Boehringer Ingelheim Veterinary Public Health Scientific newsletter on Transboundary A nimal Diseases VPH TADtalk
Summer 2023 : the acceleration
of Orbivirus emergence in Europe
Case Study of FMD Trans-Pool Movement: the emergence of SAT2 in the Middle East
French National Vaccination Plan for Avian Influenza 2022-2024
Life forward
MET-BOV-0003-2024
Table of Content
Editorial
News
Summer 2023 : the acceleration of Orbivirus emergence in Europe Case Study of FMD Trans-Pool Movement: the emergence of SAT2 in the Middle East
Scientific corner
Field evaluation of Safe, easy and low-cost protocol for shipment of samples from suspected cases of FMD to diagnostic laboratories Application of the Nagoya Protocol to veterinary pathogens: concerns for the control of FMD Inception and Progress of the French National Vaccination Plan for Ducks against Highly Pathogenic Avian Influenza (HPAI) 2022-2024
Press release
Press release editorial List of publications this quarter
Events
2023 GFRA Scientific Meeting: Focus on Africa First of its kind: VPH Experts Regional Academy (VERA) Global consultation on African Swine Fever (ASF) control
Future agenda
Editorial Welcome to the inaugural edition of VPH TADtalk! We are excited to present the latest insights and advancements in Veterinary Public Health and Transboundary A nimal Diseases (T A Ds). Through this newsletter series, our aim is to provide our partners with a regular update on the state of science and latest progress on Veterinary Public Health topics and critical infectious diseases. Our goal is to inspire and inform our readers, providing valuable knowledge and updates. Let’s delve into the highlights from 2023 and explore the significant developments in the field. The first part of this newsletter is dedicated to the latest news about epidemiology of selected animal diseases. Firstly, we follow the increasing rate of emergence of bluetongue viruses (BTV) and other orbiviruses in Europe, particularly the spread of serotypes 8 in France and serotype 3 in Northern Europe. We also investigate the concerning spread of Foot and Mouth Disease (FMD) virus serotype SAT2 into the Middle East (SAT2/XIV since 2023) and Northern Africa (SAT2/V since 2024). The second part of our Newsletter provides an overview of the latest scientific publications of interest, with abstracts as well as in-depth reviews of key publications. In this edition we delve into a seminal publication authored by 17 reference laboratories, 4 international organizations and 5 manufacturers about the negative impacts of the Nagoya Protocol on FMD control, emphasizing the need for a better understanding of the protocol that would not hamper the sharing of strains across institutions. It also underscores the importance of accurate and timely diagnosis of FMD, sample shipment challenges, and the real-time influence of academic and industrial organizations in combating FMD. The last section focuses on recent and upcoming events, with the intent of sharing key highlights with our partners. We zoom on the first edition of the VPH Experts Regional Academy (VERA), which brought together key opinion leaders from the dairy/feedlot industry and VPH distributors from the Middle East and Africa. The event allowed interactive sessions, workshops, and networking opportunities, for professionals affected by FMD and BTV. Finally, we provide highlights from the remarkable work presented at the GFRA Scientific Meeting in Uganda. In conclusion, this last year brought significant progress in the field of Veterinary Public Health, showcasing the dedication and collaboration of experts in combating transboundary animal diseases. We hope this edition of VPH TADtalk inspires you to join the global effort in advancing animal health and welfare. Thank you for being part of our inaugural edition!
Dr Pascal HUDELET Head of Technical Services, Veterinary Public Health Center Boehringer Ingelheim Animal Health
News
Summer 2023 accelerating Orbivirus emergence in Europe
Orbiviruses are a genus of viruses characterized by their segmented double stranded RNA genome, able to mutate and adapt to a changing environment in different species. These viruses are considered as arboviruses i.e., “arthropod borne viruses” meaning that mammalians can be infected through virus inoculation by arthropods such as mosquitoes, ticks, or midges. This genus of viruses is responsible for several groups of diseases, among them Bluetongue (BTV), Epizootic Hemorrhagic disease (EHD) and African Horse Sickness (AHS) are considered major threats. For each of these 3 diseases, there are several circulating serotypes leading to several clinical forms and making immunization a challenge because an animal immunized against one serotype is not protected against the others. Over the past 2 decades Europe has faced several waves of BTV infections by several serotypes coming from Africa and the Middle East. Initially, the vector was an exotic midge (Culicoides imicola which is adapted to hot climate and not to the European temperate climate), and BTV outbreaks were considered to be limited to the Southern part of Europe around the Mediterranean Basin where the exotic midge can survive. Then unexpectedly, in 2006 serotype 8 appeared in Northern Europe - starting from the Netherlands - and quickly spread across all continental Europe. BTV-8 remarkably adapted to a new competent host: a midge from the Culicoides obsoletus complex,
changing dramatically the potential spread of the virus to the ruminant populations in Europe. It took Merial less than two years to get a safe and efficient BTV-8 vaccine, and eventually Europe managed to control the expansion of this disease responsible for severe illness on sheep and cattle thanks to a combination of biosecurity measures, diagnostics and vaccination. For years, Europe has been monitoring other orbiviruses circulating in Northern Africa and making shy incursions in the more southern parts of the Old Continent. In 2022, BTV-3, known to be transmitted by Culicoides imicola was detected in Sicily and southern Sardinia originating from Tunisia. Its northward expansion was predicted to follow the movements of its insect vector. In unison, another disease transmitted by the same vector appeared: Epizootic Hemorrhagic Disease Virus (EHDV) serotype 8. This disease originally affects deers and antelopes, but a few years ago cases in cattle farms were reported in Tunisia. In 2022, cases affecting cattle in Sicily, Sardinia and extreme Southern Spain were reported. Each time the incriminated vector was Culicoides imicola and the disease was forecasted to progress slowly in Europe due to the reduced geographic distribution of this midge.
In summer and autumn 2023, as often, orbiviruses did not behave as what was forecasted:
1. EHDV Early July 2023, EHD serotype 8 started to spread amongst deer and cattle farms in Southern Spain progressing northward across the Iberic peninsula during July and August and crossing the Pyrenees moutains. The first cattle farms infected in France were confirmed by ANSES on the 21 st of September 2023. More than 3,700 farms are infected as of early January 2024 in France and nearly half of the French metropolitan territory is impacted by surveillance measures and trade restrictions on cattle. 2.BTV-8 Meanwhile, France faced an unusual BTV-8 outbreak starting early August 2023, clinical signs on sheep and cattle were much more severe than those reported previously. The French National Reference Lab for BTV confirmed an outbreak caused by a new BTV-8 strain quite different from the strains reported previously. This outbreak can be controlled by the current BTV-8 vaccine (BTVPUR) available in France. Trials performed by the Reference Lab confirmed the good protection induced by this vaccine. 3.BTV-3 Regarding BTV-3, an unpredictable scenario started in the Netherlands on the 3 rd of September 2023. The BTV free country (since 2012) witnessed its first clinical cases in sheep. BTV serotype 3 was confirmed; a strain closely related to the ones circulating in Tunisia, Sicily and Southern Sardinia. The outbreak progressed fast in sheep and cattle farms, from 4 sheep farms infected initially to the total number of cases increasing to 324 in sheep flocks and 61 in cattle herds by the third week. As of early January 2024, nearly 6,000 outbreaks have been recorded in The Netherlands and a few cases have been reported in Belgium, Germany and the UK. The outbreak is estimated to progress by 20 km per week and shows a faster spread and more severe incidence than the 2006 BTV-8 outbreak. The mortality in sheep is reported to reach up to 50%.
These orbiviral diseases have been monitored because of the significant risk of their emergence in Europe. Their historical vector has a repartition area in typical hot Mediterranean climate and until 2023 it was only observed in the Southern fringes of Europe. Their expansion was considered likely to be gradual and slow. Their sudden emergence is likely linked to the adaptation of BTV-3 and EHDV-8 to other midge vectors from the Culicoides obsoletus complex. These midges are well adapted to continental European climate and remain active at temperatures as low as 10°C. This explains the active transmission period we observed for these viruses, which lasted until December 2023, followed by a quieter period during the coldest part of the winter and, most likely, a resurgence linked to the increase of midges’ activity starting from next spring. EHDV and BTV-3 are likely to expand further in the UK and in Continental Europe in 2024.
Dr Guillaume Convert VPH Technical Service Director Veterinary Public Health Center Boehringer Ingelheim Animal Health
Case Study of FMD Trans-Pool Movement: the emergence of SAT2 in the Middle East
Dr Cédric Dézier VPH Technical Service Director Veterinary Public Health Center Boehringer Ingelheim Animal Health
A Fleeting Occurrence or an Impending Endemic Presence?
FMD is a very complex disease. To enhance the understanding and management of FMD, seven geographic pools have been established. (Map 1).
The seven pools
1
3
2
5
4
7
6
Map 1: 7 Pools have been defined by experts according to epidemiological main features.
Geographic “pools” refer to the grouping of countries or regions based on the epidemiological characteristics of FMD. These pools are defined by the World Organisation for Animal Health (WOAH, founded as OIE) and the Food and Agriculture Organization (FAO) - Table 1. Each pool is characterized by the presence of specific FMD virus serotypes and their epidemiological patterns. As already mentioned, the primary motivation for establishing geographic pools was to enhance the understanding and management of FMD. By categorizing regions based on the prevalent FMD virus serotypes and their epidemiological behaviours, it becomes easier to predict disease spread, plan control measures, and develop appropriate vaccines. This system allows for a more targeted and effective approach to FMD management,
thereby reducing the disease’s economic impact. It seems that the “Pool” concept is dynamic, with some well-known Trans-pool movements. In the early 2010s, a phenomenon known as ‘‘trans- pool’’ movements began to intensify. This refers to the movement of specific FMD virus types across different geographic pools. The first notable instance of this was the spread of the O/ME-SA/Ind-2001 type. Originally confined to the South-Asia region (Mainly India), the O/ME-SA/Ind-2001 type began to appear in regions outside its original geographic pool. This kind of unexpected movement could theoretically pose significant challenges to FMD management, as the existing vaccines in the newly affected regions were not designed to combat this specific type.
Pool
Region / countries
Serotypes present
1
Southeast Asia / Central Asia / East Asia Cambodia, China, China (Hong Kong SAR), Taiwan Province of China, Indonesia, Democratic People’s Republic of Korea, Republic of Korea, Lao People’s Democratic Republic, Malaysia, Mongolia, Myanmar, Russian Federation, Thailand, Viet Nam
A, Asia1 and O
2
South Asia Bangladesh, Bhutan, India, Mauritius 1 , Nepal, Sri Lanka
A, Asia1 and O
3
West Eurasia & Near East Afghanistan, Armenia, Azerbaijan, Bahrain, Georgia, Iran (Islamic Republic of), Iraq, Israel, Jordan, Kazakhstan, Kuwait, Kyrgyzstan, Lebanon, Oman, Pakistan, Palestine, Qatar, Saudi Arabia, Syrian Arab Republic, Tajikistan, Türkiye, Turkmenistan, United Arab Emirates, Uzbekistan
A, Asia1 and O (SAT2)
4
Eastern Africa Burundi, Comoros, Djibouti, Egypt 3 , Eritrea, Ethiopia, Kenya, Rwanda, Somalia, South Sudan, Sudan, Uganda, United Republic of Tanzania, Yemen
O, A, SAT1, SAT2 and SAT3
North Africa 2 Algeria, Libya, Morocco, Tunisia
A and O
5
West / Central Africa Benin, Burkina Faso, Cabo Verde, Cameroon, Central African Republic, Chad, Congo, Côte d’Ivoire, Democratic Republic of the Congo, Equatorial Guinea, Gabon, Gambia, Ghana, Guinea, Guinea-Bissau, Liberia, Mali, Mauritania, Niger, Nigeria, Sao Tome and Principe, Senegal, Sierra Leone, Togo
O, A, SAT1 and SAT2
The “Pool” concept is quite dynamic, with some well-known Trans-pool movements. As for Pool 3 (list of countries constituting this Pool available in Table 1), there has been some SAT2 ephemeral incursions in the past. (Table 2). It nevertheless looks like we are facing a new situation and it is legitimate to ask the question of the endemicity of SAT2 in Pool 3 today.
6
Southern Africa Angola, Botswana, Malawi, Mozambique, Namibia, South Africa, Zambia, Zimbabwe
SAT1, SAT2 and SAT3 (O 4 , A)
7
South America Venezuela (Bolivarian Republic of)
O and A
Table 1: List of the countries constituting the seven Pools. Source: https://www.wrlfmd. org/ref-lab-reports 1. FMD outbreaks in 2016/21 due to O/ME-SA/Ind-2001 demonstrate close epidemiological links between Pool 2 and Mauritius. 2. Long-term maintenance of FMDV lineages has not been documented in the Maghreb countries of North Africa and therefore this region does not constitute an Endemic Pool, but data is segregated here since FMD circulation in this region poses a specific risk to FMD-free countries in Southern Europe. 3. Egypt represents a crossroads between East African Pool 4 and the Near East (Pool 3). NB: Serotypes SAT1 and SAT3 have not been detected in this country. 4. Detection of O/EA-2 in southern/western Zambia (2018–2021), Namibia (2021), Malawi (2022) and Mozambique (2022) represent a new incursion into Pool 6.
Historical situation of SAT2 in Pool 3
Bahrain
SAT2/IV/Ken-09
5
Iraq
SAT2/XIV
6
9
Jordan
SAT2/XIV
24
Oman
SAT2/XIV
2
SAT2/VII/Alx-12
3
Palestine
SAT2/VII/Gbh-12
1
Saudi Arabia
SAT2
16
Turkey
SAT2/XIV
1
Table 2: Since 2022, SAT2 viruses seems to have taken up residence in POOL 3. Sources: https://www.wrlfmd.org/ref-lab-reports
In addition to the countries listed in Table 2, it is possible that SAT2 is present in other countries in the region but not yet detected or reported. The challenge that this new situation represents is considerable. Indeed, FMD control requires a high level of immunity against the disease (Figure 2).
Immunity against FMD virus
Animal movement restriction
FMD control
Quarantine or stamping out
Biosecurity and sanitation
Figure 2: To control SAT2 FMD disease, animals need to have a high level of immunity against SAT2 viruses. Source: http://www.fao.org/3/a-i5975e.pdf, Fig. 5, Chapter 4.1
As for immunity, since the serotype SAT2 usually circulates only in Africa, most animals in Pool 3 have never been exposed to this serotype, neither by wild infection nor through vaccination. SAT2 viruses show up in fully susceptible (naïve) populations! There is therefore a critical risk of further spread to unaffected countries in the region. On this topic, the FAO has recently issued a remarkable Risk assessment document . The good news is that WRL has vaccine matching data (heterologous VNT titers) for both of BI’s SAT2 vaccine strains, i.e SAT2 Eri 98 and SAT2 Zim 83.
The results show that the heterologous titers are satisfactory and reassuring about the ability of BI vaccines to protect against the SAT2 tested for 4 years (Figure 3). Remark: If WRL is able to produce these results, it is because BI agrees to share its reagents (serums and reference viruses) for many years, to provide our customers with an independent and complementary source of information to what we provide with our own laboratories.
https://www.fao.org/3/cc8173en/cc8173en.pdf
Heterologous titres (Indicators of cross-protection) from WRL Field isolates from 2020 onwards
Vaccine strains tested by the WRL
SAT2 ERI 98
SAT2 ZIM 83
SAT2/JOR/11/2023 SAT2/JOR/20/2023 SAT2/JOR/26/2023 SAT2/TUR/04/2023 SAT2/TUR/17/2023 SAT2/ALG/04/2023 SAT2/ALG/06/2023 SAT2/ETH/02/2022 SAT2/ETH/03/2022 SAT2/NIG/01/2021
SAT2/JOR/11/2023 SAT2/JOR/20/2023 SAT2/JOR/26/2023 SAT2/TUR/04/2023 SAT2/TUR/17/2023 SAT2/ALG/04/2023 SAT2/ALG/06/2023 SAT2/ETH/02/2022 SAT2/ETH/03/2022 SAT2/NIG/01/2021
High heterologous titre Good heterologous titre
Figure 3: The two SAT2 vaccine strains from BI generate satisfactory heterologous titers to combat the currently circulating SAT2 viruses. Source: http://www.wrlfmd.org
The concept of geographic pools has been instrumental in managing FMD. However, the emergence of Trans-pool movements poses new challenges that require further research and international cooperation. Understanding these movements and developing strategies to mitigate their impact is crucial for effective FMD management and control. The Trans-pool movement phenomenon underscores the importance of continuous surveillance, timely reporting, and the development of multivalent vaccines capable of protecting against multiple serotypes. It also highlights the need for global collaboration in sharing epidemiological data and resources to combat FMD effectively.
1. Risk of FMD disease SAT2 introduction and spread in countries in the Near East and West Eurasia. https://www.fao.org/3/cc8173en/cc8173en.pdf
Scientific corner
Safe, Easy and Low-cost Protocol for shipment of samples from suspected cases of FMD to reference labs
Dr Serena Shunmugam Junior Marketing Manager Veterinary Public Health Center Boehringer Ingelheim Animal Health
Understanding the current epidemiology of FMD through continuous surveillance and monitoring is fundamental to addressing the disease and controlling the spread of exotic serotypes. The identification and characterization of virus strains are performed in Reference laboratories (RL), meaning samples need to be shipped, which pose a challenge due to restrictions caused by cost and logistics. Recently an article was published describing the implementation of a user-friendly protocol that can
substantially reduce shipping costs and increase the submission of field samples and consequently improve knowledge of the circulating FMDV strains. This article by Romey et al. (2023), was written with the collaboration of Dr Pascal Hudelet, Head of VPH Technical Services.
https://downloads.hindawi.com/journals/ tbed/2023/9555213.pdf
Abstract of the article: Identification and characterization of foot-and-mouth disease virus (FMDV) strains in endemic countries and understanding their dynamics are crucial for global FMD control. However, the current practice of shipping FMD samples to Reference Laboratories (RL) is costly and poses biosafety challenges, leading to limited knowledge about circulating strains in some endemic areas. To address this issue, we previously developed a low-cost protocol using Lateral Flow Devices (LFDs) and 0.2% citric acid for sample shipment, simplifying the process and encouraging sample submission to RL. In this study, we evaluated the effectiveness of this protocol in the field by collecting 60 suspected FMD clinical samples from Nigeria, Pakistan, and Turkey, where FMD is endemic. Sample treatment, LFD testing, and virus inactivation were performed on-site whenever possible. The virus inactivation was confirmed at the RL, and subsequent RNA extraction from the inactivated LFDs confirmed FMDV positivity using real-time reverse transcription polymerase chain reaction (RT-PCR) for all 60 samples. Conventional RT-PCR identified the serotype for 86% of the samples, and Sanger sequencing and sequence analyses successfully determined the topotype and/or lineage for 60% of the samples. Additionally, infectious virus was rescued from 15% of the samples after chemical transfection of RNA extracted from inactivated LFDs into permissive cells. Implementing this user-friendly protocol can significantly reduce shipping costs, leading to increased submission of field samples and enhancing our understanding of circulating FMDV strains globally. Link to original article: Field Evaluation of a Safe, Easy, and Low-Cost Protocol for Shipment of Samples from Suspected Cases of Foot-and-Mouth Disease to Diagnostic Laboratories (hindawi.com)
Importance of the article:
1. Accurate and Timely Diagnosis: The article emphasizes the importance of accurate and timely diagnosis of FMD for rapid implementation of control measures. This is crucial for managing outbreaks and minimizing their impact, which aligns with the objectives of Boehringer Ingelheim’s VPH Technical Services.
2. Sample Shipment Challenges: The article highlights the challenges in shipping FMDV samples due to their classification as dangerous goods and the need for transportation in dry ice. The proposed protocol addresses these challenges, potentially making the process more efficient and cost-effective.
3. Inactivation Protocol: The study confirms the safety and effectiveness of the proposed inactivation protocol in the field with fresh samples. This could potentially improve the reliability of FMD diagnosis and control efforts.
4. Real-time Influence in Combating FMD: By facilitating easier and more cost-effective sample submission, the protocol could allow Reference Laboratories and VPH Technical Services to have real-time influence in combating FMD. Timely access to samples means quicker diagnosis, allowing for faster implementation of appropriate control measures and potentially reducing the spread and impact of FMD.
A line in the «C» position indicates a valid test
C
C
T
T
S = Sample T = Test C = Control
5. Enhanced Collaboration: The research involves collaboration with multiple countries and institutions, highlighting the importance of global cooperation in disease control. This aligns with the collaborative approach of VPH Technical Services in working with various stakeholders to combat animal diseases.
S
S
No line in the «T» position indicates a NEGATIVE test result
A line in the «T» position indicates a POSITIVE test result
Figure 1: A schematic diagram of a lateral flow device (LFD) to test for FMD virus from a field sample. This LFD can be inactivated (along with the sample) for simple sample shipment to diagnostic labs.
Application of the Nagoya Protocol to veterinary pathogens: concerns for the control of FMD To address inequality in the appropriation of resources in our global history, particularly in relation to the exploitation of natural biodiversity, the Nagoya Protocol was established in 2010. This international agreement aims to ensure equitable access and benefit-sharing of genetic resources. A recent review article by Horsington et al . (2023) provides an in- depth examination of the Nagoya Protocol within the
Dr Serena Shunmugam Junior Marketing Manager Veterinary Public Health Center Boehringer Ingelheim Animal Health
context of transboundary livestock diseases, such as Foot-and-Mouth Disease (FMD). Dr Pascal Hudelet, Head of VPH Technical Services at Boehringer Ingelheim, is a co-author of this insightful paper. https://www.frontiersin.org/articles/10.3389/ fvets.2023.1271434/full
The Nagoya Protocol, established in 2010 as a supplement to the Convention on Biological Diversity (CBD), was created to address the historical exploitation of genetic resources in developing nations. It promotes Access and Benefit-Sharing (ABS) to ensure fair compensation for the utilization of genetic resources. This international treaty grants sovereign rights to countries over their natural resources, emphasizing national authority in determining access to genetic resources. The legal framework of the Nagoya Protocol is complex and operates at the national level, resulting in diverse definitions, obligations, and procedures among provider countries. Non-compliance with the protocol carries severe consequences, contributing to legal risks for companies and institutions. The
concept of viral sovereignty, asserting a country’s rights over viruses within its jurisdiction, emerged because of the CBD. While it addresses legitimate expectations of provider countries, it raises challenges for global health and food security. In the context of Foot-and-Mouth Disease (FMD), a highly economically significant livestock disease, the Nagoya Protocol has notable impacts on global surveillance, academic research, and commercial activities. FMD research involves the exchange of materials, including the FMD virus (FMDV), for surveillance and vaccine development. However, the Nagoya Protocol’s legal complexities and variable national implementations present challenges in the exchange of FMD materials, potentially hindering the timely development of critical tools for FMD control and global health security.
Diagnostic/reference laboratories, which play a crucial role in the global surveillance of FMD, encounter uncertainties related to the long-term storage, distribution, and use of diagnostic samples due to the Nagoya Protocol. While immediate diagnostic activities fall outside the protocol’s scope, the long-term aspects may face restrictions. The laboratories often lack expertise on the Nagoya Protocol, and the complexities of Access and Benefit-Sharing (ABS) obligations may complicate their collaborative relationships. Vaccine manufacturers are also significantly affected by the Nagoya Protocol. The sourcing of pathogens for vaccine development falls within the protocol’s scope, obliging manufacturers to navigate ABS requirements. This can lead to delays in vaccine development, especially in endemic areas where FMDV evolves rapidly. These delays can have far-reaching effects, impacting livelihoods, food security, and FMD-free areas. Unrealistic expectations about monetary benefits may deter vaccine manufacturers, affecting global vaccine security.
Horsington et al.
10.3389/fvets.2023.1271434
Figure 1: Countries that are parties to the Nagoya Protocol (A) and countries where FMD is present within seven endemic virus pools (1–7) located in Asia, Africa and South America (B). Grey color defines countries that maintain an FMD-free status (with or without vaccination), dark red represents countries without any FMD-free status, while lighter red denotes countries with at least one FMD- free zone (as defined by WOAH in March 2023). FIGURE 1 Countries that are parties to the Nagoya Protocol (A) and countries where FMD is present within seven endemic virus pools (1–7) located in Asia, Africa and South America (B) . Grey colour defines countries that maintain an FMD-free status (with or without vaccination), dark red represents countries without any FMD-free status, while lighter red denotes countries with at least one FMD-free zone (as defined by WOAH in March 2023).
While pathogens clearly represent genetic resources as defined in the Nagoya Protocol, provisions to recognise specific and unique characteristics of pathogens, and clarification or further guidance on
Legislation on the sourcing and use of genetic resources includes administrative procedures and enforcement policies that vary from country to country. In its simplest form, a foreign researcher/company
Inception and Progress of the French National Vaccination Plan for Ducks against Highly Pathogenic Avian Influenza (HPAI) 2022-2024
Dr Thomas Delquigny Boehringer Ingelheim Commercial Poultry Marketing and Technical Manager Boehringer Ingelheim Animal Health
The Highly Pathogenic Avian Influenza (HPAI) epizootic that affected French poultry farming in 2022 is unprecedented. After being confined to the southwest of France since 2016, the H5N1 virus has affected the west of France and particularly populated areas where all poultry productions are represented (ducks, laying hens, chickens, turkeys, guinea fowl, game birds). This episode, which resulted in the death or culling of more than 20 million poultry and cost nearly 1.2 billion Euros to the French state, led to a rethink of public policy for HPAI control in France. Following the adoption of a new European regulation allowing the use of vaccination as a complementary tool against HPAI, the French Ministry of Agriculture began to consider the vaccination of a portion of domestic poultry as an interesting option in France. In particular, duck populations (Mulard and Muscovy) being overrepresented among reported HPAI cases (>50% for less than 10% of the population), it appeared that vaccinating them would:
recruitment of additional labour to vaccinate, the provision of 80 million emergency vaccine doses, and their proper routing from the logistics platform where they are stored to the production areas. The vaccination campaign started on October 2, 2023, and to date (29 th January 2024), 15,970,000 ducks have been vaccinated. Pharmacovigilance feedback is very limited (6 cases in total and concentrated in the early days of vaccination). The vaccination campaign is accompanied by active surveillance measures to ensure the absence of viral circulation, including regular PCR tests and end-of- life serologies to trace any potential contamination history. All administered doses are precisely traced, and the remaining vials are destroyed to avoid any risk of vaccination on non-target species. Today, most cases observed in France (N=6) during the winter of 2023-2024 involved turkeys or unvaccinated ducks. The implementation of this vaccination involved the mobilization of all stakeholders in the sector, including health veterinarians, specialist vaccination teams in farming, the pharmaceutical industry, and the government. In light of these developments, the ongoing vaccination campaign, coupled with stringent surveillance measures, signifies a critical step towards controlling the HPAI virus in France, and it is hoped that these efforts will continue to protect the poultry industry and prevent further outbreaks in the future.
1. Limit the introduction within an area 2. Lower the spread in case of introduction
In the first half of 2023, the decision to vaccinate was made and a national vaccination plan was established. It was decided that all meat ducks would be mandatorily vaccinated, while vaccination remained prohibited for all other poultry species. About 60 million ducks are expected to be vaccinated per year, with the French state sponsoring 85% of the total cost associated with this vaccination, including the entirety of the vaccine. The implementation of this vaccination involved the mobilization of all stakeholders in the sector, including health veterinarians, specialist vaccination teams in farming, the pharmaceutical industry, and the government. This mobilization allowed for the
https://agriculture.gouv.fr/tout-ce-quil-faut-savoir- sur-le-plan-daction-vaccination-iahp-en-france
Press release
Press release editorial As part of our constant aim to keep up with the trends in T A Ds and animal health, we are constantly on the look-out for new literature and studies in the field. This section of VPH TADtalk provides an overall digest of the most recent articles and a list of some of the key publications. Although all viruses included in this scouting were represented among the references collected over the first quarter of 2024, FMDV is the dominant one with 9 papers. This FMD section includes 3 articles on FMD surveillance in Abu Dhabi, Australia and China, 3 articles on innovative antigens or vaccines production, one describing an innovative sequence-based approach to identify specific pathogens in swine from complex clinical samples. An epidemiological study uses modelization to identify fomite transmission as a possible route of transmission of this virus when the viral load increases in the environment, which shows that early detection is paramount. Finally, a very interesting report clearly shows how Fasciola hepatica infestation can significantly alter the immune response to FMD vaccines. Two new BTVs have been described: one (BTV-2) in US cervids (reassortant) and one (BTV-3) in Korea (dates from 2013-2014, although no mention is done in relation to the BTV-3 presently spreading in the NL and neighbouring countries). Two papers study the relative roles of local Culicoides vectors in virus transmission. Cuba also offers 17 BTV isolates in a single publication. Regarding EHDV in Asia, serotype 10 is now present in China and not restricted to Japan anymore . Dr Vincent Dedet Vétérinaire Auzalide Santé Animale
List of key publications this quarter: BTV 1. Viadanna, P.H.O., Surphlis, A., Cheng, AC. et al. (2024). A novel bluetongue virus serotype 2 strain isolated from a farmed Florida white-tailed deer (Odocoileus virginianus) arose from reassortment of gene segments derived from co-circulating serotypes in the Southeastern USA. Virus Genes, 5 Jan. Link 2. Nan Li, Jinxin Meng, Yuwen He, Wenhua Wang, Jinglin Wang. (2024). Potential roles of Culicoides spp. (Culicoides imicola, Culicoides oxystoma) as biological vectors of bluetongue virus in Yuanyang of Yunnan, P. R. China. Front. Cell. Infect. Microbiol., 11 January. Link 3. Hyun-Jeong Kim, Jun-Gu Choi, Da-Seul Seong, Jong- Uk Jeong, Hye-Jung Kim, Sang-Won Park, Seung-Pil Yun and In-Soon Roh. (2024). The First Report on the Complete Sequence Characterization of Bluetongue Virus Serotype 3 in the Republic of Korea. Vet. Sci. 2024, 11(1), 29 - 11 Jan. Link 4. Ogola EO, Bastos ADS, Slothouwer I, Getugi C, Osalla J, Omoga DCA, Ondifu DO, Sang R, Torto B, Junglen S, Tchouassi DP. (2024). Viral diversity and blood-feeding patterns of Afrotropical Culicoides biting midges (Diptera: Ceratopogonidae). Front Microbiol. 2024 Jan 5;14:1325473. Link 5. Ana María Acevedo, Lydie Postic, Maray Curiel, Mathilde Gondard, Emmanuel Bréard, Stéphan Zientara, Fabien Vorimore, Mai-Lan Tran, Mathilde Turpaud, Giovanni Savini, Alessio Lorusso, Maurilia Marcacci, Damien Vitour, Pascal Dujardin, Carmen Laura Perera, Cristian Díaz, Yalainne Obret and Corinne Sailleau. (2024). Detection, Characterization and Sequencing of BTV Serotypes Circulating in Cuba in 2022. Viruses, 2024, 16(1), 164 - 22 Jan. Link FMDV 1. Monique Costa, Florencia Mansilla, Juan Manuel Sala, Anderson Saravia, Teresa Freire. (2024). Fasciola hepatica infection modifies IgG1 specific immune response to foot-and-mouse disease virus induced by vaccination. Vaccine, In Press, Corrected Proof, Available online 6 January. Link 2. Le NMT, So KK, Chun J, Kim DH. (2024). Expression of virus-like particles (VLPs) of foot-and-mouth disease virus (FMDV) using Saccharomyces cerevisiae. Appl Microbiol Biotechnol.,2024;108(1):81. Link 3. Yuanli Peng, Haozhen Yan, Jinsong Zhang, Ruihao Peng, Zeliang Chen. (2024). Potent immune responses against thermostable Foot-and-Mouth disease virus VP1 nanovaccine adjuvanted with polymeric thermostable scaffold. Vaccine, In Press, Corrected Proof, Available online 13 January. Link 4. John Ellis, Emma Brown, Claire Colenutt, David Schley, Simon Gubbins. (2024). Inferring transmission routes for foot-and-mouth disease virus within a cattle herd using approximate Bayesian computation. Epidemics, Available online 8 January 2024, 100740. Link
5. Zhang R, Wei Y, Liu X, Wu Y. (2024). Development and efficacy evaluation of a novel water-in-oil-in-water adjuvant for an inactivated foot-and-mouth disease vaccine. Pharm Dev Technol. 2024 Jan 12:1-11. Link 6. Sthitaprajna Sahoo, Hak-Kyo Lee, Donghyun Shin. (2024). Structure-based virtual screening and molecular dynamics studies to explore potential natural inhibitors against 3C protease of foot-and-mouth disease virus. Front. Vet. Sci., 17 January. Link 7. Alison Neujahr, Duan Loy, John D. Loy, Bruce Brodersen, Samodha C. Fernando. (2024). Rapid detection of high consequence and emerging viral pathogens in pigs. Front. Vet. Sci., Jan. 15. Link 8. Yassir M. Eltahir, Hassan Zackaria Ali Ishag, Jemma Wadsworth, Hayley M. Hicks, Nick J. Knowles, Valérie Mioulet, Donald P. King, Meera Saeed Mohamed, Oum Keltoum Bensalah, Mohd Farouk Yusof, Esmat Faisal Malik Gasim, Zulaikha Mohamed Al Hammadi, Asma Abdi Mohamed Shah, Yasir Ali Abdelmagid, Moustafa Abdel meguid El Gahlan, Mohanned Fawzi Kassim, Kaltham Kayaf, Ahmed Zahran and Mervat Mari Al Nuaimat. (2024). Molecular Epidemiology of Foot-and-Mouth Disease Viruses in the Emirate of Abu Dhabi, United Arab Emirates. Vet. Sci., 2024, 11(1), 32 - 15 Jan. Link 9. GF Mackereth, KL Rayner, AJ Larkins, DJ Morrell, EL Pierce, PJ Letchford. (2024). Surveillance for lumpy skin disease and foot and mouth disease in the Kimberley, Western Australia. Austr. Vet. J., First published: 14 January. Link 10. Yi Li, Songyin Qiu, Han Lu, Bing Niu. (2024). Spatio- temporal Analysis and Risk Modeling of Foot-and-Mouth Disease Outbreaks in China. Prev. Vet. MEd., In Press, Journal Pre-proof, Available online 22 January. Link EIAV 1. Zhang, Z., Guo, K., Chu, X. et al. (2024). Development and evaluation of a test strip for the rapid detection of antibody against equine infectious anemia virus. Appl. Microbiol. Biotechnol., 108, 1–13 (Jan. 8). Link EHDV 1. Yuwen H, Jinxin Meng, Nan Li, Zhao Li, Dongmei Wang, Meiling Kou, Zhenxing Yang, Yunhui Li, Laxi Zhang and Jinglin Wang. (2024). Isolation of Epizootic Hemorrhagic Disease Virus Serotype 10 from Culicoides tainanus and Associated Infections in Livestock in Yunnan, China. Viruses, 2024, 16(2), 175 - 24 Jan. Link PPRV 1. Olga Byadovskaya, Kseniya Shalina, Pavel Prutnikov, Irina Shumilova, Nikita Tenitilov, Alexei Konstantinov, Nataliya Moroz, Ilya Chvala and Alexander Sprygin. (2024). The Live Attenuated Vaccine Strain “ARRIAH” Completely Protects Goats from a Virulent Lineage IV Field Strain of Peste Des Petits Ruminants Virus. Vaccines, 2024, 12(2), 110 - 23 Jan. Link
Horsington et al.
10.3389/fvets.2023.127143
Researchers, especially those in academic settings, face the complexity of navigating the Nagoya Protocol. This complexity can impact efforts to develop diagnostics, therapeutics, and vaccines. Transnational collaborations may be hindered by ABS terms, and researchers in provider countries may face reduced collaboration opportunities. Provider countries, often in Africa and Asia, are impacted as their farmers and livestock keepers rely on FMD vaccines from external international companies. The Nagoya Protocol’s constraints may result in reduced access to new vaccines, affecting livestock productivity and hindering disease control efforts. Tools and products resulting from the utilization of genetic resources can directly improve livestock productivity. However, the Nagoya Protocol’s constraints may reduce access to these tools, jeopardizing international cooperation for vaccine development.
FIGURE 2 Feedback loop (pink arrows) for the utilisation of FMD resources highlighting the main actors in this process. NB: the shipment of samples to international FMD reference Laboratories does not typically involve the National NFP and their engagement in the process usually only occurs prior to utilisation of the samples once samples have been tested and characterised. Any measures to simplify the process to access FMD samples from endemic countries need to provide legal certainty and thereby ensure that global surveillance activities relating to FMD are not unintentionally impeded.
Figure 2 :Feedback loop (pink arrows) for the utilisation of FMD resources highlighting the main actors in this process. NB: the shipment of samples to international FMD reference Laboratories does not typically involve the National NFP and their engagement in the process usually only occurs prior to utilisation of the samples once samples have been tested and characterised. Any measures to simplify the process to access FMD samples from endemic countries need to provide legal certainty and thereby ensure that global surveillance activities relating to FMD are not unintentionally impeded.
involves transnational collaborations with researchers in countrie from which the materials have been sourced. Significant time and valuable resources in these institutions may be required to agree AB terms associated with projects that might yield limited benefits. In addition, researchers in provider countries may be disadvantaged through reduced collaboration opportunities, whether through reluctance from external scientists, or as a result of their own lack o motivation stemming from insufficient advice, information, and assistance when negotiating ABS exchanges (17).
activities and faster growing markets (26). This has a negative impact on global vaccine security with overall fewer FMD vaccines being produced and the absence of investment into updated high-quality and antigenically relevant vaccines. Similar constraints exist for other commercial actors such as diagnostic companies and pharmaceutical companies that may wish to utilise FMDV materials for new tests or therapeutics (Figure 2). The observation that there have not been any major epizootics to date involving countries blocking access to strains of FMDV for which current vaccines are ineffective does not diminish the need to be prepared for when such a situation arises.
2.4 Provider countries
2.3 Research projects and researchers
A perhaps overlooked group of stakeholders that is also impacted b restrictions on FMD research and development are farmers and livestoc keepers in the provider countries. Tools and products arising from th utilisation of genetic resources can directly improve livestock productivit in those countries that have provided the material (Figure 2). Fo example, most countries in Africa and Asia do not currently have th capacity to manufacture FMD vaccines at sufficient volumes and qualit required to have long-term impacts on disease control. Therefore, man endemic countries rely on FMD vaccines from external internationa companies, which are often located in the Global North. Even wher
4. An international FMDV repository could simplify access to viruses for utilization, such as for vaccine strain development, by ensuring ABS compliance in advance.
The article suggests that exempting FMDV completely out of the scope of the Nagoya protocol is not appropriate/feasible in the short term. It conflicts with CBD’s objectives. Instead, the authors propose the following: 1. Awareness about the Nagoya Protocol and related ABS frameworks is crucial. Efforts should focus on provider countries’ perspectives and improving communication between government officials in sourcing countries.
Beyond the utilisation of materials by commercial companies, the Nagoya Protocol presents a highly complex framework for scientists who work in the academic sector (including universities, governmental institutes, and not-for-profit organisations). Access to viruses, samples and data is often central to efforts to facilitate the development of prototype diagnostics, therapeutics, and vaccines and is also widely exploited to establish novel tools to understand the evolution, mechanisms of replication and infection, pathogenesis, immune responses, and host-cell interactions of FMDV. This work typically
07 5. Any solution requires political support and funding. Short-term focus could be on facilitating FMD material exchange between willing partners, while long-term solutions are sought at the international level. In conclusion, the Nagoya Protocol poses significant challenges to FMD stakeholders, affecting global surveillance, vaccine development, academic research, and livestock productivity in provider countries. A comprehensive science-policy dialogue is essential for a better understanding and effective implementation of the Nagoya Protocol. The impacts on FMD stakeholders underscore the need for clarity, streamlined processes, and global cooperation to ensure the fair and equitable sharing of benefits while addressing the complexities associated with ABS measures. Frontiers | Application of the Nagoya Protocol to veterinary pathogens: concerns for the control of foot-and-mouth disease (frontiersin.org)
Frontiers in Veterinary Science
frontiersin.or
2. Standardized terms for WOAH/FAO FMD Reference Labs would help share FMD viruses and comply with national ABS requirements. The approach could learn from the Global Influenza Surveillance and Response System (GISRS) experience.
3. A specialized multilateral ABS instrument, like the WHO Pandemic Influenza Preparedness (PIP) or the International Treaty on Plant Genetic Resources for Food and Agriculture, could be a long-term solution. It could reduce transaction costs and provide legal certainty.
Events
2023 GFRA Scientific Meeting: Focus on Africa
Dr Serena Shunmugam Junior Marketing Manager Veterinary Public Health Center Boehringer Ingelheim Animal Health
The 8 th -10 th November 2023 marked the Global FMD Research Alliance (GFRA) scientific meeting, which was held in Kampala, Uganda, an endemic country where FMD is an ongoing challenge. The GFRA has been a flagship association in the community in demonstrating how collaborations can lead to a better understanding of the FMD virus structure, infection and of the host’s immune response. Sessions for the event included presentations on FMD epidemiology, diagnostics,
virology, immunology, vaccinology, pathogenesis and specifically FMD research in Africa, the host continent. This knowledge is pertinent in designing improved control tools and measures. Boehringer Ingelheim’s Head of Technical Services at VPH, Dr Pascal Hudelet, attended the meeting and gained crucial insights:
Dr Pascal HUDELET Head of Technical Services, Veterinary Public Health Center Boehringer Ingelheim Animal Health
Could you explain the meeting’s purpose and who attended? The conference is a crucial platform for delving into FMD research in the region. It is hosted biennially by GFRA, a global alliance of scientists providing evidence and innovation that enables the progressive control and eradication of FMD. This year there were 102 delegates from 27 countries, including 14 African countries. The delegates were a diverse group of individuals: mainly expert FMD scientists, but also members of international organizations. Representatives from Boehringer Ingelheim’s VPH Middle East and Africa region team; Dr Nicolas Denormandie and Dr Mohamed Al Nahrawy also attended this meeting.
discussions after each session. Workshops focused on the creation of an African chapter, Gap Analysis Report (assessment of current scientific knowledge and the available counter measures to mitigate the impact of an FMD outbreak in an endemic country, also supporting global control and eradication initiatives in FMD-endemic countries) and new nanopore-based methods for sequencing FMDV isolates. Keynote speakers included Dr Donald King (Head of WRLFMD), Nina Henning (GalvMed, Team Lead AgResults FMD Challenge Project), Dr Carolina Stenfeldt (Research manager USDA-ARS Plum Island Animal Disease Center) and Dr Jonathan Artz (Research Leader, Agricultural Research Service- USDA).
There were more than seventy oral/poster presentations. The attendees also participated in
Figure 1: Attendees of the GFRA Scientific Meeting December, 2023 in Uganda
At the closing ceremony, Nagendra Singanallur presented awards for poster presentations. David Paton won 1 st Place for Most Scientific Impact and Tamil Selvan Ramasamy Periyasamy won 2 nd Place. Tamil Selvan’s team presented preliminary evidence from India on improved in vitro and in vivo assays to assess the quality of FMD vaccine. The expected long-term outcome of the findings would be a reduction in the turn-around time for the FMD vaccine batch release assays and replacement of the challenge-based potency testing by cattle serology. The replacement of cattle serology by guinea-pig serology would be in line with 3R principles of animal experimentation.
Figure 2: Prize winners during GFRA Scientific Meeting with Dr Ana Ludi (Left), Dr Tamil Selvan (2 nd place most scientific impact), Prof Don King (Middle) and Dr David Paton (most right, 1 st place most scientific impact)
Photo credit: Dr Tamil Selvan
What were the main topics discussed? The following are the key takeaways from the conference that the community should be aware of: • The creation of the Africa Chapter of GFRA occurred with this gathering. • New surveillance tools such as MinION, an innovative pen-side sampling tool which allows next-generation sequencing from field swabs. • There is a call for an African focus in terms of research, surveillance, and control of FMD. •GALVMed updated the community on the AgResults FMD Challenge Project, which aims to facilitate access to high-quality vaccines in East Africa. • Dr. David Paton emphasized the importance of following correct vaccine schedules and increasing the quality of locally made vaccines. • Many epidemiology studies were presented, including: • Uganda: on average, 33 declared outbreaks per year decrease livestock sales by 63%. • Nigeria: sheep were found to play a role in FMD maintenance in Northern Nigeria. • Tanzania: serological studies show frequent buffalo to cattle infection and circulation of O strains in buffalo. • Immunogenicity studies performed in the field using locally manufactured vaccines showed great differences in quality between the products. For example: • Zambia: a field trial showed that the BVI vaccine elicits a high antibody titer lasting 6 months after two shots. • Uganda: a field trial showed great batch-to-batch variability on one (local) out of previously 2 vaccines used. • Ethiopia: a local vaccine showed 39% effectiveness in the field. After participating in the session on FMD research in Africa, what can you tell us about the current regional situation? The first session of the conference was dedicated to FMD research in Africa. The session included an assessment of FMD vaccines in Uganda and heterologous protection against SAT1 strains in goats. The rise of SAT1 FMDV in East Africa could pose a potential threat in the Middle East, which imports livestock from the region. Additionally, SAT strains-specific peptide phage display libraries for epitope identification were presented, along with research on transmission dynamics and vaccine effectiveness in controlling endemic FMD in Ethiopia.
During the conference, Dr Donald King gave a keynote speech on the global FMD situation based on WRL surveillance methods. When/where is the next GFRA meeting and how can one attend? For now, there is no confirmation on the exact date or venue of the next GFRA meeting, however there are hopes that it will be hosted on the African continent for a second year. To join the meeting and stay informed I would recommend becoming a GFRA member through their website (Global Foot-and- Mouth (FMD) Research Alliance (GFRA) (usda.gov)).
For more information on the event visit: https://www.ars.usda.gov/GFRA/events.htm
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