Adverse Events Following Immunization- The Known Unknowns and Black Box

Although vaccines are one of the most rigorously tested biological products, the safety concerns persist globally. The vaccine safety concerns linked to measles, pentavalent and human papillomavirus (HPV) vaccines have affected the vaccine coverage significantly in past. While surveillance of adverse events following immunization (AEFI) is part of the national immunization program mandate, it suffers from challenges and biases related to reporting, completeness, and quality. Some conditions of concern, termed as adverse events of special interest (AESI) following vaccination, mandated specialised studies to prove/disprove the association. The AEFIs/AESIs are usually caused by one of the four pathophysiologic mechanisms, but for several AEFIs/AESIs, the exact pathophysiology remains elusive. For the causality assessment of AEFIs, a systematic process with checklists and algorithm are followed to classify into one of the four causal association categories. While the causal association primarily banks on epidemiological observations for several AEFIs, the emerging evidences indicate roles of underlying genetic, gender, age and other pro-inflammatory risk factors for AEFIs and AESIs. The emerging evidences suggest role of antigenic mimicry, autoantibody(ies) and underlying genetic susceptibility for the AEFIs/AESIs. The uncertainty about the frequency, profile, interval, and severity of AEFIs/AESIs and variations across the population, ambiguity about the exact pathophysiology mechanism, absence of definite markers, suggest a possible black box effect of the vaccines. Unless these unanswered questions concerning the AEFIs/AESIs are addressed appropriately and communicated to the stakeholders (professionals, care providers, beneficiaries, general public and media), the anti-vaccine movement shall keep challenging the vaccine and vaccination program.

Cardiorespiratory Adverse Events after First Vaccination in Preterm Neonates With Gestational Age ?30 Weeks

Objectives: To document the adverse cardiorespiratory events following first routine immunization in preterm neonates. Methods: We retrieved records of neonates with gestational age ?30 weeks, and included those who developed cardiorespiratory events after first vaccines before discharge. Our Unit’s protocol is to administer Bacillus Calmette-Guerin (BCG), hepatitis B vaccine to those discharged at <8 weeks postnatal age. Hexavalent, BCG, pneumococcal vaccine and rotavirus vaccines are given at 8 weeks of age, if hospital stay is predicted to be longer. Unit compliance to vaccination administration at appropriate ages were also measured. Results: Data of 161 neonates ?30 weeks (17.4% <27 week) who completed care in the unit was studied. Cardio-respiratory adverse events were reported in 21(13.7%). None of these required initiation of invasive ventilation. High flow nasal cannula therapy and caffeine restart were required for these events in 14 (9.3%) and 6 (3.9%) neonates, respectively. Lower gestational age, bronchopulmonary dysplasia and sepsis were significant risk factors on univariate analysis. On multivariate analysis, continued need for respiratory support at 4 weeks of age (P=aOR 14.5 (95% CI 5-59.1) was the only independent risk factor for post-vaccination cardiorespiratory adverse events. Of 38 who were not vaccinated at recommended ages by unit policy, 25 were missed opportunities, the rest were deemed unstable for vaccinations at that age by the clinical team. Conclusion: Adverse cardiorespiratory events were uncommon after first vaccinations in very preterm neonates. Administering vaccines in this group before discharge would allow monitoring for these events, especially for those who require long-term respiratory support.

Safety analysis of children of different ages vaccinated with measles, mumps and rubella combined attenuated live vaccine/measles and rubella combined attenuated live vaccine in Jilin Province from 2015 to 2022 / 中国生物制品学杂志

@#Objective To analyze the safety of children of different ages vaccinated with measles,mumps and rubella combined attenuated live vaccine(MMR in brief)/measles and rubella combined attenuated live vaccine(MR in brief)in Jilin Province from 2015 to 2022.Methods The actual vaccination data of MMR and MR from January 1,2015 to December 31,2022 were collected through the Jilin information management system for immunization programming,and all AEFI case information reported after vaccination with MMR and MR in this period was collected through the national adverse event following immunization(AEFI) monitoring and reporting system.The incidence rates of AEFI reports were compared among8-month-old children vaccinated with the first dose of MMR(MMR 8 group) and MR(MR8 group),18-month-old children vaccinated with the first dose of MMR(vaccinated with MR at 8 months old,MMR18-1 group) and the second dose of MMR(vaccinated with the first dose of MMR at 8 months old,MMR18-2 group) to preliminarily evaluate the safety of children vaccinated with MMR and MR at different ages.Results The reported incidence of AEFI in MMR8,MR8,MMR18-1 and MMR18-2 groups were 374.41/100 000,350.81/100 000,101.70/100 000 and 104.91/100 000,respectively,with significant difference among the four groups(χ~2=1 145.47,P=0.00);There was no significant difference between MMR8 and MR8,as well as MMR18-1 and MMR18-2 groups(χ~2=3.780 and 0.194,respectively,each P> 0.05);There were significant differences between MMR8 and MMR18-1,MMR8 and MMR18-2,as well as MR8 and MMR18-1groups(χ~2=920.440,412.110 and 1 021.120,respectively,each P=0.00).Most of the adverse reactions were general reactions,mainly fever,local redness and induration;A few were abnormal reactions,which were mainly allergic reactions(rash,papules,urticaria,etc.).Only one case of coincidence was reported in MMR8 group,and no psychogenic reaction,vaccine quality accident and vaccination accident occurred.All AEFI turned out to be improved or cured.Conclusion The differences of AEFI reported incidence of 8-month-old children vaccinated with MMR and MR were all small,and the difference of AEFI reported incidence of 18-month-old children vaccinated with the second dose of MMR was small regardless of the initial vaccination with MMR or MR.It is safe to use MMR instead of MR for the first vaccination in8-month-old children.

A cross-sectional study to assess the adverse events following immunization with CoviShield vaccine at a private medical college in South India

Background: The World Health Organization had proclaimed the outbreak of the novel coronavirus (COVID-19) as a worldwide pandemic on March 11, 2020. Immunization against the disease was the need of the hour to curtail the spread of COVID-19 pandemic. Two vaccines manufactured in India were approved for emergency use authorization initially. They are ChAdox1CoV-19 vaccine – CoviShield and Covaxin. Aims and objectives: This study aimed at assessing the occurrence of adverse effects following immunization (AEFI) among individuals who received the CoviShield vaccine. The objective of this research was to evaluate the type of AEFI among vaccinated beneficiaries and to determine the factors contributing to the development of AEFI. Materials and Methods: A cross-sectional study was done at a teaching hospital in Kerala. All beneficiaries who were administered CoviShield vaccine during the study period, that is, from January 2021 to June 2022 were incorporated in the study. Data regarding AEFI were collected from all vaccinated individuals by direct or telephonic enquiry. Results: The incidence rate of AEFI is 4.5/1000 doses (111/24925 doses). The reporting of AEFI was high among age group of 20–30 years and commonly seen in males (97.3%). The most common AEFI reported with CoviShield vaccine were fever (63%), myalgia (51%), and headache (40%). AEFI were seen commonly after administration of first dose (94%). Only 7 cases (6.3%) of serious AEFI were reported which included death, autoimmune encephalitis, Bell’s palsy, hypotension, and hypersensitivity reactions. There was no significant association between age and type of AEFI (P > 0.05) and dose of vaccine and type of AEFI (P > 0.05). Conclusion: The immunization with CoviShield vaccine is safe among adults (>18 years) with lesser incidence of serious adverse effects. Higher incidence of AEFI is witnessed after administration of first dose and it was commonly seen in males.

An Observational Study Comparing the Adverse Effect Profiles of Sputnik V and Covaxin COVID-19 Vaccines in Adult General Population of Eastern India

Aim : Currently no data is available on the safety profile of COVID-19 Vaccines like Covaxin and Sputnik V from Eastern India. Our aim was to evaluate the safety profiles of Covaxin and Sputnik V Vaccine in Eastern India. Methods : 0.5 ml of Covaxin and Sputnik V given to 701 adults in a two-dose regimen at a private tertiary care Hospital, Kolkata, with the doses separated by 4-7 weeks in Covaxin and 3 weeks in Sputnik V. Data regarding local and systemic Adverse Event Following Immunizations (AEFIs) was collected 30 minutes after vaccination and also on the first- and seventh-day following vaccination after each dosage. Results : Incidence of AEFI was 65% and 59% following the first dose of vaccination in Covaxin and Sputnik V groups, respectively. Incidence of AEFI was 83% and 70% after the second dose in Covaxin and Sputnik V groups. Pain in the injection site was the most common adverse effect. Body-ache, fever and tiredness were other systemic side effects. Adverse effects were noticeably more after the second dose. Over half of the reactions were mild in nature. Covaxin had a higher number of moderate adverse reactions after both doses. Adults with age >40 years, Comorbidities, Hypertension and Diabetes had a smaller number of side effects following the first dose of vaccination. People with previous COVID-19 infections had noticeably fewer adverse effects after the second dose. Allergic adults were associated with more systemic side effects, whereas Hypertensive adults had less total AEFI. Conclusion : Both Covaxin and Sputnik V had favorable safety profiles. Sputnik V vaccine had significantly fewer AEFIs compared to Covaxin. Age, co-morbidities, specifically hypertension, Diabetes, Allergy and previous history of COVID-19 infection, were important variables observed in the prevalence of side effects.

Study of immunogenicity, safety and efficacy of covishield vaccine among health care workers in a tertiary cardiac care centre

Purpose: The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be curtailed by vaccination. We assessed the safety, and immunogenicity of Covishield vaccine among Health care workers (HCWs) in a tertiary cardiac care centre. Methods: It's a prospective analytical study, conducted at Sri Jayadeva Institute of cardiovascular science and research centre, Mysore, between January 2021 to May 2021. Pre and Post vaccination SARS CoV2 IgG antibodies were assessed among 122 HCWs. Interval between two doses in this study were 4 and 6 weeks. Adverse events following immunisation b(AEFI) and efficacy were assessed and followed up for two month post vaccination. Results: Post vaccination seropositivity was 69.67% in overall study participants. Seropositivity and P/N ratio median value in uninfected and infected group were 60.43% (n ¼ 55),3.47 (IQR: 2.56–5.22) and 96.77% (n ¼ 30),9.49 (IQR: 7.57–12.30) respectively (P < 0.001). Seropositivity and P/N ratio after 4 and 6 weeks were 48.3% (n ¼ 60), 2.95 (IQR: 1.91–4.24), and 83.8% (n ¼ 31), 4.88, (IQR: 3.39–6.43) respectively (P < 0.001). AEFI after first and second dose was 72.9% and 27.8% (p < 0.05) respectively. The most common symptoms after both doses of vaccination were local pain (73% & 88.2%), followed by fever (38.2% & 26.5%). The average duration of symptoms in both doses was 1.75 days. Of 122 participants only 10 (8.19%) had breakthrough infection after two doses of vaccination with mild severity. Conclusion: Covishield vaccine has showed seropositivity of 69.67%.It has acceptable level of safety profile. Seropositivity and P/N ratio has increased with increase in interval between two doses. Though it has not prevented breakthrough infection it has certainly reduced the severity of infection.

Surveillance on the adverse events following immunization in Dazu District of Chongqing， 2016‒2020 / 上海预防医学

ObjectiveTo determine the incidence and characteristics of adverse events following immunization （AEFI） in 2016‒2020 in Dazu District of Chongqing， and evaluate the AEFI surveillance information system and provide scientific evidence for vaccine safety. MethodsDescriptive epidemiological analysis was performed on the cases collected by the AEFI surveillance system. Incidence and coverage of AEFI were then presented. ResultsA total of 319 AEFI cases were reported in 2016‒2020. Reported incidence of AEFI was determined to be 24.64/105 doses. The proportion of timely reporting AEFI within 48 hours was 94.04% and that of timely investigation within 48 hours was 98.41%. The proportion of completing the AEFI survey was 100.00% and that of AEFI classification was 99.69%. The male to female ratio was 1.28∶1. Majority of the AEFI cases were less than 1 year old （64.26%， 205/319）， from April to September （68.97%， 220/319）， and reported at 0‒1 day post-immunization （89.34%， 285/319）. Moreover， the reported incidence differed significantly between time periods （χ2=32.481，P<0.05） and time intervals from vaccination to occurrence of AEFI （χ2=961.408， P<0.05）. Coverage of reporting AEFI at county level reached 100％. In addition， non-severe AEFI cases accounted for 98.43% （314/319） and no death case was reported. General events， such as fever， redness， and scleroma， accounted for 80.56% （257/319）， whereas rare adverse events accounted for 15.99% （51/319）. The reported incidence of NIP vaccines was highest in the diphtheria tetanus acellular pertussis combined vaccine， followed by measles and rubella combined attenuated vaccine and diphtheria tetanus combined vaccine. Clinical diagnosis of rare adverse events was mainly allergic rashes. ConclusionThe AEFI surveillance information system in Dazu District of Chongqing achieves efficient monitoring of AEFI. It has proven that the vaccines are generally safe and immunization strategies may be continuously implemented. Furthermore， the sensitivity of AEFI surveillance should be improved through multiple approaches.

Farmacovigilancia de vacunas y su aplicación en Chile / Vaccine pharmacovigilance and its application in Chile

La inmunización se encuentra entre las intervenciones en salud pública más exitosas y costo efectivas de todas las épocas, siendo su beneficio tan importante como su seguridad. Las vacunas, como cualquier otro medicamento, pueden generar eventos adversos, los que deben ser monitorizados permanentemente por sistemas de vigilancia. Esta disciplina recibe el nombre de Farmacovigilancia de Vacunas (FVV), encargada de estudiar los Eventos Supuestamente Atribuidos a la Vacunación ó Inmunización (ESAVI). El objetivo de este trabajo es revisar la evolución del sistema de farmacovigilancia de vacunas en Chile. El sistema de FVV chileno se basa en la vigilancia pasiva, y contempla la notificación obligatoria al Instituto de Salud Pública (ISP) de todos los ESAVI detectados, por parte de profesionales de la salud, directores de establecimientos y titulares de registro sanitario, priorizando las notificaciones de ESAVI serios e incluyendo la monitorización de todas las vacunas usadas en el país, tanto las que se encuentran incorporadas al Programa Nacional de Inmunización (PNI), como las que se encuentran fuera de este. El sistema de FVV chileno se caracteriza por un trabajo colaborativo permanente entre el ISP y el PNI, y parte de sus desafíos incluyen generar capacidades y alianzas estratégicas con la academia para la realización de estudios post comercialización sobre seguridad de vacunas. Finalmente, es importante destacar que tanto el marco normativo promulgado el año 2010, como la elaboración de procedimientos, el trabajo permanente con el PNI, y la conformación de un comité de expertos de ESAVI, y las diferentes estrategias de retroalimentación, son medidas implementadas que han contribuido a mejorar la tasa de reporte nacional y el análisis de los casos.

Immunization is among the most successful and cost-effective public health interventions of all times, its benefits being as important as its safety. Vaccines, like any other medicine, can generate adverse events, which must be permanently monitored by surveillance systems. Vaccine Pharmacovigilance (VPV) is the discipline responsible for studying Adverse Events Following Immunization (AEFI). The objective of this article is to review the evolution of the pharmacovigilance system of vaccines in Chile. The Chilean VPV system is based on passive surveillance, and establishes the mandatory reporting of all AEFI detected by healthcare workers, directors of healthcare facilities, and Marketing Authorization holders, to the Public Health Institute of Chile (PHI), prioritizing the reporting of serious ESAVI and including the monitoring of all vaccines used in the country, both those that are incorporated into the National Immunization Program (NIP), and those that are outside of it. The Chilean VPV system is characterized by a permanent collaborative work between the PHI and the NIP, and its challenges include generating capacities and strategic alliances with the academy to carry out post-marketing studies on vaccine safety. Finally, it's important to point out that the regulatory framework promulgated in 2010, as well as the elaboration of procedures, the permanent work with the NIP, the formation of an AEFI expert committee, and the different feedback strategies implemented, have contributed in improving case analysis and the national reporting rate.

Knowledge, Attitude and Reporting Practices on Adverse Events Following Immunization among Routine Immunization Service Providers in Health Facilities of Sokoto State, Nigeria

Background/Introduction:Health workers at primary health care facilities (PHCs) are primarily involved with routine immunization activities including detection, reporting and management of Adverse Events Following Immunization (AEFI). To undertake such responsibilities effectively, they need to have good knowledge on AEFI and its management. Objective:To assess the knowledge, attitude and reporting practices of Routine Immunization Service Providers in health facilities of Sokoto State, Nigeria.Methods:This was a descriptive cross-sectional study conducted at Primary Health Care (PHC) facilities of Sokoto State, Nigeria. Using a multi-stage sampling technique, a total of 285 routine immunization service providers were recruited from all the PHCs in one selected local government from each of the three health zones of the State. A semi-structured self-administered questionnaire was used to collect relevant information from eligible participants. Data were entered into SPSS version 20.0 and analyzed. Results:Of the 285 distributed questionnaires, 258 (90.5%) were duly completed and returned. The M: F ratio was 1.4:1, with mean age of 34.24 +8.06 years. Up to 164 (63.6%) respondents had good knowledge (score >50%), while 37(14.3%) and 57(22.1%) respondents had fair (score 41-49%) and poor (score <40%) knowledge respectively. Reporting practices were appropriate in 224 (86.8%) respondents. The most common method for reporting was by manual filing of AEFI forms. Some respondents would however not report an AEFI to avoid being blamed, feeling guilty or creating unnecessary anxiety to the patient. Conclusion:Though many respondents had good knowledge and reporting practices on AEFI, knowledge gap still exists; highlighting the need for continuous on-the-job training and retraining of these personnel

Study of Common Illnesses Before and After Vaccination: A Risk-interval Approach.

Objective: To compare the proportion of children who developed a specified illness in the 7 day post-vaccination window, with the background rate of the same event in the 7 day pre-vaccination window. Study design: Risk interval approach (Self-controlled caseseries). Setting: Well Baby Clinic of Christian Medical College, Vellore. Participants: 1602 healthy infants and under-six children presenting for routine vaccination. Outcome measures: Episode of any illness. Methods: The interviewer enquired about any adverse event or illness experienced by the child for each day of the week preceding the administration of age-appropriate vaccines. A second interview (telephonic) was conducted by the same interviewer one week following vaccine administration to enquire about adverse event(s) experienced by the child for each day of the subsequent week using a similar protocol. Results: With multiple vaccines delivered at appropriate ages, common childhood illnesses that could be reported as adverse events following immunization, except fever (RR=5.7, 95% CI=4.50-7.35), occurred at higher rates pre-vaccination. Risk Ratios of fever following whole cell (RR=9.3, 95% CI=6.43-13.52) and acellular (RR=8.5, 95% CI=3.82-18.91) vaccines were similar, with both showing a decreasing trend with increasing age. The gastrointestinal adverse event profile [diarrhea (RR=0.6, 95% CI=0.14-2.51) and vomiting (RR=1.0, 95% CI=0.14-7.10)] for rotavirus vaccine was similar pre- and post-immunization. Conclusions: Since most adverse events to vaccines are also common childhood illnesses, estimating the background rates of common illnesses is important to accurately ascertain a causal relationship.

Propuesta para la creación de la unidad de farmacovigilancia de la empresa socialista para la producción de medicamentos biológicos (ESPROMED BIO) CA / Proposal for the creation of the pharmacovigilance unit of the socialist company for the production of biological medicines (ESPOMED BIO) CA

En Venezuela la producción de vacunas contra el tétanos y contra la difteria, tétanos y tosferina (DPT) se realizaba en el área de producción del Instituto Nacional de Higiene "Rafael Rangel" (INHRR), y con la construcción de la Empresa Socialista Para la Producción de Medicamentos Biológicos - ESPROMED BIO, C.A, se formularán las mismas vacunas antes mencionadas con nueva tecnología y adicionalmente las vacuna pentavalente y la vacuna antirrábica humana serán acondicionadas, por lo tanto se plantea la necesidad de crear una Unidad de Farmacovigilancia, que recolecte, registre y reporte los ESAVIS, para cumplir con las normativas nacionales y las recomendaciones internacionales, es por ello que esta investigación tiene como objetivo general, diseñar una propuesta para la creación de una Unidad de Farmacovigilancia, según la Norma Venezolana de Buenas Prácticas de Farmacovigilancia (2010). Se trata de una investigación enmarcada en la línea de Propuesta Basada en la Aplicación de Normas Regulatorias en la Industria Farmacéutica, con un diseño transversal, descriptiva, documental en modalidad tipo Proyecto Factible. Los resultados y conclusiones obtenidos en la investigación para la Propuesta de Creación de la Unidad de Farmacovigilancia presentada en esta investigación, pretende solucionar de manera práctica el problema planteado, cumplir con las normativas legales nacionales como las Buenas Prácticas de Farmacovigilancia, y adicionalmente los lineamientos establecidos por la Organización Mundial de la Salud (OMS), ya que en un futuro se plantea certificar la ESPROMED BIO, C.A, por la OMS como laboratorio productor nacional de vacunas.

In Venezuela the production of vaccines against tetanus and diphtheria, tetanus and pertussis (DPT) was carried out in the production area of the National Hygiene Institute "Rafael Rangel" (INHRR), and the construction of Socialist Company for the Production of Biological Drugs - ESPROMED BIO, CA, the same vaccines mentioned above with new technology, the pentavalent vaccine and human rabies vaccine will be formulated, therefore it requires a Pharmacovigilance Unit, to collect, record AEFI and report to comply with national regulations and international recommendations, which is why this research has the general objective to design a proposal for the creation of a Pharmacovigilance Unit, according to the Venezuelan Standard Good Pharmacovigilance Practices (2010 ). It is a research under the line of pharmacovigilance, transversal, descriptive documentary mode type Feasible Project. The results and conclusions obtained from the research and the proposed creation of the Pharmacovigilance Unit presented in this research aims to solve the problem posed practical, comply with national legal requirements as Good Pharmacovigilance Practices and additionally with the guidelines established by the World Health Organization (WHO), and that in the future arises certify ESPROMED BIO, CA, by WHO as producer national laboratory