What are we doing to arm ourselves against pathogens?

Humans, animals and pathogens are locked in a perpetual struggle – and often a battle to the death. But what exactly is going on? If we can gain a better understanding of how micro-organisms or viruses cause illness and how they spread, we will be able to intervene more quickly and take more effective action to prevent new infections. We spoke with seven researchers from Veterinary Medicine about the roles played by their respective fields.

Theoretical Epidemiology

How do infectious diseases behave when introduced to human and animal populations, and which mechanisms are at work? The field of infectious disease dynamics attempts to answer this question using a variety of quantitative methods and various sources of data. ‘Populations of people and animals form complex systems, large groups of similar individuals that are in contact with one another,’ explains Hans Heesterbeek, Professor of Theoretical Epidemiology. ‘Knowledge of the biology and behaviour of a given pathogen is not enough to fully understand how it will spread within a large population of socially active individuals. Interventions that seem useful at the individual level may turn out differently at a population-wide level – or may even prove counter-productive.’

‘The majority of new infections in humans originate in animals, with wild animals being the chief culprits’

One important example concerns efforts to understand the worldwide increase in emerging infectious diseases. ‘The majority of new infections in humans originate in animals, with wild animals being the chief culprits. Not only are such diseases growing in number, their social and economic consequences are increasing as well, due to illness, deaths and disruption. While this is usually in a specific region of the world, as was the case with Ebola, the spread of SARS-CoV-2 has demonstrated that it is possible for the kind of pandemic disruption that we have been predicting for some time now to occur quite suddenly. We really must gain greater understanding of how pathogens are able to jump from animals to humans and how – in today's complex world – this can escalate into an unmanageable and disruptive problem.’

Virology

Virology involves conducting fundamental molecular research into viruses that affect animals and humans (e.g. coronaviruses, influenza viruses and picornaviruses). ‘We study the structure of these viruses, which receptors they use to invade cells, how they use those cells to replicate their own genetic material and how viral particles are then released from the cells,’ says Frank van Kuppeveld, professor of Virology. ‘Our research also explores how viruses make the jump from one animal species to another – or to human beings – as well as how they suppress or circumvent the defence mechanisms of their host.’ Armed with this fundamental knowledge, the virologists develop innovative strategies for new diagnostic methods, antiviral drugs, therapeutic antibodies and vaccines.

Antibody inhibits novel coronavirus

The current SARS-CoV-2 outbreak offers a fantastic opportunity to apply research into coronaviruses in a real-world setting. ‘We've been conducting pioneering research aimed at the structure and function of the “spike proteins” found on the outside of coronaviruses. These proteins allow the virus to adhere to cell receptors and gain entry into the cell. We also created spike proteins and injected them into mice that make human antibodies. As it turns out, one of those antibodies also inhibits SARS-CoV-2. In time, we may be able to use this antibody to treat COVID-19 patients or protect hospital staff from the virus. We also use our spike proteins as antigens in immunological testing to demonstrate the presence of antibodies. This is crucial to determining whether someone has been infected in the past.

Immunology

Our immune systems protect our bodies from internal – and external – threats. Professor of Immunology Femke Broere explains. ‘Depending on the type of inflammation or infection, the human body must counter with a specific immune response. Sometimes this process goes awry and the body responds too strongly or not strongly enough. We are researching how to steer the immune response in order to allow the body to recover.’The body sometimes fails to respond adequately to COVID-19 as well. ‘In patients with a severe infection, the disease triggers an incredibly strong immune response. This actually does more harm than good. In such cases, the patient winds up in intensive care as a result of their immune system's overreaction, which is what makes them gravely ill.’

‘Understanding the human immune system remains a challenge. It is present everywhere in the body.’

Broere's research group is studying the immune response in connection with a variety of infections, parasites and different illnesses, such as muscle diseases, allergies and rheumatic disorders. Broere says that scientists in the field of immunology face a number of major challenges. ‘There are several diseases, such as malaria, for which developing a vaccine is an extremely complicated undertaking. What's more, understanding our immune system presents a constant challenge. The immune system is present everywhere in the body. It works in close cooperation with our hormones and other systems and is controlled by the brain. Imagine trying to simulate those conditions in a lab in order to conduct research. It is just terribly complex. You really need to have all the disciplines working together, from virology to clinical practice. That’s the Faculty of Veterinary Medicine's strong suit – we have all those disciplines in-house and are able to integrate them.’ 

Vaccinology

Vaccinology is the science of developing, preparing, evaluating and implementing vaccines. Cécile van Els is a professor of Vaccinology and her research focuses on unravelling the chain of immune responses that lead to effective and long-term protection from infectious diseases. These ‘correlates of protection’ differ for each pathogen but are still unknown for the majority of infectious diseases.

Need for new vaccines

According to Van Els, there is growing demand for knowledge of how vaccines work. ‘Within the field of human infectious disease control, vaccines make a major contribution to public health by reducing the prevalence of infectious diseases. Vaccination also has a major social and economic impact in the veterinary field. Emerging and potentially new infectious diseases in humans and animals require new or improved vaccines.’ Especially in these times of urbanisation, increasing travel and climate change, new infectious diseases may have the opportunity to spread faster. This, Van Els emphasises, is what makes prevention important. ‘But prevention requires knowledge regarding the correlates of protection and how they can be measured.’ Van Els also works at the Centre for Infectious Disease Control of the National Institute for Public Health and the Environment (RIVM). According to Van Els, this is an important bonus: ‘It enables me to forge a connection between the research and knowledge of the Faculty of Veterinary Medicine and the RIVM.’

Also see the interview with Van Els on vaccine development.

Veterinary Epidemiology

The field of Veterinary Epidemiology attempts to understand how infectious diseases spread between animals and animal populations, and what we can do to control that spread. ‘Diseases can be divided into three major groups,’ says Arjan Stegeman, Professor of Farm Animal Health. ‘There are diseases that circulate between animals but do not make the jump to humans, such as foot-and-mouth disease and swine fever. Then you have diseases than can jump to humans, but that cannot be transmitted from one person to another, or only very rarely. Examples of this group are Q fever and avian flu. While such diseases are quite nasty for the people that catch them, they do not result in pandemics. The third group of diseases, on the other hand, does. These illnesses are capable of making the jump to humans and can then spread from person to person in an efficient manner. SARS-CoV-2 is obviously an example of this, as are flu viruses.’ Stegeman's group uses mathematical models, experimentation and field observation at livestock farms to research the spread of disease.

Animal welfare versus the risk of infectious diseases

Stegeman also feels that Veterinary Epidemiology can help facilitate the transition to sustainable agriculture. ‘In sustainable agriculture, new risks of infection can arise, for example when another animal feed is introduced or there is more contact with the outside world. Pandemic viruses emerge mainly from contact between humans and wild animals, as with SARS-CoV-2, or from contact between wild animals and extensive livestock farming. In those cases you have different animals mingling together, like pigs, chickens and ducks for example. This makes it easy for viruses to exchange genetic material, which in turn gives rise to new pathogens. An example is that chickens housed outdoors are seven times more likely to catch avian flu than chickens kept indoors in a shed. Intensive livestock farming entails smaller risks because animals housed indoors have little contact with other animals. It is quite tricky to balance the opposing interests of animal welfare and a lower risk of infectious diseases. Scientific research allows us to put forth solutions to this challenge and, in that way, do our part for the transition to sustainable agriculture.’
 

Clinical Infectiology

Clinical Infectiology contributes both domestically and internationally to the fight against infectious diseases and antibiotic resistance among humans and animals. These contributions take the form of high-quality research and education programmes aimed at current and future veterinarians and physicians, along with others. At the national level, Clinical Infectiology supports policy recommendations for bodies including the Royal Netherlands Veterinary Association and the Ministry of Agriculture, Nature and Food Quality. ‘Internationally, we do so for organisations such as the European Commission, the World Health Organization (WHO), the Food and Agricultural Organization of the United Nations (FAO) and the World Organisation for Animal Health (OIE),’ says Jaap Wagenaar, Professor of Clinical Infectiology. The WHO and OIE have recognised clinical infectiology as a WHO collaborating centre and an OIE Reference Laboratory. 

‘We have an active role in fighting infectious diseases in the Netherlands’

‘We also have an active role in fighting infectious diseases in the Netherlands,’ says veterinary microbiologist Els Broens. ‘This is because of our work to identify and report zoonoses [diseases that can be transmitted between humans and animals] and antibiotic resistance in companion animals, presided over by the Veterinary Microbiological Diagnostic Centre (VMDC). For instance, we uncovered Brucella infections in imported dogs and demonstrated the first known cases of COVID-19 in dogs and cats in the Netherlands, together with our colleagues in Virology. Thanks to an extensive network of top-tier researchers, policymakers, animal owners and professionals from the veterinary and human medicine sectors, Clinical Infectiology is uniquely positioned as a bridge-builder between research and practice.

This is an article from Vetscience no. 8, July 2020.