schedule. Our data seemed to confirm, in a large population, the a good safety profile of the universal mass vaccination with 4CMENB.

Hypotonic-hyporesponsive Episodes After Diphtheria, Tetanus and Acellular Pertussis Vaccination.

Background:Hypotonic-hyporesponsive episode (HHE) after whole cell pertussis vaccination is a known adverse event. Less is known about the risk of HHE after administration of acellular pertussis vaccines.Methods:Using parental interviews, this study actively surveyed for HHE among infants after doses 1 and 2 of acellular pertussis vaccine.Results:We interviewed the parents of 52,531 infants. HHE was reported at a rate of 22.8 per 100,000 doses (95% CI: 11.8–39.9) of acellular pertussis vaccine, approximately 45 episodes per 100,000 children.Conclusions:These rates are lower than HHE rates reported after whole cell pertussis vaccines and within the range of HHE rates reported in other studies of acellular pertussis vaccines.

Characterization of hypotonia-hyporesponsiveness after pentavalent vaccine and neurodevelopmental screening in children under 6 years of age, 2013-2018, Uruguay

Hypotonic-hyporesponsive episodes (HHE) is one frequently reported neurologic adverse effect supposedly attributable to vaccination and immunization. Its long-term impact on neurodevelopment is not completely known. To characterize the post-pentavalent vaccine HHE events reported to the Uruguayan Ministry of Health (M of H) between 2014 and 2018. To perform neurodevelopment screening of those who were under 6 years of age at the time of evaluation. Descriptive study of the reports made to the National Farmacosurveillance System of the M of H. Neurodevelopment screening was performed using the National Guidelines for Developmental Surveillance. 30 cases were studied. Most cases occurred after the first doses, were of short duration and during the first hours after vaccination, with spontaneous recovery. Median time between the event and this evaluation was 2 years and 2 months. Screening tests were normal in 15. Delay in the language area was detected in one case. HHE events had similar characteristics to those described in the literature, with no severe short-term complications. Despite the limitations of the present study, no delays nor deviations were found in the development of the children who were evaluated.

Evaluation of the safety profile of rotavirus vaccines: a pharmacovigilance analysis on American and European data

Rotaviruses (RVs) are the most common cause of severe diarrheal disease. To date two rotavirus oral vaccines are licensed: Rotarix and Rotateq. Our aim was to contribute to the post-marketing evaluation of these vaccines safety profile. We collected all RV vaccines-related reports of Adverse Events Following Immunization (AEFI) in US Vaccine Adverse Events Reporting System (VAERS) and VigiBase between January 2007 and December 2017. A disproportionality analysis using Reporting Odds Ratio (ROR) was performed. A total of 17,750 reports in VAERS and 6,358 in VigiBase were retrieved. In VAERS, 86.2% of the reports concerned RotaTeq, whereas in VigiBase 67.7% of them involved Rotarix. Across the databases, diarrhea (1,672 events in VAERS, 1,961 in VigiBase) and vomiting (1,746 in VAERS, 1,508 in VigiBase) were the most reported AEFIs. Noteworthy, the RV vaccines-intussusception pair showed a ROR greater than 20 in both databases. Some new potential safety signals emerged such as fontanelle bulging, hypotonic-hyporesponsive episode, livedo reticularis, and opisthotonus. Overall, our data show that most of the reported AEFIs are listed in the Summary of Product Characteristics (SPCs). However, there remains the need to investigate the potential safety signals arose from this analysis, in order to complete the description of the AEFIs.

Safety profile of Infanrix hexa – 17 years of GSK’s passive post-marketing surveillance

ABSTRACT Introduction This paper reports 17 years of passive safety surveillance of routine use of the pediatric hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b-conjugate vaccine (DTPa-HBV-IPV/Hib, Infanrix hexa, GSK). Methods Global post-licensure passive surveillance data collected in GSK’s central safety database since DTPa-HBV-IPV/Hib’s launch (2000) are described. Results The most common spontaneously reported adverse events (AEs) after DTPa-HBV-IPV/Hib vaccination in children were fever (reporting rate: 7.74/100,000 doses distributed), crying (2.62/100,000), injection site erythema (1.87/100,000) and swelling (1.28/100,000). A review of extensive limb swelling did not reveal any safety concerns. An observed-to-expected analysis did not show an increased risk of sudden death after DTPa-HBV-IPV/Hib vaccination, in line with previous observations. The analyses confirmed that increases in spontaneous reporting proportions of convulsions with/without fever and hypotonic-hyporesponsive episodes after co-administration of DTPa-HBV-IPV/Hib and 13-valent pneumococcal conjugate vaccine remained small and their clinical significance unknown. The most common vaccination errors were mistakes in the vaccination schedule. Reporting of preparation errors (mostly reconstitution) was low and did not impact the vaccine’s benefit-risk profile. Conclusions Seventeen years of post-licensure experience confirm confidence in the safety profile of DTPa-HBV-IPV/Hib in routine use, with a favorable benefit-risk profile in infants and toddlers.

ADVANCE database characterisation and fit for purpose assessment for multi-country studies on the coverage, benefits and risks of pertussis vaccinations

IntroductionThe public-private ADVANCE consortium (Accelerated development of vaccine benefit-risk collaboration in Europe) aimed to assess if electronic healthcare databases can provide fit-for purpose data for collaborative, distributed studies and monitoring of vaccine coverage, benefits and risks of vaccines. ObjectiveTo evaluate if European healthcare databases can be used to estimate vaccine coverage, benefit and/or risk using pertussis-containing vaccines as an example. MethodsCharacterisation was conducted using open-source Java-based (Jerboa) software and R scripts. We obtained: (i) The general characteristics of the database and data source (meta-data) and (ii) a detailed description of the database population (size, representatively of age/sex of national population, rounding of birth dates, delay between birth and database entry), vaccinations (number of vaccine doses, recording of doses, pattern of doses by age and coverage) and events of interest (diagnosis codes, incidence rates). A total of nine databases (primary care, regional/national record linkage) provided data on events (pertussis, pneumonia, death, fever, convulsions, injection site reactions, hypotonic hypo-responsive episode, persistent crying) and vaccines (acellular pertussis and whole cell pertussis) related to the pertussis proof of concept studies. ResultsThe databases contained data for a total population of 44 million individuals. Seven databases had recorded doses of vaccines. The pertussis coverage estimates were similar to those reported by the World Health Organisation (WHO). Incidence rates of events were comparable in magnitude and age-distribution between databases with the same characteristics. Several conditions (persistent crying and somnolence) were not captured by the databases for which outcomes were restricted to hospital discharge diagnoses. ConclusionThe database characterisation programs and workflows allowed for an efficient, transparent and standardised description and verification of electronic healthcare databases which may participate in pertussis vaccine coverage, benefit and risk studies. This approach is ready to be used for other vaccines/events to create readiness for participation in other vaccine related studies.

ADVANCE system testing: Can safety studies be conducted using electronic healthcare data? An example using pertussis vaccination

IntroductionThe Accelerated Development of Vaccine benefit-risk Collaboration in Europe (ADVANCE) public-private collaboration, aimed to develop and test a system for rapid benefit-risk monitoring of vaccines using healthcare databases in Europe. The objective of this proof-of-concept (POC) study was to test the feasibility of the ADVANCE system to generate incidence rates (IRs) per 1000 person-years and incidence rate ratios (IRRs) for risks associated with whole cell- (wP) and acellular- (aP) pertussis vaccines, occurring in event-specific risk windows in children prior to their pre-school-entry booster. MethodsThe study population comprised almost 5.1 million children aged 1 month to <6 years vaccinated with wP or aP vaccines during the study period from 1 January 1990 to 31 December 2015. Data from two Danish hospital (H) databases (AUH and SSI) and five primary care (PC) databases from, UK (THIN and RCGP RSC), Spain (SIDIAP and BIFAP) and Italy (Pedianet) were analysed. Database-specific IRRs between risk vs. non-risk periods were estimated in a self-controlled case series study and pooled using random-effects meta-analyses. ResultsThe overall IRs were: fever, 58.2 (95% CI: 58.1; 58.3), 96.9 (96.7; 97.1) for PC DBs and 8.56 (8.5; 8.6) for H DBs; convulsions, 7.6 (95% CI: 7.6; 7.7), 3.55 (3.5; 3.6) for PC and 12.87 (12.8; 13) for H; persistent crying, 3.9 (95% CI: 3.8; 3.9) for PC, injection-site reactions, 2.2 (95% CI 2.1; 2.2) for PC, hypotonic hypo-responsive episode (HHE), 0.4 (95% CI: 0.4; 0.4), 0.6 (0.6; 0.6) for PC and 0.2 (0.2; 0.3) for H; and somnolence: 0.3 (95% CI: 0.3; 0.3) for PC. The pooled IRRs for persistent crying, fever, and ISR, adjusted for age and healthy vaccinee period were higher after wP vs. aP vaccination, and lower for convulsions, for all doses. The IRR for HHE was slightly lower for wP than aP, while wP was associated with somnolence only for dose 1 and dose 3 compared with aP. ConclusionsThe estimated IRs and IRRs were comparable with published data, therefore demonstrating that the ADVANCE system was able to combine several European healthcare databases to assess vaccine safety data for wP and aP vaccination.

ADVANCE system testing: Benefit-risk analysis of a marketed vaccine using multi-criteria decision analysis and individual-level state transition modelling

BackgroundThe Accelerated Development of VAccine beNefit-risk Collaboration in Europe (ADVANCE) is a public-private collaboration aiming to develop and test a system for rapid benefit-risk (B/R) monitoring of vaccines using electronic health record (eHR) databases in Europe. Proof-of-concept studies were designed to assess the proposed processes and system for generating the required evidence to perform B/R assessment and near-real time monitoring of vaccines. We aimed to test B/R methodologies for vaccines, using the comparison of the B/R profiles of whole-cell (wP) and acellular pertussis (aP) vaccine formulations in children as an example. MethodsWe used multi-criteria decision analysis (MCDA) to structure the B/R assessment combined with individual-level state transition modelling to build the B/R effects table. In the state transition model, we simulated the number of events in two hypothetical cohorts of 1 million children followed from first pertussis dose till pre-school-entry booster (or six years of age, whichever occurred first), with one cohort receiving wP, and the other aP. The benefits were reductions in pertussis incidence and complications. The risks were increased incidences of febrile convulsions, fever, hypotonic-hyporesponsive episodes, injection-site reactions and persistent crying. Most model parameters were informed by estimates (coverage, background incidences, relative risks) from eHR databases from Denmark (SSI), Spain (BIFAP and SIDIAP), Italy (Pedianet) and the UK (RCGP-RSC and THIN). Preferences were elicited from clinical and epidemiological experts. ResultsUsing state transition modelling to build the B/R effects table facilitated the comparison of different vaccine effects (e.g. immediate vaccine risks vs long-term vaccine benefits). Estimates from eHR databases could be used to inform the simulation model. The model results could be easily combined with preference weights to obtain B/R scores. ConclusionExisting B/R methodology, modelling and estimates from eHR databases can be successfully used for B/R assessment of vaccines.

Rate of Recurrence of Adverse Events Following Immunization: Results of 19 Years of Surveillance In Quebec, Canada.

While adverse events following immunization (AEFI) are frequent, there are limited data on the safety of reimmunizing patients who had a prior AEFI. Our objective was to estimate the rate and severity of AEFI recurrences. We analyzed data from the AEFI passive surveillance system in Quebec, Canada, that collects information on reimmunization of patients who had a prior AEFI. Patients with an initial AEFI reported to the surveillance system between 1998 and 2016 were included. Rate of AEFI recurrence was calculated as number of patients with recurrence/total number of patients reimmunized. Overall, 1350 patients were reimmunized, of which 59% were 2 years of age or younger. The AEFI recurred in 16% (215/1350) of patients, of whom 18% (42/215) rated the recurrence as more severe than the initial AEFI. Large local reactions extending beyond the nearest joint and lasting 4 days or more had the highest recurrence rate (67%, 6/9). Patients with hypotonic hyporesponsive episodes had the lowest rate of recurrence (2%, 1/50). Allergic-like events recurred in 12% (76/659) of patients, but none developed anaphylaxis. Of 33 patients with seizures following measles mumps rubella with/without varicella vaccine, none had a recurrence. Compared with patients with nonserious AEFIs, those with serious AEFIs were less often reimmunized (60% versus 80%; rate ratio: 0.8; 95% confidence interval: 0.66-0.86). Most patients with a history of mild or moderate AEFI can be safely reimmunized. Additional studies are needed in patients with serious AEFIs who are less likely to be reimmunized.

Recurrence risk of a hypotonic hyporesponsive episode in two Australian specialist immunisation clinics

BackgroundA hypotonic hyporesponsive episode (HHE) is a well-described adverse event following immunisation (AEFI) in young children. There is limited data regarding recurrence post re-vaccination. MethodA retrospective analysis of HHEs reported to two tertiary paediatric hospitals in Australia: The Royal Children’s Hospital, Melbourne [2006–11] and the Children’s Hospital Westmead, Sydney [1997–2014].HHE definition level of confidence was allocated according to Brighton Collaboration (BC) criteria and defined immediate if within 30 min post vaccination. The Australian Immunisation Register (AIR) was utilised to document current immunisation status. Results235 HHE cases (135 Melbourne, 100 Sydney) were identified: 47% were female and 67% (157/235) occurred following the routine dose one vaccines at 6–8 weeks of age. Median time following immunisation was 120 min (range 1 min to 14 days) An immediate HHE occurred in 43% (102/235) and by BC criteria, 74% (173/235) were level 1 (definite). Subsequent vaccines were administered under supervision in hospital in 37% overall (86/235); 43% (58/135) in Melbourne and 28% (28/100) in Sydney. HHE recurrence rate was 3% (7/235) [95% confidence interval 1–6%]. AIR records were available in 94% (221/235). At a median age of 3.1 years, 84% (186/221) were up-to-date with recommended vaccines. ConclusionThis study highlights the importance of specialist immunization clinics in supporting the National Immunisation Program, through follow-up and management of serious adverse events following immunization.

Case Series Analysis of Hypotonic-Hyporesponsive Episodes following Pertussis Immunization: The Importance of an Accurate Diagnosis

Background: The Hypotonic-Hyporesponsive Episode (HHE) is characterized by the sudden onset of reduced muscle tone, hyporesponsiveness and change of skin colour (pallor or cyanosis). It is reported mainly after the first doses of pertussis component vaccines and less frequently with other vaccines. The recognition and diagnosis are essential for correct management. Methods & Materials: Descriptive study of a retrospective case series was performed. All children diagnosed with HHE according to the Brighton Criteria, who consulted at the immunization area of a pediatric hospital between January 2010 and August 2017, were included. Variables analyzed: age, sex, medical history, vaccines received, dose, interval between immunization and HHE, symptoms, medical resources and the vaccination schedule follow up. Results: There were 13 cases, one of which was excluded due to insufficient data (category 4). The mean age was 3.5 months (range: 2-18). Ten of the episodes occurred after the 1st dose (83.3%). Eleven patients received pentavalent whole-cell vaccine (DTwPHibHB) and one, hexavalent (DTaPHibHBSalk). Symptoms were onset immediately in 3 patients; < 1 h in 1; 2- < 3hs in 1; 3- < 4hs in 2; 4- < 5hs in 2; 6- < 12hs in 1, 12 - < 24 hours in 2. Brighton Classification: category 1: five, 2: four and 3: three cases. Most frequent concomitant symptoms were: fever in 4 cases and irritability in 3. History of prematurity 2/12 cases, required medical consultation 10/12 and hospitalization 8/12. Evolution: 11 recovered completely and from 1 data were missed. Eight of the patients who were followed up continued with acellular vaccine, one with pentavalent whole-cell vaccine. None presented complications. Conclusion: All patients presented the EHH within 24 hours after the administration of pertussis component vaccines. HHE has been observed most frequently during the primary immunization series, mainly after the first dose (83.3%) and pentavalent vaccine. The recovery was complete and without sequelae in all cases. More than 80% required medical consultation and 67% hospitalization. The follow up of the schedule was not associated with recurrences of HHE or other complications

Adverse Events Following Immunization in Brazil: Age of Child and Vaccine-Associated Risk Analysis Using Logistic Regression.

Objective: Vaccines are effective in controlling and eradicating infectious diseases. However, adverse events following immunization (AEFI) can occur in susceptible individuals. The objective of this study was to analyze the Brazilian AEFI database and compare eight vaccines in order to profile risks of AEFIs related to the mandated pediatric schedule of immunization, considering the age and sex of the child, type of vaccine, and reported adverse events. Methods: We analyzed the Brazilian AEFI database integrating reports between 2005 and 2010 for children less than 10-years old immunized with eight mandated vaccines: diphtheria, pertussis, tetanus, Haemophilus influenzae type b (TETRA); diphtheria, tetanus, and pertussis (DTP); Bacillus Calmette–Guerin (BCG); oral poliovirus vaccine (OPV); measles, mumps, and rubella (MMR); oral rotavirus vaccine (ORV); hepatitis B (HB); and yellow fever (YF). We compared the children’s age regarding types of AEFI, evaluated AEFI factors associated with the chance of hospitalization of the child, and estimated the chance of notification of an AEFI as a function of the type of vaccine. In total, 47,105 AEFIs were observed for the mandated vaccines. Results: The highest AEFI rate was for the TETRA vaccine and the lowest was for the OPV vaccine, with 60.1 and 2.3 events per 100,000 inoculations, respectively. The TETRA vaccine showed the highest rate of hypotonic hyporesponsive episode, followed by convulsion and fever. The MMR and YF vaccines were associated with generalized rash. BCG was associated with enlarged lymph glands but showed the largest negative (protective) association with hyporesponsive events and seizures. Compared with children aged 5–9-years old, young children (<1 year) showed significantly higher odds of hospitalization. Conclusions: The Brazilian AEFI registry is useful to compare the magnitude and certain characteristics of adverse events associated with mandated pediatric vaccines.

Use of electronic immunization registry in the surveillance of adverse events following immunization.

ABSTRACTOBJECTIVETo describe adverse events following vaccination (AEFV) of children under two years old and analyze trend of this events from 2000 to 2013, in the city of Araraquara (SP), Brazil.METHODSThis is a descriptive study conducted with data of the passive surveillance system of AEFV that is available in the electronic immunization registry (EIR) of the computerized medical record of the municipal health service (Juarez System). The study variables were: age, gender, vaccine, dose, clinical manifestations and hospitalization. We estimated rates using AEFV as numerator and administered doses of vaccines as denominator. The surveillance sensitivity was estimated by applying the method proposed by the Centers for Disease Control and Prevention. We used Prais-Winsten regression with a significance level of 5.0%.RESULTSThe average annual rate of AEFV was 11.3/10,000 administered doses, however without a trend in the study period (p=0.491). Most cases occurred after the first dose (41.7%) and among children under one year of age (72.6%). Vaccines with pertussis component, yellow fever and measles-mumps-rubella were the most reactogenic. We highlighted the rates of hypotonic-hyporesponsive episodes and convulsion that were 4.1/10,000 and 1.5/10,000 doses of vaccines with pertussis component, respectively, most frequently in the first dose; 60,0% of cases presented symptoms in the first 24 hours after vaccination, however, 18.6% showed after 96 hours. The sensitivity of surveillance was 71.9% and 78.9% for hypotonic-hyporesponsive episodes and convulsion, respectively.CONCLUSIONSThe EIR-based AEFV surveillance system proved to be useful and highly sensitive to describe the safety profile of vaccines in a medium-sized city. It was also shown that the significant increase of the vaccines included in the basic vaccination schedule in childhood in the last decade did not alter the high safety standard of the National Immunization Program.

Adverse Events Following Immunization: Will It Happen Again?

* Abbreviations: AEFI — : adverse event following immunization HHE — : hypotonic-hyporesponsive episode “Vaccines save lives.” “Vaccines are safe.”1⇓–3 These are critical concepts that pediatricians everywhere seek to convey to parents. However, for many reasons, primarily because of the successes in reduction of vaccine-preventable diseases, parents are increasingly concerned about the safety of and need for vaccines.4,5 Parents may come to well-child checkup appointments equipped with lists of questions about vaccine safety and effectiveness. In this context, pediatricians may struggle to explain the value of vaccines when confronted with a difficult situation: an actual untoward event after administration of childhood vaccines. Often referred to as an adverse event following immunization (AEFI),6 these events range from mild and uncommon to rare but serious. There are few experiences more challenging for a pediatrician than trying to convince a parent to continue vaccinating their child after they have witnessed a febrile seizure or a hypotonic-hyporesponsive episode (HHE) not long after a vaccination. Although … Address correspondence to Sean T. O’Leary, MD, MPH, Children’s Hospital Colorado, 13199 East Montview Blvd, Suite 300, Aurora, CO 80045. E-mail: sean.oleary{at}ucdenver.edu

Risk of Recurrence of Adverse Events Following Immunization: A Systematic Review.

Reimmunizing patients who had an adverse event following immunization (AEFI) is sometimes a challenge because there are limited data on the risk and severity of AEFI recurrence. To summarize the literature on the risk of AEFI recurrence. PubMed, Embase, and Cochrane library. We included articles in English or French published before September 30, 2016. Articles were selected if they estimated the risk of AEFI recurrence in at least 5 individuals. Studies with experimental vaccines were excluded. Data on study design, setting, population, vaccines, and AEFI recurrence were extracted. Twenty-nine articles were included. Among patients with a history of hypotonic hyporesponsive episode (n = 398), anaphylaxis (n = 133), or seizures (n = 60) who were reimmunized, events recurred in 0% to 0.8%. Allergic-like events recurred in 30 of 594 reimmunized patients. Fever recurred in 0% to 84% of 836 reimmunized patients, depending on the vaccine and dose number. Among children with extensive limb swelling after the fourth dose of diphtheria-tetanus-acellular pertussis vaccine, recurrence was higher when the fifth dose was given withthe full-antigen formulation (78%) compared with the reduced-antigen formulation (53%, P = .02) LIMITATIONS: Many studies, included few patients, and those with severe AEFIs were often not reimmunized. Despite vaccines being administered to millions of people annually, there are few studies in which researchers evaluated AEFI recurrence. Published studies suggest that reimmunization is usually safe. However in these studies, severe cases were often not reimmunized.

Frequently asked questions on seven rare adverse events following immunization.

Routine mass immunization programs have contributed greatly to the control of infectious diseases and to the improvement of the health of populations. Over the last decades, the rise of antivaccination movements has threatened the advances made in this field to the point that vaccination coverage rates have decreased and outbreaks of vaccine-preventable diseases have resurfaced. One of the critical points of the immunization debate revolves around the level of risk attributable to vaccination, namely the possibility of experiencing serious and possibly irreversible adverse events. Unfortunately, the knowledge about adverse events, especially rare ones, is usually incomplete at best and the attribution of a causal relationship with vaccinations is subject to significant uncertainties. The aim of this paper is to provide a narrative review of seven rare or very rare adverse events: hypotonic hyporesponsive episode, multiple sclerosis, apnea in preterm newborns, Guillain-Barré syndrome, vasculitides, arthritis/ arthralgia, immune thrombocytopenic purpura. We have selected these adverse events based on our experience of questions asked by health care workers involved in vaccination services. Information on the chosen adverse events was retrieved from Medline using appropriate search terms. The review is in the form of questions and answers for each adverse event, with a view to providing useful and actionable concepts while not ignoring the uncertainties that remain. We also highlight in the conclusion possible future improvements to adverse event detection and assessment that could help identify individuals at higher risk against the probable future backdrop of ever-greater abandonment of compulsory vaccination policies.

Behind the scenes in public health: Adverse events following immunization (AEFI) signal investigation in British Columbia.

In British Columbia, vaccine safety is monitored through a passive surveillance system with voluntary reporting of adverse events following immunization (AEFIs) from immunizers to five regional health authorities and onward to the British Columbia Centre for Disease Control (BCCDC). To review and summarize all documented AEFI cluster or signal investigations carried out by BCCDC between November 2007 and July 2014. Documented cluster or signal investigations were reviewed to summarize year, alerting mechanism, event type and vaccine, investigative analysis approach, results, and public health actions. The findings and public health actions of two cluster investigations are described in detail. There were two fatality investigations and thirteen cluster investigations. The two fatalities were found to be due to sudden infant death syndrome and were not vaccine-related. Clusters were predominantly identified through notification from regional medical health officers or public health nurses, and the majority were local injection site reactions (54%), or allergic events (39%). Most investigations did not identify a specific association to a vaccine or a lot of vaccine, and no public health actions were taken. Two recent investigations-reports of hypotonic-hyporesponsive episodes with or without severe vomiting and diarrhea following receipt of a single lot of DPT-IPV/Hib/hepatitis B vaccine, and reports of severe pain past nearest joint following administration of a single lot of influenza vaccine-were thought to be vaccine-related. The former investigation did not find an association to vaccine, while the severe local reactions post-influenza immunization were determined to be a result of improper injection technique. Public health actions included communication to federal/provincial/territorial vaccine safety partners and additional injection technique training. This investigative aspect of public health immunization programs is often not in the public eye but is an important component of behind the scenes activities that serve to protect public safety.

Myocarditis with Hypotonic–Hyporesponsive Episode after Multiple Vaccination

Myocarditis with Hypotonic–Hyporesponsive Episode after Multiple Vaccination