IAHJ Volume 10 Issue 3

Volume 10 Issue 3

PEER REVIEWED

Emerging Zoonoses A Human-wildlife Interface?

Increasing Livestock Sustainability with Methane-mitigating Feed Additives Leveraging Scientific Advances to Improve Tablet Manufacturing for Animal Health Controlling Rabies in Foxes Unprecedented Success in Europe

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CONTENTS 04 FOREWORD TALKING POINT 06 Global Food Security and Health IAHJ speaks with Hsin Haung, Secretary General, International Meat Secretariat, Chair, FAO LEAP Steering Committee, on the big issues of our time: global food security and health, widespread poverty, resource scarcity and climate change and how this can all be addressed with more sustainable livestock systems.

MANAGING DIRECTOR Mark A. Barker EDITORIAL MANAGER Beatriz Romao beatriz@senglobalcoms.com

WATCH PAGES 08 Increasing Aquaculture Productivity with Mobile Microscopes

RESEARCH AND CIRCULATION Virginia Toteva virginia@senglobalcoms.com

The United Nations forecasts that the population of the world will reach 9.8 billion by 2050. With many experts being concerned as how to feed so many people, fish farming is growing dramatically to fill the gap. As with any farming, growing large amounts of food in a small space increases the incidence of infection and disease can spread extremely rapidly. Andrew Monk of ioLight identifies how rapid diagnosis through mobile microscopes can fight against listed diseases and increase aquaculture productivity.

DESIGNER Jana Sukenikova www.fanahshapeless.com BUSINESS DEVELOPMENT Jerome D’Souza info@senglobalcoms.com ADMINISTRATOR Jessica Chapman jessica@senglobalcoms.com

10 An In-house ELISA for Treponema Antibodies In Bulk Milk is useful for Monitoring Claw Health Bovine digital dermatitis (DD) is a painful, infectious claw disorder that causes ulcerative lesions mainly at the coronary band of the hind legs of dairy cows and lameness. DD is not only a serious issue in terms of animal welfare, but also has significant economic consequences due to milk loss, decreased fertility and treatment costs. The objective of this study presented by Jet Mars, Menno Holzhauer, Manon Holstege and Harold van der Heijden by Royal GD, is to develop, validate and implement a Treponema antibody ELISA in bulk milk to monitor and assess DD prevalence at the herd level.

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The opinions and views expressed by the authors in this journal are not necessarily those of the Editor or the Publisher. Please note that although care is taken in the preparation of this publication, the Editor and the Publisher are not responsible for opinions, views, and inaccuracies in the articles. Great care is taken concerning artwork supplied, but the Publisher cannot be held responsible for any loss or damage incurred. This publication is protected by copyright.

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Emerging Zoonoses: A Human-wildlife Interface?

Preservation of natural habitats of wildlife must be undertaken and injudicious cutting or burning of forests must be prohibited. Human access for livestock grazing, hunting or other recreational activities must be minimised in the buffer zone and strictly restricted in core forest regions. Hina Malik at Guru Angad Dev Veterinary and Animal Sciences University examines how humans have ruined the balance of the ecosystem and exploited flora and fauna for their own gain.

15 Controlling Rabies in Foxes – Unprecedented Success in Europe

Volume 10 Issue 3 Autumn 2023 Senglobal Ltd.

The European Union (EU) aims to eliminate foxmediated rabies from its territory by 2020. At first sight, this seems a rather ambitious goal considering that this horrifying disease has tormented humans and animals in Europe since ancient times. However, Dr. Conrad Freuling (WHO), Dr. Ad Vos (Ceva) and Dr. Thomas Müller (WHO) are confident that collecting and sharing rabies surveillance data through the RBE will safeguard

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CONTENTS the unprecedented success in rabies control achieved in Europe.

additives, while offering recommendations to improve pathways to market.

RESEARCH AND DEVELOPMENT

FOOD & FEED

20 Improving Animal Production Biosecurity to Minimise Global One Health Risks Despite remarkable advances in human and veterinary medicine over the past century, infectious diseases remain an important cause of morbidity and mortality for both humans and animals around the world.

Patricia Turner of Charles River Laboratories writes that One Health is essential for continued improvements in animal and human medicine for the future.

23 Increasing Livestock Sustainability with Methane-mitigating Feed Additives Demand for animal protein in developed countries is stable and increasing strongly in emerging countries.

The combination of their nutrient density, desire of people to improve their diets and a growing world population will continue to drive future growth. The United Nations Food and Agriculture Organisation (FAO) projects that global demand for milk and meat will rise by 58% and 74% between 2010 and 2050. Carel du Marchie Sarvaas at HealthforAnimals analyses political, regulatory, practical and market considerations related to the introduction and use of methane-reducing feed

26 Feeding People while Preserving the Planet Agriculture is at the heart of many important conversations in 2023. And whether the issue at hand is environmental concerns, the production of enough nutritious food for the global population or one of many other contentious topics, agricultural producers are often seen as anti-heroes – when, in reality, the agriculture industry has the greatest potential to make a positive impact on the world. Dr. Vaughn Holder at Alltech explains how to feed people while preserving the planet.

MANUFACTURING 28 Leveraging Scientific Advances to Improve Tablet Manufacturing for Animal Health In the pharmaceutical industry, prioritising product control, patient safety, and adherence to standards is crucial. This responsibility extends to maintaining the quality of solid dosage forms which are frequently utilised in veterinary medicine. Rob Blanchard at I Holland outlines the scientific advances to improve tablet manufacturing for animal health.

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FOREWORD Animal breeding must be seen within sustainability that includes human health and the health of the planet (ecology), without neglecting the economic and ethical aspects. The relationship with human health is dual, since in the absence of food of animal origin there is malnutrition, but excesses increase non-communicable diseases.

However, animal farming is considered a cause of serious environmental impact, as well as a cause of suffering for animals (ethics). Therefore, it is proposed to modify the diet in relation to foods of animal origin, properly reducing them in rich countries, but increasing them in poor ones. To reduce the environmental impact of the animals, they must be reduced in number, but the quantities of food needed imply an increase in productivity and efficiency. Their good health is fundamental for these last objectives: to fight infectious and parasitic diseases, but also to ensure optimal feeding and living conditions to guarantee their welfare.

To discuss the concepts of animal health and sustainability, we must remind ourselves that ASF (animal source foods) can play a large role in human health, but that animals are assumed to have a negative role in the environment. Indeed, ASF can compromise human health, both in excess and in deficiency, so a proper amount of them is important. In addition, the environmental impact of farmed animals: land occupation, greenhouse gas (GHG) emissions, energy use and water utilization, acidification, and eutrophication, must be minimized by reducing ASF consumption, as well as by increasing productivity. To achieve this, besides genetics, feeding and good management, the

hygienic-sanitary and comfort conditions that ensure good health and welfare are essential. Impaired animal health can cause zoonosis and food-borne diseases and be responsible for economic and socio-economic losses (lower productionproductivity and profitability) with consequential effects on the planet’s health too, and there are big differences between developing and developed countries. In the former, a prevalence of endemic infectious diseases and parasites is observed, and there is a lack of tools to restrain them; in the latter there is a decline of the above diseases, but an increase of stress-related diseases. Their reduction is equally important but requires a different strategy. In developing countries, the strategy should be to facilitate the availability of prevention and treatment means, while in developed countries it is necessary to use drugs correctly (to reduce residues, especially antimicrobials which are associated with important resistance risks to antibiotics) and improve the living conditions of animals (welfare).

In this issue of IAHJ we have some fantastic feature, addressing some of the key challenges of our time: global food security and health, widespread poverty, resource scarcity and climate change and how this can all be addressed with more sustainable livestock systems.

Hsin Haung, Secretary General, International Meat Secretariat, Chair, discusses, Circular-bio economy. Livestock production upcycles agricultural products that cannot be consumed by humans, into valuable and nutritive food.

Reusing and recycling waste and residues also contribute to agrifood systems that are more sustainable and efficient globally, and Andre Monk of Iolight, discuss increasing Aquaculture Productivity with Mobile Microscopes.

In the article titled, Emerging Zoonoses: A Human-wildlife Interface? Hina Malik at Guru Angad Dev Veterinary and Animal Sciences University examines how humans have ruined the balance of the ecosystem and exploited flora and fauna for their own gain.

Carel du Marchie Sarvaas at HealthforAnimals analyses political, regulatory, practical and market considerations related to the introduction and use of methane-reducing feed additives, while offering recommendations to improve pathways to market.

I hope you all enjoy this edition of IAHJ, and I look forward to working closely with the IAHJ team to bring more exciting features in the Winter issue.

Kevin Woodword, Managing Director, KNW Animal Health Consulting

EDITORIAL ADVISORY BOARD

Amanda Burkardt, MSc, MBA – CEO of Nutripeutics Consulting Germán W. Graff – Principal, Graff Global Ltd

Fereshteh Barei – Health Economist & Strategy Advisor, Founder of BioNowin Santé Avenue Association Carel du Marchie Sarvaas Executive Director Health For Animals

Kimberly H. Chappell – Senior Research Scientist & Companion Animal Product Development Elanco Animal Health Dr. Sam Al-Murrani – Chief Executive Officer Babylon Bioconsulting & Managing Director at Bimini LLC Sven Buckingham – Buckingham QA Consultancy Ltd.

Dan Peizer – Director Animal Health at Catalent Pharma Solutions

Dawn Howard – Chief Executive of the National Office of Animal Health (NOAH) Jean Szkotnicki – President of the Canadian Animal Health Institute (CAHI) Dr. Kevin Woodward – Managing Director KNW Animal Health Consulting

Norbert Mencke – VP Global Communications & Public Affairs Bayer Animal Health GmbH 4 International Animal Health Journal

Volume 10 Issue 3

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TALKING POINT Global Food Security and Health

What challenges are we facing today to make the transition towards a sustainable livestock production possible?

On current trends, it is clear is that we need to produce more food. As the global population continues to grow, more livestock products are needed, particularly in countries where people currently don’t even have enough to meet basic nutritional requirements.

Nearly 1 billion people are still under nourished. Livestock production is a pillar of livelihood, rural development and culture in numerous countries. Providing nutritious food in a sustainable and equitable manner will be a significant challenge, to which the livestock industries are well positioned to respond. Livestock can significantly contribute to deliver on the UN Sustainable Development Goals.

To be efficient, livestock production systems depend very much on where you are in the world. Thanks to this diversity we can maximise opportunities, but at the same time, we need to respond to the socio-economic questions and livelihood-related challenges that vary greatly from one country to another. This is also why it becomes very difficult today to have a balanced discussion on livestock. Too often we are looking for simple – or one size fits all – solutions to address very complex production systems. We need to engage the public in a two-way discussion to better explain [this complexity] and create a shared understanding.

How can we encourage international co-operation to improve the sustainability of livestock production and supply chains?

Livestock production systems have been on a continuous journey of improvement, and this culture of improving sustainability is needed in international cooperation. However, the needs are very different depending on the context (country, culture, level of economic development, etc.)

IMS has longstanding cooperation with several international initiatives to improve sustainability: •

United Nations Food and Agriculture Organisation (UN FAO) hosted Global Agenda for Sustainable Livestock

•

UN FAO hosted Livestock Environment and Performance Assessment

•

World Organisation for Animal Health (WOAH) cooperation to improve animal health and welfare, including the concept of One Health; that human, animal and plant health are interdependent and bound to the health of the ecosystems in which they exist. Therefore, what is proposed is a collaborative, whole of society, whole of government approach to understanding, anticipating and addressing risks to global health

What are the IMS priorities this year and how can the industry support them?

IMS is currently participating in a three-year cycle (2022–2024) of international cooperation on: 6 International Animal Health Journal

1.

Circular-bio economy. Livestock production upcycles agricultural products that cannot be consumed by humans,into valuable and nutritive food. Reusing and recycling waste and residues also contribute to agrifood systems that are more sustainable and efficient globally.

2.

Ecosystem services. Whenever food is produced there are ecosystem services that come with it. But as they are difficult to identify and price in the market, they are often not paid for. For instance, the beautiful landscape of a countryside with cultivated fields, and pastures on mountains and valleys, including the associated biodiversity, soil preservation, flood control, and so on are all ecosystem services for which farmers should be paid.

How can industry help support these initiatives? At the most basic level, do whatever is necessary to inform your own politicians (Ministry of Agriculture, Ministry of the Environment, Ministry of Health, etc.) the many contributions of livestock to a sustainable food system. Put another way, a food system cannot be sustainable without livestock.

What are you most looking forward to at Livestock Supply Chain Connect this year?

I am looking forward to meeting professionals in all aspects of livestock production. Learning from each other, working together is becoming more and more important in an increasingly interconnected world.

The BIG issues of our time: global food security and health, widespread poverty, resource scarcity and climate change can all be addressed with more sustainable livestock systems.

I am looking forward to discussing with colleagues examples of how they have approached these issues.

Hsin Huang Hsin Huang is Secretary General of the International Meat Secretariat (IMS).

Prior to joining IMS, he was responsible for climate change analysis in the Organisation for Economic Cooperation and Development (OECD)'s Trade and Agriculture Directorate.

Volume 10 Issue 3

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Increasing Aquaculture Productivity with Mobile Microscopes The United Nations forecasts that the population of the world will reach 9.8 billion by 2050. Many experts are concerned about the earth’s ability to feed so many people. Land-based agricultural resources increasingly struggle to meet this huge increase in demand and fish farming is growing dramatically to fill the gap.

More Fish in the Sea The UN Food and Agriculture Organisation reports that the average amount of fish eaten per capita globally has more than doubled from 9.0kg in 1961 to 20.2kg in 2015. Of course, there are well-publicised cases of overfishing, but much of this growth has been from aquaculture which has grown from 25.7% of production in 2000 to 46.8% in 2016. These data includes finfish, crustaceans and molluscs.

As with any farming, growing large amounts of food in a small space increases the incidence of infection and disease can spread extremely rapidly through a stock of 90,000 fish confined to a pen. Fish farms work hard on hygiene and diet, and minimising stress, to ensure that fish are kept healthy, minimising losses and producing a highquality product.

Rapid Diagnosis Fights Against Listed Diseases A key to keeping the stock healthy is the rapid diagnosis of disease and parasites. Large farms use continuous monitoring of the water, but there is no substitute for visual inspection of the fish, and early detection of small parasites means that facilities need a microscope.

Traditional compound microscopes are difficult to transport and use in remote environments and usually have no way of sharing images for records or a second expert opinion.

A new generation of portable microscopes can capture and share images and videos of parasites and other fish pathology instantly from a standard mobile phone.

The image quality is now close to that of a laboratory microscope, but the digital product fits in a jacket pocket and has a flat wipe-clean surface. This new class of high-

A high-resolution image of Fish Gills. Courtesy of AquaSolver.

resolution, portable microscope dramatically improves the speed of diagnosis and therefore the productivity in aquaculture environments. It is now possible to sample, diagnose, and treat serious health conditions within a few minutes. Site staff can even get a second expert opinion in the time it takes to send and receive an email.

The importance of rapid diagnosis can be understood by looking at Gyrodactylus salaris, or salmon fluke, a microscopic parasite that feeds on the flesh and mucus of salmon and other freshwater fishes. It has caused mortalities of up to 98% in wild Atlantic salmon populations in Norway.

Some stocks have been lost completely or destroyed by adding pesticide to infected rivers, killing parasites and fish, though this treatment is no longer common. Gyrodactylus salaris is so serious that it is classified as a listed disease that must be reported to the authorities. Rapid detection is vital in the removal of infected fish and the fight against these contagious diseases.

Pocket Digital Microscopes Ready to Go Anywhere The step forward in digital microscopes has been enabled by using high-quality, low-cost parts designed for mobile phones to make highly compact, robust instruments.

Originally these devices were low-cost, low-resolution, USB-connected devices, with limited application in the aquaculture market. However, more recent microscopes are pocket-sized and use a wireless connection to deliver 1-micron resolution images to a standard mobile phone.

The newer products feature a robust stage and transmitted illumination, like a compound microscope. Best of all, highresolution images and even videos can be shared instantly for a second opinion.

Portable high-resolution microscopes are meeting with approval from experienced aquaculture experts:

Copepod parasite egg sacks found on a Striped Bass. Courtesy Paul Curtis, AquaSolver 8 International Animal Health Journal

Bill Manci is the President of Fisheries Technology Associates where he has specialised, since 1982, in fisheries management, characterisation and evaluation of wild fisheries, and technical and economic feasibility analysis Volume 10 Issue 3

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Salmon fish farm in Norway

of fish farming and aquaculture facilities. “Without a doubt, the portability and ruggedness of these units and the high quality of the images are the innovations that truly wowed me.” Manci concludes, “For me, this was one of those moments when you say to yourself, ‘How did I ever get along without this device?’”

Dr. Rod Getchell works in the Aquatic Animal Health Program at the Cornell University College of Veterinary Medicine. “When examined side-by-side with pictures taken with my $10,000 microscope/camera set-up in our laboratory, the images stood up pretty well – for 10 times less money. I think this instrument has value for our fish farming friends in the field who do not want to deal with a traditional microscope.”

For Getchell, the connectivity is a real winner: “The fact that you can immediately send your images to colleagues

adds to the kind of instant communication that the next generation of fish health professionals will appreciate.”

Productivity If aquaculture is to continue its remarkable contribution to feeding the growing population of the world, fish farms need both new tools and new processes. Productivity and sustainability rely heavily on the ability to detect fastmoving diseases instantly, in remote locations. Referring samples to a laboratory back at base will be too slow and will result in significant stock losses and further spread of disease. Not only do microscopes and other tools have to be portable, but they must also have the performance required to make accurate diagnoses.

It will be interesting to watch how point-of-care diagnostics grows with the aquaculture industry, enabling the production of low-cost, high-quality food.

Andrew Monk Andrew Monk is passionate about getting scientific innovation to the forefront of animal health and into the veterinary community.

With Richard Williams, he is a cofounder of ioLight Limited. Together, they realised that there was an opportunity for a high-quality portable microscope using the latest developments in smartphone technology. Previously Andrew was CEO of semiconductor fab Innos Limited and Président of GLOphotonics SAS. He has a masters degree in physics from the University of Oxford.

Portable microscopes can capture and share images and videos of parasites and other fish pathology instantly www.international-animalhealth.com

Email: andrew.monk@iolight.co.uk

International Animal Health Journal 9

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An In-house ELISA for Treponema Antibodies In Bulk Milk is useful for Monitoring Claw Health Bovine digital dermatitis (DD) is a painful, infectious claw disorder that causes ulcerative lesions mainly at the coronary band of the hind legs of dairy cows and lameness. DD is not only a serious issue in terms of animal welfare, but also has significant economic consequences due to milk loss, decreased fertility and treatment costs.

Prevalence of DD in the Netherlands is estimated to be 20% to 30%. DD was first described in 1974, in Italy.

Common bacteria associated with DD are multiple phylotypes from the genus Treponema, of which T. medium/T. vincentii-like, T. phagedenis-like, and T. pedis are most representative. Lesions can be classified using the M-scoring system, developed by Döpfer et al.

Evaluation of lesions by lifting the cow’s feet for visual inspection is the most accurate DD identification system but is expensive, time consuming, labor-intensive, and stressful for cattle. Regular claw trimming and inspection of feet in the West-European countries is mostly performed twice a year. In the meantime, it is useful for dairy farmers to obtain information about the prevalence of Treponema spp. in the herd.

Main Results ELISA results in milk samples of all individual cows and the bulk milk samples of the seven herds obtained during three visits showed a good association (n=20, r2= 0.82, p<0.001) between the average S/P ratio of the individual samples and the S/P ratio of the bulk milk. When the average S/P ratios of the individual milk samples in ELISA were set off against the average M-scores or the M2-prevalence in these herds, in both cases a weak, but statistical significant association between the severity of the lesions and the S/P ratio was found (Figure 1 and 2).

Current laboratory tests for DD diagnostics in individual cows are based on histology, cultivation, PCR techniques and also ELISA for antibody detection. The advantage of the use of ELISA in milk is the availability of samples and the limited costs.

Aim The objective of this study was to develop, validate and implement a Treponema antibody ELISA in bulk milk to monitor and assess DD prevalence at the herd level.

Materials and Methods The farms used in this study were chosen by convenience sampling based on the willingness of the farmers to participate. In 2017 and 2018, seven herds were visited by trained GD employees three times in 2017-2018, with six months between each visit at the moment of regular preventive claw trimming. In these seven herds, all claws were scored according to the M-score system for presence and severity of DD. This M-score classification comprises six classes (M0, M1, M2, M3, M4, and M4.1). Class M0 is coding for healthy skin without lesions, M1 for an active granulomatous area of 0–2 cm, M2 for an ulcerative lesion of >2 cm, M3 for an ulcerative lesion covered by a scab, class M4 for alteration of the skin with hyperkeratotic lesions and class M4.1 codes for scar tissue with a new small lesion. In general, M2 stage is seen as most painful, but chronic lesions might be more infectious. After scoring, claws were trimmed and treated topically by the claw trimmer when necessary. Four weeks after each trimming, milk from all lactating cows was sampled. From another 110 herds, DD scores from one regular claw trimming were obtained, and one bulk milk sample was taken. Milk samples were tested for antibodies against Treponema spp. using an indirect ELISA based on a mixture of whole cell antigens from T. medium/T. vincentiilike, T. phagedenis-like, and two strains of T. pedis of which one was formerly known as T. denticola. The optical densities (OD) were measured and S/P values were calculated.

10 International Animal Health Journal

Figure 1. Scatterplots of trimming scores and bulk milk ELISA S/P-ratio’s on 7 herds sampled thrice; average M-score and S/P-ratio (n=20, r2=0.504, P); and M2-prevalence and S/P-ratio (n=20, r2=0.513, p<0.001).

To be able to distinguish herds with high and low level of Treponema antibodies in bulk milk, two cut-off values (0,87 and 1,24) were determined based on the 25 and 75 percentile of the S/P-ratio obtained for all bulk milk samples from the seven herds. These ELISA cutoff’s were evaluated in the 110 herds. Comparing the M2 prevalence with the bulk milk results, a good association was found. Only one of the herds had a high ELISA S/P-ratio in bulk milk, but a low M2 prevalence, while eleven herds were found with a high M2 prevalence and a low ELISA S/P-ratio.

Volume 10 Issue 3

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Figure 2. Comparison of M-scores and bulk milk ELISA S/P-ratio’s on 95 herds with information on both M2-scores and the bulk milk S/P ratio (r2=0.23, p<0.001).

From 2019 on, the Treponema ELISA was added to the Royal GD Claw Health program, using quarterly bulk milk testing. Other parameters tested in this programme are feed associated parameters biotin, zinc and manganese.

Results of these tests help farmers to improve claw health.

Conclusions A Treponema bulk-milk ELISA was developed to get insight in the DD status at herd level, and the ELISA is suitable to be used in a claw-health monitoring programme for dairy cattle in the Netherlands. Periodically bulk milk testing for antibodies against Treponema spp. is valuable to monitor the DD prevalence at herd level and may support dairy farmers in applying the correct curative and preventive measures.

Jet Mars After her study veterinary medicine in Utrecht, Jet Mars worked at the Veterinary Faculty in Utrecht, the Animal Health Service in Boxtel, and the Central Veterinary Institute in Lelystad. She joined Royal GD as a senior veterinary researcher having expertise in immune diagnostics, epidemiology, laboratory quality, and ruminant infectious diseases. She is a veterinary cattle specialist, a member of the Dutch Veterinary Association of Epidemiology & Economics (VEEC) and the European Society for Veterinary Virology.

Co-authors: Menno Holzhauer, Manon Holstege and Harold van der Heijden

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International Animal Health Journal 11

REGULATORY & MARKETPLACE

Emerging Zoonoses: A Human-wildlife Interface?

Outbreaks of emerging zoonotic diseases have increased in the past decade and have affected the population worldwide. Often the blame for such spillover events is put on animals; however, it is humans who have ruined the balance of the ecosystem and exploited flora and fauna for their own gain. The intrusion of humans into wild habitats has increased the human-wild interface thereby increasing the chances of interspecies transmitting diseases in both directions. At the same time, globalisation has increased the likelihood of the rapid dissemination of the infection worldwide. Not wildlife but anthropogenic determinants behind the occurrence of such events should be realised and addressed vehemently.

Millions of years ago when life began on earth, numerous species emerged and co-evolved sharing earth's resources and habitat. Homo sapiens, which evolved as the most intelligent species, dominated and exploited the major share of resources pushing the other species towards extinction or (at the very least) struggling to thrive. Humans expanded their habitat, croplands and livestock into the forests, which disrupted the natural ecosystem and thus ruined the harmonious coexistence with other wild species. Meanwhile, broken barriers by close human-animal interfaces enabled the interspecies transmission of pathogens to distant and diverse species. Incidences of novel pathogen emergence by animal to human transmissions and the extermination of millions of humans from Earth have been witnessed on various occasions. Outbreaks from emerging infectious diseases have been reported to increase every decade since the 1980s and most of them have been linked to wildlife.

Increased human-wildlife interactions brought about the recent pandemics of Human Immunodeficiency Virus, Ebola, swine flu, avian influenza, Severe Acute Respiratory Syndrome, Middle East Respiratory Syndrome, Nipah and many more. At this moment during the COVID-19 pandemic, its causative agent (SARS-CoV-2) is found to be closely related to the SARS-like coronavirus in bats1 and we must examine the anthropogenic determinants behind such circumstances, rather than pointing our fingers towards bats or other wildlife species.

In 2019, when the whole world was busy celebrating New Year's Eve, China encountered a cluster of cases suffering from pneumonia detected in Wuhan city and linked its emergence to the Huanan wet market. Taking into account the zoonotic emergence of the disease, Chinese authorities closed those animal markets in the city and reported the incident to the World Health Organization (WHO). Within two months, the disease spread globally and caused more than 200,000 casualties out of more than 3 million cases thus far. Considering the spread and severity of the disease, WHO declared the disease as a pandemic on 11th March, 2020. A pandemic is defined as "an epidemic occurring worldwide, or over a very wide area, crossing international boundaries and usually affecting a large number of people"2. Simply put, it includes widespread diseases causing large-scale morbidity and mortality. Pandemics not only affect public health but also disturb the sociopolitical structure of the countries. The underlying cause reported for the most recent pandemic is the emergence of a new virus or virus strain/ subtype, due to genetic reassortment. These new viruses are 12 International Animal Health Journal

usually highly contagious and after initial transmission from animals readily spread between humans, causing worldwide dissemination. Increased wild-human interface over the past years have increased interspecies transmission of the virus from maintenance hosts to new hosts, seen as a spillover, as well as reverting from spillover hosts to the maintenance hosts, which is known as spillback. These continuous spillover and spillback cycles have expedited the evolution of viruses where wildlife acts as reservoirs together with "living test tubes" facilitating mutation and recombination of the viruses.

Out of more than 1400 documented human pathogens, approximately 61% are considered to be zoonotic. In a study during 2007, Woolhouse and team listed out 87 novel pathogens which were reported to be pathogenic to humans during 1980–2005.

Two-thirds of these were viruses and 85% had single-stranded RNA (ssRNA) genomes3. Most of the emerging viruses are ssRNA viruses, which lacks the proofreading capabilities of DNA polymerase or post-replication mismatch repair, leading to the high rate of error during RNA replication which is around 10 times more than DNA viruses. Most RNA viruses are zoonotic in nature as they are capable of a species jump; they were transmitted, at least initially, to humans from non-human mammals or avian hosts. Examples of RNA viruses retaining the capacity to be directly transmitted from animals to humans include influenza, Nipah, and SARS viruses, but even some viruses commonly transmitted exclusively between humans, such as HIV and hepatitis C, likely have animal origins.

Usually the interactions between wildlife and humans take place in two ways, either by the encroachment of their habitat by the human, or having an interest in wildlife tourism, souvenirs and exotic pets. The expanding human population compels intrusion of forests for human habitation, destroying wild habitats which leave wild animals concentrated in a smaller area facing a shortage of food. The dense population of wild animals in a limited area facilitates the interspecies transmission and maintenance of pathogens. Nutrient deficiency and low immunity due to food scarcity further contribute to the proliferation of the pathogens in reservoir hosts. Shortage of food pulls wildlife towards abundant food supply near human habitation bringing wildlife, livestock and human in close contact, which consequently provides a highly conducive environment for the spillover of the pathogens. An appropriate example to be cited here is, during 1998, deforestation and intensive farming of fruit trees with pig farming brought bats near fruit trees, shedding the virus to pigs through partially-eaten fruit droppings4. Similarly, human immunodeficiency viruses HIV1 and HIV-2 are closely related to the simian immunodeficiency virus which was spilled over to humans by coming into contact with SIV-infected non-human primates during hunting and butchering5. A fancy for wildlife fur, leather, ivory and souvenirs, as well as beliefs in traditional medicines, had served as a ground for an illegal yet highly lucrative trade in wildlife, worldwide. These trade industries are known to introduce pathogens to new places along with the introduction of exotic animals and their body parts.

The outbreak of monkeypox in the USA, in 2003, is a good example, where prairie dogs introduced the disease into Midwestern states of the US, by acquiring the infection from infected Gambian rats in transportation6. The first incidence of Marburg haemorrhagic fever was observed in the researchers of Germany in 1967, which were exposed to African green monkeys or their tissues imported Volume 10 Issue 3

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Figure 1. Animals visiting human habitation in search of food

from the handling, preparation and consumption of meat from chimpanzees found dead8. Intensely dense live animals’ markets, also known as wet markets, bring different animal species into close contact, where butchering of an infected animal contaminates the environment with blood spills, which thus provide a highly favourable environment for interspecies transmission and mutations of pathogens. Wet markets in Southeast Asian countries had contributed to the emergence and spread of highly pathogenic avian influenza H5N1 in 2006.

Outbreaks of Severe Acute Respiratory Syndrome (SARS)9 in 2003 and ongoing COVID-1910 have also been linked to the trade in civet cats and pangolins, respectively, in Chinese wet markets.

New trends of captivating wildlife in the name of exotic pets bring human and wild animals under the same roof, increasing the duration of exposure and odds of disease transmission.

Figure 2: Interference in animals’ natural habitat via recreational activities

from Africa. Social and traditional values attached to bushmeat consumption make its hunting and trade a million-dollar industry in China and African countries. In the past 20 years, poaching of gorillas for bushmeat has reduced its population to half in forests in the Democratic Republic of Congo. In 1970, the first incidence of monkeypox virus disease to human was linked to non-human primates hunting followed by human-to-human transmission7. The outbreak of Ebola in Gabon in 1995 emerged www.international-animalhealth.com

Despite the emergence of deadly pandemics with wildhuman interactions, the control measures for minimising human interference are either inadequate or infringed very frequently. Stringent laws on killing, captivity and trade of wild species must be framed and employed rigorously.

Preservation of natural habitats of wildlife must be undertaken and injudicious cutting or burning of forests must be prohibited. Human access for livestock grazing, hunting or other recreational activities must be minimised in the buffer zone and strictly restricted in core forest regions. Despite the reports stating wildlife as reservoirs of many pathogens, there is a dearth of monitoring, surveillance and baseline data of diseases in wild animals. Lack of baseline data on disease and population of wildlife in an area render the health authorities incapable of identifying the source of disease. Wildlife International Animal Health Journal 13

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Figure 3: Schematic representation of common emerging zoonoses from wildlife

surveillance requires a multi-sectoral approach, including native people, animal health agencies, public health agencies and forest departments. Adequate awareness of people interacting with wildlife is needed to facilitate the monitoring and data gathering. Adequate active and passive surveillance of transmission, carriers and reservoirs of diseases in wildlife is an essential precondition for rapid identification of a spillover.

Latest models to predict future spillovers ahead of time must be employed in surveillance studies. Measures like diagnosis, treatment, vector reduction and vaccination in wild animals must be taken to reduce the pathogen load and diminish the likelihood of disease transmission to human.

REFERENCES 1.

2.

3.

4.

5.

6.

Xu, X., Chen, P., Wang, J., Feng, J., Zhou, H., Li, X., Zhong, W. & Hao, P. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Science China Life Sciences, 63(3), 457460(2020).

Last, J. M., Harris, S. S., Thuriaux, M. C. & Spasoff, R. A. A dictionary of epidemiology. International Epidemiological Association, Inc. (2001).

Woolhouse, M. & Gaunt, E. Ecological origins of novel human pathogens. Crit. Rev. Microbiol. 33, 231–242 (2007).

Epstein, J. H., Field, H. E., Luby, S., Pulliam, J. R. & Daszak, P. Nipah virus: impact, origins, and causes of emergence. Current Infectious Disease Reports, 8(1), 59-65(2006).

Myers, G., MacInnes, K. & Korber, B. The emergence of simian/ human immunodeficiency viruses. AIDS research and human retroviruses, 8(3), 373-386(1992).

Centers for Disease Control and Prevention (CDC). Update: multistate outbreak of monkeypox--Illinois, Indiana, Kansas, Missouri, Ohio, and Wisconsin, 2003. MMWR. Morbidity and mortality weekly report, 52(26), 616 (2003).

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8.

9.

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Jezek, Z., Arita, I., Mutombo, M., Dunn, C., Nakano, J. H. & Szczeniowski, M. Four generations of probable person-toperson transmission of human monkeypox. American journal of epidemiology, 123(6), 1004-1012 (1986).

World Health Organization. Outbreak of Ebola haemorrhagic fever in Gabon officially declared over. Weekly Epidemiological Record= Relevéépidémiologiquehebdomadaire, 71(17), 125-126 (1996).

Daszak, P., Tabor, G. M., Kilpatrick, A. M., Epstein, J. O. N. & Plowright, R. Conservation medicine and a new agenda for emerging diseases. Annals of the New York Academy of Sciences, 1026(1), 1-11 (2004).

Zhang, T., Wu, Q. & Zhang, Z. Probable pangolin origin of SARS-CoV-2 associated with the COVID-19 outbreak. Current Biology (2020).

Hina Malik Hina Malik graduated in Veterinary Medicine and post graduated in Veterinary Public Health. She has been working at the Uttarakhand Animal Husbandry Department as a veterinary clinician for last five years.

She is also pursuing a PhD in Veterinary Public Health from the School of Public Health and Zoonoses, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, India. Her area of research is Zoonoses and emerging antimicrobial resistance in zoonotic pathogens.

Email: hinamalik.vet@gmail.com

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Controlling Rabies in Foxes Unprecedented Success in Europe The European Union (EU) aims to eliminate foxmediated rabies from its territory by 2020. At first sight, this seems a rather ambitious goal considering that this horrifying disease has tormented humans and animals in Europe since ancient times.

Highly efficacious and safe vaccines for humans are available in Europe and, consequently, human rabies cases are extremely rare, the majority being reported in Russia.

However, the potential threat remains, as the disease has not been eliminated from the main reservoir host species, the red fox (Vulpes vulpes). This zoonotic disease has the highest fatality rate among humans of any infectious disease known, so its elimination from such a large geographical area as the EU would be a major accomplishment. This is especially so when considering the red fox is an evasive wildlife species making control difficult to implement.

The latest rabies epidemic among red foxes is believed to have started in the Kaliningrad region of Russia, which borders Poland and Lithuania, in the 1940s. It then spread to most countries of Eastern, Central and Western Europe by the mid-1970s. Initially, control efforts concentrated on reducing the density of the fox population, through intensified hunting, culling cubs, poisoning and gassing of dens, to below a threshold that could sustain transmission. These population reduction efforts were not only highly controversial, they had little impact and, retrospectively, were actually considered to be counterproductive.

by the WHO Collaborative Centre for Rabies Surveillance and Research. Initially, it was compiled at the Federal Research Institute for Virus Disease of Animals in Tübingen, Germany, but now it is based at the Friedrich-Loeffler-Institute in Insel Riems – Greifswald, Germany.

This availability of detailed European rabies data – spanning four decades of oral rabies vaccination (ORV) campaigns – gives a unique opportunity to analyse progress in the elimination of fox-mediated rabies in Europe.

Rabies Incidence During the past four decades, 31 European countries implemented ORV programmes within their territories. The total area ever covered, at least once, with vaccine baits between 1978 and 2018 encompassed 2.73 million km2 (Fig 1). This peaked in 2007 when baits were concurrently distributed over approximately 1 million km². As a result of the implementation of ORV, the number of rabies cases reported annually in Europe to the RBE steadily declined from 15,355 in 1978 to 4027 in 2018, with intermediate peaks in 1984 and 1989.

However, to appraise the true impact of ORV on the rabies incidence, it is necessary to differentiate geographical and time-based use of this disease management tool.

With the development of oral vaccination of foxes against rabies – using vaccine-loaded baits distributed in the environment – a completely new approach to wildlife disease management became available. The first field trial took place in Switzerland in 1978, followed by efforts in other European countries, starting with Germany, Italy, France and Belgium.

Rabies Bulletin Europe By coincidence, shortly before the first field trial, a European database and rabies reporting system was established by the World Health Organization (WHO), in 1977. Called the WHO Rabies Bulletin Europe (RBE), it aimed to meet the demand for adequate and reliable rabies surveillance data across borders.

The use of this single reporting system has encouraged collaborative control efforts in neighbouring countries through the evaluation of shared epidemiological data – even across political boundaries! Cross-border cooperation is essential for sustained rabies control, especially for a disease with a wildlife reservoir species that does not respect borders or political boundaries.

Of course, during the initial years of RBE when the Cold War was nearing its height, the political climate in Europe sometimes hindered uncensored data- sharing. However, despite this situation, RBE did not only collect and analyse data across political divides, it also enabled certain countries to improve their rabies surveillance data collection system.

Initially, RBE appeared in printed form on a quarterly basis but nowadays is available electronically (www.who-rabiesbulletin.org). This European rabies database is maintained www.international-animalhealth.com

Figure 1: Map of Europe and the areas covered by ORV. All maps were kindly created by Patrick Wysocki, IfE, FLI.

Data from the RBE database has been stratified into four geographical regions: 1.

2.

3.

4.

The west – and central European countries that started with ORV campaigns early (1978-1993).

Countries that started relatively late with sustained optimised ORV programmes (Baltic countries).

Countries that started with coherent cross-border ORV programmes within the last 10 years.

Countries in far-Eastern Europe with no comprehensive ORV programme (Belarus, Russia, Ukraine and Moldovia).

Of the European countries that have implemented ORV programmes, Turkey is excluded from this analysis. Turkey is the only country in Europe with dog-mediated rabies.

Sustained rabies transmission in foxes occurred in the Aegean region of Turkey following a spill-over from dogs in International Animal Health Journal 15

REGULATORY & MARKETPLACE the late 1990s. ORV campaigns targeted at red foxes were undertaken during the periods 2008–2010 and 2014–2016.

Although these campaigns clearly demonstrated the feasibility of fox rabies control by ORV in Turkey, the impact on the rabies incidence is hampered by persistent dogmediated rabies.

Trial-and-error Phase – Geographical Area 1 (West and Central Europe) In west and central Europe, the red fox was the main reservoir for rabies. In the early 1970s, innovative research in the US had shown that red foxes could be immunised by the oral route against rabies using attenuated rabies viruses. West and central European countries were the first to test the principal concept of ORV under field conditions. They developed the basis for future successful implementation of large-scale ORV with Switzerland, Germany and France spearheading those developments.

During the initial years between 1978 and 1989, a trialand-error approach was used. No detailed protocol was available on the geographical and time-based distribution of oral rabies vaccine baits for the countries pioneering this novel method of controlling rabies. In addition, vaccines as well as baits were still under development and subject to improvement, especially regarding potency, safety and stability. Consequently, progress was sometimes protracted during the first decade as setbacks had to be experienced and lessons learned. Notwithstanding, it soon became evident that ORV was a breakthrough in fox rabies control.

In 1989, the EU decided to include rabies in its co-financing policy for disease eradication, turning ORV field trials into true rabies eradication programmes. This has been a strong stimulus for fox rabies control in Member States ever since. In 2002, the European Commission issued a report evaluating ORV efforts within the EU, thus providing a standard operating protocol for ORV campaigns and subsequent monitoring.

Significant progress was only reported after this optimised ORV-strategy occurred, having gained sustained financial support from the EU for Member States and neighbouring countries (Fig. 3). In the final phase, residual foci of infection or re-infections contributed to outbreaks in Hungary and Poland, respectively. However, with improved distribution of baits, these outbreaks were successfully controlled. In 2018, only one rabies case was reported in the EU, in Poland at the border with Belarus.

This observation seemed to jeopardise control efforts.

Fortunately, however, the ORV approach used for foxes also worked for this species. This was revealed in outbreaks of rabies in southern Finland in 1988 that were exclusively driven by this species. They were brought under control using ORV within just two years. The much more rapid decline in reported rabies cases, compared with western and central Europe, is obvious (see Figure 4). This was because the Baltic countries that started sustained ORV programmes in the early 2000s (2004–2007) benefited from experience and optimised ORV protocols, including the use of machine-made baits and implementation of aerial distribution of baits. Within 10 years, rabies incidence fell to zero. Re-infection from neighbouring endemic areas in Russia and Belarus caused only single rabies cases in recent years with no sustained onwards transmission.

Figure 3: Map of geographical area 2 (left) with starting year of ORV indicated. Right: Number of reported rabies cases in this area from 2000–2018.

Coherent ORV – Geographical Area 3 (Balkan Countries) As in western and central Europe, on the Balkan peninsula fox-mediated rabies had been predominant with cyclical fluctuations that peaked in 2008. Slovenia and Croatia were the first countries to implement ORV in this region – in 1989 and 1991, respectively. Thanks to financial support from the EU, sustained ORV programmes were launched in the remaining rabies endemic Balkan countries between 2009 and 2011. Emergency-response campaigns conducted in Northern Greece in 2013 eliminated fox rabies, after incursion from neighbouring Northern Macedonia, within a short period of time.

What makes the performance of ORV in this region truly remarkable is that, in contrast to the other two ORV regions, here a coherent cross-border vaccination strategy was implemented. The entire endemic region was almost continuously targeted right from the beginning. Also, computer-supported, automatic aerial distribution and geographic information systems (GIS)-based assessment of bait distribution, developed in the meantime, became standard. Within nine years, rabies cases in the Balkan decreased from 1647 cases in 2009 to only five in 2018 (Figure 4).

Figure 2: Map of geographical area 1 (left) with starting year of ORV indicated. Right: Number of reported rabies cases in this area from 1977 – 2018. The peak in 2010 and the following years is exclusively related to outbreaks in Poland and Hungary

Optimised ORV – Geographical Area 2 (Baltic Countries) The epidemiology of rabies in the Baltic countries is also driven by the raccoon dog (Nyctereutes procyonoides), since this is the second most reported species, next to the red fox, as the main reservoir for the disease. The racoon dog is an invasive species, originally introduced in the 1920s as hunting game to the European part of the former Soviet Union. It readily adapted to the local environment. As a result, there was a dramatic increase of the incidence of rabies after the turn of the millennium.

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Figure 4: Map of geographical area 3 (left) with starting year of ORV indicated. Right: Number of reported rabies cases in this area from 2000–2018.

Impaired Use of ORV Currently, Eastern Europe and adjacent parts of Asia still remains an endemic area for fox-mediated rabies. The pattern of rabies appears different compared with other European counties, for example: Volume 10 Issue 3

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2.

The size of the infected area is enormous, and A very low human population density may bias rabies surveillance towards domestic animals.

Although Belarus, Russia and the Ukraine implemented ORV field trials in parts of their territories, for various reasons they did not have any impact on the rabies incidence; these countries are still far from implementing comprehensive ORV programmes (Fig. 5).

Figure 5: Map of geographical area 2 (left) with starting year of ORV indicated. Right: Number of reported rabies cases in this area from 2000–2018.

Conclusion Within the past 40 years, the implementation of ORV has reduced the rabies incidence in Europe by 74 per cent.

While this may not seem effective considering the financial efforts, 99 per cent of all reported rabies cases (4027) in Europe in 2018 (excluding Turkey) originated from the far Eastern European countries with no sustained ORV programme (geographical area 4). In contrast, in all other European countries (excluding Turkey), only 10 cases were reported in 2018.

Getting rid of the last remaining one per cent of rabies cases costs disproportionately more time and effort than the first 99 per cent. However, it seems that the challenging target of extinguishing fox rabies from the EU is feasible by the year 2020. Since 2000, indeed, after successful rabies elimination ORV programmes have been discontinued in several countries. However, due to the rabies situation in the far Eastern European countries, the establishment of a vaccination belt is required to prevent the re-emergence of rabies in neighbouring countries. This has been implemented in Finland since the 1990s. The EU has been supporting the establishment of such a ‘cordon sanitaire’ by co-financing ORV in Member States and neighbouring non-EU countries. As this vaccination belt covers large areas in several countries, long-term sustainability is required.

In Eastern Europe, vast endemic areas still have to be covered by ORV. The fact that these countries would have to bear all costs related to ORV themselves probably hampers the implementation of large-scale

ORV programmes over their entire territories in the near future. Therefore, support for the development and design of alternative, more cost-efficient and new vaccination and surveillance strategies, should be considered. In this context, natural barriers like rivers need to be taken into account.

However, although largely effective, these barriers to immunity, artificial or natural, are not entirely impermeable so vigilance remains of utmost importance. In case of a breach, a rapid response through emergency ORV campaigns can quickly restore the rabies-free status.

Hence, collecting and sharing rabies surveillance data through the RBE remains essential for safeguarding the unprecedented success in rabies control achieved in Europe.

Challenges Ahead One of the major challenges will be upholding the rabies-free status within the EU. The threat of becoming re-infected through invading rabies-infected wildlife from the far eastern European countries and possible preventive measures (“vaccination belt”) have already been discussed. However, another possible way of reintroduction is a sustained spill-over from imported pets originating from rabies-endemic countries. Until now, these cases have not been able to spread to susceptible wildlife, predominantly thanks to immediate control measures employed. However, the risk cannot be ignored.

As for other diseases, such as foot-and-mouth disease (FMD), some countries have established a vaccine bank for an emergency vaccination campaign in case of an outbreak. Unfortunately, the establishment and maintenance of such a vaccine bank is relatively expensive. Hence, the establishment of an EU vaccine bank for oral rabies vaccine baits could be more costeffective than for maintaining them in the individual Member States.

Recently, other potential rabies reservoir species have become more abundant and their population range has expanded considerably in Europe. These include the raccoon (Procyon lotor), golden jackal (Canis aureus), small Indian mongoose (Herpestes auropunctatus) and Egyptian mongoose (H. ichneumon). All these species cannot be reached by a single oral rabies vaccine bait type due to, for example, different food preferences, animal size and vaccine dose needed. Furthermore, for some of these species no product is available; not licensed and/or under development.

Vaccine, delivered by oral bait, has been a highly successful method of controlling rabies in wildlife. www.international-animalhealth.com

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The red fox is the major host species for rabies in Europe, a zoonotic disease with the highest fatality rate among humans.

REFERENCES 1.

2.

3.

4.

Cliquet F, Robardet E, Must K, Laine M, Peik K, PicardMeyer E, et al. (2012) Eliminating rabies in Estonia. PLOS Negl Trop Dis.;6(2):e1535.

Cliquet F, Aubert M. Elimination of terrestrial rabies in Western European countries. In: Schudel A, Lombard M, editors. Control of infectious diseases by vaccination.

Dev Biol. Basel: Karger; 2004. p. 185-204.

Freuling CM, Klöss D, Schröder R, Kliemt A, Müller T (2012) The WHO Rabies Bulletin Europe: a key source of information on rabies and a pivotal tool for surveillance and epidemiology. Rev Sci Tech Bull Off Int Epiz, 31(3):799807 Freuling CM, Hampson K, Selhorst T, Schröder R, Meslin FX, Mettenleiter TC, Müller T (2013) The elimination of

5.

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fox rabies from Europe: determinants of success and lessons for the future. Phil Trans R Soc B, 368:20120142.

Müller TF, Schröder R, Wysocki P, Mettenleiter TC, Freuling CM (2015) Spatio-temporal Use of Oral Rabies Vaccines in Fox Rabies Elimination Programmes in Europe. PLoS Negl Trop Dis 9(8): e0003953.

Müller T, Freuling CM, Wysocki P, Roumiantzeff M, Freney J, Mettenleiter TC, Vos A (2013) Terrestrial rabies control in the European Union: Historical achievements and challenges ahead. Vet J, 203(1): 10-17 Müller T, Freuling C (2018) Rabies control in Europe: an overview of past, current and future strategies. Rev. Sci. Tech. Off. Int. Epiz., 2018, 37 (2):409-419 European Commission (2002) The oral vaccination of foxes against rabies. Report of the SCAHAW.

Raccoon dogs, next to the red fox, as the main reservoir of rabies in Eastern Europe.

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Aerial distribution of vaccine-loaded baits has enabled vaccination to take place in habitats, not otherwise easily accessible.

1.

2.

3.

European Commission (2015) Update on oral vaccination of foxes and raccoon dogs against rabies.

EFSA Journal, 13(7):4164 European Commission (2017) Rabies eradication in the EU: Overview Report.

Wandeler A (2004) Epidemiology and ecology of fox rabies in Europe. In: King AA, Fooks AR, Aubert M, Wandeler AI, editors. Historical perspective of rabies in Europe and the Mediterranean Basin. Paris: OIE;. p. 201-14.

Dr. Ad Vos Dr. Ad Vos has worked on oral rabies vaccination as a wildlife biologist at the WHO Collaborating Centre for Rabies Research and Surveillance at the Federal Research Institute for Virus Diseases of Animals in Tübingen – Germany, from 1988 to 1993. Subsequently, he joined IDT Biologika GmbH and Ceva Santé Animale in 1994 and 2019, respectively.

www.international-animalhealth.com

Dr. Conrad Freuling Dr. Conrad Freuling has been responsible for the WHO Rabies Bulletin Europe as editor, both for the journal, the database and website at the WHO Collaborating Centre for Rabies Research and Surveillance at the Friedrich-Loeffler-Institute for the past 15 years.

Dr. Thomas Müller Dr. Thomas Müller has been head of the National Reference Laboratory for Rabies in Germany since 1995.

Additionally, he serves as head of the WHO Collaborating Centre for Rabies Surveillance and Research and the OIE Reference Laboratory for Rabies at the FriedrichLoeffler-Institute.

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Improving Animal Production Biosecurity to Minimise Global One Health Risks Despite remarkable advances in human and veterinary medicine over the past century, infectious diseases remain an important cause of morbidity and mortality for both humans and animals around the world1–4. At least 60% of existing human infectious diseases and up to 75% of newly emerging diseases in humans are thought to have an animal origin, underscoring that the health of animals and humans are irrevocably intertwined5.

An estimate of the combined human and animal burdens of specific zoonotic diseases can be calculated to provide tangible evidence of the significant impact of a particular zoonotic disease on a given society6,7. For example, the World Health Organization (WHO) has estimated the annual global cost of cysticercosis, a parasitic infection transmitted through consumption of infected pork, to exceed $760,000 USD in terms of human health considerations and over $2 billion USD in terms of economic losses in livestock production8. Risks associated with spread of infectious diseases from animals are likely only to increase with increasing globalisation and transboundary movement of animals and animal products. The practice of routinely taking into account the health outcomes of humans and animals (and the environment), known as One Health (Figure 1), is essential for continued improvements in animal and human medicine for the future.

its direct impact on human health outcomes, enhancing biosecurity for food animal production directly targets at least six of the UN’s 17 sustainable development goals (https:// www.un.org/sustainabledevelopment/sustainable-development-goals/).

Biosecurity – A Definition In this context, biosecurity refers to the integrated practices and policies applied at a national, regional or local level to minimise and manage the various threats that may contribute to illness or unthriftiness in animals being raised for food or fibre. Biosecurity generally refers to keeping infectious agents out of an animal operation or farm, whereas biocontainment refers to keeping any infectious agent(s) present on a farm or within a region contained to that region.

A better understanding of basic biosecurity principles by farmers and more consistent application of them can significantly reduce the burden of zoonotic disease and pre-empt animal disease outbreaks in a given region or country. Recent epidemiologic modelling of known patterns of pathogen transmission across pig farms in countries with defined biosecurity practices have demonstrated that production efficiency and animal welfare could be improved with more consistent attention to enhanced biosecurity practices11. Further, biosecurity principles may be combined with vaccination or preventative therapeutic administration to reduce or eradicate diseases in a region, such as cysticercosis in swine6. An effective regional biosecurity programme therefore requires training of producers and dissemination of educational resources as well as respectful local support and oversite networks to be sustainable12.

In extensive settings, assistance to farmers often can be effectively accomplished through grassroots or peer-topeer organisations.

Figure 1: The ‘One Health’ umbrella, which recognises the intertwined fates of humans, animals, and the environment (from9).

Basic Principles of Biosecurity in Animal Production and Management Implementation of an effective on-farm or livestock management biosecurity programme does not have to be an expensive or complicated undertaking. Several key principles have been shown to be highly effective for promoting biosecurity, regardless of the species being considered, and these are discussed in more detail below10.

These principles relate to access management, animal management, and operational management. Even in remote and extensive farming situations, basic biosecurity principles can be practised.

There are many areas of consideration for minimising global One Health risks, such as prudent antimicrobial use, competent food inspection authorities, and the use of vaccines to reduce and eliminate key infections. Another significant area of attention is enhancement of biosecurity employed in animal production. In addition to improving animal health and welfare, improved biosecurity practices lead to an increased human health index, because of increased farm stability, better profitability of marketed goods and livestock, and improved food safety, and thus human health. Well defined animal biosecurity programmes are part of sustainable agricultural practices.10 Because of

Controlled access to animals, through the use of pens, sheds, barns, and other shelters can minimise intraand interspecies exposure to animals and transmission of pathogens. Routinely practising good hygiene, such as regular handwashing (particularly before eating or preparing human food), cleaning clothing and footwear heavily soiled with animal waste, and removing or burying human faeces to prevent animals, such as pigs, from contacting or consuming them is important for reducing bioburden and breaking parasitic transmission cycles between animals and humans. Exclusion of pests and vermin is important to reduce disease transmission by

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RESEARCH AND DEVELOPMENT arthropod and rodent vectors, and because insects and vermin can infest animal feeds, such as grain, and reduce feed quality. Physical separation of sick and healthy animals, and handling and attending to the needs of healthy animals first will help to reduce disease transmission within a group of animals. These practices also apply when introducing new animals into a herd or flock. A period of quarantine and stabilisation can be helpful to ensure that new stock are healthy and free from disease. Ensuring that animal feed is unspoiled and that water is clean and uncontaminated will help to minimise the spread of disease within a group of animals. Timely and appropriate disposal of deadstock is important as poorly managed disposal of carcasses can lead to persistence of pathogens in the environment and can also attract pests. Similarly, animal wastes and manure need to be appropriately managed to reduce pathogen burden. More sophisticated programmes can incorporate written plans, self-assessment schemes and ongoing monitoring.

Numerous examples of species-specific biosecurity guidelines are available to assist farmers with understanding these practices and developing robust programmes.

Biosecurity Risk Management Despite the apparent sensibility of adopting better biosecurity practices there can be resistance to changing traditional management and husbandry practices as well as daily habits and routines. This has led to spectacular outbreaks of disease in animals and humans, such as multiple outbreaks of virulent and unusual forms of avian influenza in China when pigs, poultry and other animal species are mixed in public markets4. Even in economically well developed countries with regulated production oversight systems and national production standards, producers may fail to see the value of implementing robust biosecurity practices, leading to increased risks to both human and animal health13-15.

Traditionally, the responsibility for biosecurity risk management, assessment, and communication has fallen largely on the shoulders of farmers, their veterinarians, and their associated marketing groups and these programmes have been managed for better or for worse within any given country. This has resulted in inconsistent implementation of recommended practices and gaps in programmes often aren’t identified until health problems have occurred, for example, transmission of Salmonella enteriditis in farmed eggs16. Because all people have a vested interest in their own health as well as in the health and welfare of animals raised around them and because animals and animal byproducts are often shipped from the origin to distant places around the world it is critical that an integrated approach be taken for farmed animal biosecurity risk management. This builds on strengths that may already exist in local or regional oversight.

Health Security Interface – An Integrated Approach The global interdependence of countries for food emphasises the need for better coordination and management of food animal biosecurity at national and international levels. The OIE (http://www.oie.int/for-the-media/press-releases/detail/ article/investing-in-biosecurity-a-key-step-to-curb-thespread-of-animal-diseases/), FAO (http://www.fao.org/biosecurity/) and WHO (http://www.who.int/influenza/human_ animal_interface/en/) all strongly espouse the need for better integrated approaches to biosecurity management to protect human and animal health. With a One Health approach for biosecurity risk management, there can be better accounting and reporting of biosecurity risks at regional and national levels with assistance and support www.international-animalhealth.com

provided, as needed, at international levels. Additional benefits of an integrated approach to biosecurity risk management include improved monitoring for human health concerns, better information-sharing nationally when biosecurity concerns arise, minimising trade disruptions related to biosecurity risks, addressing consumer concerns about animal biosecurity and One Health issues, and providing a better perspective from which to observe, monitor and act on transboundary diseases in animals.10 Conclusions It is no longer possible for countries to consider the health and care of their food animals as an isolated and private affair. Increasing recognition of shared diseases between animals and humans together with a better understanding of foodborne pathogens and knowledge about complex global food distribution systems have only served to emphasise gaps in food animal biosecurity risk management around the world. To address these gaps and to ensure safer and more secure food for populations around the world, there is a need for governments to adopt a consistent, proactive and integrated approach to farm animal biosecurity risk management. Adoption of this approach should result in better biosecurity risk assessment, analysis, and preventative action to improve the lives of animals, humans, and their ecosystems.

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Anderson BD, Ma MJ, Wang GL, Bi ZQ, Lu B, Wang XJ, Wang CX, Chen SH, Qian YH, Song SX, Li M, Zhao T, Wu MN, Borkenhagen LK, Cao WC, Gray GC. Prospective surveillance for influenza. virus in Chinese swine farms. Emerg Microbes Infect. 2018;7(1):87. doi: 10.1038/s41426-018-0086-1.

Khaing TA, Bawm S, Wai SS, Htut Y, Htun LL. Epidemiological survey on porcine cysticercosis in Nay Pyi Taw Area, Myanmar. J Vet Med. 2015:340828. doi: 10.1155/2015/340828.

Steinmuller N, Demma L, Bender JB, Eidson M, Angulo FJ. Outbreaks of enteric disease associated with animal contact: not just a foodborne problem anymore. Clin Infect Dis. 2006;43(12):1596-602.

Su S, Bi Y, Wong G, Gray GC, Gao GF, Li S. Epidemiology, evolution and recent outbreaks of avian influenza virus in China. J Virol. 2015; 89:8671-6.

Vorou RM, Papavassiliou VG, Tsiodras S. Emerging zoonoses and vector-borne infections affecting humans in Europe.

Epidemiol Infect. 2007;135(8):1231-47.

Maurice J. Of pigs and people – WHO prepares to battle cysticercosis. Lancet. 2014; 384:571-2.

Torgerson PR, Rüegg S, Devleesschauwer B, Abela-Ridder B, Havelaar AH, Shaw APM, Rushton J, Speybroeck N. zDALY: An adjusted indicator to estimate the burden of zoonotic diseases. One Health. 2017;5:40-5. doi: 10.1016/j. onehlt.2017.11.003.

WHO. Some figures on neglected diseases. http://www. who.int/neglected_diseases/diseases/zoonoses_figures/ en/ (last accessed Nov 11, 2018).

Gibbs EPJ. The evolution of One Health: a decade of progress and challenges for the future. Vet Rec. 2014; 174:85–91.

FAO. Part 1: Biosecurity principles and components. http:// www.fao.org/docrep/pdf/010/a1140e/a1140e01.pdf (last accessed Nov 12, 2008).

Filippitzi ME, Brinch Kruse A, Postma M, Sarrazin S, Maes D, Alban L, Nielsen LR, Dewulf J. Review of transmission routes of 24 infectious diseases preventable by biosecurity measures and comparison of the implementation of these measures in pig herds in six European countries.

Transbound Emerg Dis. 2018;65(2):381-398. doi: 10.1111/ tbed.12758.

Rezaei A. Food safety: The farmer first health paradigm.

One Health. 2018;5:69-73. doi: 10.1016/j.onehlt.2018.04.001.

Kylie J, Brash M, Whiteman A, Tapscott B, Slavic D, Weese International Animal Health Journal 21

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JS, Turner PV. Biosecurity practices and causes of enteritis on Ontario meat rabbit farms. Can Vet J. 2017, 58(6):571-8.

Compo N, Pearl DL, Tapscott B, Storer A, Hammermueller J, Brash M, Turner PV. On-farm biosecurity practices and causes of preweaning mortality in Canadian commercial mink kits. Acta Vet Scand. 2017; 59(1):57. doi: 10.1186/s13028017-0326-8.

Graham JP, Leibler JH, Price LB, Otte JM, Pfeiffer DU, Tiensin T, Silbergeld EK. The animal-human interface and infectious disease in industrial food animal production: rethinking biosecurity and biocontainment. Public Health Rep. 2008; 123(3):282-99.

Trampel DW, Holder TG, Gast RK. Integrated farm management to prevent Salmonella Enteriditis contamination of eggs. J Appl Poultr Res. 2014; 23:353-65.

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Patricia V. Turner, Patricia V. Turner, MS, DVM, DVSc, DACLAM, DABT, DECAWBM (AWSEL) is President-Elect of the World Veterinary Association and Chair of the WVA’s Animal Welfare Working Group and Veterinary Education Working Group. She lives in Canada and works in a global capacity overseeing animal welfare policy and risk management for Charles River.

Email: patricia.turner@crl.com

Volume 10 Issue 3

RESEARCH AND DEVELOPMENT

Increasing Livestock Sustainability with Methane-mitigating Feed Additives Demand for animal protein in developed countries is stable and increasing strongly in emerging countries.

The combination of their nutrient density, desire of people to improve their diets and a growing world population will continue to drive future growth. The United Nations Food and Agriculture Organisation (FAO) projects that global demand for milk and meat will rise by 58% and 74% between 2010 and 2050.

Demand at that scale cannot be met solely through expansion; livestock must also be raised more efficiently and sustainably, and animal health solutions offer a path to achieve this goal. Reducing animal disease and optimising yield, through better genetics and preventative care means fewer animals are needed to meet global demand for protein.

An emerging class of animal feed supplements that inhibit methane production in ruminants offers a promising new way to further reduce the climate footprint of livestock production. This article analyses political, regulatory, practical and market considerations related to the introduction and use of methane-reducing feed additives, while offering recommendations to improve pathways to market.

The Emissions Challenge The main GHG emissions (carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O) are emitted from both natural and man-made sources (see Chart 1). Scientifically, the sources of emissions are irrelevant because the warming effect is the same, yet from a societal acceptance perspective there are differences. Society tends not to question naturally occurring biological processes created through millions of years of evolution – including for example ruminant enteric fermentation. But society does increasingly question the effect of many man-made activities, especially if they are wasteful and the emissions are significant.

To illustrate, unintentional methane leaks from energy production – often from poorly maintained pipelines –release about as much methane (3.11 billion tonnes CO2 equivalent annually) as all of agriculture (3.45 billion tonnes CO2 equivalent), and certainly more than ruminant enteric fermentation.

Chart 1: Global greenhouse gas emissions by sector

their stomachs convert into methane, 90% of which is belched out and 10% of which is flatulence. Considering methane emissions from agriculture, enteric fermentation by ruminants represents about 31% as shown in Chart 2.

Animal Health and Animal Feed Solutions The animal health sector can play a contributing role in both GHG mitigation and adaption strategies. Mitigation strategies are those that aim to reduce existing GHGs from the environment or reduce the rate of new GHG emissions.

Feed additives are part of both the mitigation and adaptation stories. Adaptation strategies aim to reduce the effects of climate change. For the animal health sector, this can include helping animals manage heat stress, increase capacity to address emerging diseases, and responding to diseases in new geographies.

Methane is different than CO2 – it is 28 times more potent than CO2, but unlike CO2, which has a life span of centuries, methane breaks down after 10 or so years. Cutting methane emissions therefore almost immediately reduces its concentrations in the atmosphere and slows warming. It is no surprise that over 150 countries support the Global Methane Pledge to lower methane overall emissions by 30% by 2030, and this target could be sharpened further.

40% of methane is emitted from natural biological sources like decomposition, ocean release, etc. and 60% is from manmade sources like landfills, oil and natural gas systems, mining, combustion, wastewater treatment, and industrial processes, according to the International Energy Agency.

Beef and dairy cows eat plants which contain carbon, which www.international-animalhealth.com

Chart 2: Sources of methane emissions by agricultural sector International Animal Health Journal 23

RESEARCH AND DEVELOPMENT Further improving animal health is the most efficient way to ensure that as few as possible greenhouse gasses are emitted. Healthier animals are more productive, less prone to disease, weight loss or death, leading to more animal protein being produced using fewer resources. In addition, existing good feed practices and products that improve digestibility, reduce pathogens, or increase weight, also contribute significantly to lower emissions. The feed sector is constantly developing new fats, oils, carbohydrates, minerals, etc. with positive effects on digestion.

Various new natural and synthetic supplements specifically geared at reducing methane emissions are either on the market or in development. Most of them function by disrupting methane production, or by moving the composition of the microbial community away from methane-producing microbes. The most prevalent are considered here.

Red seaweed (Asparagopsis) fed to ruminants has shown encouraging results of 80% methane reduction. A large-scale trial in Australia concluding in 2023 showed methane reductions of around 28%. The active ingredient is bromoform which is categorized by the U.S. EPA as a probable human carcinogen with a potential human safety concern. Commercial developers state the product is safe given the very low bromoform levels. In addition, some research has found residues in some animal proteins, and this, combined with a possible carcinogenic effect, raises challenges regarding acceptance in international trade of animal products fed the additive. Although a promising product, its likely more safety data will be needed before permits are granted in major markets.

3-Nitrooxypropanol or 3-NOP is a feed additive that reduces enteric methane emissions from dairy and reproductive cows. It is approved for commercial use in 45 markets including large ruminant markets like Brazil and the European Union, with approval expected in the U.S. in 2024.

Application works by adding a small amount daily to feed, and this can reduce beef cattle emissions by about 45% and dairy cow emissions reductions by an average 30%.

The product has no negative production quality effects and leads to an increase in milk fat.

There are a range of other products and approaches.

For example, one commercially available product blends plant-based products including wild carrot and coriander seed oil and claims to reduce enteric emissions from dairy cattle by 11%, though these claims are questioned by several academics. Another blend brings together garlic and citrus extracts and claims a 38% reduction. Another company has an additive that stimulates a natural process in the rumen, creating ammonia from hydrogen, which would otherwise become methane, and states that it leads to a 10% methane reduction. There is a probiotic formula which claims to reduce methane emissions by 20%.

Research is ongoing in many public and private entities including into areas such as adding natural gas ozone into cattle drinking water (reduce emissions by 20%), and new vaccines that can reduce methane emissions.

Success Criteria for Products These products are at different stages of development, acceptance, and commercialisation. Some have generated large amounts of scientific data and credibility, others have not. Looking ahead it is important that products meet certain requirements, the most important of which are considered here.

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Proven safety. An additive must be proven to be safe for consumption by animals, consumption by humans through animal protein, for handling by humans (on-farm and in production), and for the environment (excretion).

The only acceptable way to guarantee these safety conditions is through an assessment by a government agency.

Effect on performance. An additive will not be used if it has a negative effect on an animal’s welfare or on output/ performance. This is not a trade-off farmers will accept.

Methane reduction efficacy. An additive must reduce sufficient qualities of methane, and the assessments showing such quantities must be based on independent and accessible scientific evidence. A life cycle analysis of a product needs to incorporate all the GHG's emitted including during its production.

Usability. An additive must be easily usable by dairy and beef farmers. Globally, 37% of ruminant enteric methane emissions are generated by ruminants on free-ranging systems on rangelands and grasslands, 60% in mixed systems, and 2% from beef cattle in feedlots. How to get the right amounts to the cattle at the right times in different settings is an important consideration.

Production. An additive must be produced in the right quantities. This may present challenges for some technologies. For example, how to grow, harvest, process, and transport red seaweed in sufficient quantities? What is the full life GHG emissions from such processes?

Consumer acceptance. If an additive meets the first three conditions, it should not be challenging to gain consumer acceptance of a product which reduces methane emissions and contributes positively to reducing greenhouse gas emissions.

Value. Farmers will use additives if they can recoup the cost outlay. There are different ways costs can be recouped.

Market incentives through enhanced feed efficiency.

Up to 12% of ingested gross energy (feed) can be lost in the form of methane. Additives that enhance efficiency by helping the ruminant to conserve energy that would otherwise be lost as methane are an incentive to pay for methane reducing feed additives.

Market prices. Charging higher (premium) prices for meat and milk from animals fed the additives. This is challenging as the evidence shows that few consumers are prepared to pay more for this type of societal benefit, and this means there will be a de facto niche market for animals that have being fed the additives. In addition, asking consumers in emerging markets to pay more does not work.

Government intervention. For example, providing a subsidy for feeding additives that allow farmers to reduce their emissions. Some governments may go this way, some may not. Another government intervention is standards – requiring farmers to produce more sustainably – may work in some areas, though not in others.

Methane tax. Such a tax could make it more attractive for farmers to use feed additives to reduce emissions.

This could include a carbon credit/market approach.

Taxes are politically undesirable and technically difficult to implement and would not work in emerging countries.

Market Perspectives Many food processors, retailers, food and beverage companies and farm operations have a true interest in reducing their emissions, and many companies have taken significant action. Many corporations have climate pledges to lower their emissions and are increasingly being held Volume 10 Issue 3

RESEARCH AND DEVELOPMENT emissions is desirable from an environmental point of view, and some additives will have secondary benefits attractive for farmers. For better adoption of animal health solutions, the following areas need to progress.

Governments should incorporate animal health tools into their National Climate Action Programs, including the use of methane reducing additives.

There needs to be consensus that assessment of product claims is needed. This is usually done by governments, and such assessment benefits farmers and society, reassuring that products are safe and have the claimed effect.

Stakeholders and governments need to work together to implement proactive political strategies to promote animal health research and encourage uptake. Such strategies could include financing of research, encouraging uptake through financial benefits, regulatory fast lanes, farmer carbon credits, and consideration of public subsidies to achieve public good. Similar financing has happened in many other areas to promote uptake of carbon friendly technologies.

The wider food and agriculture chain and support industries have a responsibility to promote the uptake of all technologies that reduce methane, including feed additives.

This responsibility runs from farm to fork. Different models exist to work together. Proactive communication about benefits and drawbacks needs to be part of this. accountable by shareholders regarding what actions they are taking. There is pressure to do better.

Animal health solutions, including feed additive technologies, offer these companies real and immediate possibilities to reduce emissions in their production chains.

Groups such as the Global Dairy Platform – that brings together all major global dairy companies, have called for increased use of feed additives and other animal health approaches. Several meat companies have also actively called for adoption and application of these techniques.

A major challenge for many of these companies are the costs related to the additives, as well as the credibility of the accounting systems of methane emissions avoided through use of the products.

Political and Regulatory Considerations The United Nations Food and Agriculture Organisation (FAO) states most countries are not properly leveraging animal health as a pathway for emissions reductions. Only 14 of 148 countries who submitted national climate action plans in 2021 included improving animal health as a way to do so.

Some regions are moving. For example, the European Union specifically mentions, as part of its overall methane reduction strategy, the use of technologies such as feed to reduce emissions. It approved a 3-NOP product in 2022 stating “Cutting farming-related methane emissions is key in our fight against climate change and today’s approval is a very telling example of what we can achieve through new agricultural innovations.”

Whichever regulatory approach is taken, it requires some level of political drive from policy makers who would like to facilitate animal health methane emission reduction strategies and tools.

Looking Ahead Adoption of any animal health solution that reduces methane www.international-animalhealth.com

There needs to be clarity and standardisation regarding how to calculate methane reductions claims. A life cycle approach is best. Currently there are too many ways of calculating emissions from ruminants. To illustrate this point, is an example of a large convenience food company that had its beef farmers use a lemongrass-based additive. Claims were made that methane emissions were reduced by some 33%. Upon rigorous scientific review, 33% applied only to part of the emissions and the actual emissions saved was 3%.

There was no suggested mal intention by the company, only unclear calculations.

Research into any approaches or mechanisms that inhibit methane emissions from cattle and other ruminants needs to continue and be supported. This includes ongoing existing partnerships, public and private research.

Authors note: A new FAO report called ‘Methane emissions in livestock and rice systems. Sources, quantification, mitigation and metrics’ is set to be launched presently and provides a good overview of methane reducing approaches and technologies.

Carel du Marchie Sarvaas Carel du Marchie Sarvaas is Executive Director of HealthforAnimals, the global animal health association.

HealthforAnimals represents the top 10 global animal health companies developing and manufacturing veterinary pharmaceuticals, vaccines, parasiticides, diagnostics, digital products, etc. It also represents the interests of 200+ companies in its 27 national animal health associations – in total 85% of the global animal health sector.

International Animal Health Journal 25

FOOD & FEED

Feeding People while Preserving the Planet

Agriculture is at the heart of many important conversations in 2023. And whether the issue at hand is environmental concerns, the production of enough nutritious food for the global population or one of many other contentious topics, agricultural producers are often seen as anti-heroes – when, in reality, the agriculture industry has the greatest potential to make a positive impact on the world.

Proof of this positive impact was on display during the opening keynote addresses at Alltech ONE Dublin, the second stop on the Alltech ONE World Tour. Dr. Mark Lyons, president and CEO of Alltech, opened the conference with an assertion that the widespread image of agriculture as a villain makes it more important than ever to tell the story of how animal and food production benefits our planet.

“Bad news is out there, and it does get the eyeballs,” said Lyons. “That’s why I think it's critical for every business to be dedicating resources to communicating. And to me, that's the headline: ‘We need our animals. We capture more carbon with them than we would without them.’”

Lyons was joined onstage by Dr. Vaughn Holder, ruminant research director at Alltech, who illustrated how agriculture plays a vital role in both protecting the environment and ensuring the health of all people.

“We have two of the most important jobs in the world: We have to nourish our population and we have to preserve our planet for future generations,” Lyons said. “The challenge to all of us is to come up with the solutions that are going to help us."

“This is about ideas,” he continued. “It's about inspiration – and, I think, taking some risks, because we all know what the challenges are. And we need to think about them in a different way.”

Cattle: The Secret Weapon to Sequestering Carbon Climate change is widespread and will only continue to intensify, placing a great strain on the world’s resources.

Agricultural production is often cited as a significant factor in climate change – but in reality, as Holder outlined in his address at Alltech ONE Dublin, agriculture is one of the only industries with the ability to not only reduce its own greenhouse gas (GHG) emissions but to capture and sequester emissions released by other industries.

“We exist at the interface between the world's biggest carbon-capture and machinery industry, and that's agriculture,” he said.

Alltech has been studying the agriculture industry’s ability to sequester carbon through a research alliance based on the 10,000-acre Buck Island Ranch in Lake Placid, Florida. During their research at Buck Island, the Alltech team has seen firsthand that cattle can help sequester carbon through grazing – which counters the popular argument that eliminating cattle production will also reduce emissions.

26 International Animal Health Journal

“We have more than enough capacity to put this carbon away,” Holder said. “So, this is what we're focusing on as a research group, is trying to understand this entire carbon cycle so that we can design interventions and identify levers that can allow us to use this cycle to ameliorate not only the methane side of carbon cycle but the big elephant in the room, which is CO2.”

As Holder referenced, much of the general conversation about agricultural – and, specifically, livestock – production focuses on the issue of methane, but the data has borne out that carbon dioxide is a much more dangerous foe.

“Carbon dioxide is the problem,” Holder said. “And if we don't figure out a way to suck carbon dioxide out of the environment, no matter what we do to methane, it's not going to make a difference."

“I think methane is important; don't get me wrong,” he added. “But we have to look at it in a little bit of a different framing. Fossil fuels are one-way highway.”

To explain this concept further, Holder argued that the methane produced by cows is fundamentally different from carbon dioxide, which accumulates in the atmosphere. “It stays where it was; it goes nowhere,” he said. Methane, on the other hand, can be mitigated and cycled out much more quickly.

“Methane has some pretty cool characteristics that allows it to be somewhat of an opportunity for us, rather than a threat to the industry,” he said.

To start with, contrary to popular belief, methane isn’t just produced by cows; it’s produced by “things that ferment,” Holder explained, including the feeds eaten by cattle herds.

“And whether that's in a cow’s rumen or whether that's in the field, you're still going to be getting methane out of that.”

So, what would happen to these feeds and their byproducts if cattle production was eliminated? The consequences would be dire, Holder warned.

“Eighty-six percent of global livestock feed currently goes through livestock,” he said. “And that does two things for us: It allows us to actually get some of that food back to our food systems, but it also prevents that feed from fermenting out in the field and causing their own source of greenhouse gases. And if you put it into compost, which is what a lot of people would have you do, five times the amount of greenhouse gases will come off of those byproducts.”

This is the kind of fact that Holder wishes made headlines, as it is somewhat counterintuitive to what the average person might believe.

“When we are making recommendations on changing our food systems to save the environment, we've got to be thinking about these types of things,” he said. “The systemic effects of what we are doing are probably much more Volume 10 Issue 3

FOOD & FEED

important than the direct interventions that we are trying to make in the first place.”

Holder has seen first-hand the positive impact of agriculture on the planet – and he hopes the rest of the world can see it, too, so that ag producers can get back to their original mission.

“We have a massive role play in climate change, and I don't think there's another industry that has a similar position,” Holder said. “But we can't lose sight of what our primary purpose is, and that's feeding people, sustaining the world. That's the most important component, in my opinion, of sustainability. We have to keep food production primary when we are thinking about changing these systems.” www.international-animalhealth.com

Dr. Vaughn Holder Dr. Holder is the ruminant research director at Alltech based at the company’s North American Bioscience Center in Kentucky, USA, where he heads the company’s global nutritional research related to ruminant species.

Holder holds a bachelor’s degree in animal science from the University of Pretoria, a master’s degree in ruminant nutrition and microbiology from the University of Pretoria, and a doctoral degree in ruminant nutrition from the University of Kentucky.

International Animal Health Journal 27

MANUFACTURING

Leveraging Scientific Advances to Improve Tablet Manufacturing for Animal Health In the pharmaceutical industry, prioritising product control, patient safety, and adherence to standards is crucial. This responsibility extends to maintaining the quality of solid dosage forms which are frequently utilised in veterinary medicine.

A tablet used in animal health consists of one or more active ingredients and numerous excipients and may be a conventional tablet that is swallowed whole, a chewable tablet, or a modified-release. Conventional and chewable tablets are used to administer drugs to dogs and cats, whereas modified-release boluses are administered to cattle, sheep, and goats. Tablets offer advantages in terms of physical and chemical stability compared to liquid dosage forms.1 Ensuring the quality and effectiveness of tablets in veterinary medicine is of utmost importance. However, there are a number of challenges that can occur during manufacture that may affect this, with the most common hurdle being sticking. Sticking issues can compromise the tablet's appearance, structural integrity, and dissolution properties, potentially affecting the delivery and efficacy of the medication.

Sticking occurs when granules build up on the punch-tip face of the tablet tooling. This issue is not only problematic for human tablets but also those used for animals and can result in considerable tablet press downtime and unpredictable production delays. Ensuring consistent tablet quality is vital for consistent mass production of quality tablets.

A Common Problem So, why is sticking so common? The answer lies in several factors, including the formulation's physicochemical properties and the punch face's surface characteristics. These factors can be particularly challenging to manage when formulating tablets for animals, as their specific health requirements and dosage needs must be taken into account.

To reduce picking, font styles should be designed with large open counters and no sharp corners where granule can become trapped. Additionally, the right font style can also help avoid coating problems, tooling failures, and lack of distinction.

Open islands or counters are highly susceptible to picking, and granule can easily become trapped in these areas on the face of the punch tip. To minimise this issue, the counter should be modified by reducing the depth of the stroke, thereby increasing the surface area and minimising the likelihood of picking.

Fortunately, advancements in tabletting science have helped to find solutions to address sticking issues during tablet manufacturing. When these solutions are applied, they can dramatically improve production efficiency and tablet quality.

It is important to prioritise proper quality control measures and adhere to dosage requirements in order to ensure the safety of animal medications. Minimising problems such as sticking during the tablet manufacturing process plays a vital role in achieving these objectives.

Distinguishing Picking from Sticking Sticking can sometimes be confused with another common problem encountered during tablet production – picking.

Picking is when the formulation becomes trapped in the embossing or design feature, leaving the finished product with visibly poor definition. Various approaches can be employed to address picking, with product design alterations such as the inclusion of embossed counters and tapered features.

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Volume 10 Issue 3

MANUFACTURING molecules attract each other. Within a formulation, elements naturally attract to the materials of the tablet punch. Although these forces are relatively weak, measuring only in nanonewtons, their cumulative effect on the tablet face can lead to sticking.

Capillary forces arise from moisture present in the formulation. When moisture condenses between a particle and the tool surface, it forms capillary bridges. The strength of these forces are influenced by factors such as relative humidity, gap geometry, and surface chemical conditions.

Another effective approach is the use of tapered peninsulas, which involve enhancing the corner radii in sharp, compound angles of the embossing detail. This tapered design blends the tablet face's surface with the stroke angle, resulting in a softer profile and reducing the risk of powder entrapment. By employing this method, definition can be maintained without compromising the overall stroke depth of the embossing, and ultimately helping to preserve a clear brand identity.

Understanding Sticking Having looked at picking and its solutions, let's now focus on the most significant challenge in tablet manufacturing: sticking.

Sticking refers to the undesirable adhesion of the formulation to the surface of the punch tip face. This accumulation of granules leads to tablet defects, initially affecting the tablet's appearance and potentially progressing to issues like double compression and damage to the tooling and press.

Consequently, production is stopped while regular cleaning and maintenance are carried out on the tablet tooling to eliminate the granular build-up. This, in turn, results in costly tablet press downtime and reduced productivity.

Sticking can be understood as a battle between the cohesive forces that hold the tablet together and the adhesive forces between the ingredients in the formulation and the materials used for the tablet tooling. If the adhesive forces outweigh the cohesive forces, sticking becomes inevitable.

Electrostatic forces occur when there is a transfer of electrical charges between contacting materials. For instance, during pharmaceutical powder processing operations, powder particles frequently come into contact with each other and the equipment walls, leading to electrostatic charging through a process called triboelectrification Conductive or non-conductive tool coatings or treatments can also influence tribo-charging. These long-ranged and strong forces contribute to both cohesive and adhesive forces.

Adhesive Forces Multiple factors influence the adhesive forces leading to sticking between the formulation and punch tip faces. The tablet production environment and formulation preparation process play a role. Temperature, for instance, can affect certain Active Pharmaceutical Ingredients (APIs) present in formulations. It is crucial to consider this and lower the compression room temperature during compaction to minimise sticking.

Moisture or humidity levels in the air can also increase adhesive forces, forming capillary bridges between the granule and the tablet tool face. Additionally, the chemistry at the interfaces and the spatial heterogeneity of the formulation contribute to adhesive forces. Various techniques and equipment, such as scanning electron microscopy, X-ray photoelectron spectroscopy, time-of-flight secondary ion mass spectrometry, and Atomic Force Microscopy (AFM), can be employed to investigate these factors.

Deformation Mechanics represents an additional adhesive force that can result in sticking. The granule's physical properties during compression can demonstrate either elastic or plastic behaviour. Under compression, a particle can either maintain its deformed shape or return to its original form.

Where the tablet profile is a concave shape, and the core is lower in hardness, there is a tendency for sticking to occur at the centre of the punch face. This is because the concave punch tip profile applies more compression to the formulation along the tablet's edges compared to the centre, making it stick. To address this issue, incorporating a flatter profile in the tablet design and utilising a double radius can help minimise the soft area at the tablet's centre. This adjustment promotes a more uniform tablet hardness, thereby mitigating sticking problems by increasing cohesive forces.

To effectively address the challenge posed by cohesive and adhesive forces, it is crucial to delve deeper into the intricacies of both elements.

Cohesive Forces When examining cohesive forces, it is essential to consider three key elements: Van der Waals forces, capillary forces, and electrostatic forces. Van der Waals forces occur when www.international-animalhealth.com

International Animal Health Journal 29

MANUFACTURING

Formulations with time-dependent consolidation behaviour necessitate a longer dwell time to facilitate the formation of robust bonds between the particles. Consequently, extended dwell time during the main compression phase becomes particularly crucial for formulations exhibiting predominantly elastic deformation instead of brittle fracture behaviour.

The utilisation of extended dwell flat tooling (XDF) enables an adequate compression dwell time without negatively impacting the press' performance.

The correct morphology or surface roughness in tablet tooling is crucial for preventing sticking issues. While many tooling suppliers assume that highly-polished punch tip faces effectively prevent sticking, this assumption does not always hold true. By carefully examining the interaction between different surface textures, the standard specification for tablet punch tip faces can incorporate a range of surfaces that interact with formulations in diverse ways. For example, the required standard surface roughness for a punch tip typically falls within the range of 0.1 to 0.025 Ra (Roughness Average).

Even this slight difference in roughness can significantly impact sticking.

Understanding the influence of the interaction between the granule and the surface finish is key to preventing sticking.

Techniques such as optical surface profilometry, which measures surface roughness after polishing, can help draw conclusions. Additionally, scanning electron microscopy can be employed to study the structure of the steels and coatings, while Atomic Force Microscopy (AFM) allows for the measurement of adhesion forces and the creation of a nanoscale map of the surface. These analytical methods aid in comprehending the intricacies of the granule-surface interaction and inform effective strategies for preventing sticking.

The Solution to Sticking Sticking is a pervasive issue in the production of solid dose forms, prompting tablet tooling experts to study anti-stick solutions extensively. The TSAR (Tabletting Science Anti-Stick Research) project investigated the reasons behind sticking and sought solutions through a predictive mathematical model. It conducted tests with various excipients and APIs, measuring the forces exerted by each against a range of tool coatings. This research provided insights into the appropriate punch or die coating for preventing sticking in specific formulations. Importantly, this approach eliminates costly and time-consuming in-the-field testing, allowing tablet production to proceed uninterrupted.

Choosing a suitable anti-stick coating is crucial, as both conductive and non-conductive tool coatings can impact cohesive and adhesive forces. Specialised punch and die coatings can significantly enhance the efficiency and output of tablet manufacturing when used alongside high-quality tooling steel. They minimise the need for tools to be removed from production for additional cleaning, thus improving tabletting efficiency.

Since the physical properties of sticky formulations are unique to each case, there is no universal anti-stick solution.

Therefore, consulting with an experienced tooling equipment supplier who can accurately identify the specific reasons for sticking through tried-and-tested scientific calculations and provide a tailored resolution.

Consistent Quality In conclusion, sticking is a common challenge faced

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MANUFACTURING

during tablet manufacturing, which can compromise the tablet's appearance, structural integrity, and dissolution properties, potentially affecting the delivery and efficacy of the medication. However, advancements in tabletting science, such as the TSAR project, have paved the way for effective anti-stick solutions. By understanding the complex interplay of cohesive and adhesive forces and leveraging specialised punch and die coatings, tablet manufacturers within the animal health sector can significantly improve production efficiency and maintain consistent quality.

REFERENCES 1.

https://www.msdvetmanual.com/pharmacology/ pharmacology-introduction/routes-of-administrationand-dosage-forms

www.international-animalhealth.com

Rob Blanchard Since joining I Holland in 2004 Rob has been instrumental in the development of I Holland's PharmaCote® range of surface treatments and coatings for tablet compression tooling designed to improve properties such as wear resistance, corrosion resistance and antistick characteristics. He was also part of the Eurostandard steering committee and responsible for I Holland's registration to ISO 9001:2008. Rob holds multiple patents linked to solid dose manufacture and co-ordinates I Holland's close collaboration with various respected academic research bodies.

International Animal Health Journal 31

Media and Communications

IPI

Peer Reviewed, IPI looks into the best practice in outsourcing management for the Pharmaceutical and BioPharmaceutical industry. www.international-pharma.com

JCS

Peer Reviewed, JCS provides you with the best practice guidelines for conducting global Clinical Trials. JCS is the specialist journal providing you with relevant articles which will help you to navigate emerging markets. www.journalforclinicalstudies.com

IAHJ

Peer Reviewed, IAHJ looks into the entire outsourcing management of the Veterinary Drug, Veterinary Devices & Animal Food Development Industry. www.international-animalhealth.com

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Peer reviewed, IBI provides the biopharmaceutical industry with practical advice on managing bioprocessing and technology, upstream and downstream processing, manufacturing, regulations, formulation, scale-up/technology transfer, drug delivery, analytical testing and more. www.international-biopharma.com

PNP

Pharma Nature Positive, is a platform for all stakeholders in this industry to influence decision making by regulators, governments, investors and other service providers to achieve Nature Net Positive Results. This journal will enable pharma the ability to choose the right services to attain this goal. www.pharmanaturepositive.com

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