Data collection systems for active safety surveillance of vaccines during pregnancy in low- and middle-income countries: developing and piloting an assessment tool (VPASS).

BACKGROUND: There is an urgent need for active safety surveillance to monitor vaccine exposure during pregnancy in low- and middle-income countries (LMICs). Existing maternal, newborn, and child health (MNCH) data collection systems could serve as platforms for post-marketing active surveillance of maternal immunization safety. To identify sites using existing systems, a thorough assessment should be conducted. Therefore, this study had the objectives to first develop an assessment tool and then to pilot this tool in sites using MNCH data collection systems through virtual informant interviews. METHODS: We conducted a rapid review of the literature to identify frameworks on population health or post-marketing drug surveillance. Four frameworks that met the eligibility criteria were identified and served to develop an assessment tool capable of evaluating sites that could support active monitoring of vaccine safety during pregnancy. We conducted semi-structured interviews in six geographical sites using MNCH data collection systems (DHIS2, INDEPTH, and GNMNHR) to pilot domains included in the assessment tool. RESULTS: We developed and piloted the "VPASS (Vaccines during Pregnancy - sites supporting Active Safety Surveillance) assessment tool" through interviews with nine stakeholders, including central-level systems key informants and site-level managers from DHIS2 and GNMNHR; DHIS2 in Kampala (Uganda) and Kigali (Rwanda); GNMNHR from Belagavi (India) and Lusaka (Zambia); and INDEPTH from Nanoro (Burkina Faso) and Manhica (Mozambique). The tool includes different domains such as the system's purpose, the scale of implementation, data capture and confidentiality, type of data collected, the capability of integration with other platforms, data management policies and data quality monitoring. Similarities among sites were found regarding some domains, such as data confidentiality, data management policies, and data quality monitoring. Four of the six sites met some domains to be eligible as potential sites for active surveillance of vaccinations during pregnancy, such as a routine collection of MNCH individual data and the capability of electronically integrating individual MNCH outcomes with information related to vaccine exposure during pregnancy. Those sites were: Rwanda (DHIS2), Manhica (IN-DEPTH), Lusaka (GNMNHR), and Belagavi (GNMNHR). CONCLUSION: This study's findings should inform the successful implementation of active safety surveillance of vaccines during pregnancy by identifying and using active individual MNCH data collection systems in LMICs.

Evaluation of BNT162b2 Covid-19 Vaccine in Children Younger than 5 Years of Age.

BACKGROUND: Safe and effective vaccines against coronavirus disease 2019 (Covid-19) are urgently needed in young children. METHODS: We conducted a phase 1 dose-finding study and are conducting an ongoing phase 2-3 safety, immunogenicity, and efficacy trial of the BNT162b2 vaccine in healthy children 6 months to 11 years of age. We present results for children 6 months to less than 2 years of age and those 2 to 4 years of age through the data-cutoff dates (April 29, 2022, for safety and immunogenicity and June 17, 2022, for efficacy). In the phase 2-3 trial, participants were randomly assigned (in a 2:1 ratio) to receive two 3-µg doses of BNT162b2 or placebo. On the basis of preliminary immunogenicity results, a third 3-µg dose (≥8 weeks after dose 2) was administered starting in January 2022, which coincided with the emergence of the B.1.1.529 (omicron) variant. Immune responses at 1 month after doses 2 and 3 in children 6 months to less than 2 years of age and those 2 to 4 years of age were immunologically bridged to responses after dose 2 in persons 16 to 25 years of age who received 30 µg of BNT162b2 in the pivotal trial. RESULTS: During the phase 1 dose-finding study, two doses of BNT162b2 were administered 21 days apart to 16 children 6 months to less than 2 years of age (3-µg dose) and 48 children 2 to 4 years of age (3-µg or 10-µg dose). The 3-µg dose level was selected for the phase 2-3 trial; 1178 children 6 months to less than 2 years of age and 1835 children 2 to 4 years of age received BNT162b2, and 598 and 915, respectively, received placebo. Immunobridging success criteria for the geometric mean ratio and seroresponse at 1 month after dose 3 were met in both age groups. BNT162b2 reactogenicity events were mostly mild to moderate, with no grade 4 events. Low, similar incidences of fever were reported after receipt of BNT162b2 (7% among children 6 months to <2 years of age and 5% among those 2 to 4 years of age) and placebo (6 to 7% among children 6 months to <2 years of age and 4 to 5% among those 2 to 4 years of age). The observed overall vaccine efficacy against symptomatic Covid-19 in children 6 months to 4 years of age was 73.2% (95% confidence interval, 43.8 to 87.6) from 7 days after dose 3 (on the basis of 34 cases). CONCLUSIONS: A three-dose primary series of 3-µg BNT162b2 was safe, immunogenic, and efficacious in children 6 months to 4 years of age. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04816643.).

Vaccines and Autoimmunity-From Side Effects to ASIA Syndrome.

Since vaccines are in fact manufactured chemical compounds such as drugs, the appearance of side effects following their use is not surprising. Similarly, as the main goal of vaccines is to stimulate the immune system bringing out the production of protective antibodies, autoimmune-related side effects as a consequence of increased immune activity do not seem irrational. Fortunately, the rate of such side effects is low; however, the importance of reporting adverse events following vaccinations, understanding the mechanisms behind their appearance, making early diagnosis, and appropriate treatment cannot be overemphasized. In fact, autoimmune-related side effects of vaccines, particularly those based on adjuvants, were reported long before the introduction of the autoimmune/inflammatory syndrome induced by adjuvants (ASIA). Nevertheless, ASIA gathered and united the side effects of vaccines under one title, a step which helped organize the research and call for better immune stimulators than adjuvants. New technologies and methods of making vaccines were clearly noticed during the pandemic of COVID-19 after the introduction of mRNA-based vaccines. In our current paper, we introduce the notion of side effects to vaccines, particularly those of autoimmune nature, the mechanisms of ASIA, and the main vaccines linked with the syndrome including the recent COVID-19 vaccines. The transition from side effects to ASIA is the main idea behind our work.

Genetic Risk Factors for Neurological Disorders in Children with Adverse Events Following Immunization: A Descriptive Study of a Polish Case Series.

Studies conducted on large populations show a lack of connection between vaccination and serious neurological symptoms. However, there are isolated cases that indicate such a relationship. These reports on adverse effects following immunization (AEFI) reduce social confidence in vaccination; however, their background may be rare genetic defects. The aim of the presented study was to examine if neurological AEFI in children may be associated with variants in genes related to neurodevelopment. To identify such possible associations, a descriptive study of the Polish case series was conducted. We performed next-generation sequencing in patients who, up to 4 weeks of injection of any vaccine, manifested neurological AEFI. We included 23 previously normally developing children with first seizures that occurred after vaccination. We identified pathogenic/likely pathogenic variants in genes engaged in neurodevelopment in nine patients and variants of uncertain significance in another nine patients. The mutated genes belonged to the group of genes related to epilepsy syndromes/epileptic encephalopathy. We showed that AEFI might have a genetic background. We hypothesized that in some AEFI patients, the vaccine might only trigger neurological symptoms that would have been manifested anyway as a result of a pathogenic variant in a gene engaged in neurodevelopment.

A systematic review of communication interventions for countering vaccine misinformation.

BACKGROUND: Misinformation and disinformation around vaccines has grown in recent years, exacerbated during the Covid-19 pandemic. Effective strategies for countering vaccine misinformation and disinformation are crucial for tackling vaccine hesitancy. We conducted a systematic review to identify and describe communications-based strategies used to prevent and ameliorate the effect of mis- and dis-information on people's attitudes and behaviours surrounding vaccination (objective 1) and examined their effectiveness (objective 2). METHODS: We searched CINAHL, Web of Science, Scopus, MEDLINE, Embase, PsycInfo and MedRxiv in March 2021. The search strategy was built around three themes(1) communications and media; (2) misinformation; and (3) vaccines. For trials addressing objective 2, risk of bias was assessed using the Cochrane risk of bias in randomized trials tool (RoB2). RESULTS: Of 2000 identified records, 34 eligible studies addressed objective 1, 29 of which also addressed objective 2 (25 RCTs and 4 before-and-after studies). Nine 'intervention approaches' were identified; most focused on content of the intervention or message (debunking/correctional, informational, use of disease images or other 'scare tactics', use of humour, message intensity, inclusion of misinformation warnings, and communicating weight of evidence), while two focused on delivery of the intervention or message (timing and source). Some strategies, such as scare tactics, appear to be ineffective and may increase misinformation endorsement. Communicating with certainty, rather than acknowledging uncertainty around vaccine efficacy or risks, was also found to backfire. Promising approaches include communicating the weight-of-evidence and scientific consensus around vaccines and related myths, using humour and incorporating warnings about encountering misinformation. Trying to debunk misinformation, informational approaches, and communicating uncertainty had mixed results. CONCLUSION: This review identifies some promising communication strategies for addressing vaccine misinformation. Interventions should be further evaluated by measuring effects on vaccine uptake, rather than distal outcomes such as knowledge and attitudes, in quasi-experimental and real-life contexts.

Unique features of vaccine-induced immune thrombotic thrombocytopenia; a new anti-platelet factor 4 antibody-mediated disorder.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a highly prothrombotic disorder caused by anti-PF4 antibodies that activate platelets and neutrophils, leading to thrombosis. Heparin-induced thrombocytopenia (HIT) is a related anti-PF4 mediated disorder, with similar pathophysiology and clinical manifestations but different triggers (i.e., heparin vs adenoviral vector vaccine). Clinically, both HIT and VITT typically present with thrombocytopenia and thrombosis, although the risk of thrombosis is significantly higher in VITT, and the thromboses occur in unusual anatomical sites (e.g., cerebral venous sinus thrombosis and hepatic vein thrombosis). The diagnostic accuracy of available laboratory testing differs between HIT and VITT; for VITT, ELISAs have better specificity compared to HIT and platelet activation assays require the addition of PF4. Treatment of VITT and HIT is anticoagulation non-heparin anticoagulants; however, heparin may be considered for VITT if no other option is available.

Searching for the 'Trigger': An ethnographic analysis of parental beliefs regarding autism causation and vaccination in Puerto Rico.

This study examines the personal beliefs held by parents of autistic children in Puerto Rico regarding the cause of their child's autism and how these beliefs may influence parental vaccination decision-making. This study seeks to contribute towards diversifying the autism literature by focusing on an autism community living in a relatively lower income, resource-deficit context. These findings expand our understandings of how parents of autistic children may perceive vaccines and how these perceptions are informed by various sources of knowledge. This ethnographic research study was conducted between May 2017 and August 2019. Methods included 350+ hours of participant-observation and semi-structured interviewing of 35 Puerto Rican parents of autistic children. 32 of these 35 parents interviewed believed autism to be the result of genetic risks that are 'triggered' by an unknown environmental factor. Suggested 'triggers' included various environmental contaminants and vaccinations. The subject of vaccination came up in every interview; 18 interviewed parents did not believe vaccines 'triggered' autism, 3 parents attributed their child's autism entirely to vaccines, while 14 considered vaccines to be one of several possible 'triggers'. It is important to note that no parents interviewed perceived vaccinations to be inherently or universally harmful. Rather, they perceived vaccinations to be one of many possible 'triggers' for a child predisposed to develop autism. In some cases, this perception prompted parents to oppose mandatory vaccination policies on the island. Parents shared nuanced, complex understandings of autism causation that may carry implications for COVID-19 vaccine uptake within the Puerto Rican autistic community.

Phase 2 study of AV-GBM-1 (a tumor-initiating cell targeted dendritic cell vaccine) in newly diagnosed Glioblastoma patients: safety and efficacy assessment.

BACKGROUND: Vaccine immunotherapy may improve survival in Glioblastoma (GBM). A multicenter phase II trial was designed to determine: (1) the success rate of manufacturing the Aivita GBM vaccine (AV-GBM-1), (2) Adverse Events (AE) associated with AV-GBM-1 administration, and (3) survival. METHODS: Fresh suspected glioblastoma tissue was collected during surgery, and patients with pathology-confirmed GBM enrolled before starting concurrent Radiation Therapy and Temozolomide (RT/TMZ) with Intent to Treat (ITT) after recovery from RT/TMZ. AV-GBM-1 was made by incubating autologous dendritic cells with a lysate of irradiated autologous Tumor-Initiating Cells (TICs). Eligible patients were adults (18 to 70 years old) with a Karnofsky Performance Score (KPS) of 70 or greater, a successful TIC culture, and sufficient monocytes collected. A cryopreserved AV-GBM-1 dose was thawed and admixed with 500 µg of Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) before every subcutaneous (s.c.) administration. RESULTS: Success rates were 97% for both TIC production and monocyte collection. AV-GBM-1 was manufactured for 63/63 patients; 60 enrolled per ITT; 57 started AV-GBM-1. The most common AEs attributed to AV-GBM-1 were local injection site reactions (16%) and flu-like symptoms (10%). Treatment-emergent AEs included seizures (33%), headache (37%), and focal neurologic symptoms (28%). One patient discontinued AV-GBM-1 because of seizures. Median Progression-Free Survival (mPFS) and median Overall Survival (mOS) from ITT enrollment were 10.4 and 16.0 months, respectively. 2-year Overall Survival (OS) is 27%. CONCLUSIONS: AV-GBM-1 was reliably manufactured. Treatment was well-tolerated, but there were numerous treatment-emergent central nervous system AEs. mPFS was longer than historical benchmarks, though no mOS improvement was noted. TRIAL REGISTRATION: NCT, NCT03400917 , Registered 10 January 2018.

Optimising reporting of adverse events following immunisation by healthcare workers in Ghana: A qualitative study in four regions.

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.

Adverse events following administration of COVID-19 vaccines in Saudi Arabia.

Previous studies investigated the frequency of different adverse events of COVID-19 vaccines. However, this study compares these adverse events between the two main COVID-19 vaccines used in Saudi Arabia (Pfizer-BioNTech and Oxford-AstraZeneca) using telemedicine technology. A cross-sectional study was conducted among 958 individuals, 7 days after receiving either Pfizer-BioNTech or Oxford-AstraZeneca vaccines during June 2021. Immediate adverse events were reported by 1.04% and 2.09% for Pfizer-BioNTech and Oxford-AstraZeneca vaccines, respectively, with no serious events. Recipients of Pfizer-BioNTech vaccine had a higher percentage of local adverse events (24.8% versus 9.8% in AstraZeneca vaccine). The most common reported systemic adverse events in both vaccines respectively were general fatigue (23.1% and 25.1%), fever (18.5% and 27.2%), myalgia (20.6% and 20.3%), and headache (15.2% and 17.2%). No significant difference was recorded between both vaccines regarding overall systemic adverse events; however, they were more frequent following the first dose of AstraZeneca vaccine compared to Pfizer-BioNTech vaccine, while the reverse was observed for the second dose. Adverse events were more frequent in females and younger age groups for both vaccines. Most of systemic and local adverse events were mild in nature. Further cohort studies are recommended to investigate the long-term adverse events of COVID-19 vaccines.

Emergence of Vaccine-Preventable Diseases: The Perfect Storm of Hesitancy, Refusal, a Pandemic, and War.

The landscape of pediatric vaccination has changed dramatically due to changing attitudes toward immunizations and recent world events. The rise of vaccine hesitancy and refusal related to the concurrent rise of social media and anti-vaccination messages with misinformation campaigns have led to populations of children being unimmunized or under-immunized. These populations have been left vulnerable to the rapid spread of vaccine-preventable infection. Additionally, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the clinical syndrome known as coronavirus disease 2019 (COVID-19) resulted in the emergence of a worldwide pandemic. Control measures to mitigate the spread of COVID-19 resulted in numerous reports of children missing routine vaccines along with the stopping of many public health immunization programs. Finally, armed conflicts and war have led to large family migrations from their homelands to various countries and regions leading to increased risk for missed maternal and child immunization as well as difficulty in keeping vaccination records. [Pediatr Ann. 2022;51(11):e426-e430.].