Given its enhanced genetic stability, novel oral poliovirus vaccine type 2 was deployed for type 2 poliovirus outbreak responses under World Health Organization Emergency Use Listing. We evaluated the safety profile of this vaccine. No safety signals were identified using a multipronged approach of passive and active surveillance.

This report introduces a Brighton Collaboration (BC) case definition for autoimmune hepatitis (AIH), which has been classified as a priority adverse event of special interest (AESI), as there were possible cases seen following COVID-19 vaccination. The case definition was developed by a group of subject matter and BC process experts to facilitate safety data comparability across pre- and post-licensure clinical trials, as well as pharmacovigilance activities in multiple settings with diverse resources and healthcare access. The usual BC case definition development process was followed in an expedited manner, and took two months to complete, including finalising the manuscript for publication, instead of the usual 1 year development time. It includes a systematic review of the literature and an expert consensus to define levels of diagnostic certainty for AIH, and provides specific guidelines for data collection and analysis. Histology, serological and biochemical tests and exclusion of alternate diagnosis were considered necessary to define the levels of certainty (definitive, probable and possible). AEFI reports of suspected AIH were independently classified by the WG members to test its useability and these classifications were used to finalise the case definition. The document underwent peer review by external AIH experts and a Reference Group of vaccine safety stakeholders in high-, low- and middle-income countries to ensure case definition useability, applicability, and scientific integrity. The expedited process can be replicated for development of other standardised case definitions for priority AESIs for endemics and epidemics. While applicable to cases reported following immunisation, the case definition is independent of lapsed time following vaccination and, as such, can also be used to determine background incidence for vaccinated and unvaccinated control groups in studies of causal association. While use of this case definition is also appropriate for the study of safety of other products including drugs, it is not meant to guide clinical case management.

Effective surveillance of adverse events following immunization (AEFIs) primarily relies on the collaboration of two partners: national regulatory authorities (NRAs) and national expanded programs on immunization (EPIs). In December 2020, the World Health Organization (WHO) Global Advisory Committee for Vaccine Safety recommended a new case-based indicator of national capacity to monitor immunization safety: at least one serious AEFI reported per 1 million total population per year. To achieve this indicator, WHO-affiliated countries and territories (WHO countries) rely upon data generated from functional AEFI surveillance systems. This report describes 2020-2022 global, regional, and national progress in use of the newly introduced immunization safety monitoring indicator and progress on joint AEFI reporting from national EPIs and NRAs. Among WHO countries, 51 (24%) of 214 implemented the new indicator in 2020, 111 (52%) of 214 implemented it in 2021, and 92 (43%) of 215 in 2022. In 2020, 41 (19%) WHO countries reported AEFI data jointly from EPIs and NRAs; this increased to 55 (26%) in 2021 and 57 (27%) in 2022. These findings, resulting in part from the intensified support for COVID-19 vaccination, demonstrate that national AEFI surveillance systems increasingly support the timely use and sharing of case-based immunization safety data, but work is still needed to strengthen global vaccine safety monitoring.

Despite significant advances in child survival, infectious diseases continue to be among the leading causes of neonatal deaths [1]. Maternal immunization is a well-recognized public health intervention to reduce vaccine-preventable disease-related morbidity and mortality in the pregnant woman, her foetus, and infant from tetanus, pertussis, seasonal influenza, and COVID-19 [2]. The development of new maternal vaccines against respiratory syncytial virus (RSV) and group B streptococcus (GBS) may significantly decrease the morbidity and mortality from these diseases in neonates and infants [2], with the U.S. Food and Drug Administration (FDA) approval for licensure of an RSV vaccine to be administered in pregnancy occurring in August 2023 [3]. | | Ongoing safety assessment of novel vaccines administered during pregnancy requires well-functioning passive and active surveillance systems to collect and assess adverse maternal and neonatal outcomes [4]. In high-income countries (HICs), regulatory authorities, such as the European Medicines Agency (EMA) and the U.S. FDA, require extensive post-authorization safety monitoring activities for products used during pregnancy, including active surveillance for safety-related events through pregnancy registries and observational cohort studies [4], [5], [6]. However, safety surveillance for vaccines used in pregnancy in many low- and middle-income countries (LMICs) currently relies on passive surveillance systems whose output cannot be interpreted appropriately due to lack of information on background rates of adverse events in pregnancy in general and lack of data on the number of pregnant women vaccinated as the relevant specific comparator [4], [5], [6].

BACKGROUND: In 2016, the World Health Organization recommended that a fractional dose of yellow fever (YF) vaccine could be used in persons 2 years of age or older in response to an emergency that resulted in a global shortage of available YF vaccine. However, this recommendation did not extend to the youngest age group licensed for YF vaccine because there were no published data on the use or safety of fractional dose YF vaccination in children aged 9-23 months. We conducted a single-blind randomized controlled trial, comparing the immunogenicity and safety of fractional one-fifth and one-half doses of Bio-Manguinhos 17DD YF vaccine with full dose in children aged 9-23 months old in Uganda. In this paper, we present the interim analysis on safety. METHODS: Children aged 9-23 months presenting for routine well-child services were recruited for inclusion at one of three study sites. We collected data during March 26, 2019-August 31, 2020, on all adverse events following immunization (AEFI) during active surveillance for 28 days post-vaccination using multiple collection tools including a diary card with an objective measurement of fever. An independent team from the Uganda national AEFI Committee investigated and classified serious AEFI (SAE) according to Brighton Collaboration Criteria. RESULTS: Among 1053 enrolled children, 672 (64%) were reported to have a non-serious AEFI (NSAE) and 17 (2%) were reported to have a SAE. The most common AEFI were diarrhoea, fever, and rash, each reported by 355 (34%), 338 (33%), and 188 (18%) participants, respectively. Among 17 participants with SAE, eight were reported to have had seizures and five were hospitalised for seizures or other causes (respiratory symptoms, gastrointestinal illness, malaria). Four SAEs (deaths) occurred >28 days after vaccination. There were no reported cases of pre-specified or vaccine-related SAEs. We observed no significant difference in frequency or severity of adverse events among the study groups. CONCLUSIONS: Using comprehensive active surveillance monitoring, we did not identify any unexpected safety concerns among children aged <2 years receiving YF vaccination, including with the fractional doses. Although we identified a high number of both serious and non-serious AEFI, none were determined to be causally related to YF vaccination. These results provide evidence for the safety of fractional dose YF vaccination among children aged 9-23 months.

The US Centers for Disease Control and Prevention (CDC) supports international partners in introducing vaccines, including those against SARS-CoV-2 virus. CDC contributes to the development of global technical tools, guidance, and policy for COVID-19 vaccination and has established its COVID-19 International Vaccine Implementation and Evaluation (CIVIE) program. CIVIE supports ministries of health and their partner organizations in developing or strengthening their national capacities for the planning, implementation, and evaluation of COVID-19 vaccination programs. CIVIE's 7 priority areas for country-specific technical assistance are vaccine policy development, program planning, vaccine confidence and demand, data management and use, workforce development, vaccine safety, and evaluation. We discuss CDC's work on global COVID-19 vaccine implementation, including priorities, challenges, opportunities, and applicable lessons learned from prior experiences with Ebola, influenza, and meningococcal serogroup A conjugate vaccine introductions.

INTRODUCTION: Despite the emphasis on reporting of Adverse Events Following Immunisation (AEFIs) during didactic training sessions, especially prior to new vaccine introductions, it remains low in Ghana. We explored the factors underlying the under-reporting of AEFI by healthcare workers (HCWs) to provide guidance on appropriate interventions to increase reporting. METHODS: We conducted an exploratory descriptive in-depth study of the factors contributing to low reporting of AEFI among HCWs in four regions in Ghana. Key informant interviews (KII) were held with purposively selected individuals that are relevant to the AEFI reporting process at the district, regional, and national levels. We used KII guides to conduct in-depth interviews and used NVivo 10 qualitative software to analyse the data. Themes on factors influencing AEFI reporting were derived inductively from the data, and illustrative quotes from respondents were used to support the narratives. RESULTS: We conducted 116 KIIs with the health managers, regulators and frontline HCWs and found that lack of information on reportable AEFIs and reporting structures, misunderstanding of reportable AEFIs, heavy workload, cost of reporting AEFIs, fear of blame by supervisors, lack of motivation, and inadequate feedback as factors responsible for underreporting of AEFIs. Respondents suggested that capacity building for frontline HCWs, effective supervision, the provision of motivation and feedback, simplification of reporting procedures, incentives for integrating AEFI reporting into routine monitoring and reporting, standardization of reporting procedures across regions, and developing appropriate interventions to address the fear of personal consequences would help improve AEFI reporting. CONCLUSION: From the perspectives of a broad range of key informants at all levels of the vaccine safety system, we found multiple factors (both structural and behavioural), that may impact HCW reporting of AEFI in Ghana. Improvements in line with the suggestions are necessary for increased AEFI reporting in Ghana.

BACKGROUND: During February 25-March 4, 2019, Zimbabwe's Ministry of Health and Child Care conducted an emergency campaign using 342,000 doses of typhoid conjugate vaccine (TCV) targeting individuals 6 months-15 years of age in eight high-risk suburbs of Harare and up to 45 years of age in one suburb of Harare. The campaign represented the first use of TCV in Africa outside of clinical trials. METHODS: Three methods were used to capture adverse events during the campaign and for 42 days following the last dose administered: (1) active surveillance in two Harare hospitals, (2) national passive surveillance, and (3) a post-campaign coverage survey. RESULTS: Thirty-nine adverse events were identified during active surveillance, including 19 seizure cases (16 were febrile), 16 hypersensitivity cases, 1 thrombocytopenia case, 1 anaphylaxis case, and two cases with two conditions. Only 21 (54%) of 39 patients were hospitalized and 38 recovered without sequelae. Attack rates per 100,000 TCV doses administered were highest for seizures (6.27) and hypersensitivity (5.02). Only 6 adverse events were reported through passive surveillance by facilities other than the two active surveillance hospitals. A total of 177 (10%) of 1,817 vaccinees surveyed reported experiencing an adverse event during the post-campaign coverage survey, of which 25 (14%) sought care. CONCLUSIONS: In line with previous evaluations of TCV, enhanced adverse event monitoring during an emergency campaign supports the safety of TCV. The majority of reported events were minor or resulted in recovery without long-term sequelae. Attack rates for seizures and hypersensitivity were low compared with previous active surveillance studies conducted in Kenya and Burkina Faso. Strengthening adverse event monitoring in Zimbabwe and establishing background rates of conditions of interest in the general population may improve future safety monitoring during new vaccine introductions.

Despite didactic training on adverse events following immunization (AEFI) in Ghana, the reporting ratio of AEFI was 1.56 per 100,000 surviving infants in 2015, below the minimum reporting ratio of 10. We aimed to estimate the proportion of health care workers (HCWs) reporting AEFI and to identify barriers to reporting. We conducted a cross-sectional survey of HCWs in four regions in Ghana. A simple random sample of 176 health facilities was selected and up to two HCWs were randomly selected per facility. We used the Rao-Scott Chi-squared test to compare factors associated with reporting of AEFI in the last year. We used an open-ended question to identify reasons for low reporting. One supervisor from each facility, responsible for overall reporting and management of AEFI, was also interviewed. A total of 306 HCWs from 169 facilities were interviewed. Of these, 176 (57.5%) reported they had ever encountered an AEFI. Of the 120 who had encountered an AEFI in the last year, 66 (55.0%) indicated they had reported the AEFI, and 38 (31.7%) completed a reporting form. HCWs (n=120) reported multiple barriers to reporting of AEFI; the most common barriers were fear of personal consequences (44.1%), lack of knowledge or training (25.2%), and not believing an AEFI was serious enough to report (22.2%). Discussion of AEFI during the last supervisory visit was significantly associated with reporting in the past year (OR 7.39; p<.001). Of 172 supervisors interviewed, 65 (37.8%) mentioned their facilties had ever encountered an AEFI; over 90% of facilities had reporting forms. We identified low reporting of AEFI and multiple barriers to reporting among HCWs in the four selected regions of Ghana. Discussing AEFI during supervisory visits with HCWs might improve reporting. Additionally, strategies to address fear of personal consequences as a barrier to reporting of AEFI are needed.

The success of immunization programs in lowering the incidence of vaccine preventable diseases (VPDs) has led to increased public attention on potential health risks associated with vaccines. As a result, a scientifically rigorous response to investigating reported adverse events following immunization (AEFI) and effective risk communications strategies are critical to ensure public confidence in immunization. Globally, an estimated 257 million people have chronic hepatitis B virus (HBV) infection, which causes more than 686,000 premature deaths from liver cancer and cirrhosis. Hepatitis B vaccination is the most effective way to prevent mother-to-child transmission of HBV infection, especially when a timely birth dose is given within 24h of birth. However, an infant's risk of dying is highest in the neonatal period, and thus, administering HepB-BD within 24h of birth overlaps with the most fragile period in an infant's life. A working group formed in July 2016 following the publication of the case reports of the effects on vaccination coverage of media reports of infant deaths after HepB-BD administration in China and Vietnam. The goal of the working group was to create a framework and describe best practices for preparing for and responding to AEFI reported after HepB-BD administration, using existing resources. The framework includes six steps, including three preparation steps and three response steps. This document is written for national and regional immunization program staff. Prior to using the framework for preparation and response to AEFIs reported after HepB-BD administration, staff members should be familiar with how AEFI are detected, reported, and investigated in the country. The document might also be of interest to national regulatory staff members who monitor vaccine safety within the country.

Reporting of adverse events following immunization (AEFI) is a key component for functional vaccine safety monitoring system. The aim of our study is to document trends in the AEFI reporting ratio globally and across the six World Health Organization (WHO) regions. We describe the number of AEFI reports communicated each year through the World Health Organization/United Nations Children's Fund Joint Reporting Form on Immunization from 2000 to 2015. The AEFI reporting ratios (annual AEFI reports per 100,000 surviving infants) were calculated to identify WHO countries (n=191 in 2000 and n=194 by 2015) that met a minimal reporting ratio of 10, a target set by the Global Vaccine Action Plan for vaccine safety monitoring as a proxy measure for a functional AEFI reporting system. The number of countries reporting any AEFI fluctuated over time but with progress from 32 (17%) in 2000 to 124 (64%) in 2015. In 2015, the global average AEFI reporting ratio was 549 AEFI reports per 100,000 surviving infants. The number of countries with AEFI reporting ratiosgreater than10 increased from 8 (4%) in 2000 to 81 (42%) in 2015. In 2015, 60% of countries in the WHO Region of the Americas reported at least 10 AEFI per 100,000 surviving infants, followed by 55% in European Region, 43% in Eastern Mediterranean Region, 33% in Western Pacific Region, 27% in South-East Asia Region and 21% in African Region. Overall, AEFI reporting has increased over the past sixteen years worldwide, but requires strengthening in a majority of low- and middle- income countries. The AEFI reporting ratio is useful for benchmarking and following trends over time; but does not provide information on the quality of the reporting system and does not guarantee capacity to detect and manage a vaccine safety problem at a national level. Additional efforts are required to ensure and improve data quality, AEFI reporting and surveillance of immunization safety in every country.

Facial nerve palsy is classified based on the location of its lesion. Central facial nerve palsy is the consequence of an upper motor neuron (UMN) lesion of the 7th cranial nerve, while peripheral palsy is due to a lesion of a lower motor neuron (LMN). Peripheral facial nerve palsy is the partial (i.e., paresis) or complete (i.e., paralysis) loss of function of some or all the structures innervated by the facial nerve (i.e. cranial nerve VII). Facial nerve palsy is also classified by the time course of its development depending on whether acute (minutes to days), subacute (days to weeks) or chronic (longer than weeks). Acute onset facial palsies are common. The most common cause of acute onset, central facial palsy is stroke. However, of the acute onset, peripheral facial palsies, the most common syndrome is that of idiopathic, acute onset, peripheral facial palsy, better known as Bell's palsy. Henceforth in this document, it will be understood that, when discussing Bell's palsy, we are referring to peripheral facial palsy that is ‘acute-onset’. | Clinical signs of peripheral facial nerve palsy include loss of facial tone with obliteration of the naso-labial fold, inability to raise the eyebrows and wrinkle the forehead, smile, open or draw the corner of the mouth, and completely close the eye on the affected side [1], [2], [3], [4]. They may further include hyperacusis, dryness of eye and decreased salivation. Peripheral facial nerve palsy most commonly presents on one side of the face, leading to facial asymmetry, or “facial droop” [1], [5]. Simultaneous bilateral acute-onset cases have also been described and are now recognised as an uncommon clinical feature [6], [7], [8], [9], [10], [11], [12], [13].

Pain is defined as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage” (International Association for the Study of Pain, IASP) [1]. Pain is the most frequent local adverse event following immunization (AEFI) [2], [3], [4], [5]. It results from the stimulation of nociceptive sensory neurons at the time of vaccine administration or inflammatory process in the damaged tissue afterward. | To date, there has not been a commonly accepted, standardized definition and related assessment of immunization site pain as an AEFI [6], [7], [8], [9], [10], [11], [12], [13], [14], [15]. This hinders comparability and uniform reporting of pain across study settings or surveillance systems. Establishing criteria for assessing immunization site pain during and following immunization is important for individuals collecting, analyzing, presenting and/or communicating data on immunization pain as AEFIs.