Brand-specific influenza vaccine effectiveness estimates during 2019/20 season in Europe – Results from the DRIVE EU study platform

DRIVE (Development of Robust and Innovative Vaccine Effectiveness) is an IMI funded public–private platform that aims to annually estimate brand-specific influenza vaccine effectiveness (IVE), for public health and regulatory purposes. IVE analyses and reporting are conducted by public partners in the con- sortium. In 2019/20, four primary care-based test-negative design (TND) studies (Austria, England, Italy (n = 2)), eight hospital-based TND studies (Finland, France, Italy, Romania, Spain (n = 4)), and one population- based cohort study (Finland) were conducted. The COVID-19 pandemic affected influenza surveillance in all participating study sites, therefore the study period was truncated on February 29, 2020. Age- stratified (6 m-17y, 18-64y, !65y), confounder-adjusted, site-specific adjusted IVE estimates were calcu- lated and pooled through meta-analysis. Parsimonious confounder-adjustment was performed, adjusting the estimates for age, sex and calendar time. TND studies included 3531 cases (351 vaccinated) and 5546 controls (1415 vaccinated) of all ages. IVE estimates were available for 8/11 brands marketed in Europe in 2019. Most children and adults < 64y were captured in primary care setting and the most frequently observed vaccine brand was Vaxigrip Tetra. The estimate against any influenza for Vaxigrip Tetra in primary care setting was 61% (95%CI 38–77) in children and 32% (95%CI 13–59) in adults up to 64y. Most adults ! 65y were captured in hospital setting and the most frequently observed brand was Fluad, with an estimate of 52% (95%CI 27–68)

Original Article

By using a new method for estimation of histamine, evolved in Pharmacological Department of our Univesity, a study was made on the relation between histamine and hemothorax, in order to determine the part which a vascular factor may play in the development of hemothorax following resection of the lung. In animal experiments using grown-up dogs, it was observed that performing thoracotomy and lung operation, as well as anoxia, caused histamine in the pulmonary veins to increase. In rabbits in which pleurisy and hemothorax had been experimentally induced, it was observed that the amount of histamine in the blood and thoracic exudation showed an increase immediately after induction of inflammation. Histopathologic investigation showed a multiplication of mast cells in the pleural cavity of rabbits in which hemothorax had experimentally been induced. There was an increase in the amount of histamine in the blood and thoracic exudation in 23 patients who had undergone resection of the lung ; some showed a sudden decrease, while some a gradual increase. A study made on the relation between the amount of histamine and the amount of blood lost during operation and aspirated after operation showed that the greater the amount of histamine, the greater was the amount of blood wasted during and after operation and the higher was a tendency to postoperative development of hemothorax. Histamine, having actions of dilating the capillaries and promoting their permeability and of lowering resistance of the blood vessels, may cause hemothorax to occur when it is abnormally increased in amount

Vaccine safety surveillance in pregnancy in low- and middle-income countries using GAIA case definitions: A feasibility assessment

Background: Global efforts to adequately monitor safety of new vaccines for pregnant women in low and middle-income countries (LMICs) are needed. The Global Alignment of Immunization Safety Assessment in pregnancy (GAIA) project recently published case definitions based on levels of diagnostic certainty for pregnancy- and neonatal outcomes and maternal vaccination. As a preliminary step to assessing the applicability of these definitions in LMICs, WHO selected sites and conducted a feasibility assessment to evaluate their ability to identify and classify selected outcomes (preterm birth, neonatal death, neonatal invasive bloodstream infection (NI-BSI), stillbirth) and maternal vaccination. Methods: Candidate sites were initially screened using a questionnaire. For each outcome, eligible sites were asked to retrospectively identify and collect information for three individuals born in 2016. Subsequently, outcomes were classified by level of diagnostic certainty. Results: Fifty-one sites (15 countries) were screened; 32 of them (9 countries) participated in the assessment and identified 315 subjects with the outcomes of interest. Twenty-four sites (8 countries) identified at least one subject per outcome and agreed to continue participating. The majority (80%) of preterm births, neonatal deaths, and NI-BSI subjects, but only 50% of stillbirths, could be assessed for diagnostic certainty. The main reasons for not classifying stillbirths were insufficient information to distinguish between antepartum and intrapartum stillbirth (29%); or that not all data for one subject fit into a single level of diagnostic certainty (35%). Forty-nine percent of mothers were considered vaccinated, 6% not-vaccinated, and vaccination status could not be assessed in 44% of them. Discussion: GAIA case definitions for four neonatal outcomes and maternal vaccination were successfully piloted in 24 sentinel sites across four WHO regions. Our assessment found that modification of the stillbirth definition could help avoid potential misclassification. Vaccine safety monitoring in LMICs will benefit from systematic recording of all vaccinations during pregnancy

WHO global vaccine safety multi-country collaboration project on safety in pregnancy: Assessing the level of diagnostic certainty using standardized case definitions for perinatal and neonatal outcomes and maternal immunization.

Standardized case definitions strengthen post-marketing safety surveillance of new vaccines by improving generated data, interpretation and comparability across surveillance systems. The Global Alignment of Immunization Safety Assessment in Pregnancy (GAIA) project developed standardized case definitions for 21 key obstetric and neonatal terms following the Brighton Collaboration (BC) methodology. In this prospective cohort study, we assessed the applicability of GAIA definitions for maternal immunization exposure and for low birth weight (LBW), preterm birth, small for gestational age (SGA), stillbirth, neonatal death, neonatal infection, and congenital microcephaly. We identified the missing data elements that prevented identified cases and exposures from meeting the case definition (level 1-3 of BC diagnostic certainty). Over a one-year period (2019-2020), all births occurring in 21 sites (mostly secondary and tertiary hospitals) in 6 Low Middle Income Countries and 1 High Income Country were recorded and the 7 perinatal and neonatal outcome cases were identified from routine medical records. Up to 100 cases per outcome were recruited sequentially from each site. Most cases recruited for LBW, preterm birth and neonatal death met the GAIA case definitions. Birth weight, a key parameter for all three outcomes, was routinely recorded at all sites. The definitions for SGA, stillbirth, neonatal infection (particularly meningitis and respiratory infection) and congenital microcephaly were found to be less applicable. The main barrier to obtaining higher levels of diagnostic certainty was the lack of sonographic documentation of gestational age in first or second trimester. The definition for maternal immunization exposure was applicable, however, the highest level of diagnostic certainty was only reached at two sites. Improved documentation of maternal immunization will be important for vaccine safety studies. Following the field-testing of these 8 GAIA definitions, several improvements are suggested that may lead to their easier implementation, increased standardization and hence comparison across studies

Measuring underreporting and under-ascertainment in infectious disease datasets: a comparison of methods

Gibbons CL, Mangen M-JJ, Plaß D, et al. Measuring underreporting and under-ascertainment in infectious disease datasets: a comparison of methods. BMC Public Health. 2014;14(1): 147.Background: Efficient and reliable surveillance and notification systems are vital for monitoring public health and disease outbreaks. However, most surveillance and notification systems are affected by a degree of underestimation (UE) and therefore uncertainty surrounds the 'true' incidence of disease affecting morbidity and mortality rates. Surveillance systems fail to capture cases at two distinct levels of the surveillance pyramid: from the community since not all cases seek healthcare (under-ascertainment), and at the healthcare-level, representing a failure to adequately report symptomatic cases that have sought medical advice (underreporting). There are several methods to estimate the extent of under-ascertainment and underreporting. Methods: Within the context of the ECDC-funded Burden of Communicable Diseases in Europe (BCoDE)-project, an extensive literature review was conducted to identify studies that estimate ascertainment or reporting rates for salmonellosis and campylobacteriosis in European Union Member States (MS) plus European Free Trade Area (EFTA) countries Iceland, Norway and Switzerland and four other OECD countries (USA, Canada, Australia and Japan). Multiplication factors (MFs), a measure of the magnitude of underestimation, were taken directly from the literature or derived (where the proportion of underestimated, under-ascertained, or underreported cases was known) and compared for the two pathogens. Results: MFs varied between and within diseases and countries, representing a need to carefully select the most appropriate MFs and methods for calculating them. The most appropriate MFs are often disease-,country-, age-, and sex-specific. Conclusions: When routine data are used to make decisions on resource allocation or to estimate epidemiological parameters in populations, it becomes important to understand when, where and to what extent these data represent the true picture of disease, and in some instances (such as priority setting) it is necessary to adjust for underestimation. MFs can be used to adjust notification and surveillance data to provide more realistic estimates of incidence

Rapid assessment of the reactogenicity of a 2016-2017 seasonal influenza vaccine: results from a feasibility study

Background: ​​The European Medicines Agency (EMA) calls for a strategy for enhanced safety surveillance of seasonal influenza vaccines. Objective: We assessed the feasibility of collecting reactogenicity data within one month of the start of the vaccination campaign in Belgium. Methods: One hundred subjects aged 18 to 65 years who had received inactivated seasonal influenza vaccine in occupational setting were enrolled. For 7 days after vaccination, subjects received a daily SMS with a link to a web-based questionnaire where reactogenicity events and their severity were solicited. Results: Data collection was completed by October 13th, 2016, before the peak of the vaccination campaign in Belgium. 68% of participants reported a local reaction and 65% a general reaction; 51% reported both a local and a general reaction. Conclusion: Here we show that it has been possible to collect reactogenicity data in adults for enhanced safety surveillance in Belgium in a timely manner. The observed reactogenicity is higher compared to previous observations for this vaccine measured in clinical trials

Rapid assessment of the reactogenicity of a 2016-2017 seasonal influenza vaccine: results from a feasibility study

<p><b>Background:</b> ​​The European Medicines Agency (EMA) calls for a strategy for enhanced safety surveillance of seasonal influenza vaccines.</p> <p><b>Objective</b>: We assessed the feasibility of collecting reactogenicity data within one month of the start of the vaccination campaign in Belgium.</p> <p><b>Methods</b>: One hundred subjects aged 18 to 65 years who had received inactivated seasonal influenza vaccine in occupational setting were enrolled. For 7 days after vaccination, subjects received a daily SMS with a link to a web-based questionnaire where reactogenicity events and their severity were solicited.</p> <p><b>Results</b>: Data collection was completed by October 13th, 2016, before the peak of the vaccination campaign in Belgium. 68% of participants reported a local reaction and 65% a general reaction; 51% reported both a local and a general reaction.</p> <p><b>Conclusion</b>: Here we show that it has been possible to collect reactogenicity data in adults for enhanced safety surveillance in Belgium in a timely manner. The observed reactogenicity is higher compared to previous observations for this vaccine measured in clinical trials.</p

Impact of universal mass vaccination with monovalent inactivated hepatitis A vaccines – A systematic review

The WHO recommends integration of universal mass vaccination (UMV) against hepatitis A virus (HAV) in national immunization schedules for children aged ≥1 year, if justified on the basis of acute HAV incidence, declining endemicity from high to intermediate and cost-effectiveness. This recommendation has been implemented in several countries. Our aim was to assess the impact of UMV using monovalent inactivated hepatitis A vaccines on incidence and persistence of anti-HAV (IgG) antibodies in pediatric populations. We conducted a systematic review of literature published between 2000 and 2015 in PubMed, Cochrane Library, LILACS, IBECS identifying a total of 27 studies (Argentina, Belgium, China, Greece, Israel, Panama, the United States and Uruguay). All except one study showed a marked decline in the incidence of hepatitis A post introduction of UMV. The incidence in non-vaccinated age groups decreased as well, suggesting herd immunity but also rising susceptibility. Long-term anti-HAV antibody persistence was documented up to 17 y after a 2-dose primary vaccination. In conclusion, introduction of UMV in countries with intermediate endemicity for HAV infection led to a considerable decrease in the incidence of hepatitis A in vaccinated and in non-vaccinated age groups alike