A feasibility assessment of real-world data capabilities for monitoring vaccine safety and effectiveness in China: Human papillomavirus vaccination in the Yinzhou district as a use case.

BACKGROUND: Real-world data (RWD) are increasingly used to generate real-world evidence (RWE) of vaccine safety and effectiveness for regulatory purposes. Assessing feasibility of using RWD sources prior to implementing observational studies is recommended. As a use case, we described the process and findings of a feasibility assessment to identify reliable and relevant data sources for monitoring the safety and effectiveness of the AS04-HPV-16/18 human papillomavirus (HPV) vaccine in China. METHODS: Iterative multi-step process: (1) targeted literature review and data source mapping; (2) expert opinion from national RWD experts; (3) survey to evaluate the identified data source operational infrastructure; and (4) continuous appraisal of published studies using the identified data source. RESULTS: The Yinzhou Regional Health Information Platform (YRHIP) was identified as a data source of main interest, based on its large population coverage, high cervical cancer screening rates, and availability of adult electronic immunization records. Field meetings with national RWD experts confirmed its suitability for post-authorization vaccine studies. Survey results showed that exposure data and relevant safety and effectiveness endpoints were recorded and linkable at the individual level across the platform. Iterative appraisal of emerging evidence from the literature corroborated these findings. CONCLUSIONS: This feasibility assessment indicates that the YRHIP has the capacity to capture demographic, exposure, outcome and other data required to generate RWE on HPV vaccine safety and effectiveness in China. Studies using the YRHIP to monitor the AS04-HPV-16/18 vaccine in routine use building on this feasibility assessment are ongoing.

Meta-analysis of the risk of autoimmune thyroiditis, Guillain-Barré syndrome, and inflammatory bowel disease following vaccination with AS04-adjuvanted human papillomavirus 16/18 vaccine.

PURPOSE: To assess the risk of three autoimmune diseases - autoimmune thyroiditis (AIT), Guillain-Barré syndrome (GBS), and inflammatory bowel disease (IBD) - in females following AS04-HPV-16/18 vaccination. METHODS: This meta-analysis included data from 18 randomized controlled trials, one cluster-randomized trial, two large observational retrospective cohort studies, and one case-control study. Following vaccination, a risk window of 2 years was defined for AIT and IBD and 42 days for GBS. Odds ratios (ORs) were estimated using three methods: meta-analysis inverse-variance with continuity correction (primary analysis), pooled estimate, and beta-binomial regression. RESULTS: In all studies apart from the case-control study, 154 398 exposed and 1 504 322 non-exposed subjects were included, among whom there were 141 and 1972 cases of (autoimmune) thyroiditis; 2 and 2 cases of GBS; and 43 and 401 cases of IBD, respectively. In the case-control study, there were 97 cases of AIT and 13 of GBS; matched with 802 and 130 controls, respectively. The primary analysis OR estimates were 1.46 (95% confidence interval [CI] 1.22-1.76), 11.14 (2.00-61.92), and 1.11 (0.75-1.66) for (autoimmune) thyroiditis, GBS, and IBD, respectively. CONCLUSIONS: This meta-analysis did not show an increased risk of IBD following vaccination with AS04-HPV-16/18. The 1.5-fold increased risk of (autoimmune) thyroiditis does not allow us to conclude about a causal association. For GBS, the very low number of cases and wide 95% CIs negate any firm conclusion.

Age- and strain-dependent differences in the outcome of experimental infections of domestic pigs with wild boar pseudorabies virus isolates.

Although pseudorabies virus (PRV) has been eradicated in domestic swine in many countries, its presence in wild boars remains a threat for a reintroduction into the currently unprotected swine population. To assess the possible impact of such a reintroduction in a naive herd, an in vivo infection study using two genetically characterized wild boar PRV isolates (BEL24043 and BEL20075) representative for wild boar strains circulating in south-western and central Europe and the virulent NIA3 reference strain was performed in 2- and 15-week-old domestic pigs. Our study revealed an attenuated nature of both wild boar strains in 15-week-old pigs. In contrast, it showed the capacity of strain BEL24043 to induce severe clinical symptoms and mortality in young piglets, thereby confirming that the known age dependency of disease outcome after PRV infection also holds for wild boar isolates. Despite the absence of clinical disease in 15-week-old sows, both wild boar PRV strains were able to induce seroconversion, but to a different extent. Importantly, differences in infection and transmission capacity of both strains were observed in 15-week-old sows. Strain BEL24043 induced a more prolonged and disseminated infection than strain BEL20075 and was able to spread efficiently to contact animals, indicative of its capacity to induce a sustained infection. In conclusion, it was shown that a reintroduction of a wild boar isolate into the domestic swine population could have serious economic consequences due to the induction of clinical symptoms in piglets and by jeopardizing the PRV-negative status.

Prevalence of Mycoplasma gallisepticum and Mycoplasma synoviae in commercial poultry, racing pigeons and wild birds in Belgium.

Mycoplasma gallisepticum is the most important pathogenic avian Mycoplasma species and causes chronic respiratory disease in poultry. In addition, the prevalence of Mycoplasma synoviae is of increasing concern in several EU member states. We investigated the prevalence of M. gallisepticum in commercial poultry (5220 layers, 1224 broilers and 1020 meat turkeys), 56 racing pigeons and 890 wild birds (Order Anseriformes, Galliformes, Pelecaniformes, Accipitriformes, Gruiformes, Charadriiformes, Columbiformes, Strigiformes, Falconiformes and Passeriformes). Broilers and wild birds were also evaluated for Mycoplasma synoviae. Dependent on the bird lifespan and the nature of the sample, different diagnostic tests were used including the rapid plate agglutination test, enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction and real-time polymerase chain reaction. A low prevalence of M. gallisepticum was found in both layers (0.9%; 95% CI: 0.7-1.2%) and broilers (2.7%; 95% CI: 1.9-3.8%) possibly due to reduced vertical transmission by breeder farms, which are under official surveillance. None of the samples from turkeys or racing pigeons tested positive. In wild birds, we found five birds were positive (1.7%; 95% CI: 0.7-3.9%): one wood pigeon, two grey herons, one mallard and one Eurasian magpie. For M. synoviae a high prevalence was found in broilers (12.9%: 95% CI: 11.1-14.9%). Four samples collected by hunters gave a positive result for M. synoviae (4%: 95% CI: 1.6-9.8%): one carrion crow and three wood pigeons. In addition, 12 house sparrows were found to be positive (3%; 95% CI: 1.7-5.2%). Wild birds probably play a limited role as a reservoir but we cannot exclude a possible impact on transmission of Mycoplasmas.

Assessing evidence of a potential Salmonella transmission across the poultry food chain.

Enhanced Salmonella surveillance programmes in poultry were implemented in all European Member States, with minimum prevalence targets for a list of targeted serotypes to safeguard food and public health. Based on the Belgian Salmonella surveillance programme and focusing on poultry, the overarching aim of this study was to highlight possible Salmonella transmissions across the food chain (FC). For this purpose, firstly, the prevalence patterns of Salmonella (targeted and the most prevalent non-targeted) serotypes along the FC were described over time. Secondly, the effectiveness of the control measures against vertical transmission (breeders to 1-day-old broiler and layer chicks) was indirectly assessed by looking into the odds of targeted serotypes detection. Thirdly, it was appraised if Salmonella prevalence can significantly increase during broilers and layers production. In addition, it was tested if being tested negative at the end of production in broilers when tested positive at the entrance is serotype dependent (targeted vs. non-targeted serotypes). Results showed that, firstly, the prevalence patterns of the listed serotypes were inconstant over time and across the FC. Secondly, the odds of Salmonella targeted serotype detection in 1-day-old broiler and in 1-day-old layer flocks were lower than in breeder flocks while, thirdly, infection during broiler and layer production can lead to significant increase in positivity in subsequent samples. Finally, being infected by a targeted or by non-targeted serotype at the entrance of the flock poorly reflects the Salmonella status at the end of production. Note that this study did not make a distinction between the different sources of contamination and the effects of sampling methods and isolation methods should be subject to further investigation.

MOnitoring human papillomavirus Vaccine effect on Infection and cErvical diseases (MOVIE): Protocol for a cohort study using electronic health records from Yinzhou, China.

Cervical cancer is the fourth most common cancer in women, with a high disease burden worldwide. Human papillomavirus (HPV) vaccination reduces HPV-related infection and associated cervical lesions and cancers. Few studies have explored HPV vaccination impact in real-world settings in China. This study aims to monitor HPV vaccine uptake and its effects on HPV-related diseases, evaluating vaccine effectiveness in a real-world context and complementing clinical trial results. Electronic health records (EHRs) from 2010 to 2020 from the Yinzhou Regional Health Information Platform (YRHIP) will be queried/extracted to identify and monitor HPV vaccine uptake in females aged 9-45 years, and HPV-related screening and prevalence (i.e., cervical HPV infection, cervical intraepithelial neoplasia [CIN] grades 1-3, and cervical cancer) in a cohort of females aged 9-70 years. Cervical cancer screening guidelines and expert consultation will be used for intra-database validation, to determine the best algorithm for identifying HPV-related disease. Pre-launch (2010-2016) and post-launch (2018-2020) periods are predefined. A time trend analysis will be performed to describe the vaccination impact on disease prevalence and, if prerequisite conditions are met, vaccine effectiveness will be computed using logistic regression, adjusting for age, calendar year, history of screening and HPV infection. Cohort study design, outcomes validation, data linkage, and multi-step statistical analyses could provide valuable experience for designing other real-world studies in the future. The study outcomes can help inform policy-makers about uptake and HPV vaccination policy in girls and women in Yinzhou District, and provide insights on progress toward achieving goals set by the World Health Organization.

Prospective, multi-center post-marketing surveillance cohort study to monitor the safety of the human papillomavirus-16/18 AS04-adjuvanted vaccine in Chinese girls and women aged 9 to 45 years, 2018-2020.

Following the approval of Cervarix for the immunization of girls and women in China against high-risk human papillomavirus types 16 and 18, a non-interventional post-authorization safety study was performed. A multi-center prospective cohort study assessed safety following Cervarix vaccination of Chinese girls and women aged 9-45 years between 31 May 2018 and 3 December 2020. Adverse events following immunization (AEFIs), potential immune-mediated diseases (pIMDs), and pregnancy-related outcomes were collected up to 12 months from the third immunization or 24 months from the first immunization, whichever came first. Among 3,013 women who received 8,839 Cervarix doses, 167 (5.5%) reported ≥ 1 any AEFI, and 22 (0.7%) reported 40 serious AEFIs. During the 30 days after each dose, 147 women (4.9%) reported 211 medically attended AEFIs, including 3 serious AEFIs reported by 1 woman (0.03%). One woman reported a pIMD. Cervarix was inadvertently administered to 65 women (2.2%) within 60 days before conception or during pregnancy. Of these women, 34 (52.3%) gave birth to live infant(s) with no apparent congenital anomalies, and 1 (1.5%) woman gave birth to a live infant with a congenital anomaly. No serious AEFIs or pIMDs were considered to be related to the vaccination. In Chinese women aged 9-45 years, immunization with the Cervarix three-dose schedule was well tolerated. Overall, no safety concerns were identified, although rare adverse events may have been missed due to the study sample size.Clinical trial registration: NCT03438006.

Infection with high-risk human papillomavirus is a prerequisite for cervical cancerCervarix is a human papillomavirus-16/18 AS04-adjuvanted vaccineMulti-centre prospective cohort study to monitor safety of Cervarix immunisationSafety was monitored in 3,013 girls/women aged 9­45 years in China (8,839 doses)Cervarix was well tolerated, and no safety concerns were identified.

Quantitative decision making in animal health surveillance: Bovine Tuberculosis Surveillance in Belgium as case study.

Despite eradication and control measures applied across Europe, bovine tuberculosis (bTB) remains a constant threat. In Belgium, after several years of official bTB-free status, routine movement testing, as currently practiced, revealed itself inadequate to detect some herds affected by sporadic breakdowns. The aim of this study was to assess different surveillance system components that strike a balance between cost and effectiveness and to identify sustainable alternatives, which substantiate a bTB-free claim while ensuring early detection and acceptance by various animal health stakeholders. For this pupose, a stochastic iteration model was used to simulate the current surveillance system's expected performance in terms of detection sensitivity and specificity. These results were then descriptively compared with observed field results. Second, the cost and effectiveness of simulated alternative surveillance components were quantified. Sensitivity analyses were performed to measure key assumptions' impacts (i.e. regarding diagnostic tests and true prevalence). The results confirmed discrepancies between the observed and simulated expected performance of bTB surveillance in Belgium. Second, simulated alternatives showed that interferon gamma (IFN-γ) and serological testing with antibody-enzyme linked immunosorbent assay (Ab-ELISA) targeting at-risk herds would enable an increase in the overall cost effectiveness (sensitivity and specificity) of the Belgian bTB surveillance system. Sensitivity analyses showed that results remained constant despite the modification of some key assumptions. While the performance of the ongoing bTB surveillance system in Belgium was questionable at the time of the study, this exercise highlighted that not only sensitivity but specificity also are key drivers of surveillance performance. The quantitative approach, taking into consideration various stakeholders' needs and priorities, revealed itself to be a useful tool in allowing evidence-based decision making for future tuberculosis surveillance in Belgium, in line with the international standards.

Progression from human papillomavirus (HPV) infection to cervical lesion or clearance in women (18-25 years): Natural history study in the control arm subjects of AS04-HPV-16/18 vaccine efficacy study in China between 2008 and 2016.

BACKGROUND: Cervical cancer is the third most frequent cancer in Chinese women aged 15-44 years old. Human papillomavirus (HPV) is recognized as the main etiologic agent of cervical carcinomas. This study aims to better understand the natural history of HPV infections in Chinese women aged 18-25 years. RESEARCH DESIGN AND METHODS: Data from 3,025 control arm women (AS04-HPV-16/18 vaccine trial) were analyzed to assess the probability of progression or clearance from a 6-month persistent infection (6MPI) to a cervical intraepithelial neoplasia grade 2 or greater (CIN2+), and the association with clinical determinants. Data were analyzed using univariate and multivariable Cox models. RESULTS: A total of 1,324 women with 3,814 HPV infections were included, and 65.7% of the women had at least one 6MPI. Among those 6MPI, 5.0% progressed to CIN2+, while 61.0% cleared within 6 months. The risk of progression from 6MPI to CIN2+ was substantially higher for oncogenic versus non-oncogenic HPV types. CONCLUSIONS: Oncogenic HPV infections showed lower clearance and higher risk to progress to CIN2 +. These findings observed in a population of Chinese women, confirmed previous findings from multinational studies. TRIAL REGISTRATION: The PATRICIA and AS04-HPV-16/18 vaccine trials are registered at ClinicalTrials.gov (NCT00779766 and NCT00122681).

Importance of quick attainment of minimal disease activity for a positive impact on lives of patients with psoriatic arthritis.

OBJECTIVE: To compare patient-reported outcomes (PROs) from the first year to the third year between patients with psoriatic arthritis (PsA) who achieved minimal disease activity (MDA) in the first year after diagnosis and those who did not. METHODS: Consecutive, newly diagnosed, patients with DMARD naïve PsA with oligoarthritis or polyarthritis were selected from the Dutch southwest Early PsA cohoRt. Patients were categorised in three groups: (1) Patients who were in MDA at both 9 months and 12 months after diagnosis (sustained MDA); (2) Patients who achieved MDA in the first year but in whom it was not sustained at both 9 months and 12 months (non-sustained MDA); (3) Patients who did not achieve MDA in the first year (no MDA). PROs were compared between groups from the first year to the third year after diagnosis using a linear mixed model. RESULTS: 240 patients were selected; 104 (43%) were classified as sustained MDA, 60 (25%) as non-sustained MDA and 76 (32%) as no MDA. Patients who did not achieve MDA in the first year experienced remarkably lower PROs during follow-up, compared with the sustained MDA group: health status (European Quality of life 5-Dimensions 5-Levels) was 0.23 units lower (95% CI -0.28 to -0.18), functional impairment (Health Assessment Questionnaire-Disability Index) was 0.81 units higher (95% CI 0.70 to 0.92), pain (Visual Analogue Scale) was 35.38 mm higher (95% CI 30.57 to 40.18), fatigue (Bristol Rheumatoid Arthritis Fatigue-Multidimensional Questionnaire) was 17.88 units higher (95% CI 14.60 to 21.16), and anxiety and depression (Hospital Anxiety and Depression Scale) were, respectively, 3.26 units (95% CI 2.25 to 4.27) and 4.04 units higher (95% CI 3.10 to 4.99). CONCLUSION: Failure to achieve MDA in the first year after PsA diagnosis was associated with worse PROs that persisted over the years.

Comparison of Salmonella enteritidis phage types isolated from layers and humans in Belgium in 2005.

OBJECTIVES: The aim of this study was to investigate the available results for Belgium of the European Union coordinated monitoring program (2004/665 EC) on Salmonella in layers in 2005, as well as the results of the monthly outbreak reports of Salmonella Enteritidis in humans in 2005 to identify a possible statistical significant trend in both populations. MATERIALS AND METHODS: Separate descriptive statistics and univariate analysis were carried out and the parametric and/or non-parametric hypothesis tests were conducted. A time cluster analysis was performed for all Salmonella Enteritidis phage types (PTs) isolated. The proportions of each Salmonella Enteritidis PT in layers and in humans were compared and the monthly distribution of the most common PT, isolated in both populations, was evaluated. RESULTS: The time cluster analysis revealed significant clusters during the months May and June for layers and May, July, August, and September for humans. PT21, the most frequently isolated PT in both populations in 2005, seemed to be responsible of these significant clusters. PT4 was the second most frequently isolated PT. No significant difference was found for the monthly trend evolution of both PT in both populations based on parametric and non-parametric methods. DISCUSSION AND CONCLUSION: A similar monthly trend of PT distribution in humans and layers during the year 2005 was observed. The time cluster analysis and the statistical significance testing confirmed these results. Moreover, the time cluster analysis showed significant clusters during the summer time and slightly delayed in time (humans after layers). These results suggest a common link between the prevalence of Salmonella Enteritidis in layers and the occurrence of the pathogen in humans. Phage typing was confirmed to be a useful tool for identifying temporal trends.

Hepatitis A antibody persistence 8 and 10 years after 1-dose and 2-dose vaccination in children from Panama.

BACKGROUND: Hepatitis A virus (HAV) remains a global public health concern, which is potentially growing in Latin America, due to an expected shift from high to intermediate endemicity levels. The use of HAV vaccines in pediatric national immunization programs (NIPs), either as a 2-dose or a 1-dose schedule, has been explored in Latin American countries; however, evidence demonstrating long-term protection in this population is limited in the region. We evaluated long-term antibody persistence following a 1-dose partial series and the recommended 2-dose schedule used in Panama's pediatric NIP. METHODS: Two independent cross-sectional serological surveys were conducted at year 8 (Y8) and Y10 following vaccination under the NIP with 1 or 2 doses of an inactivated HAV vaccine (Havrix, GSK). Seropositivity (anti-HAV antibody concentration ≥ 15 mIU/mL) rates and antibody geometric mean concentrations (GMCs) were assessed at each serosurvey. Non-inferiority of 1 dose versus 2 doses was also explored. RESULTS: This study (NCT02712359) included 600 and 599 children at Y8 and Y10 post-vaccination, respectively. Seropositivity rates were 74.3% (95% confidence interval [CI]: 69.0; 79.2) and 97.7% (95% CI: 95.3; 99.1) at Y8 and 71.9% (95% CI: 66.4; 76.9) and 96.3% (95% CI: 93.5; 98.2) at Y10, in the 1-dose and 2-dose groups, respectively. Antibody GMCs were lower in the 1-dose versus the 2-dose group in both surveys. Non-inferiority was not demonstrated since the lower limit of the 2-sided 95% CI for the between-group difference in seropositivity rates (1-dose minus 2-dose) was < -10%. CONCLUSION: Anti-HAV antibody persistence was observed in lower percentages of children receiving 1 dose versus 2 doses of Havrix, at 8 and 10 years post-vaccination in Panama. Further investigations are needed to confirm antibody persistence and conclude on the protection afforded beyond 10 years in the pediatric population in Latin America.

Improving laboratory diagnostic capacities of emerging diseases using knowledge mapping.

Over the last decade, European countries faced several emerging and re-emerging animal diseases as well as zoonotic diseases. During these episodes, the laboratory diagnostic capabilities were a key factor to rapidly control and/or eradicate them. Because of the associated socio-economic and health consequences, it is crucial to react rapidly and efficiently, not only during crisis but also in peacetime (i.e. preparedness). However, to date, there is no published method to identify diseases with diagnostic gaps and to prioritize assays to be implemented. This study was conducted based on the outcome of a prioritization exercise in which 29 epizootic and exotic diseases with high risk of emergence or re-emergence in Belgium (Bianchini et al., [2020] Transboundary and Emerging Diseases, 67(1), 344-376) were listed. Knowledge mapping was used to visualize and identify gaps in the diagnostic procedures for different epidemiological scenarios at national level. To fill these gaps, an overview of diagnostic capabilities at national and international level (laboratories and kits providers or manufacturers) as well as the published assays in the scientific literature and the prescribed assays by international institutions and kits providers was carried out. The outcome of this study revealed the usefulness of knowledge mapping as a tool to identify gaps and ultimately gain insight on alternatives for better preparedness and responsiveness. While this exercise was limited to Belgium, we believe this exercise can benefit other countries and thereby enhancing knowledge sharing and collaboration to increase diagnostic capabilities for a common list of (re-) emerging diseases in crisis situation.

Redesigning the serological surveillance program for notifiable avian influenza in Belgian professional poultry holdings.

This study was aimed at redesigning the Belgian active surveillance program for domestic birds in professional poultry holdings based on a risk analysis approach. A stochastic quantitative analysis, combining all data sources, was run to obtain sensitivity estimates for the detection of an infected bird in the different risk groups identified. An optimal number of holdings for each risk group was then estimated on the basis of the different sensitivities obtained. This study proved to be a useful tool for decision makers, providing insight on how to reallocate the total amount of samples to be taken in the coming year(s) in Belgium, thus optimizing the field resources and improving efficiency of disease surveillance such as required by the international standards.

Safety evaluation of adverse events following vaccination with Havrix, Engerix-B or Twinrix during pregnancy.

BACKGROUND: Vaccination of pregnant women against hepatitis A virus (HAV) or hepatitis B virus (HBV) may benefit the mother and the fetus but is not routinely recommended. However, the risk associated with vaccination should be weighed against the risk of HAV or HBV infection. Data on safety profiles after hepatitis A, B or combined AB immunization during pregnancy are limited. METHODS: We searched the GSK Worldwide Safety Database for adverse events (AEs) following immunization of pregnant women with HAV (Havrix, GSK), HBV (Engerix-B, GSK) or the combined hepatitis AB (Twinrix, GSK) vaccine since market authorization through 31 January 2018, covering at least 25 years. AE reports (spontaneous, post-marketing surveillance and clinical trial cases) in the GSK Worldwide Safety Database were identified using a systematic search and were reviewed by clinicians to ascertain pregnancy status at time of vaccination and characterize adverse pregnancy outcomes, including pregnancy-related AEs and AEs in infants regardless of the causality assessment. RESULTS: Overall, 613, 700 and 363 pregnancies with exposure to Havrix, Engerix-B and Twinrix, respectively, were reported. Of these, 378, 339 and 194 were analyzed. The most frequently identified pregnancy outcomes were live infants (288, 223 and 151), spontaneous abortions (43, 57 and 26) and elective terminations (25, 24 and 9). A total of 19, 29 and 10 cases of congenital anomalies were reported. Of these, 17, 20 and 7 were major birth defects. The most commonly reported pregnancy-related AE and AE in infants were premature delivery (28) and jaundice (11), respectively. No maternal deaths were reported. Congenital anomalies were reported in all recorded infant deaths. CONCLUSIONS: This review did not indicate any concerning pattern of adverse pregnancy outcomes following exposure to any of the 3 vaccines during pregnancy.

Effectiveness and cost-benefit study to encourage herd owners in a cost sharing vaccination programme against bluetongue serotype-8 in Belgium.

Bluetongue (BT) is a ruminant viral infectious disease transmitted by Culicoides spp. midges. In 2006, when bluetongue virus serotype 8 (BTV-8) appeared for the first time in Northern Europe, it rapidly spread and infected a large proportion of animals. BThas a significant economic impact due to a direct effect on animal health and to an indirect effect in disrupting international trade of animals and animal products. In spring 2008, a compulsory subsidized vaccination programme in Europe resulted in a drastic decrease in the number of reported cases. However, due to the turn-over of the population, without a continuous vaccination programme, the animal population was becoming progressively susceptible. Vaccination would enable Belgium to maintain its status of freedom from infection of BTV-8 that could possibly be re-introduced. Subsidizing it could be an incentive to convince more farmers to vaccinate. To finance this programme, both decision-makers and stakeholders need to be persuaded by the effectiveness and the cost-benefit of vaccination. The study evaluated the effectiveness of vaccination against BTV-8 in Belgium. The change in serology which has shown the effectiveness of the vaccine to induce antibody production has been significantly associated with the time between the first injection and the sampling date and the number of injections of the primo-vaccination. This study also clearly confirms the benefit of vaccination by reducing economic impact of treatment and production losses, especially in dairy cattle. Based on a participating epidemiological approach, a national voluntary and subsidized vaccination was accepted, and permitted Belgium to vaccinate more than 9,000 herds in 1 month. Because this mass vaccination occurred before the vector season, it probably helped Belgium remain free from BTV-8.

Seroprevalence and risk factors related to small ruminant lentivirus infections in Belgian sheep and goats.

Maedi-Visna virus (MVV) and caprine arthritis encephalitis virus (CAEV) are two prototype members of the group of small ruminant lentiviruses (SRLVs). Both result in progressive and persistent infections of sheep and goats that impact animal health and cause economic losses. In Belgium, the sheep and goat sector is small and consists mostly of hobbyist farmers keeping few animals. A voluntary control program however exists, but less than 2% of the farmers participate to the program. The current lack of SRLV seroprevalence data and knowledge on risk factors related to SRLV seropositivity in this hobbyist sector makes it difficult to evaluate the risk of SRLV transmission from non-certified to SRLV free certified farms. We performed a nationwide SRLV seroprevalence study based on a stratified sampling proportional to the number of sheep and goat holders per province. Randomly selected sheep and goat owners were invited to participate and subject to a short questionnaire to collect information about flock size, animal health condition, age, flock constitution and housing conditions. Samples were collected from maximum 7 animals per farm and tested in a commercial ELISA. In total, we received samples from 87 sheep and 76 goat farms. Sheep flocks showed an overall seroprevalence of 9% (CI 95%: 5-15) and a between-herd seroprevalence of 17% (CI 95%:11-27). Seroprevalence at animal level in goat flocks was 6% (CI 95%: 3-12) and the between-herd seroprevalence was 13% (CI 95%: 7-23). Multiple sheep and goat breeds were found SRLV seropositive. Answers provided during the questionnaire confirmed the mostly hobbyist nature of the sector and showed that more than 65% of sheep and goat farmers had never heard of the disease. The only risk factor found to be related to SRLV seroprevalence was flock size. Herds of more than 10 goats had significantly higher chance to harbor seropositive animals (OR: 4.36; CI: 1.07; 17.73). In conclusion, it was shown that participants to the SRLV free certification program are at risk for reintroduction of the disease in their herds since SRLVs are present on about 15%-20% of non-certified farms. Except from flock size, no clear risk factors were found that are helpfull to identify flocks at risk. Greater effort should be made to inform sheep and goat farmers about the existence and consequences of this disease in order to promote the voluntary control program and further reduce the disease prevalence.

Associations between a decreased veterinary antimicrobial use and resistance in commensal Escherichia coli from Belgian livestock species (2011-2015).

In this study the possible association between antibiotic use and resistance was explored, focusing on commensal Escherichia coli from livestock (veal calves, young beef cattle, pigs and broiler chickens) in Belgium between 2011 and 2015. A continuous decreasing trend in antibiotic use was observed for all classes, except for the phenicols. Antibiotic resistance of commensal E. coli significantly decreased for several of the tested antibiotics in all livestock species. A more rapidly reverted resistance was seen to 3th/4th generation cephalosporins and fluoroquinolones. Moderate to strong correlations between antibiotic use and resistance were found, except for antibiotic resistance to chloramphenicol and gentamicin and the use of the corresponding antibiotic class. Yet, total antibiotic use was positively correlated with chloramphenicol resistance, showing the potential importance of co-selection for chloramphenicol resistance. These results suggest that national antimicrobial usage reduction campaigns have beneficial effects on the overall resistance levels. Analyses were performed on small datasets, though, and care must be taken while making inference. For more detailed analysis, antibiotic use data at an animal species level are required.

Optimising cost-effectiveness of freedom from disease surveillance-Bluetongue Virus Serotype 8 as an example.

The aim of this study was to propose a procedure for optimising the cost-effectiveness of vector borne disease surveillance using a scenario tree model and cost-effectiveness analysis. The surveillance systems for Bluetongue Virus serotype 8 (BTV-8) implemented in Switzerland and Belgium were used as examples. In twenty four different, simulated population structures, passive surveillance and five designs of active surveillance were investigated. The influence of surveillance system design and parameters such as farmer disease awareness, veterinary disease awareness, herd and within-herd design prevalence on the overall surveillance system sensitivity were assessed. Furthermore, the cost-effectiveness of mandatory and voluntary vaccination regimes in relation to disease surveillance was investigated. Under the assumption that BTV-8 manifests clinically, freedom from disease in a population can be established with almost certainty over the period of one year using clinical surveillance alone. Additional investment in active surveillance would therefore economically only be justified, if no clinical manifestation is suspected or other surveillance objectives are to be provided such as early detection. The best cost-effectiveness is obtained by sampling more herds rather than more animals within a herd. Mandatory vaccination reduces the cost of surveillance by 0.26 € per vaccine and voluntary vaccination only marginally reduces the cost of risk-based surveillance, by reducing the population at risk. Finally, in populations with predominantly dairy cattle, bulk-tank milk testing is the method of choice to actively demonstrate freedom from disease.