VPH TADtalk Boehringer Ingelheim Veterinary Public Health Scientific newsletter on Transboundary Animal Diseases September 2024, Issue 2
The General Session of the World Organization of Animal Health (WOAH)
One Health: French farmers facing
the epizootic haemorrhagic disease
Can we improve our preparedness against Culicoides -borne diseases using atmospheric dispersion model?
Life forward
Summary Editorial
News
• One Health: French farmers facing the Epizootic Haemorrhagic Disease (EHD) • Transforming lives for generations in Animal Health: Stop Rabies Initiative
Scientific corner
• A new approach to Foot-and-Mouth Disease (FMD) serotype C: towards establishing extinction • Post Vaccination Monitoring (PVM): a win-win approach for enhancing FMD control strategies • Can we improve our preparedness against Culicoides -borne diseases using atmospheric dispersion model? • Asian flu outbreak (H5N1) in cattle in the USA
Press review section
• Press review editorial • List of recent publications
Events
• 50 th COSALFA meeting at Rio de Janeiro, Brazil - May 2024 • The General Session of the World Organization of Animal Health (WOAH) • 3 rd joint conference of the AITVM-STVM (Association of Institutions for Tropical Veterinary Medicine & Society for Tropical Veterinary Medicine) • openFMD: Revolutionizing Global Epidemiological Intelligence of FMD
Meet the VPH team
• Meet our Head of Technical Services at VPH: Dr Pascal Hudelet
Future agenda
Editorial Dear Reader,
We have all witnessed in the past twenty years the rise of severe infectious diseases outbreaks, in humans and animals, with devastating social and economic impacts worldwide. These diseases, which respect no borders, require collaboration, innovation, and constant vigilance to ensure the well-being of livestock, humans, and the global economy. As a global leader in Veterinary Public Health, Boehringer Ingelheim remains steadfast in its commitment to advancing animal health and addressing the growing challenges posed by Transboundary Animal Diseases (TADs). In this second issue of the VPH TADtalk newsletter, several topics illustrate the notion that we can “expect the unexpected” from infectious diseases. FMD continues to be a major threat to livestock industries worldwide. For once, this edition features a story demonstrating that some diseases can be eradicated, as illustrated by FMD serotype C, for which the goal is to prove its extinction. Such advancements underscore the importance of sustained global surveillance and preparedness, critical to mitigating the risk of serotype emergence in non-endemic regions. With FMD our efforts go beyond research; through initiatives like Post-Vaccination Monitoring (PVM), we are enhancing the effectiveness of FMD vaccination campaigns globally. PVM is more than just a technical exercise – it is a win-win strategy that ensures the best use of resources and provides crucial insights to optimize vaccination outcomes, benefiting both the health of animals and the economic stability of the regions affected. The growing incidence of Culicoides-borne diseases such as EHDV (Epizootic Hemorrhagic Disease Virus) and BTV (Blue Tongue Virus), exacerbated by climate change, presents another pressing challenge. In response, Boehringer Ingelheim, in collaboration with leading academic partners, has pioneered the use of atmospheric dispersion models to predict and mitigate the spread of these diseases. Our survey on EHDV in France and our recent article on harnessing the power of a wind-model shown in this issue are excellent examples of how we strive to collect valuable insights into disease spread, helping veterinary and agricultural stakeholders prepare more effectively for future outbreaks. At the heart of our strategy is collaboration. Whether through partnerships with international organizations like the World Organisation for Animal Health (WOAH) or by working directly with farmers and local veterinary authorities, our efforts are grounded in the belief that solving these global challenges requires joint action. This philosophy is embodied in our commitment to the Stop Rabies initiative, which combines education, vaccination, and surveillance to combat one of the deadliest zoonotic diseases globally. As we look ahead, we remain focused on driving sustainable impact across all facets of Veterinary Public Health. Our work aligns closely with the United Nations’ Sustainable Development Goals (SDGs), particularly in promoting health, improving food security, and supporting the livelihoods of those who depend on agriculture and livestock. In this edition of VPH TADtalk, we invite you to explore the latest research, success stories, and innovative strategies that define our shared journey. Together, we can build a healthier, more resilient future for both animals and humans.
Dr Pascal HUDELET Head of Technical Services, Veterinary Public Health Center
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News
One Health: French farmers facing the Epizootic Haemorrhagic Disease (EHD)
Dr Hajar Boutayeur Technical Officer Veterinary Public Health Center
Dr Guillaume Convert VPH Technical Service Director Veterinary Public Health Center Boehringer Ingelheim Animal Health
Dr Albert Picado de Puig Principal Scientist Animal Health Global innovation
Emergence of Epizootic Hemorrhagic Disease in Europe: A One Health Challenge Epizootic Hemorrhagic Disease (EHD) is a vector- borne, viral illness impacting both domestic and wild ruminants. Recognized as a notifiable disease by the World Organisation for Animal Health (WOAH) since 2008, EHD virus (EHDV) belongs to the Reoviridae family, genus Orbivirus, sharing structural similarities with Blue Tongue Virus (BTV), African Horse Sickness (AHS) and Equine Encephalosis Virus (EEV).
vectors are found. Previously, the disease was known to be transmitted by tropical midges like Culicoides imicola, but transmission patterns have likely shifted due to environmental changes such as global warming. In Europe, EHD has been detected in regions where other vectors, such as C. obsoletus and C. scoticus , are present. This indicates a change in vector competence, suggesting that Northern European Culicoides species can now transmit the disease. EHDV serotype 8 (EHDV-8), initially confined to Australia until detected in Tunisia in 2021, was reported in Europe for the first time in 2022 with outbreaks in Sardinia, Sicily, Spain and Portugal. In France, the first EHD outbreaks were reported in September 2023 on cattle farms in the southwest. This has since escalated into a major veterinary and agricultural challenge, with more than 4000 outbreaks recorded across 20 departments as of July 2024. Control measures are enforced within a 150 km radius of detected outbreaks.
First identified in the USA in 1955, EHD has since spread globally, with at least seven known serotypes. While the disease was mostly pathogenic in wild ruminants in the USA, outbreaks of other EHDV variants/serotypes reported in Asia (EHDV serotype 2 in Japan known as the Ibaraki disease), in the middle east (EHDV serotype7 in Israel, EHDV serotype 6 in Turkey and Oman) and in north of Africa (EHDV serotype 6 in Tunisia, Morocco, Algeria) were associated with clinical signs in domestic cattle. EHD is transmitted by adult female species of Culicoides biting midges, meaning its spread is inherently restricted to areas where these competent
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The One Health Implications of EHD : The spread of EHD in France underscores the interconnectedness of animal health, human well- being, economics, and environmental factors: • Animal Health: EHD can cause severe illness and mortality in cattle, compromising livestock productivity and welfare. • Economic Impact: Outbreaks lead to substantial financial losses for farmers due to decreased milk and meat production, increased veterinary costs, and potential trade restrictions.
• Environmental Factors: Midges that spread EHD are influenced by environmental conditions like temperature and wind, and mutations in the virus can make the spread and the impact of the disease worse. • Human Activities: Farmers experience significant psychological stress due to the outbreak. The suffering of animals, the financial pressure, and the challenge of managing sick livestock without being able to prevent the disease can lead to mental health issues and feelings of failure.
A recent survey among French farmers aimed to assess their perception of EHD’s impact and their willingness to vaccinate cattle. The survey covered three regions: A) Regions with no virus circulation B) Regions with sporadic cases within the regulated zone C)Endemic regions in the southwest of France.
Figure 1: Mapping of the EHD regulated zone based on outbreaks in the southwest as of 4 July 2024. Region A, B and C are represented by the green, yellow and red pins, respectively.
We received 61 responses from the three regions: 26% from region A, 63% from region B, and 11% from region C. The low number of responses from endemic regions could possibly be due to the trauma experienced by local stakeholders (veterinarians and farmers) during the last EHD outbreak. Farmers exhibited a good understanding of EHD and its epidemiology, and they are using reliable information channels. Farmers across all three regions recognized the severity of EHD for animal health. In regions with sporadic cases within the regulated zone (Region B), farmers viewed the economic impact as quite severe to very severe. This was attributed to animal movement restrictions, which limit their ability to trade and move livestock freely. Consequently, farmers in these areas experience
significant psychological distress due to the lack of effective control measures, increased workload, reduced income, and a bleak outlook for the future. Across all regions, 62% of farmers expressed willingness to vaccinate. According to the respondents, the most important aspects of the vaccine are efficacy, duration of protection, and cost. To conclude, a One Health approach is crucial to manage EHD in France as it requires a comprehensive and collaborative approach involving public institutions, the pharmaceutical industry, veterinarians, farmers and institutions providing mental health support to farmers. As we consider the way forward, it is important to consider how can we ensure fair distribution of vaccination responsibilities among stakeholders.
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Transforming lives for generations in Animal Health: Stop Rabies Initiative
Dr Serena Shunmugam Junior Marketing Manager Veterinary Public Health Center Boehringer Ingelheim Animal Health
Mi-Kyung Lee-Lange Communications Lead Boehringer Ingelheim Animal Health
Dr Thais Vila Rabies Franchise Manager & Project Leader Boehringer Ingelheim Animal Health
Boehringer Ingelheim’s global sustainability framework - Sustainable Development for Generations - takes a holistic approach and is based on three pillars – MORE HEALTH, MORE POTENTIAL and MORE GREEN. It reflects our commitment
to human and animal health, to our people and communities, and health to the planet. Within this framework we have defined commitments 2030, which are in alignment with the United Nations Sustainable Development Goals (SDGs).
Our Sustainable Development for Generations framework translate our sustainability commitments to transform lives for generations
3 Pillars
6 impact aeras
Our 2030 commitments
Contributing to UN SDGs
MORE HEALTH Good Health for People and Animals
• Access to healthcare • Address unmet needs in non-communicable diseases • Combat infectious diseases in human and animal health • Contribute to food security and safety
• Expand access to healthcare for 50 million people in underserved communities • Invest EUR 35 billion in health innovation to tackle non-communicable disease • Invest EUR 250 million in partnership to combat emerging infectious diseases
MORE POTENTIAL Good Health for Communities and our People
• Co-create healthy, inclusive and sustainable communities
• Impact 50 million people in underserved communities by empowering our employees, partners and social entrepreneurs • Intensify efforts in the areas of human rights, ethics, employee health and wellbeing, people development and diversify, equity & inclusion
MORE GREEN Good Health for the Planet
• Care for our environment
• Protect clean water and further reduce water footprint in all communities we operate in • Become carbone neutral in our operations and halve natural resources footprint across value chain
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This article delves into the three animal-health-specific programs of the Sustainable Development for Generation framework: Stop Rabies, Nagana and our advances in parasitology
In this issue, we focus on the ‘Stop Rabies’ initiative:
3 things we do
Stop rabies
Nagana (Sleeping sickness)
Advance in Parasitology
Challenge
There are 60,000 worldwide from rabies on an annual basis, most of whom are children, and all of which are preventable Contribute to UN Zero-by-30 goal through increased education, vaccination and surveillance
$4 billion annual negative GDP impact on 36 nations, millions of smallholders
Public, political and regulatory scrutiny of pet parasiticides is increasing
Ambition
To develop a breakthrough solution that mineralises?
We have 10 sustainable development ambitions in pet parasitology
Impact
To save ≈ 2,000 human lives each year
To improve the livelihoods of hundred of thousands of families by 40-60%
To improve efficacy and our environmental profile
Stop Rabies: A Global Initiative Rabies still kills thousands of people every year. It is common in more than 150 countries, and 40% of victims are children in Asia and Africa. However, rabies is 100% vaccine preventable. Our Stop Rabies program has been launched to reinforce our mission to improve the health of both animals and humans worldwide.
We believe that, together with health authorities, governments, NGOs, and pet owners, we can achieve sustainable impact by focusing on three pillars: vaccination, education, and surveillance.
Vaccination
Education
Surveillance
Providing high quality vaccines and sharing best practices for dog vaccination campaigs
Building greater awarness and knowledge of rabies and dog bite prevention in communities
Monitoring dog vaccination, dog bites, and rabies cases, using tools developed by Global Alliance for Rabies Control (GARC)
Over 1.5 billion doses of rabies vaccines have been delivered worldwide in the past 20 years. To date, through collaboration with the Global Alliance for Rabies Control (GARC) and local partners, contributions have been made to implement of dog vaccination programs across Indonesia, Kenya, Malaysia, Philippines, South Africa, Thailand, and Vietnam. For education, the target is to reach one million children per year around the world by educating them about rabies and how to live harmoniously alongside dogs, with initiatives already underway in the Philippines, Ghana, Kenya, Malaysia, South Africa, Thailand, Vietnam and Ecuador. Surveillance is an important element of all on-the-ground efforts to ensure the desired impact is being made.
References: World Health Organization (WHO). Rabies Fact Sheet. Available at: https://www.who.int/news-room/ fact-sheets/detail/rabies.
World Health Organization (WHO), Food and Agriculture Organization of the United Nations (FAO) and World Organization for Animal Health (WOAH). Zero by 30: the global strategic plan to end human deaths from dog-mediated rabies by 2030. Available at: https:// www.who.int/publications/i/ item/9789241513838.
Centers for Disease control and Prevention. Rabies around the World. Available at: https://www.cdc.gov/ rabies/location/world/index.html.
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Local collaboration initiatives to support national strategic plans for rabies elimination
Vietnam: A Collaborative Effort to Stop Rabies In Vietnam, rabies kills more than 70 people per year and most rabies cases in the country are caused by rabid dog bites (WHO | World Health Organization). By collaborating since 2021 with the People’s Committee of Duc Hue District, Long An Province and Nong Lam University to provide free vaccination for dogs and cats, vaccine coverage has exceeded 70%; together with veterinary students from Nong Lam University, a rabies and dog bite education program was conducted for school children in Duc Hue District. Bringing together experts and representatives from the Department of Animal Health, the Ministry of Agriculture and Rural Development, Nong Lam University and Boehringer Ingelheim Vietnam, a roundtable discussion, held in 2024, focused on enhancing rabies prevention measures and fostering collaboration between public and private sectors across Vietnam. Boehringer Ingelheim Vietnam will continue to join hands with the Long An Province community to pursue a rabies-free status by 2025.
Phillipines: A coalition for rabies awareness In Puerto Galera in the Philippines, a program utilizing a 3-pronged approach that comprises an Information & Education Campaign (IEC), animal rabies vaccination, and spay & castrate initiatives began in 2022. The mission was made possible through the alliance of volunteer veterinarians and para-veterinarians from Marinduque, Oriental and Occidental Mindoro representing the MIMAROPA OTBT (One Time Big Time) Project, the Barangay Health Workers (BHW) and Local Government Unit (LGU) of Puerto Galera, the Rural Health Unit (RHU) of the Department Of Health (DOH), GARC (Global Alliance for Rabies Control), and Boehringer Ingelheim. The coalition created a unified approach in raising awareness about rabies elimination by educating and reinforcing public knowledge about the disease and more importantly, sustaining the animal rabies vaccination efforts in Puerto Galera.
Representatives from the Department of Animal Health, the Ministry of Agriculture and Rural Development, Nong Lam University and Boehringer Ingelheim Vietnam at the ‘Joining Hands to Eliminate Rabies’ roundtable discussion, 20 April 2024.
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Dr Leonard Kibet, Veterinarian, child instruction in Kenya, July 2023.
Educating children in Kenya Children, given their smaller stature and increased likelihood to play with dogs, are disproportionately affected by rabies, which is always fatal after the onset of symptoms. The Boehringer Ingelheim Stop Rabies program has begun support of the Mara North Conservancy Dog Project to provide rabies and dog bite education to school children in rural southwestern Kenya. The aim of the initiative is to increase community awareness and knowledge of rabies, dog behavior, how to prevent dog bites, and what to do when bitten, by educating school children and their family members in rural Kenya. The program consists of a 1-hour interactive training session given by 2 veterinary professionals, one veterinarian and one veterinary technician, to school children aged between 5 and 16. These professionals have delivered more than 334 training sessions in Bomet county and 380 in Narok county including a few health professional and students, but mainly targeting children. Thanks to this program, over 129 000 children have been educated since the end of 2022 which, represents about 20% of the child population in this area.
Last mile delivery challenges were numerous (geographic distance, roads and small school size), but the initiative was successful thanks to the good collaboration between all key stakeholders including the County Director of Veterinary Services, County Director of Health Services and Chiefs of municipalities. Participants understood the need for implementing dog vaccination campaigns. They particularly appreciated benefits brought not only to the learners themselves but to the wider community. Through these initiatives, the company is making significant strides and demonstrating its unwavering commitment to animal health and welfare. For Veterinary Public Health Key Opinion Leaders, these initiatives offer valuable insights into the untapped potential of collaborative, innovative and holistic approaches to tackling some of the most pressing challenges in animal health.
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Scientific corner
A new approach to foot-and-mouth disease serotype C: towards establishing extinction
Dr Cédric Dézier VPH Technical Service Director Veterinary Public Health Center
Current evidence and risk assessment The taskforce has been analyzing surveillance data from the WRLFMD and the Network, spanning from 1942 to 2021. The risk assessment process involves making certain epidemiological assumptions, such as the equal risk of introduction for serotype C across years. It also uses three detection prevalence thresholds (1%, 2%, and 5%) to test the 95% probability of detecting serotype C. Preliminary results support the claim of serotype C extinction in all seven pools when data is unstratified by year and country. However, when looking at specific countries without considering the year, the evidence becomes less well supported. Many countries do not reach the 95% probability at the different prevalence thresholds. Challenges and future directions Proving the extinction of a disease serotype is a complex task. It requires comprehensive and continuous surveillance, as well as robust data analysis. The limitations of current data and the need for more extensive surveillance are challenges that need to be addressed.
Foot-and-mouth disease (FMD) is a highly contagious viral disease affecting cloven-hoofed animals, with severe implications for livestock industries worldwide. Among the seven serotypes of FMD, serotype C has not been detected since 2004, leading to speculation about its extinction. A new initiative by the Food and Agriculture Organization (FAO) and the World Organisation for Animal Health (WOAH) aims to substantiate this claim, marking a significant shift in our approach to managing this disease. The taskforce and its phases In 2022, a taskforce comprising members from FAO, WOAH, and the World Reference Laboratory for Foot and Mouth Disease (WRLFMD) has been established to spearhead this initiative. The taskforce’s work is divided into two phases. The first phase involves gathering evidence and measuring the risk associated with serotype C. The second phase focuses on reducing this risk, if any, and maintaining preparedness for potential outbreaks.
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To reduce risk laboratory and maintain preparedness, efforts are underway to improve training infrastructure and enhance national lab capacity for transboundary animal diseases diagnosis. Global surveillance is also being enhanced through funding to ANSES and IZSLER for sample collection, shipment, and data analysis. Research projects supported under the EU’s 10 th Fund for Applied Research (FAR) call are also contributing to these efforts. Conclusion Establishing the extinction of FMD serotype C is a significant milestone in disease control strategies. However, it also underscores the need for continued vigilance, research, and preparedness. As we move forward, the lessons learned from this initiative will undoubtedly inform our approach to managing other FMD serotypes and similar diseases.
1. Gathering evidence and measuring risk (2021-2022)
2. Reducing risks and maintaining preparedness (2023-2026)
Estimate confidence FMD-C is no longer circulating
Gather information regarding location and use of FMD-C materials
Activities to reduce risk of re-introduction
Promote contingency planning for FMD-C outbreaks
Communication & outreach with stakeholders
Figure 1: The FAO and WOAH task force activities towards establishing serotype extinction.
Source: WOAH-FAO FMD Ref Lab Network Report 2022.pdf (foot-and-mouth.org) https://foot-and-mouth.org/sites/foot/files/user-files/research-paper/pdf/11-23/WOAH-FAO%20FMD%20 Ref%20Lab%20Network%20Report%202022.pdf
Figure 2: Geographic and temporal distribution of historical FMDV serotype C events The map provides the most likely timing and spatial directionality of the historical events attributed to serotype C by examining historical information on outbreaks, the genetic relationship between sampled isolates and the results generated by the phylogeographic analysis. Reference: https://www.researchgate.net/publication/350214767_The_history_of_foot-and-mouth_disease_virus_serotype_C_ the_first_known_extinct_serotype#fullTextFileContent
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Post Vaccination Monitoring (PVM): a win-win approach for enhancing FMD control strategies
Amélie Poulard Clinical Trials manager Veterinary Public Health Center
Dr Nicolas Denormandie Technical Service Director Veterinary Public Health Center
“Post-vaccination monitoring (PVM) is necessary to optimise the vaccination regimen and programme and the use of limited resources in attaining expected objectives. […] Demonstrating the impact of vaccination programmes on the disease burden helps to justify the vaccination cost, while identification of weaknesses in the vaccination programme enables improvements to be put in place.” This quotation illustrates the reasoning behind the creation of - The World Organisation for Animal Health WOAH/FAO guidelines for “Foot and mouth disease (FMD) vaccination and Post-vaccination monitoring (PVM).
PVM is process of an evaluation and monitoring conducted to meet diverse and specific objectives. These include assessing the efficacy of vaccine formulations, managing the logistics of vaccination campaigns, monitoring serological responses to vaccination, evaluating vaccination effectiveness during outbreaks, and gauging the success of the program in reducing virus circulation. This comprehensive approach contributes to the sustainable control of FMD at both farm and regional levels, whether in public or private sectors. The primary stakeholders in this process can be categorized into two principal groups. The first group comprises decision-makers who are tasked with clearly defining the objectives and allocating adequate resources. The second group consists of scientists who are responsible for devising appropriate methodologies that align with the defined objectives.
PVM is often narrowly associated with serological monitoring. However, the scope of PVM extends far beyond the mere assessment of vaccine effectiveness or efficacy. The primary concern of national veterinary departments lies in addressing the challenges posed by the vaccine, rather than merely the actions associated with its administration. Nevertheless, the evaluation of vaccination coverage remains a critical component of the process. The true value of PVM is derived from the integration of both vaccination coverage data and serological monitoring information.
Post Vaccination serological Monitoring
Reliable Assessment of vaccination coverage
National vet Services
Figure 1: The success of PVM relies on reliable assessment of vaccination coverage held by National vet authorities.
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Boehringer Ingelheim VPH is home to one of the few laboratories equipped to handle FMD viruses. It demonstrates technical proficiency in Virus Neutralizing Tests (VNTs), as well as epidemiological and technical field trial expertise to address inquiries related to PVM. A medium-scale controlled field trial employing a protection-correlated method such as VNT is more valuable than a large-scale field trial using a poorly protection-correlated method like ELISA, even when extrapolating findings to a larger population (Figure 2). In other words, conducting a PVM with a smaller number of animals via a VNT-based study carries more weight than a study involving a larger number of animals using a poorly correlated method such as ELISA. However, both methods have their respective advantages and disadvantages, which should be carefully considered when planning a PVM (Figure 2).
Which type of trial for PVM?
100-500
30-60
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Small scale
Medium scale
Large scale
EXPERIMENTAL TRIAL • Experimental unit • Homogeneous group of animals (animal segment, age, breed...) • Full control
CONTROLLED FIELD TRIAL • One or few farm(s) • Homogeneous group of animals (animal segment, age, breed...) and recorded • Vaccination controlled
FIELD TRIAL • Several farms
• Heterogeneous groups of animals (animal segment, age, breed...) preferably recorded
• Vaccination recorded (not fully controlled…)
Real life. Potential of a vaccine in the field, in normal conditions. Risks of interfering events
Not real life. Assess best potential of a vaccine
Close to real life. Potential of a vaccine in the field, in good condition
Efficacy of vaccine
Effectiveness of vaccination campaign
Figure 2: PVMs can consist of experimental, controlled field trial or field trial and is largely dependent on the size of the tested population. It can be directly correlated to vaccine efficacy in small scale trials and effectiveness of a vaccination campaign in larger-scale trials.
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Serological tests depend on available resources
ELISA
VNT
VNT
ELISA
PROS
• Best correlated with protection • Quantitative
• No BSL3 needed • Low expertise • Cheap • Quick
CONS
• BSL3 lab containment • High expertise • Expensive (~50€/test) • Time consuming (10 days)
• Poorly correlated with protection • Qualitative or semi-quantitative
Figure 2: There are two types of tests to dose FMD antibodies: namely viral neutralizing tests (VNTs) and enzyme-linked immune substrate assays (ELISAs), both with their respective advantages and disadvantages. A small trial using VNT is more valuable than a larger using ELISA, to extend the findings to a larger population.
Our Veterinary Public Health (VPH) approach does not propose a one-size-fits-all protocol applicable to all customers. Instead, each PVM project is a bespoke field trial, adjusted according to the specific context and objectives. This PVM approach, which we share with our customers, can offer insights into the immune status of animals at the time of booster vaccination. It can also can assess the level of Maternally Derived Antibodies (MDA) without interfering with the primary vaccination in young animals. Finally, PVM can evaluate the effectiveness of a vaccination schedule by assessing the Onset of Immunity (OOI) and/or Duration of Immunity (DOI). The insights gained from PVM allow Boehringer Ingelheim to augment its technical expertise about the effectiveness of FMD vaccines under real- world conditions. This knowledge empowers us to implement corrective actions and improvements to field technical recommendations.
For example, some PVM findings in a cattle farm using FMD vaccines demonstrated that the level of FMD immunity in adult cows was sufficient in controlling the spread of the virus and limiting clinical disease. However, it was noted that calves may be more susceptible due to the heterogeneity of MDA levels and their interference with active immunity. Recommendations suggested adjusting the vaccination program for calves, not only to protect them from the disease, but also to prevent them from potentially spreading the infection within the herd in the event of an outbreak. The trust and proximity afforded by customers in implementing the PVM allows Boehringer Ingelheim to stay abreast of epidemiological and field health practices in the fight against FMD, providing a combination of tailor-made premium vaccines and technical advice
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Can we improve our preparedness against Culicoides -borne diseases using atmospheric dispersion model?
Amandine Bibard PhD Fellow in Epidemiology, Animal health Global Innovation
Europe faces regular introductions and re-introductions of Culicoides -borne diseases, most recently exemplified by the first introduction of the Epizootic Hemorrhagic Disease Virus (EHDV) in Europe in 2022 and the recent incursion of Bluetongue Virus (BTV) serotype 3 in the Netherlands. Both hemorrhagic fevers are recognized as global veterinary and public health concerns due to their economical and animal health impact.
Several routes of virus introduction have been imputed solely or in combination: import of live animals through legal or illegal trade, import of germplast (semen and/or embryos), movement of wild animals, airborne dispersion of vectors, import of immature stages of vectors or use of poorly attenuated modified live vaccines. While the long- distance wind dispersal of the disease virus vector, Culicoides spp., is recognized as a virus introduction pathway, it remains understudied in risk assessments. On the other hand, evidence of long-distance wind dispersion of Culicoides spp. has been shown for up to 700 km and 500 km over sea (Ducheyne et al. , 2011; D. Eagles et al. , 2012; Debbie Eagles et al. , 2014) and over land (García-Lastra et al. , 2012) respectively, under suitable conditions. Although considered important, the windborne dispersal of insects is extremely challenging to monitor since it is technically unfeasible to sample large volumes of air at the needed frequency, while predicting potential dispersal can only rely on modelling approaches based on atmospheric simulations. In recent years, the use of atmospheric dispersion models to mimic the atmospheric trajectories of flying vectors has been on the rise. Among these, HYSPLIT (Stein et al. , 2015), an open-source model originally developed
to simulate the trajectories of inert particles in the atmosphere, has been increasingly used to assess dispersal of fungus spores (Radici et al. , 2022), Culicoides spp. (Aguilar-Vega et al. , 2019; Debbie Eagles et al. , 2014; Jacquet et al. , 2016) and other flying insect (Hall et al. , 2022). Boehringer Ingelheim and academic partners developed a wind connectivity matrix, based on simulations from HYSPLIT model that has been adapted to Culicoides survival conditions (temperature, altitude, duration of flight), to evaluate when and how often two locations anywhere in Europe could be connected by the wind. A recent application of this methodology for EHDV- 8 in France showed that we predicted with good sensitivity the newly EHDV-infected areas in the south-west of France over a period of 5 weeks after its first introduction in the country. The predicted zone in France (excluding the source locations) captured 99.9% of the emerging outbreaks (Figure 1). However, 23.1% of EHDV outbreaks also occurred in low-risk areas, mostly at source sites, demonstrating that our model should be used primarily to estimate long-range dispersal, not short-range dispersal.
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Figure 1: Spatial overlay between risk predictions H j (Z 1 ,T 5 )
, the daily probability averaged over 5 weeks from week 37 to week 41) and
the 186 EHDV outbreaks emerging within the same period of time in France. H j (Z 1 ,T 5 ) outbreaks started in France in week 36, and the meteorological conditions of 2023.
is computed here considering the first 3 EHDV
Looking forward from the whole of the EHDV infected area in December 2023, we predict that the midges dispersal zone in early 2024 could expand to cover most of the western half of France (Figure 2). The south- eastern quarter of France was not exposed to a risk, probably due to the Massif central acting as an orographic barrier, similarly to the role played by the Pyrenees in the South. The dispersal zone could also sporadically reach free countries despite their long distance from the source, both over vast bodies of water (such as UK and Ireland towards north, and the Balearics and continental Italy towards south) and over land (such as Belgium, Germany, and the Netherlands). However, those events could be considered rare and highly dependent on meteorological conditions.
Figure 2: Spatial distribution of H j (Z April) of long-distance dispersal. H j (Z France and the 4-year period 2020-2023.
2 ,T 5 ) , the daily probability averaged over 5 weeks ( T 5 - from W11 to W15; from mid-March to mid- 2 ,T 5 ) is computed here considering the whole EHDV-infected area at early December 2023 in
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Globally, the wind dispersal zones followed a preferred direction from south to north/northwest, influenced by wind direction, wind speed, topography, and temperature. This highlights the anisotropic nature of the wind, which contrasts with the usual radius surveillance zone established around infected outbreaks. The extent of the predicted risk zone exceeded the usual 150 km distance to the north and was more limited to the south. In conclusion, despite limitations and high uncertainties in future meteorological conditions, the model provides valuable insights into precise risk zones of dispersal adapted to local environmental conditions on a European scale. These findings can be used to raise awareness and guide future risk assessment frameworks, making them a useful tool for the management and prevention of future Culicoides -borne virus outbreaks.
References:
Aguilar-Vega, C., Fernández-Carrión, E. and Sánchez- Vizcaíno, J. M. (2019). The possible route of introduction of bluetongue virus serotype 3 into Sicily by windborne transportation of infected Culicoides spp. Transboundary and Emerging Diseases, 66(4), 1665–1673. https://doi.org/10.1111/tbed.13201 Ducheyne, E., Lange, M., Stede, Y. V. der, Meroc, E., Durand, B. and Hendrickx, G. (2011). A stochastic predictive model for the natural spread of bluetongue. Preventive Veterinary Medicine, 99(1), 48–59. https://doi.org/10.1016/j.prevetmed.2011.01.003 Eagles, D., Deveson, T., Walker, P. J., Zalucki, M. P. and Durr, P. (2012). Evaluation of long-distance dispersal of Culicoides midges into northern Australia using a migration model. Medical and Veterinary Entomology, 26(3), 334–340. https://doi.org/10.1111/j.1365-2915.2011.01005.x Eagles, Debbie, Melville, L., Weir, R., Davis, S., Bellis, G., Zalucki, M. P., Walker, P. J. and Durr, P. A. (2014). Long- distance aerial dispersal modelling of Culicoides biting midges: case studies of incursions into Australia. BMC Veterinary Research, 10(1), 135. https://doi.org/10.1186/1746-6148-10-135 García-Lastra, R., Leginagoikoa, I., Plazaola, J. M., Ocabo, B., Aduriz, G., Nunes, T. and Juste, R. A. (2012). Bluetongue Virus Serotype 1 Outbreak in the Basque Country (Northern Spain) 2007–2008. Data Support a Primary Vector Windborne Transport. PLoS ONE, 7(3), e34421. https://doi.org/10.1371/journal.pone.0034421
Hall, D. R., Torpy, J., Nye, R., Emma and Cowled, B. (2022). Quantitative risk assessment for the introduction of lumpy skin disease virus into Australia via non-regulated pathways. CABI Compendium, CABI Compendium https://doi.org/10.1079/cabicompendium.76779 Jacquet, S., Huber, K., Pagès, N., Talavera, S., Burgin, L. E., Carpenter, S., Sanders, C., Dicko, A. H., Djerbal, M., Goffredo, M., Lhor, Y., Lucientes, J., Miranda-Chueca, M. A., Fonseca, I. P. D., Ramilo, D. W., Setier-Rio, M.-L., Bouyer, J., Chevillon, C., Balenghien, T., … Garros, C. (2016). Range expansion of the Bluetongue vector, Culicoides imicola, in continental France likely due to rare wind-transport
events. Scientific Reports, 6(1), 27247. https://doi.org/10.1038/srep27247
Radici, A., Martinetti, D. and Bevacqua, D. (2022). Early- detection surveillance for stem rust of wheat: insights from a global epidemic network based on airborne connectivity and host phenology. Environmental Research Letters, 17(6), 064045. https://doi.org/10.1088/1748-9326/ac73aa Stein, A. F., Draxler, R. R., Rolph, G. D., Stunder, B. J. B., Cohen, M. D. and Ngan, F. (2015). NOAA’s HYSPLIT Atmospheric Transport and Dispersion Modeling System. Bulletin of the American Meteorological Society, 96(12), 2059–2077. https://doi.org/10.1175/bams-d-14-00110.1
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H5N1 in cattle in the USA
Dr Albert Picado de Puig Principal Scientist Animal Health Global innovation
In January 2024, a mystery illness began affecting dairy cows in Texas. The affected cattle exhibited flu-like symptoms like fever and thick and discolored milk. The illness impacted nearly 10% of the animals in the affected herds, causing reduced feed consumption and up to 20% decline in milk production. Despite the significant impact of this illness, the causative agent remained unidentified for several weeks. It was not until March 25, 2024, that the pathogen responsible for this illness was identified as the H5N1 virus, also known as avian influenza virus or bird flu 1 . By then, cases were reported in several states in the USA. This marked a significant change in the epidemiology of this disease, as the detection of H5N1 in cattle was never before reported. H5N1 is a type of influenza virus that primarily affects birds but can also infect various mammals, including humans. H5N1 was first reported in domestic waterfowl in Southern China in 1996. Since then, it has spread across the globe and has caused the deaths of millions of birds and it has been reported in multiple mammals including cats, pigs, coyotes, and marine mammals such as sea lions causing thousands of deaths in some of these species. The identification of H5N1 in cattle has raised concerns among public health officials and the agricultural industry due to the potential implications for both human and animal health as well as the economy. It represents an expansion of the host range of the virus, which increases the risk of human exposure, especially among those who have close contact with infected cattle, such as farmers and veterinarians. The presence of H5N1 in a new host species could potentially facilitate the emergence of a new, more dangerous strain of the virus. Finally, the detection of H5N1 in cattle could have significant implications for food safety, particularly in relation to dairy products. The risk has been mainly associated with high viral loads in raw milk. However, pasteurization, a process that involves heating milk to a specific temperature for a set period of time, has been found to be effective in destroying the H5N1 virus. This process is a standard safety measure in the dairy industry and is crucial in preventing the spread of pathogens. To date (12 th July 2024) 146 herds in 12 states have been infected by H5N1 avian influenza according to the US Department of Agriculture (USDA) (Figure 1) 2 . Four human cases of H5N1 virus infection have been reported in people exposed to sick cows 3 . All cases showed mild symptoms and the CDC continues to believe that the overall risk to human health associated with the ongoing outbreaks of H5N1 viruses remains low. Surveillance and control measures have been put in place to limit the spread of H5N1 in cattle herds and to protect people at
higher risk of exposure (e.g. farm workers, veterinarians) and the general public. A program to test dairy cattle and milk has been put in place. In conclusion, the recent identification of H5N1 in cattle in the USA underscores the need for ongoing surveillance of influenza viruses in both humans and animals, as well as the importance of implementing effective measures to prevent the spread of the virus and protect public health.
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Figure 1: H5N1 confirmed cases in livestock herds in the USA (12th July 2024). Source: USDA.
References: 1. Federal and State Veterinary, Public Health Agencies Share Update on HPAI Detection in Kansas, Texas Dairy Herds | Animal and Plant Health Inspection Service (usda.gov) https://www.aphis.usda.gov/news/agency- announcements/federal-state-veterinary-public- health-agencies-share-update-hpai 2. HPAI Confirmed Cases in Livestock | Animal and Plant Health Inspection Service (usda.gov) https://www.aphis.usda.gov/livestock-poultry- disease/avian/avian-influenza/hpai-detections/ hpai-confirmed-cases-livestock 3. CDC Reports Fourth Human Case of H5 Bird Flu Tied to Dairy Cow Outbreak | CDC Online Newsroom | CDC https://www.cdc.gov/media/releases/2024/p- 0703-4th-human-case-h5.html
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Press review section
Transboundary Animal Diseases (TADs) continue to pose significant threats to global livestock health. The research from the first half of this year has made significant strides in understanding disease mechanisms, improving diagnostic techniques, and developing effective vaccines for diseases such as Bluetongue Virus (BTV), Foot-and-Mouth Disease Virus (FMDV), and Peste des Petits Ruminants Virus (PPRV).
Dr Pascal HUDELET Head of Technical Services, Veterinary Public Health Center
Press review editorial
BTV The volume of publications related to BTV has been quite high, showing a renewed interest in orbiviruses, probably in link with the current European oubreaks. The majority of published studies focus on epidemiology of the disease and they cover multiple regions: Peru, Brazil, USA, Australia, Pakistan, Morocco, Tunisia, and of course Europe, with several papers dedicated to the recent BTV3 outbreak. Several of those papers highlight the role of various Culicoides species as vectors, with a particular focus on the impact of climate change on vector distribution and disease transmission. The financial impact of BTV, particularly in regions like Tunisia, has been a significant area of research. An interesting study from Bibard et al. evaluated the risk of dispersion of BTV3 from Sardinia and concluded that multiple areas of the Mediteranean Basin are at risk because Culicoides can be transported over long distances by winds.
A couple of publications are related to live vaccines -existing ones as well as future candidates: the full genome of the 15 strains included in the South African live vaccine has been published, and a recombinant BTV vaccine candidate expressing reporter genes has shown promising results in mice. These works are extremely relevant to Europe now considering the current BTV3 outbreak, helping us to better understand the virus we need to combat.
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FMD FMDV research has been particularly extensive, with over 50 publications in the period since our last review. Notably, almost half of these are related to vaccines, including several reports from Korea on inactivated vaccine development and production and some next generation vaccine candidates based on poly-epitope constructs, nanoparticles or new adjuvants. It is comforting to see that post- vaccination monitoring studies are being published, that evaluate the actual efficiency of vaccines in field conditions. For example a recent small- scale study in Georgia, Azerbaijan and Armenia demonstrated that the combo vaccines used in these countries did not induce the expected protective and long-lasting population immunity. In contrast, a large scale study reports the success of the eradication program in Taiwan between 2010 and 2018, which used high quality vaccine with an extensive coverage. An interesting paper from Makau et al. targeted the difficult question of vaccine matching using a machine-learning approach, which allowed prediction with 96% sensitivity of the cross- neutralization potential among serotype O strains. Several epidemiological studies were also published, covering the FMD situation in Ethiopia, Pakistan, Algeria, Taiwan, Vietnam, and Abu Dhabi. A meta-analysis of FMD vaccine efficacy in Africa pointed that if properly applied, FMD vaccination campaigns can be successful. EHDV Several reports were published about the current EHDV, serotype 8 outbreak in Europe. Another paper by Bibard el al. demonstrated the accuracy of the wind dispersal model to predict the spread of EHDV in France, and anticipates potential further spread to other European countries during the upcoming vector season. Two papers were also published reporting EHDV transmission patterns in the USA and in Israel. A first report of an inactivated EHDV8 vaccine from Italy showed clinical protection against virulent challenge in cattle.
PPRV PPRV research has revealed the emergence of Lineage IV strains in regions like Senegal, replacing previous Lineage II strains. This highlights the evolving nature of the virus and the need for continuous monitoring and adaptation of control strategies. The progress towards PPR eradication in India is also a noteworthy development. An investigation of PPRV circulation in Uttarakhand, India, has been a step towards the global eradication of PPR by 2030. This study underscores the importance of continuous surveillance and control measures in the fight against PPRV. AHSV Research on African Horse Sickness Virus (AHSV) has also made some progress, with a study revealing the potential of plant-produced virus-like particle vaccines for the disease. This finding could potentially pave the way for the development of more cost-effective and accessible vaccines. In conclusion, the dynamic nature of these diseases, coupled with factors like climate change and geographical spread, necessitates ongoing research and vigilance. The groundbreaking work in this field underscores the importance of interdisciplinary collaboration and innovation in safeguarding global livestock health. The research findings you will find below can help the VPH community stay updated on the latest advancements in TADs and implement effective strategies for disease control and prevention.
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List of recent publications
Dr Vincent Dedet Vétérinaire Auzalide Santé Animale
BTV 1. Seroprevalence of reproductive and infectious diseases in cattle: the case of Madre de Dios in the Peruvian southeastern tropics. Link 2. The Study of Bluetongue Virus (BTV) and Epizootic Hemorrhagic Disease Virus (EHDV) Circulation and Vectors at the Municipal Parks and Zoobotanical Foundation of Belo Horizonte, Minas Gerais, Brazil (FPMZB-BH). Link 3. Engineering recombinant replication-competent bluetongue viruses expressing reporter genes for in vitroand non-invasive in vivo studies. Link 4. First molecular evidence of potential Culicoides vectors implicated in bluetongue virus transmission in Morocco. Link
10. Culicoides Midge Abundance across Years: Modeling Inter-Annual Variation for an Avian Feeder and a Candidate Vector of Hemorrhagic Diseases in Farmed Wildlife. Link 11. Seasonal change and influence of environmental variables on host-seeking activity of the biting midge Culicoides sonorensis at a southern California dairy, USA. Link 12. Recruitment of multi-segment genomic RNAs by Bluetongue virus requires a preformed RNA network. Link 13. Genome sequences of the 15 bluetongue virus vaccine strains incorporated in the South African live-attenuated vaccine. Link 14. Bluetongue Virus Serotype 3 and Schmallenberg Virus in Culicoides Biting Midges, Western Germany, 2023. Link 15. Reference Material Production and Milk Protein Concentration as Elements to Improve Bluetongue Serological Diagnosis in Bulk Tank Milk. Link
5. Estimation of the economic impact of a Bluetongue Serotype 4. Link
6. Reemerging/Notifiable Diseases to Watch
7. Evaluating Temperature Effects on Bluetongue Virus Serotype 10 and 17 Coinfection in Culicoides sonorensis. Link 8. Spatial Transmission Characteristics of the Bluetongue Virus Serotype 3 Epidemic in The Netherlands, 2023. Link
9. The effect of climate change on the spread of predicted bluetongue in Australian livestock. Link
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