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.

Surveillance of adverse events following immunization with combined attenuated live measles, mumps and rubella vaccines in Huzhou City from 2015 to 2021 / 预防医学

Objective@#To monitor the adverse events following immunization (AEFI) with combined attenuated live measles, mumps and rubella vaccines (MMR) in Huzhou City from 2015 to 2021, so as to provide insights into the implementation of the MMR immunization strategy.@*Methods@#All AEFI caused by MMR immunization in Huzhou City from 2015 to 2021 were captured from the AEFI Monitoring Information Management System of the Immunization Planning System of Chinese Disease Control and Prevention Information System, and the incidence, clinical features and epidemiological features of AEFI were analyzed descriptively.@*Results@#The reported incidence of AEFI caused by MMR immunization appeared a tendency towards a rise in Huzhou City from 2015 to 2021 (χ2trend=124.126, P<0.001). Totally 324 386 doses of MMR vaccines were immunized, and 317 cases with AEFI were reported, with an reported incidence rate of 9.77/104 doses. Following two-dose immunization, the reported incidence of AEFI caused by two-dose MMR immunization was significantly lower than by one-dose immunization (6.01/104 doses vs. 25.43/104 doses; χ2=113.692, P<0.001). The incidence rates of general reactions, abnormal reactions and coincidental events were 6.20/104 doses, 3.42/104 dose and 0.15/104 doses, respectively. Fever and allergic rash were predominant clinical manifestations of AEFI, and no vaccine quality accident, inoculation accident or psychogenic reaction were reported. There were 246 (77.60%) cases with AEFI within 24 hours following vaccination, and among children with AEFI, there were 173 boys (54.57%), and 200 children (63.09%) age ages of less than one year (63.09%). AEFI was reported in each quarter, and 99 cases (31.23%) were reported in the fourth quarter. The largest number of children with AEFI was reported in Wuxing District (78 cases, 24.61%).@*Conclusions@#The safety of MMR vaccination is high in Huzhou City. General reaction is the predominant AEFI, which mainly occurs within 24 hours following vaccination. Two-dose MMR vaccination does not increase the risk of AEFI.

Surveillance of adverse events following immunization with human papillomavirus vaccines in Hangzhou City from 2017 to 2021 / 预防医学

Objective@#To investigate the incidence of adverse events following immunization (AEFI) of human papillomavirus (HPV) vaccines in Hangzhou City from 2017 to 2021, so as to provide insights into safety monitoring and evaluation for HPV vaccines.@*Methods@#The AEFI caused by immunization of bivalent (HPV2), quadrivalent (HPV4) and nonavalent HPV vaccines (HPV9) reported in Hangzhou City from 2017 to 2021 were captured from the AEFI Surveillance Module of Chinese Disease Control and Prevention Information System, and HPV vaccination data were captured from the Zhejiang Municipal Immunization Information Management System. The incidence, temporal distributions and clinical symptoms of AEFI were analyzed.@*Results@#Totally 922 310 doses of HPV vaccines were immunized in Hangzhou City from 2017 to 2021, and 232 cases with AEFI were reported, with an overall incidence rate of 25.15/105 doses. The reported incidence rates of AEFI caused by HPV2, HPV4 and HPV9 vaccination were 31.13/105 doses, 25.93/105 doses and 22.01/105 doses, respectively. General reactions and abnormal reactions were predominant AEFI, and the reported incidence rates of general reactions and abnormal reactions were 21.58/105 doses and 2.60/105 dose, respectively. AEFI predominantly occurred 0 to 1 day post-immunization (165 cases, 71.12%), and the main clinical symptoms included local swelling of injection sites, hard tubercle and fever, with reported incidence rates of 10.30/105 doses, 5.96/105 doses and 6.18/105 doses, respectively. @*Conclusions@#Low incidence of AEFI was reported following HPV vaccination in Hangzhou City from 2017 to 2021, and all AEFI were mild. The safety of HPV2, HPV4 and HPV9 remains high.

Vasculitis leucocitoclástica posterior a vacuna contra la COVID-19 / Leukocytoclastic vasculitis after COVID-19 vaccine

Varios reportes comunicaron diferentes tipos de vasculitis en asociación temporal con una variedad de vacunas, y más recientemente con las vacunas para enfermedad por SARS-CoV-2 (COVID-19). Sin embargo, la escasez de estudios controlados y la heterogeneidad metodológica de los reportes no permiten una conclusión clara sobre su relación causal. Informamos el caso de un varón que desarrolló vasculitis leucocitoclástica, confirmada por biopsia de piel y sin compromiso sistémico, luego de la inmunización contra la COVID-19 con la vacuna de AstraZeneca.

Several reports have described different types of vasculitis in temporal association with a variety of vaccines, and more recently with vaccines for COVID-19 disease. However, the scarcity of controlled studies and the methodological heterogeneity of the reports do not allow a clear conclusion about its causal relationship. We report the case of a male who developed leukocytoclastic vasculitis, confirmed by skin biopsy and without systemic involvement, after the second dose of AstraZeneca's anti-COVID-19 vaccine.

A Pharmacovigilance Study of Covishield in a Tertiary Care Teaching Hospital in Tamil Nadu

Objective: To study the adverse events following immunization (AEFI) with Covishield, a coronavirus disease– 2019 (COVID-19) vaccine. Materials and Methods: A prospective observational study was conducted among 422 Covishield vaccinees based on the inclusion and exclusion criteria after the institutional ethics committee approval. They were followed up at the end of 1 and 2 weeks following the first dose of Covishield vaccine, and the details of adverse events were collected. AEFIs were classified using system organ classification, World Health Organization-Uppsala Monitoring Center (WHO-UMC) causality assessment, AEFI causality assessment, and Modified Hartwig Severity Scale. Various classifications of AEFI were analyzed using descriptive statistics. ANOVA and independent t-test were used for age group and gender comparison of the duration and number of AEFI, respectively. Results: Around 625 AEFIs were reported by 422 vaccinees. Majority of the vaccinees (62.8%) developed adverse events on the day of vaccination. The mean duration of AEFI was 2.52 ± 0.871 days. On WHO-UMC causality assessment, 98.08% were found to be probable, 1.12% possible, and 0.8% unclassifiable. AEFI causality assessment revealed 98.88% vaccine product-related reactions and 1.12% anxiety-related reactions. Regarding the severity, 83.52% of AEFIs were mild and 16.32% were moderate. On comparison of mean duration of AEFI (P = 0.298) and mean number of AEFI (P = 0.569) between different age groups, no statistical significance was observed. Conclusion: The majority of AEFIs reported in this study were mild to moderate in severity for a short duration. The protection offered against the deadly disease and its complication potentially outweighs the mild AEFIs or inconvenience caused by them. Hence, covid-19 vaccination is an important tool to break the pandemic chain.

Analysis of suspected adverse events following immunization based on surveillance data in Xiaogan City in 2012- 2017 / 公共卫生与预防医学

Objective To analyze the data of suspected adverse events following immunization (AEFI) in Xiaogan City from 2012 to 2017, and to evaluate the sensitivity of the monitoring system and the safety and quality of vaccine use. Methods The AEFI surveillance information system of China Immunization Program was used to derive the AEFI report case data from 2012 to 2017 in Xiaogan City. The descriptive methods were used for epidemiological analysis. Results There were 2 457 cases of AEFI reported in Xiaogan City from 2012 to 2017. The incidence rate of reported AEFI was 22.37 / 100 000. Among them, the incidence rate of the general reaction reported was 20.04 / 100 000, and the reactions were mainly fever, redness, and induration. The abnormal reaction report rate was 1.98/100 000, mainly with allergic skin rashes. There were no accidents caused by the quality of the vaccine and negligence of related persnonnels. There were case reports every month, but there was a big difference in the time distribution of case reports throughout the year (χ2= 54.86, P=0.01). The most reported cases were from April to June, and there were obvious differences in the number of reported cases in different counties (cities and districts) (χ2=29.99, P=0.02). The ratio of male to female was 1.5:1. There were 2 025 cases in the age group of 0~3, accounting for 82.42%. Conclusion The sensitivity of AEFI surveillance in Xiaogan City increased year by year, and the safety of vaccination was good. It is necessary to further strengthen the monitoring of AEFI among young children, especially within 24 hours of vaccination.

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.

Assessment of knowledge of multipurpose health workers regarding adverse events following immunization in a rural block of Haryana, India

Background: No vaccine is entirely free from the risk of adverse reactions or remote sequel. Knowledge and reporting of AEFI is very important in this vaccine era. Objective of the study was to assess the knowledge of Multipurpose Health Workers (MPHWS) regarding AEFI.Methods: A cross-sectional study was undertaken on randomly selected 30 MPHWs of Beri block. A semi-structured questionnaire was administered after taking verbal consent. The MPHWs had a minimum of one year experience and had received the latest formal training during measles catch up campaign. Data compiled and analysed using appropriate statistical tests.Results: A total of 30 MPHWs duly completed and returned their questionnaires. The mean age was 36.5'2.54 years and mean post-qualification experience was 5.3 years. About 83% of the MPHWs knew that fever, pain, redness and swelling at injection site were symptoms of AEFI and 93% knew about proper storage temperature, dose, route and site of vaccines. Only 56% knew about the storage temperature of diluents and risk of its contamination, 30% knew proper reconstitution of the vaccine. Only 33% knew about filling an adverse event form to report an AEFI. Twenty-five (83.5%) MPHWs had encountered an AEFI and only 14(46.6%) reported such within 24 h. It was observed that level of correct knowledge was decreasing with increasing age of respondents.Conclusions: There was a lack of knowledge about the cause, identification and reporting of AEFI despite periodic training programmes. There is need to train the health workers to improve reporting and prevent complications due to vaccines. There is also further need to ponder over the lacunae in training programmes responsible for persistent inadequate knowledge among MPHWs. Last but not the least 'DO NOT FURTHER HARM' should always be the primary aim.

Scoping review of active surveillance systems for vaccine safety world-wide / 中华预防医学杂志

Objective@#To identify post-marketing active surveillance systems for vaccine safety around the world and understand their features and mechanisms, in order to provide guidance for vaccine administration activities in China.@*Methods@#Following the steps of scoping review, literature about active surveillance system for vaccine safety and published by 30 June 2018 were identified by searching electronic databases, including PubMed, Scopus, and Cochrane Library. Grey literature were also sought by exploring relevant websites. Identified literature were screened according to eligibility criteria, and informative data from included literature were then charted. Framework Synthesis and Thematic Analysis were performed to integrate the charted data.@*Results@#97 pieces of literature were included for review, and 11 active surveillance systems for vaccine safety were identified, mostly located in developed countries. These systems were constructed by 3 types of organizations: administration departments, academic or research institutions, and health care providers. Their data sources included immunization registries, electronic medical records, claims data, case reports of adverse events following immunization electronic questionnaires, and epidemiologic study data. According to their operation procedures, these systems were grouped into 4 modes of active surveillance: Data Linkage, Investigator Network, Automatic Follow-up System, Studies Consortium.@*Conclusion@#Practice of active surveillance for vaccine safety greatly varies across countries, with different conditions and advantages. It is suggested that developing countries should choose suitable mode of active surveillance considering their local situations.

Analysis on the characteristics of suspected vaccine-related deaths in Fujian Province, 2012-2017 / 中华预防医学杂志

Objective@#To analyze the characterisitics of the death cases suspected to be related to vaccination in Fujian Province from 2012 to 2017.@*Methods@#A total of 33 death cases information which was suspected to be related to the vaccinations from 2012 to 2017 were extracted from Chinese Adverse Events Following Immunization Information System (AEFI). The autopsy reports and the conclusions made by AEFI investigation diagnosis expert committee were collected at the same time. The inoculation data were obtained through the Fujian province Immunization Program Information System. The AEFI incidence, rare vaccine reaction incidences and mortality rates following immunization were figured out to analyze the characterisitics of the death cases associated with vaccination.@*Results@#The age of deuths cases was from 26 days to 52 months. Among 33 cases, 23 were males, and 8 were due to vaccine-related reaction, and the others were due to coincidental events. The number of rare vaccine reaction cases from 2012 to 2017 were 2,3,6,8,7 and 7, respectively. The highest AEFI incidence was measles and rubella combined attenuated live vaccine [38.88 (95%CI: 36.85-40.91)/100 000 dose], and the lowest was trivalent oral poliomyelitis attenuated live vaccine [2.01 (95%CI: 1.73-2.30)/100 000 dose]. The highest rare vaccine reaction incidence was measles and rubella combined attenuated live vaccine [15.04 (95%CI: 13.78-16.30)/100 000 dose], and the lowest was trivalent oral poliomyelitis attenuated live vaccine [0.38 (95%CI: 0.25-0.50)/100 000]. The highest mortality rate was inactivated poliomyelitis vaccine [0.26 (95%CI: 0.04-0.54)/100 000 doses], and the lowest mortality rate was measles, mumps and rubella combined attenuated live vaccine [0.01 (95%CI: 0.00-0.08)/100 000 doses]. The Spearman correlation analysis showed that there were correlations between AEFI incidence and rare vaccine reaction incidence (r=0.64, P=0.048), there were no correlations between AEFI incidence and mortality rate (r=-0.34, P=0.329), and there were no correlations between rare vaccine reaction incidence and mortality rate (r=-0.25, P=0.484).@*Conclusion@#Neither AEFI incidence nor rare vaccine reaction incidence was correlation with mortality rate. The main causes of death following vaccination were coincidental events.

Develop the active surveillance system for vaccine safety in China / 中华预防医学杂志

Post-marketing surveillance of vaccine safety is an important measure to detect adverse events following immunization and therefore reduce the harms to public health. The conventional method for safety surveillance is a passive way through spontaneous reporting, which suffer from under-reporting and incomplete. While active surveillance, a newly proposed surveillance method in developed countries, is capable to make up the deficiencies of passive surveillance. The surveillance system of vaccine safety in China is currently using passive surveillance, and facing many problems and challenges. This arouses a need to promote development of an active surveillance system for vaccine safety in China, learning from the experience world-wide. This commentary aims to throw out suggestions for establishing the active surveillance system, according to the specific situation in China and based on a scoping review of literature.

Occupational burnout of vaccination personnels in Haining / 预防医学

Objective @#To understand the current situation and influencing factors of occupational burnout among vaccination personnels in Haining.@*Methods @#The vaccination staffs of all vaccination clinics in Haining were investigated by the general questionnaire and Maslach Burnout Inventory. Logistic regression model was used to analyze the influencing factors for job burnout of vaccination personnels. @*Results @#A total of 160 questionnaires were distributed and 158 valid questionnaires were collected. The effective rate of questionnaires was 98.75%. A total of 91 vaccination staffs suffered from occupational burnout,accounting for 57.59%. Among them,the median（inter-quartile range）of the scores of emotional exhaustion,depersonalization and personal achievement were 13.00（14.00）,4.00（6.00）and 26.50（17.00）,respectively,which were all lower than the normalized scores（22.19,7.12 and 36.53,P<0.05）. The results of logistic regression analysis showed that having confidence in vaccination was a protective factor for emotional failure（OR=0.175,95%CI：0.058-0.523）and low sense of achievement（OR=0.272,95%CI：0.079-0.937）in vaccination personnels;having experience in adverse event following immunization（AEFI）was a risk factor for depersonalization（OR=3.125,95%CI：1.472-6.633）and occupational burnout（OR= 2.391,95%CI：1.189-4.807）in vaccination personnels. @*Conclusion @#A certain proportion of vaccination staffs in Haining suffered from occupational burnout. The experience of AEFI was a risk factor for their occupational burnout.

Analysis on death from adverse event following immunization surveillance system of Shandong Province during 2011-2016 / 中华预防医学杂志

Objective@#To analyze the occurrence and death of Adverse Event Following Immunization (AEFI) in Shandong province.@*Methods@#Collecting the information of AEFI cases from 2011 to 2016, which were reported through the National AEFI Management System in Shandong province up to January 15, 2017. The autopsy reports of death following immunization were issued by the qualified institutions. The inoculation data from 2011 to 2016 was obtained through Immunization Information Management System of Shandong province. Chi-square test was used to compare the incidence rate of AEFI and mortality related to immunization among different time and age groups.@*Results@#A total of 189 864 512 doses of vaccine were administered in Shandong province during 2011-2016, the total number of AEFI cases was 89 973 and the incidence rate of AEFI was 473.88/1 000 000. The number of death cases was 52 and the mortality rate was 0.27/1 000 000. The incidence rate of AEFI from 2011 to 2016 respectively was 273.63/1 000 000, 405.22/1 000 000, 479.88/1 000 000, 545.13/1 000 000, 500.66/1 000 000, and 627.09/1 000 000 (P<0.001), respectively. The mortality rate from 2011 to 2016 was 0.17/1 000 000, 0.16/1 000 000, 0.25/1 000 000, 0.39/1 000 000, 0.26/1 000 000, and 0.40/1 000 000 (P=0.285), respectively.The mortality rates of HepB, BCG and IPV were the top three. There was statistical significance of the mortality rate among different month-old children (P<0.001). The highest mortality rate was<2 month-old (1.09/1 000 000), and the next was 4-5 month-old (0.54/1 000 000), and the lowest was ≥10 month-old (0.06/1 000 000). The mortality rate of spring (from February to April), summer (from May to July), autumn (from August to October) and winter (from November to January of next year) was 0.41/1 000 000, 0.16/1 000 000, 0.08/1 000 000 and 0.48/1 000 000 (P<0.001), respectively. Among 52 death cases, 26 cases were anatomized, including 3 rare vaccine reaction following immunization and 23 coincidental events; 26 cases were not anatomized, including 17 coincidental events and 9 unknown causes.@*Conclusion@#The AEFI mortality rate of<2 month-old, spring and winter, and the second dose was higher than else, which was similar to normal child mortality. Immunization did not increase the risk of death, and the most deaths following immunization were coincidental events.

Adverse Event Following Immunization (AEFI) Surveillance in India: Position Paper of Indian Academy of Pediatrics, 2013.

Adverse event following immunization (AEFI) is a critical component of immunization program. The risk of AEFI with vaccination is always weighed against the risk of not immunizing a child. There is an evolving AEFI surveillance system in India for the vaccines delivered through ‘universal immunization program’ (UIP) of government sector, but the reporting remained suboptimal for long in the country, and there is almost no participation from private sector. The AEFI reporting from private sector will provide vital information on the safety of new and underutilized vaccines, not part of the UIP in India. The national guidelines are recently revised and updated. The Indian Academy of Pediatrics believes that pediatricians, especially in private sector have a crucial role to play with reporting of AEFI with newer/underutilized vaccines. Programmatic error, vaccine reaction, injection reactions, coincidental and unknown are the five broad categories of AEFI for programmatic purposes. The serious AEFIs (death, disability, cluster and hospitalization) need to be reported immediately and investigated in detail as per the laid down procedures. Once a serious AEFI happens, primary or urban health centre should be immediately informed by the pediatricians practicing in rural or urban areas, respectively. This advocacy paper from the academy provides guidelines to practitioners on how to report cases, and suggests ways for IAP members to help in ongoing efforts of the government in improving AEFI surveillance in the country. The details about the diagnosis and management of known/expected AEFI with UIP and newer vaccines shall be published later.