That, at its simplest, is the approach Mohamed Seleem’s lab at the Center for One Health Research has found may be a key treatment strategy in the battle against Candida auris, a frighteningly deadly fungal pathogen discovered in 2009 that is considered an urgent threat by the Centers for Disease Control and Prevention (CDC).
Candida auris, first discovered in Japan as an ear infection, has a staggering 60 percent mortality rate among those it infects, primarily people with compromised health in hospitals and nursing homes.
Recently, Seleem and Ph.D. students Yehia Elgammal and Ehab A. Salama published a paper in the American Society for Microbiology’s Antimicrobial Agents and Chemotherapy journal detailing the potential use of atazanavir, an HIV protease inhibitor drug, as a new avenue to improving the effectiveness of existing antifungals for those with a Candida auris infection.
A perfect storm of antimicrobial resistance, global warming and the COVID-19 pandemic has resulted in the rapid spread of Candida auris around the world, said Seleem, director of the center, a collaboration between the Virginia-Maryland College of Veterinary Medicine and the Edward Via College of Osteopathic Medicine.
We don’t have lots of drugs to use to treat fungal pathogens. We have only three classes of antifungal drugs. With a fungal pathogen, it’s often resistant to one class, but then we have two other options. What’s scary about Candida auris is it shows resistance to all three classes of the antifungal.
The CDC has a list of urgent threats, but on that list there is just one fungal pathogen, which is Candida auris. Because it’s urgent, we need to deal with it.”
Mohamed Seleem, the Tyler J. and Frances F. Young Chair in Bacteriology at Virginia Tech
Widespread use of fungicides in agriculture, in addition to the three classes of antifungal drugs used widely in medicine, has contributed to fungal pathogens developing more resistance, particularly Candida auris.
if (g_displayableSlots.mobileMiddleMrec) {
pushDisplayAd(function() { googletag.display(‘div-gpt-mobile-middle-mrec’); });
}
Also, its rise has been linked to rising global temperatures and to easier spread through hospitals filled with COVID-19 patients in recent years during the global pandemic.
Atazanavir, an HIV protease inhibitor drug, has been found by Seleem’s lab to block the ability of Candida auris to excrete antifungals through its efflux pumps.
Think of a boat taking on water and hoses siphoning that water out of the boat to keep it afloat. Atazanavir stops up the hoses.
That allows the azole class of antifungal drugs to not be expelled as easily and perform better against Candida auris, the Seleem lab’s research has found.
The research on atazanavir builds on work three years ago by Seleem’s lab, then at Purdue University, finding potentially similar benefit in lopinavir, another HIV protease inhibitor.
HIV protease drugs are already in wide use among HIV patients, who can also be extra susceptible to Candida auris. Some HIV patients have likely been taking HIV protease drugs and azole-class antifungals in tandem for separate purposes, providing a potential source of already existing data that can be reviewed on whether those patients had Candida auris and what effects the emerging pathogen had on them.
Repurposing drugs already on the market for new uses can allow those treatments to reach widespread clinical use much more rapidly than would happen with the discovery of an entirely new drug, as existing drugs have already been tested and approved by the Food and Drug Administration and have years of further observation of effects in prescriptive use.
In 2022, the Center for One Health Research received a $1.9 million grant from the National Institutes of Health for the Seleem lab’s research on repurposing already approved drugs for treating gonorrhea.
if (g_displayableSlots.mobileBottomLeaderboard) {
pushDisplayAd(function() { googletag.display(‘div-gpt-mobile-bottom-leaderboard’); });
}
African and European partners join forces to enable the World Health Organisation’s (WHO) “Road Map for Neglected Tropical Diseases” (NTDs) and reduce the burden of disease associated with worm infections.
Worm infections (helminthiases) affect around 1.5 billion people worldwide, making them one of the most prevalent infections in humans. Parasitic worms (helminths) are often transmitted through insect bites or contaminated soil in areas with limited access to clean water, sanitation, and healthcare. These infections can cause chronic and debilitating health problems, such as lymphatic filariasis, onchocerciasis (river blindness), loiasis (African eye worm), mansonellosis, and trichuriasis (whipworm infection).
To combat various soil-transmitted helminths (STH) and filarial worms, a new multidisciplinary consortium of research institutes, universities and not-for-profit organisations in sub-Saharan Africa (SSA) and Europe, coordinated by the University Hospital Bonn (UKB) in Germany, will work together to establish a new adaptive clinical trial platform and improve the clinical research infrastructure in several SSA countries. While each partner will bring unique know-how and complementary experience to achieve the project’s objectives, strong representation from the Global South will drive eWHORM activities. eWHORM will be funded with EUR 7.9 million from the European Union’s European and Developing Countries Clinical Trials Partnership (EDCTP3) programme and additional EUR 3.4 million from the Swiss Government over the next five years.
Achieving the ambitious WHO Road Map goals
Despite significant progress in preventing and controlling helminthiases, many existing drugs have proven problematic in terms of efficacy, treatment duration, and safety. In addition, the chronic underinvestment in healthcare in developing countries has led to poor infrastructure and inadequately trained technical staff.
The eWHORM project aims to address these issues by further developing and testing more efficacious and safe treatment options that act across different helminth species. The project will also train healthcare professionals to enable the diagnosis of multiple diseases in four endemic countries: the Democratic Republic of the Congo, the Gabonese Republic, the Republic of Cameroon, and the United Republic of Tanzania.
This major leap will help to achieve two pressing WHO objectives: (1) eliminating filarial and STH infections and (2) building capacity in endemic countries.
if (g_displayableSlots.mobileMiddleMrec) {
pushDisplayAd(function() { googletag.display(‘div-gpt-mobile-middle-mrec’); });
}
Responding to persisting and future health challenges
Establishing a robust and equitable clinical research infrastructure is crucial to sustaining the progress that will be brought about by eWHORM. To this end, project partners will promote research network building, knowledge exchange, skill sharing, and gender equality awareness. Early career scientists in SSA will be supported through a Master’s and PhD programme, mentorship programme, and dedicated webinars on all aspects of clinical trial conduct and research. This will, in turn, increase effectiveness and preparedness for both current and future health crises and ensure equitable access to treatment, care, and support for all patients.
Cutting-edge clinical trial to end multiple neglected tropical diseases
The broad-spectrum helminth-killing (pan-nematode anthelmintic) drug oxfendazole (OXF) is used since several decades in the veterinary field to treat multiple species of helminths safely and effectively. In the recent drug development initiative “Helminth Elimination Platform” (HELP), a field-applicable formulation of the cost-effective and easy-to-manufacture drug OXF was developed and a bioavailability study was performed in humans. Several partners, who worked towards a superior, pan-nematode anthelmintic in HELP, are now continuing their ground-breaking research in eWHORM.
Our mission in eWHORM is to assess the efficacy of OXF for simultaneous evaluation against onchocerciasis, loiasis, mansonellosis, and trichuriasis. To do this, we plan to set up a state-ofthe-art adaptive basket trial that can test OXF against multiple diseases at once. This will help us to quickly find out if OXF works and get it to patients faster.”
Marc Hübner, project coordinator, professor of translational microbiology at the Institute for Medical Microbiology, Immunology and Parasitology (IMMIP) at the University Hospital Bonn
“The Drugs for Neglected Diseases initiative (DNDi) and Dr. Sabine Specht, Head of Filarial Disease at DNDi, have a long-standing track record in developing and enabling access to more effective and affordable drugs for Neglected Tropical Diseases,” adds Hübner. “Together with some of the most eminent research and development partners and national stakeholders worldwide, we are looking forward to contributing to what can generate a profound change in the treatment and elimination of helminth diseases.”
Next to the University of Buea, the Centre de Recherches Médicales de Lambaréné, and the Institut National de Recherche Biomédicale, the consortium includes experts from the Bernhard-Nocht-Institute for Tropical Medicine, the Medical University of Vienna, the Erasmus University Medical Center, the Swiss Tropical and Public Health Institute and Eurice – European Research and Project Office GmbH.
if (g_displayableSlots.mobileBottomLeaderboard) {
pushDisplayAd(function() { googletag.display(‘div-gpt-mobile-bottom-leaderboard’); });
}
Since the beginning of the COVID-19 pandemic, researchers have been working on mucosal vaccines that can be administered through the nose. Now, scientists in Berlin have developed a live attenuated vaccine for the nose. In “Nature Microbiology”, they describe the special immune protection it induces.
Coronaviruses spread primarily through the air. When infected people speak, cough, sneeze or laugh, they expel droplets of saliva containing the virus. Other people then breathe in these airborne pathogens and become infected themselves. A research team in Berlin decided to try to fight the virus that causes COVID-19 where it first takes hold: the mucous membranes of the nose, mouth, throat, and lungs. To do so, the scientists developed a live attenuated SARS-CoV-2 vaccine that is administered through the nose. In the latest issue of the journal “Nature Microbiology“, the interdisciplinary team describes how this live attenuated vaccine confers better immunity than vaccines injected into muscle.
Already in the fall of last year, two nasal vaccination formulations were approved for use in India and China. These contain modified adenoviruses – which typically cause respiratory or gastrointestinal illnesses – that are self-attenuating, meaning they either replicate poorly or stop replicating altogether, and therefore never trigger disease. Other live nasal vaccines are currently undergoing development and testing around the world.
Protection at the site of infection
The benefits of a nasal vaccine go far beyond just providing an alternative for people afraid of needles. When a vaccine is injected, it infers immunity primarily in the blood and throughout the entire body. However, this means that the immune system only detects and combats coronaviruses relatively late on in an infection, as they enter the body via the mucous membranes of the upper respiratory tract. “It is here, therefore, that we need local immunity if we want to intercept a respiratory virus early on,” explains the study’s co-last author Dr. Jakob Trimpert, a veterinarian and research group leader at the Institute of Virology at Freie Universität Berlin.
“Nasal vaccines are far more effective in this regard than injected vaccines, which fail or struggle to reach the mucous membranes,” emphasizes Dr. Emanuel Wyler, another co-last author. He has been researching COVID-19 since the start of the pandemic as part of the RNA Biology and Posttranscriptional Regulation Lab, which is led by Professor Markus Landthaler at the Berlin Institute for Medical Systems Biology of the Max Delbrück Center (MDC-BIMSB).
In an ideal scenario, a live intranasal vaccine stimulates the formation of the antibody immunoglobulin A (IgA) directly on site, thus preventing infection from occurring in the first place. IgA is the most common immunoglobin in the mucous membranes of the airways. It is able to neutralize pathogens by binding to them and preventing them from infecting respiratory tract cells. At the same time, the vaccine stimulates systemic immune responses that help provide effective overall protection from infection.
Memory T cells that reside in lung tissue play a similarly useful role to antibodies in the mucosa. These white blood cells remain in affected tissue long after an infection has passed and remember pathogens they have encountered before. Thanks to their location in the lungs, they can respond quickly to viruses that enter through the airways.” The co-first author draws attention to one of the observations the team made during their study: “We were able to show that prior intranasal vaccination results in the increased reactivation of these local memory cells in the event of a subsequent SARS-CoV-2 infection. Needless to say, we were particularly pleased with this result.”
Dr. Geraldine Nouailles, immunologist and research group leader at the Department of Pneumology, Respiratory Medicine, and Intensive Care Medicine at Charité
Local immunity impedes viral infection
The scientists tested the efficacy of the newly developed intranasal COVID-19 vaccine on hamster models that had been established by Trimpert and his team at Freie Universität Berlin at the beginning of the pandemic. These rodents are currently the most important non-transgenic model organisms for research into the novel coronavirus, as they can be infected with the same virus variants as humans and develop similar symptoms. They found that after two doses of the vaccine, the virus could no longer replicate in the model organism. “We witnessed strong activation of the immunological memory, and the mucous membranes were very well protected by the high concentration of antibodies,” Trimpert explains. The vaccine could therefore also significantly reduce the transmissibility of the virus.
Drug Discovery eBook
Compilation of the top interviews, articles, and news in the last year.
In addition, the scientists compared the efficacy of the live attenuated vaccine with that of vaccines injected into the muscle. To do so, they vaccinated the hamsters either twice with the live vaccine, once with the mRNA and once with the live vaccine, or twice with an mRNA or adenovirus-based vaccine. Then, after the hamsters were infected with SARS-CoV-2, they used tissue samples from the nasal mucosa and lungs to see how strongly the virus was still able to attack the mucosal cells. They also determined the extent of the inflammatory response using single-cell sequencing. “The live attenuated vaccine performed better than the other vaccines in all parameters,” Wyler summarizes. This is probably due to the fact that the nasally administered vaccine builds up immunity directly at the viral entry site. In addition, the live vaccine contains all components of the virus – not just the spike protein, as is the case with the mRNA vaccines. While spike is indeed the virus’s most important antigen, the immune system can also recognize the virus from about 20 other proteins.
Better than conventional vaccines
The best protection against the SARS-CoV-2 was provided by double nasal vaccination, followed by the combination of a muscular injection of the mRNA vaccine and the subsequent nasal administration of the live attenuated vaccine. “This means the live vaccine could be particularly interesting as a booster,” says the study’s co-first author Julia Adler, a veterinarian and doctoral student at the Institute of Virology at Freie Universität Berlin.
The principle of live attenuated vaccines is old and is already used in measles and rubella vaccinations, for example. But in the past, scientists generated the attenuation by chance – sometimes waiting years for mutations to evolve that produced an attenuated virus. The Berlin researchers, on the other hand, were able to specifically alter the genetic code of the coronaviruses. “We wanted to prevent the attenuated viruses from mutating back into a more aggressive variant,” explains Dr. Dusan Kunec, a scientist at the Institute of Virology at Freie Universität Berlin and another co-last author of the study. “This makes our live vaccine entirely safe and means it can be tailored to new virus variants,” stresses Kunec, who was instrumental in developing the vaccine.
The next step is safety testing: The researchers are collaborating with RocketVax AG, a Swiss start-up based in Basel. The biotech company is developing the live attenuated SARS-CoV-2 vaccine and preparing a phase 1 clinical trial in humans. “We are thrilled to be at the forefront of developing and manufacturing the live attenuated SARS-CoV-2 vaccine as a nasal spray at RocketVax. Our goal is to rapidly scale-up production and advance clinical development towards market access to provide protection against post-COVID symptoms for all. We see great potential in the market for seasonal nasal vaccines”, says Dr. Vladimir Cmiljanovic, CEO of RocketVax.
The future will show which nasal vaccine will ultimately provide better protection. The manufacturers of the nasal adenovirus vaccines developed in India and China have not yet applied for approval in Europe. But one thing is clear to the scientists: since they are administered as nasal sprays or drops, nasal vaccines are a good option for use in places with limited access to trained medical staff. They are also inexpensive to produce and easy to store and transport. Last but not least, live attenuated vaccines such as this one have been proven to provide cross-protection against related viral strains, and thus presumably also against future SARS-CoV-2 variants.
Nouailles, G., et al. (2023). Live-attenuated vaccine sCPD9 elicits superior mucosal and systemic immunity to SARS-CoV-2 variants in hamsters. Nature Microbiology. doi.org/10.1038/s41564-023-01352-8
Yersinia bacteria cause a variety of human and animal diseases, the most notorious being the plague, caused by Yersinia pestis. A relative, Yersinia pseudotuberculosis, causes gastrointestinal illness and is less deadly but naturally infects both mice and humans, making it a useful model for studying its interactions with the immune system.
These two pathogens, as well as a third close cousin, Y. enterocolitica, which affects swine and can cause food-borne illness if people consume infected meat, have many traits in common, particularly their knack for interfering with the immune system’s ability to respond to infection.
The plague pathogen is blood-borne and transmitted by infected fleas. Infection with the other two depends on ingestion. Yet the focus of much of the work in the field had been on interactions of Yersinia with lymphoid tissues, rather than the intestine. A new study of Y. pseudotuberculosis led by a team from Penn’s School of Veterinary Medicine and published in Nature Microbiology demonstrates that, in response to infection, the host immune system forms small, walled-off lesions in the intestines called granulomas. It’s the first time these organized collections of immune cells have been found in the intestines in response to Yersinia infections.
The team went on to show that monocytes, a type of immune cell, sustain these granulomas. Without them, the granulomas deteriorated, allowing the mice to be overtaken by Yersinia.
“Our data reveal a previously unappreciated site where Yersinia can colonize and the immune system is engaged,” says Igor Brodsky, senior author on the work and a professor and chair of pathobiology at Penn Vet. “These granulomas form in order to control the bacterial infection in the intestines. And we show that if they don’t form or fail to be maintained, the bacteria are able to overcome the control of the immune system and cause greater systemic infection.”
The findings have implications for developing new therapies that leverage the host immune system, Brodsky says. A drug that harnessed the power of immune cells to not only keep Yersinia in check but to overcome its defenses, they say, could potentially eliminate the pathogen altogether.
A novel battlefield
Y. pestis, Y. pseudotuberculosis, and Y. enterocolitica share a keen ability to evade immune detection.
“In all three Yersinia infections, a hallmark is that they colonize lymphoid tissues and are able to escape immune control and replicate, cause disease, and spread,” Brodsky says.
Earlier studies had shown that Yersinia prompted the formation of granulomas in the lymph nodes and spleen but had never observed them in the intestines until Daniel Sorobetea, a research fellow in Brodsky’s group, took a closer look at the intestines of mice infected with Y. pseudotuberculosis.
“Because it’s an orally acquired pathogen, we were interested in how the bacteria behaved in the intestines,” Brodsky says. “Daniel made this initial observation that, following Yersinia pseudotuberculosis infection, there were macroscopically visible lesions all along the length of the gut that had never been described before.”
Antibodies eBook
Compilation of the top interviews, articles, and news in the last year.
The research team, including Sorobetea and later Rina Matsuda, a doctoral student in the lab, saw that these same lesions were present when mice were infected with Y. enterocolitica, forming within five days after an infection.
A biopsy of the intestinal tissues confirmed that the lesions were a type of granuloma, known as a pyogranuloma, composed of a variety of immune cells, including monocytes and neutrophils, another type of white blood cell that is part of the body’s front line in fighting bacteria and viruses.
Granulomas form in other diseases that involve chronic infection, including tuberculosis, for which Y. pseudotuberculosis is named. Somewhat paradoxically, these granulomas-;while key in controlling infection by walling off the infectious agent-;also sustain a population of the pathogen within those walls.
The team wanted to understand how these granulomas were both formed and maintained, working with mice lacking monocytes as well as animals treated with an antibody that depletes monocytes. In the animals lacking monocytes “these granulomas, with their distinct architecture, wouldn’t form,” Brodsky says.
Instead, a more disorganized and necrotic abscess developed, neutrophils failed to be activated, and the mice were less able to control the invading bacteria. These animals experienced higher levels of bacteria in their intestines and succumbed to their infections.
Groundwork for the future
The researchers believe the monocytes are responsible for recruiting neutrophils to the site of infection and thus launching the formation of the granuloma, helping to control the bacteria. This leading role for monocytes may exist beyond the intestines, the researchers believe.
We hypothesize that it’s a general role for the monocytes in other tissues as well.”
Igor Brodsky, senior author
But the discoveries also point to the intestines as a key site of engagement between the immune system and Yersinia.
“Previous to this study we knew of Peyer’s patches to be the primary site where the body interacts with the outside environment through the mucosal tissue of the intestines,” says Brodsky. Peyer’s patches are small areas of lymphoid tissue present in the intestines that serve to regulate the microbiome and fend off infection.
In future work, Brodsky and colleagues hope to continue to piece together the mechanism by which monocytes and neutrophils contain the bacteria, an effort they’re pursing in collaboration with Sunny Shin’s lab in the Perelman School of Medicine’s microbiology department.
A deeper understanding of the molecular pathways that regulate this immune response could one day offer inroads into host-directed immune therapies, by which a drug could tip the scales in favor of the host immune system, unleashing its might to fully eradicate the bacteria rather than simply corralling them in granulomas.
“These therapies have caused an explosion of excitement in the cancer field,” Brodsky says, “the idea of reinvigorating the immune system. Conceptually we can also think about how to coax the immune system to be reinvigorated to attack pathogens in these settings of chronic infection as well.”
Sorobetea, D., et al. (2023). Inflammatory monocytes promote granuloma control of Yersinia infection. Nature Microbiology. doi.org/10.1038/s41564-023-01338-6.
In their evolutionary battle for survival, viruses have developed strategies to spark and perpetuate infection. Once inside a host cell, the Ebola virus, for example, hijacks molecular pathways to replicate itself and eventually make its way back out of the cell into the bloodstream, where it can spread further.
But our own cells, in the case of Ebola and many other viruses, aren’t without defenses. In a study published in the Proceedings of the National Academy of Sciences, a team led by University of Pennsylvania School of Veterinary Medicine scientists discovered a way human cells hamper the Ebola virus’ ability to exit.
An interaction between viral and host proteins prompts host cells to ramp up activity of a pathway responsible for digesting and recycling proteins, the team found. This activity, known as autophagy “self-eating,” allows fewer viral particles to reach the surface of a host cell, thus reducing the number that can exit into the bloodstream and further propagate infection.
This interaction seems to be part of an innate defense mechanism. Human cells appear to specifically target a key Ebola virus protein and direct it into the autophagy pathway, which is how cells process and recycle waste.”
Ronald N. Harty, professor at Penn Vet and senior author on the study
The investigation emerged from a longtime area of focus for Harty’s lab: the interaction between the viral protein VP40, found in both Ebola and Marburg viruses, and various human proteins. In the group’s previous work, they’ve found that one area of VP40, known as a PPXY motif, binds corresponding motifs known as WW domains on specific host proteins.
In many instances, this PPXY-WW interaction causes more viral particles to exit the cell in a process called “budding.” But in screening various host proteins thought to play a role in the process, Harty and postdoc Jingjing Liang, the study’s lead author, uncovered some that did the opposite upon binding VP40, causing budding to decrease. One of these was a protein called Bag3, on which they reported in a PLOS Pathogenspaper in 2017.
Though Ebola is a potentially deadly virus, Harty and colleagues can safely study its workings in a Biosafety Level 2 laboratory, substituting virus-like particles (VLPs) that express VP40 for the virus itself. These VP40 VLPs are not infectious but can bud out from host cells like the real thing.
In the new work, the Penn Vet researchers and colleagues from the Texas Biomedical Research Institute dug deeper to learn about the mechanism by which Bag3 reduced budding. Bag3 is known as a “co-chaperone” protein, involved in forming a complex with other proteins and chaperoning them on their trip to be digested, ultimately in organelles called autolysosomes, part of the process of autophagy. Using VP40 VLPs, Harty’s group confirmed that VP40 bound to Bag3 and formed the protein complex. When the researchers added a compound that is known to block formation of this complex, they saw VP40 being released; VLP budding activity subsequently increased.
To follow the activity of VP40 in real time, the team used powerful confocal microscopy, labeling each actor of interest with a different fluorescent tag. They observed that Bag3 was involved in sequestering VP40 in vesicles in the cell that would go on to undergo autophagy. Stuck in these vesicles and destined for the cellular “recycling center,” VP40 was unable to move to the cell membrane and bud.
Immunology eBook
Compilation of the top interviews, articles, and news in the last year.
“I think one of the most interesting things that we showed is the selectivity of the cargo,” Liang says. “We show that autophagy doesn’t just happen passively. Bag3 acts through the PPXY-WW interaction to specifically target VP40 to undergo autophagy.”
When the researchers added the drug rapamycin, which enhances autophagy, VP40 sequestration went up and VLP budding went down. Rapamycin works by inhibiting the activity of a pathway governed by a protein complex called mTORC1, a cellular sensor that turns on protein synthesis when a cell needs raw material to grow. The researchers found this pathway appeared to be important in regulating Ebola infection; in experiments with live virus conducted in a Biosafety Level 4 laboratory, they observed that the virus could activate mTORC1 signaling, causing the cellular “factory” to produce materials the virus would need to expand and spread. In contrast, inhibiting mTORC1 with rapamycin directed the virus toward the autophagy pathway, where it would be digested by the cell’s autolysosomes.
“The virus wants the cell growing so it activates mTORC1,” says Harty. “Autophagy does the opposite, keeping the cellular materials in balance.”
Autophagy is important for normal cellular processes, ensuring that the cell doesn’t become cluttered with unnecessary or misfolded proteins and other materials floating around. But this work also suggests autophagy can be harnessed by the body to defend against harmful infection.
“Our conception is that this is part of the arms race between our bodies and the virus,” Liang says. “The virus wants to shape its environment to benefit itself and its own survival, so it evolved to manipulate mTORC1. But the cell can also use this pathway to defend against viral infection.”
With these insights into the human body’s innate defenses against Ebola, the researchers hope to see if autophagy may be a factor in other hemorrhagic viral infections, such as those that cause Marburg and Lassa fever. And while the current experiments were primarily conducted using human liver cell lines, the team would also like to test whether autophagy and the mTORC1 pathway are involved in viral defense in other cell types, such as the immune system’s macrophages, the primary cells involved in propagating infection.
Ultimately, Harty, Liang, and colleagues hope to find as many viral vulnerabilities as possible, helping inform drugs that could be one component of a therapeutic cocktail, each targeting different stages of infection, from viral entry to exit.
“This all ties together in our overall goal of understanding viral-host interactions and, by understanding them, working to intervene to slow or stop infection,” Harty says.
Liang, J., et al. (2023) Chaperone-assisted selective autophagy targets filovirus VP40 as a client and restricts egress of virus particles. PNAS.doi.org/10.1073/pnas.2210690120.
Global Access Diagnostics (GADx), a social enterprise prioritizing equitable access to diagnostics and driving local manufacturing, today announced the development of RaDiCal, a one-step molecular lateral flow test to enable rapid diagnosis of pneumonia, one of the most significant diseases affecting calves. The test is being developed through a collaborative consortium, including representatives from the University of Surrey, University of Glasgow, Cardiff University, and Westpoint Farm Vets, to provide a low-cost platform to be used by vets or farmers on-farm. The project is funded by the Biotechnology and Biological Sciences Research Council (BBSRC).
Pneumonia is one of the most significant diseases affecting calves, costing the UK cattle industry an estimated £50 million a year 1. Resulting from GADx’s participation in a BBSRC Endemic Livestock Disease Priming Partnerships workshop and driven by challenges outlined by farmers, the consortium is combining expertise in microbiology, veterinary infectious disease, and diagnostic test development to create RaDiCal. The test is a pioneering molecular lateral flow platform which can be linked to a mobile phone digital platform for easy interpretation of results, enabling farmers and vets to diagnose calves on-farm, and subsequently take rapid and informed action to facilitate improved disease management and support responsible antibiotic stewardship.
Dr Alison Wakeham, Head of Agriculture and Animal Health, GADx, said: “GADx’s expertise in lateral flow technology allows us to support a variety of disease areas. By applying our platform within the livestock industry, we are glad to be able to help improve disease management for one of the most significant diseases affecting calves. Working alongside other experts in this field through the consortium and with the support of BBSRC funding, we are looking forward to progressing the project and bringing the transformative test to market. Being able to accurately diagnose and treat early in the disease cycle is critical to prevent spread and control outbreaks.”
Professor Mark Chambers, Professor of Microbiology and Disease Intervention, University of Surrey, who is leading the project, commented: “The University of Surrey is delighted to be leading the RaDiCal project and will be using its experience of veterinary infectious diseases and test development within an exciting consortium of other academics and representatives from industry, large animal veterinary practice, and farmers themselves at the sharp end of managing calf pneumonia. Through this close partnership and on-going consultation we shall ensure we develop a test that meets the needs of the cattle industry.”
Abi Reader, project partner, dairy farmer, Goldsland Farm, Chair NFU Cymru Milk Board and Chair CHeCS, added: “Calf Pneumonia puts an enormous burden on UK dairy farmers, causing increased veterinary costs and farming losses. RaDiCal will help reduce this impact and support farmers by enabling early intervention and improved calf welfare.”
To support this research, the University of Surrey School of Veterinary Medicine is looking for veterinary surgeons who work with calves to share their experiences of using diagnostic tests and managing calf pneumonia.
If you would like to participate, please complete this short, anonymous survey:
In the food processing industry, the deadly bacteria Listeria monocytogenes is monitored closely. Not only can the bacteria make people extremely ill, it is known to be developing resistance to various food safety measures across the world.
However, two ‘harmless’ species of Listeria are also developing a surprising number of characteristics potentially harmful to humans.
A Whole Genome Sequencing study in South Africa, from a team of researchers with first author Dr Thendo Mafuna at the University of Johannesburg, shows some of the changing characteristics of Listeria found in the country.
The study shows that Listeria innocua strains are developing resistance to temperature, pH, dehydration and other stresses; as well as hypervirulence genetically identical to that of Listeria monocytogenes.
Some strains of L. innocua and L. welshimeri in the study show all three genes for resistance to a widely-used disinfectant, from the quaternary ammonium compound (QAC or QUAT) group of chemicals.
Two strains of L. innocua they analyzed have developed three or more concerning pathogenic characteristics, including CRISPR CAS-type adaptive immune systems.
The two non-pathogenic strains of Listeria were sampled in raw, dried and processed meats at commercial food processing facilities in the country.
The study confirms other research showing growing resistance in non-pathogenic Listeria species in other parts of the world.
Shared genes with pathogenic species
The Listeria innocua that we tested has some of the genes that are also found in pathogenic Listeria monocytogenes.“
Dr Thendo Mafuna, First Author, University of Johannesburg
Mafuna is from the Department of Biochemistry at the University of Johannesburg.
These shared genes between L. innocua and L. monocytogenes are also responsible for disease in humans; and stress tolerance such as resistance to the disinfectant Benzalkonium chloride (BC or BAC).
Research from others has shown that though Listeriosis is rarely caused by L. innocua, it does happen more often in people with compromised immune systems, he adds.
Benzalkonium chloride (BAC) is a member of a group of chemicals called Quaternary ammonium compounds, or QUATs. Quats are found in many common disinfectant products. They have been shown to be highly effective at killing bacteria, fungi and viruses.
Genetics & Genomics eBook
Compilation of the top interviews, articles, and news in the last year.
All the L. innocua strains they tested also had the complete LIPI-4 hypervirulence gene sequence, which can cause disease in humans, he says. The LIPI-4 sequence they found in L. innocua is identical to that found in pathogenic L. monocytogenes, as recorded by the Pasteur Institute in Paris, France.
From raw, dried and processed meats
The samples and isolates analyzed in this study were collected between 2014 and 2019 by the South African Government’s Department of Agriculture, Land Reform and Rural Development (DALRRD). These were submitted to the Agricultural Research Council (ARC) at Onderstepoort Veterinary Research SA for analysis.
In total, 258 isolates from butcheries, abbatoirs, retail outlets, cold stores and processing facilities all over the country were studied. Of these, 38 were found to be nonpathogenic L. Innocua; and another three isolates found to be nonpathogenic L. welshimeri.
The isolates came from raw whole, raw processed, dried, and processed cooked, beef, chicken and pork meats. Dr. Itumeleng Matle at the Bacteriology Division, ARC in Onderstepoort did the microbiological analysis of Listeria isolation and identification.
The Whole Genome Sequencing (WGS) was done by Dr. Rian E. Pierneef at the ARC’s Biotechnology Platform at Onderstepoort.
Mafuna then compared the genome sequences with those recorded by the Pasteur Institute, in Paris, France; and performed the analysis for the study.
On the lookout
“We need to look at our own facilities in South Africa to really see what is happening. Our analyses of these bacteria can help us predict which sequence types to be on the look out for,” says Mafuna.
It is the number of harmful characteristics that the L. innocua strains share with L. monocytogenes that is concerning, he adds.
Food processors need to look out for Listeria innocua because it is becoming resistant to disinfectants that are used in industry to get rid of them. It would also be helpful to try different types of disinfectants to surfaces, he says. Switching from one type to another may prevent or delay the bacteria developing resistance to one type of disinfectant.
“Big industrial food processors may want to investigate how efficient BC or quat disinfectants are in their facilities. This can be done by taking swabs before cleaning and again after cleaning, culturing those, to see how well the disinfectant regimes are working,” says Mafuna.
Mafuna, T., et al. (2022) Comparative Genomics of Listeria Species Recovered from Meat and Food Processing Facilities. Microbiology Spectrum.doi.org/10.1128/spectrum.01189-22.
Thought LeadersDr. Tomislav MeštrovićAffiliate Associate ProfessorUniversity of WashingtonAs part of World Antimicrobial Resistance Week 2022, News-Medical speaks to Dr. Tomislav Meštrović about his new research discussing the burden of bacterial antimicrobial resistance in the WHO European region, as well as about how we can prevent antimicrobial resistance together.
Please can you introduce yourself and tell us about your background and interest in antimicrobial resistance (AMR)?
Before participating in the research on the global burden of antimicrobial resistance (AMR), as a medical doctor, clinical microbiologist, and biomedical scientist, I was a part of relevant research endeavors on antibiotic resistance in my home country Croatia – such as a nationwide study on extended-spectrum beta-lactamases and plasmid diversity in urinary Escherichia coli isolates, as well as describing the emergence of multidrug-resistant Proteus mirabilis in long-term care facilities.
Since my Ph.D. thesis was on addressing AMR in the most common sexually transmitted bacterial agent, Chlamydia trachomatis, I was also a part of the team that aimed to standardize the method for laboratory susceptibility testing of chlamydiae by using both special cell culture and direct molecular-based monitoring, which was published in one methodological textbook.
Therefore, I would say AMR in different microorganisms was always my passion – from the diagnostic standpoint and the therapeutic one. More specifically, I was also involved in certain aspects of drug research, such as proposing a novel dual antagonist to prevent and treat urinary Escherichia coli infections and the usage of liposomal encapsulation to increase the efficacy of azithromycin against Chlamydia trachomatis. The latter technology gained a lot of prominence when liposome-based mRNA COVID-19 vaccines entered the market, so it is no wonder that we tried to capitalize on the positive aspects of such an approach.
Regarding my other professional positions, I am also a Secretary General of the Croatian Society for Clinical Microbiology, Executive Committee Member of the ESCMID study group for Mycoplasma and Chlamydia Infections, and External Affairs Committee Member of the Society for Healthcare Epidemiology of America (SHEA). I have several leadership roles in the American Society for Microbiology (ASM), where I organized conference sessions on antibiotic resistance, such as the Track Hub Session for ASM Microbe, “The global scenario of antimicrobial resistance: do developing and developed countries share the same threats?”. Finally, I am very invested in science communication. As one of the writers for News-Medical, I have written several pieces on the topic of antimicrobial resistance and many other topics.
AMR is a threat to not only humans but also animals, plants, and the environment. Can you tell us more about what exactly AMR is?
Antimicrobial resistance (AMR) is regarded as one of the predominant and most salient public health issues of the 21st century, as it threatens the effective treatment and prevention of an ever-growing range of infections caused by bacteria, viruses, fungi, and parasites. In other words, these groups of microorganisms are no longer susceptible to the common medical agents used to treat them, and the issue is particularly serious and urgent in bacteria. This is an evolving issue that took place over several decades, resulting in frequent pathogenic bacteria harboring some type of resistance to each new antibiotic coming to the market. This means there is an urgent call for action to avoid a global crisis in health care when we can lose the ability to perform surgeries and other types of quotidian medical procedures.
In an attempt to define AMR, we can say that this is a natural phenomenon arising when microorganisms are exposed to antimicrobials or antibiotics. Under such selective pressure, susceptible bacteria are inhibited or killed, whereas those that are naturally (or intrinsically) resistant or those with antibiotic-resistant traits have a much greater chance of surviving and multiplying. The issue arises not only as a result of the overuse of antimicrobial agents but also when they are used inappropriately (such as inadequate drug choices, faulty dosing regimens, and/or low compliance to relevant treatment guidelines). All of this can have a compounding effect and contribute to the rise of antibiotic resistance.
During the last few years, the importance of animal reservoirs and the environment in spreading AMR has been widely recognized. In the past several decades, we have witnessed an increased awareness of the potential problems that resistance among food-producing animals could have on human health. In addition, the soil is regarded as a reservoir of AMR genes since most antibiotics are derived from soil microorganisms that are intrinsically resistant to the antibiotics produced. Finally, water potentially contaminated with organic fertilizers and fecal microorganisms may disseminate resistant bacteria in the soil and is considered a principal way of bacterial propagation between various environmental compartments.
Given the dangers of AMR and the slogan of World Antimicrobial Awareness Week – ‘Antimicrobials: Handle with Care,’ why is it crucial to handle antimicrobials with care?
Judicious and careful use of antimicrobial agents is one of the pillars of successfully diminishing the threat of AMR. In the clinical milieu, there is an important concept of antimicrobial stewardship that refers to a set of coordinated strategies for improving patient care and outcomes by instituting optimal therapy, minimizing collateral damage by reducing antimicrobial usage (which translates to lower resistance rates), and lowering the price of antimicrobials. This concept is also amenable to global implementation to help control AMR by increasing awareness of the public and educating healthcare professionals on the prudent use of antimicrobials.
In the hospital setting, antimicrobial stewardship programs and infection control measures are of utmost importance to prevent the emergence and transmission of antibiotic-resistance microorganisms and preserve the effectiveness of currently available antimicrobial drugs. Hence, multidisciplinary teams of experts (such as infectious disease specialists, medical microbiologists, and clinical pharmacists) participate in such endeavors. Moreover, as the ongoing COVID-19 pandemic can lead to the increased indiscriminate usage of antimicrobials (which was particularly the case in the early days of SARS-CoV-2 spread), handling antibiotics with care can result in lower bacterial resistance and, subsequently, a lower death toll.
Nevertheless, the antimicrobial stewardship concept has to be extended to family doctors in the community, where there is often a very high consumption of antibiotics. Relevant public health actions that are needed to reduce inappropriate antimicrobial prescriptions and antibiotic misuse should consider adequate information campaigns for the consumers, training of healthcare professionals, enhanced diagnostics to improve treatment decisions, the development of treatment guidelines, as well as regular prescription audits. In a nutshell, different healthcare organizations should strive to make coordinated efforts to institute new policies and put more emphasis on antimicrobial stewardship in professional curricula.
Image Credit: dturphoto/Shutterstock
You recently published research concerning the burden of bacterial antimicrobial resistance in the WHO European region. Can you tell us more about this study and the results you identified?
To our knowledge, this new study brings the most comprehensive analysis of the AMR burden in the WHO European region, and our estimates span across 53 countries, 23 bacterial pathogens, and 88 pathogen–drug combinations in 2019. There are several advances in comparison to previous work on this topic, primarily in scope (as not only the European Union is included, but all countries of the WHO European region), as well as in the number of included pathogen-drug combinations.
Furthermore, we used major methodological innovations that were first identified in the 2019 global burden of bacterial AMR study. The magnitude of the problem was described with the use of two scenarios, which means we provided estimates for both deaths directly caused by AMR (attributable mortality) and deaths that occurred from a drug-resistant infection, but for which AMR may or may not have been the cause (associated mortality).
Finally, our study allows comparisons with other causes of death since it builds on estimates of disease incidence, prevalence, and mortality from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019.
And results were striking. By identifying more than half a million deaths associated with AMR and more than 130 thousand deaths attributable to AMR, we have shown that antibiotic resistance is a considerable and potentially neglected problem in the WHO European region as a whole, with evident differences between subregions and specific countries. The largest fatal burden of AMR in the region came from bloodstream infections, followed by intra-abdominal infections and respiratory infections. The leading pathogens that we identified were (in descending order of death) Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa and Enterococcus faecium.
Such estimates of the impact of AMR on morbidity and mortality are crucial for informing public health investment decisions for each country in this region. Furthermore, highlighting specific pathogens and pathogen–drug combinations with the highest estimated burden – which we showed were methicillin-resistant Staphylococcus aureus (MRSA) and aminopenicillin-resistant Escherichia coli – might specifically inform policy targets and policy design. Our results emphasize that the most effective way to address AMR in this region will necessitate targeted efforts and investments, together with continuous outcome-based research endeavors.
Study: fizkes/Shutterstock
What do you believe are some of the challenges with approximating the magnitude of the AMR crisis and its downstream effect on human health?
There are indeed many challenges with this type of complex estimation process, and the biggest one is definitely data scarcity, as the availability of data on AMR can differ from one country to the next. This is not the only problem with our study but is universal for all research projects that aim to assess the burden of AMR. We also acknowledge that the effect of resistance on mortality may differ across locations, which can be pertinent when we pursue a global estimation of the AMR crisis.
More specifically, certain locations might not be well-suited to treat susceptible infections, which means that the effect of resistance is minimized; conversely, other locations might not have access to second-line antimicrobials; thus, the effect of resistance is magnified. It is also possible that the relative risk of death attributable to resistance can be different across anatomical sites of infection due to variable antibiotic penetrance.
Moreover, countries with low socio-demographic index (which is a summary measure that combines information on the education, economy, and fertility rate) might have much less stringent surveillance systems, as well as insufficient laboratory support – potentially resulting in an underestimation of attributable and associated AMR mortality globally and the countries of the WHO European Region. Nonetheless, our estimates are informed by data from all countries included in the study. When data for a specific country were lacking, estimates and model building relied on regional patterns, co-variates, and out-of-sample predictive validity.
Despite these limitations, our analysis reflects the widest and presently best available range of data, as well as the use of models that have been developed and implemented specifically for incorporating disparate data sources for the Global Burden of Disease analysis. We are in agreement with other studies that highlight and underscore critical data gaps on resistant organisms in certain parts of the world; therefore, solving this problem which will be extremely important in the future to fine-tune our estimates additionally.
WHO: What is antimicrobial resistance (AMR)?
The specific theme of World Antimicrobial Awareness Week (WAAW) 2022 is ‘Preventing antimicrobial resistance together.’ What does this theme mean to you personally, and how do you believe we can take steps toward this goal?
It is without any doubt that manifold joint efforts from healthcare workers (acting as prescribers) and patients to policymakers and international regulators are necessary to stand a chance against the global spread of antibiotic resistance. In other words, different stakeholders have to join forces in order to tackle this issue from many angles, as no single action will provide an acceptable solution in isolation.
Also, this issue is a truly global problem. Together with rational and prudent usage of currently available antimicrobial drugs and the introduction of antibiotics where there is a lack of them, the development of new and effective compounds, as well as the introduction of new diagnostic approaches, are all recognized as urgent priorities.
Governments should introduce several essential processes to inspire change by all stakeholders related to AMR, as appropriately described within the WHO policy package for combating drug resistance. More specifically, this policy package refers to a national plan that strives to be comprehensive, engages civil societies, and insists on the accountability of everyone involved. Also, strengthened surveillance systems, improved laboratory capacity, wide access to essential medicines of sufficient quality, regulated use of antibiotics, the emphasis on infection prevention and control, as well as promotion of innovations will be crucial in the near future. There has to be a commitment to a rather high level of human health protection.
How do you believe that different sectors, for example, healthcare, animal care, farming, and agriculture, can work collaboratively to help curb AMR?
Our quest against AMR should be addressed through the lens of a One Health approach. This means more stringent infection prevention/control in healthcare facilities, food industry premises, and farms, as well as insisting on best practices in agriculture, clean water, sanitation and waste management. A set of diverse but coordinated strategies against antibiotic resistance should be implemented, taking into account the type of pathogen (either human or zoonotic), the setting (healthcare or the community) and possibly other specific factors contributing to the emergence of resistance.
In veterinary medicine, the required interventions consist in enforcing regulations for improved surveillance and monitoring, governing the use of antimicrobials in food-producing animals, and decreasing the need for antibiotics through improved animal husbandry. Naturally, more research is needed to elucidate the exact pathways of transmission of resistant microbial agents between animals and humans (but also their subsequent impact). There is a need to adequately implement legislation if we are to achieve long-lasting effects.
In addition, innovative approaches are needed for the development of new antibiotics and other products to limit AMR. There is a shortage of new antibiotics in the pipeline and few incentives for the industry to invest in research and development in this field. Research into digital technologies and eHealth solutions has to be strengthened to improve prescription practices, care solutions, and overall awareness of this issue. All of this necessitates a well-designed roadmap to orchestrate further collaboration efforts between governments, industry, and non-governmental organizations.
Image Credit: AnaLysiSStudiO/Shutterstock
What are the next steps for you and your research? Do you have any exciting projects coming up?
The Global Research on AntiMicrobial resistance (GRAM) Project will definitely continue to be one of the most important global projects in years to come. Assessing the burden of bacterial antimicrobial resistance in the WHO European region in 2019 was our first regional endeavor, which will be followed by research publications covering other regions of the world. We believe it is of utmost importance to obtain a full picture of this pressing issue not only on a global but also on a regional and country level. In the future, one of the goals is to pursue a time-series analysis of the AMR burden through the years, which will be helpful in forecasting, preparedness planning, and key policy decisions.
Furthermore, we have already mentioned how the animal and environmental sectors present a plethora of opportunities for resistance to evolve and be introduced into human populations. Therefore, we believe it will be important to assess data gaps and links between animal and human resistance in one of our future projects. Our goal is also to assess significant indirect effects of AMR, such as the effect of AMR on antibiotic prophylaxis in transplant recipients or for the prevention of surgical site infections. One of the salient goals is to assess AMR in the context of health equity, particularly considering the results from the paper on the global burden of AMR.
Finally, there is a need to prioritize the improved collection of high-quality AMR data in both the human and animal sectors, as well as the environment, in order to improve all our future estimation processes. One of our goals is to facilitate data and resource sharing between countries to improve policy-making and capacity building. Finally, continuously broadening both the quantity and quality of data acquisition worldwide will allow us to monitor levels of resistance much more effectively and course-correct action where needed. We are confident that our data-driven approach will result in even more stringent estimates and help in tackling this enormous challenge.
Dr. Tomislav Meštrović is an Associate Professor at the University North in Croatia and an Affiliate Associate Professor at the Institute for Health Metrics and Evaluation (IHME) and the Department of Health Metrics Sciences of the University of Washington. He finished his medical and doctoral training at the University of Zagreb School of Medicine (Croatia), his MPH at the London School of Hygiene and Tropical medicine of the University of London (United Kingdom), and his MBA in International Healthcare Management at the Frankfurt School of Finance & Management (Germany). He is a board-certified clinical microbiology and sexual medicine specialist, with an additional one-year training in clinical research from Harvard Medical School.
His primary research interest with IHME is the public health significance and impact of antimicrobial resistance (AMR) within the Global Burden of Antimicrobial Resistance (GRAM) project, working in the AMR research team led by Professor Mohsen Naghavi. He joined this group as a Fulbright Visiting Scholar during the academic year 2021/2022, and was a lead author on the comprehensive assessment of AMR burden in the WHO European Region. Alongside his ongoing work in antibiotic resistance, he participates in other IHME-led and GBD-related projects, providing expertise for many pivotal global and public health research questions (particularly those in relation to infectious diseases). He is also a member of the WHO/HIFA Working Group Member on Learning for Quality Health Services, which is a part of the WHO Global Learning Laboratory (GLL) for Quality Universal Health Coverage (UHC).
IHME was established at the University of Washington in Seattle in 2007. Its mission is to deliver to the world timely, relevant, and scientifically valid evidence to improve health policy and practice.
Thought LeadersDr. Javier Yugueros-MarcosHead of Department World Organisation for Animal Health (WOAH)
In this interview, News-Medical talks to Dr Javier Yugueros-Marcos, Head of the Antimicrobial Resistance and Veterinary Products Department at the World Organisation for Animal Health, about how the world can work together to promote the sustainable and responsible use of antimicrobials.
Please could you introduce yourself and tell us about your role within the World Organisation for Animal Health (WOAH)?
My name is Javier Yugueros-Marcos, and I joined the World Organisation for Animal Health (WOAH, founded as OIE) one year ago in November 2021. I am leading the department in charge of the quality of veterinary products, which encompasses diagnostics, vaccines and therapeutics, including antimicrobials. Because of the importance of antimicrobials and antimicrobial resistance, about 80% of our activity revolves around them.
We monitor antimicrobial use all over the world, develop standards on the responsible and prudent use of antimicrobials, and assess the quality of actions in the field so that we can increase capacity-building and change practices.
WOAH’s mission is to help create a future in which humans and animals benefit and support each other for a healthier, more sustainable world. Why is this mission so important given the current state of global health, and how is the health of humans and animals interlinked?
Our work began in 1924 after an animal disease had a big impact on food security: Rinderpest. Since then, we have been working on improving animal health worldwide, bringing about transparency in terms of the status of animal health, and ensuring safe international trade of animals and animal products. All of this leads to better health for humans.
Today, the situation is not much different because animal diseases still exist, and we still care about transparency and reporting animal disease outbreaks for safe international trade. However, human and animal health are interlinked in terms of more than just international trade. Let me give you two examples.
One is zoonoses. It is estimated that 60% of infectious diseases in humans originate from animals. This percentage is increasing to three out of four, when talking about emerging pathogens. Notable examples include Ebola virus, Middle East respiratory syndrome-related coronavirus (MERS-CoV) and the first generation of severe acute respiratory syndrome coronavirus (SARS-CoV). We suspect the same for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus behind COVID-19, although we have not identified the intermediate species yet, if ever.
It is not only food-producing animals that humans risk contracting disease from, but also wildlife. And vice versa, as diseases can also be transmitted from humans to animals. Human population expansion is displacing animals from their environment, and the new contact that humans have with these displaced wild animals increases the risk of zoonotic disease occurrence and transmission.
The second example is antimicrobial resistance (AMR), which is the main topic of this interview. Pathogens have no borders, and the overuse and misuse of antimicrobials in any sector will immediately impact the others. When tackling this problem, it does not make sense to monitor the responsible use of antimicrobials in humans if we do not collect the same information in animals, and vice versa. Everything is connected. As long as we do not work together in this interconnected world, we will not be able to solve its problems. It took us a while, but I think that many stakeholders are finally acknowledging that.
World Organisation for Animal Health (WOAH, founded as OIE) – It’s Everyone’s Health.
Improving global health and well-being can only be achieved by also considering animals and the environment. How will the improvement of animal health consequently improve the health of humans and the environment?
Consider the examples I have just given of infectious human diseases coming from animals. Improving animal health will prevent many of these events from happening and will eventually ensure that we have a healthier human sector. This includes not only food-producing animals and wildlife but also companion animals which are increasingly present in our lives.
The other aspect of all this is to consider how dependent we are on animals for our livelihoods. Today, one out of five people depend on production animals for their income and livelihoods. This is not so evident in high-income countries, but it is highly present in low and middle-income countries which represent a huge proportion of the global population.
Whenever we talk about animals, we tend to think about terrestrial animals, but we also have to think about aquatic animals. Over 20 million people depend on the aquaculture sector. This is the fastest growing sector of those supplying protein for the world.
Every year you and your partners at the WHO, the FAO and UNEP celebrate World Antimicrobial Awareness Week. The theme for 2022 is “Preventing Antimicrobial Resistance Together”. What does this theme mean to you?
There is no more effective way to avoid antimicrobial misuse than employing them only when other approaches do not work, only when they are necessary. Prevention is the first thing that we have to bear in mind. We have to maximise the technologies existing today to improve biosecurity and ensure best-in-class animal husbandry practices. One way this is well underway is through the use of vaccination across the sectors.
Before this, I was working in the human health sector, so I am accustomedto promoting the term ‘hygiene’. Hygiene is the best way to prevent infection. And we have seen this with the recent COVID-19 pandemic, where we employed social distancing, hand sanitizer use, and other measures. Thus, hygiene was enhanced. The same applies for animals. And it is not only our hands that pose a risk – for example, farm workers need to think about changing their boots when they go into the farm, and checking visitors when they come onto the property.
All these factors, as well as how animals are raised and live, affect their capacity to fight infections. Maximising their immunity prevents them from getting sick, preventing all of us from using more antimicrobials.
This is something that has been somehow forgotten, and we would like to emphasise this message. Simple and easy measures can save a lot of trouble down the road.
Image Credit: World Health Organization
With antimicrobial resistance being described by WHO as one of the top 10 threats to global health, what impact is it actually having on animals worldwide?
We would like to be as advanced as our colleagues from the human health sector in this regard. Unfortunately, there is currently no data available on the burden of antimicrobial resistance in animals at global level, but we are working on it.
There are several regional initiatives (i.e. Europe, Asia, Americas…) collecting data on the prevalence of antimicrobial resistance in the animal health sector. But as I said, we do not have any comprehensive global data yet. Our colleagues from FAO are working on this. This year they have started a pilot to collect data on antimicrobial resistance in animals. They are beginning in Asia, and their goal is to collect data globally by the end of next year.
The other initiative that I wanted to mention is one that we are leading in collaboration with the University of Liverpool, which is called the Global Burden of Animal Diseases (or GBADs). It follows the same methodology as something that was done for humans a few years ago. We have recently developed a component on the economic impact of AMR in animals, particularly the socioeconomic impact on livelihoods where antimicrobial resistance is present.
One key objective of World Antimicrobial Awareness Week is improving awareness of AMR. Despite continued awareness, many people still do not fully understand the wider implications it has not only for human health, but for animal health and environmental health. What more can people and policymakers do to continue educating about this global health threat?
There are a couple of basic things that we must keep doing. One is repeating. Education is the simple exercise of repeating things. Something that we are starting to work on is making the messages evolve and targeting populations where the message can trigger actions.
We were discussing this with our Quadripartite colleagues (the Quadripartite alliance for One Health: FAO, UNEP, WHO and WOAH) a few weeks ago. One of the populations that were identified as powerful drivers of communication is the youth and children in particular. They learn everything; they listen to everything; they repeat everything that we can teach them. They represent the future. If we succeed in educating them and making them understand that antimicrobials do not have to be overused or misused, then we will be achieving a level of understanding that has not been gained until now.
In this regard, we have already engaged with young people and students. For example, we will participate in the upcoming Global AMR Youth Summit, organised by the World Health Students Alliance and taking place during the World Antimicrobial Awareness Week.
In terms of targeting populations and adapting the messages, we are currently working on renewing our web content and making it more understandable for non-technical populations, for example, concerned citizens.
In terms of the policymakers, the two actions needed are 1) bringing them the data to showcase that there is a problem, and 2) providing alternatives. It is then our responsibility as an organisation to set standards on how antimicrobials can be used responsibly and prudently. These recommendations are then used to guide the development of national regulations or legislation.
We are working on expanding the breadth of actions from food-producing animals to all animals, companion animals and wildlife included. We are making the role and the responsibilities of every actor within the chain much clearer, from the veterinary authorities to the farmer and pet owners. We are providing these overarching principles that in the end can be translated into legislation or regulation, and therefore have an action in the field. It is also within our responsibility to highlight the priority research areas for research agencies and countries to fund so that in the end we can provide alternatives to antimicrobials.
It has been described that to work collaboratively between sectors to tackle AMR, we need to use a One Health approach. What is meant by the term One Health and what are its advantages for global health?
One Health, in very simple words, is about working together. We are all interconnected. What is happening in the animal health sector is eventually going to impact the human sector. And the behaviour of humans has an impact on the animal health sector, as well as in food systems and ecosystems.
Translated into the world of governments, One Health is not much more than making all the sectors work together. We are trying to promote dialogue across sectors. At global level, the Quadripartite organisations have learned to dialogue, work together, and undertake actions in collaboration.
How will this level of international collaboration, especially between animal and human health professionals, help to tackle other problems such as rabies?
AMR is a health challenge and it can be taken as a model on how collaboration could improve our response. The same model can be applied to zoonotic diseases, those that may transmit from animals to humans, or humans to animals. When working on a human disease, if there is an animal component, we need to pick up the phone, write emails, and work with the department in charge of animal health.
The Quadripartite organisations have been working together on AMR since 2014/15. Today, AMR is one action track of the One Health joint action plan, which has been recently launched to advance One Health at global, regional and national levels. Our experience can be an asset to other people working in similar areas. AMR is a model, and then the model can be applied to other shared health challenges.
Alongside your current work surrounding antimicrobial resistance, what are some other priorities you are currently addressing within WOAH?
Our AMR strategy has four pillars: awareness, surveillance and research, capacity-building, and standards implementation.
In terms of awareness, this conversation is a good example. The World Antimicrobial Awareness Week, a global campaign to raise awareness and understanding of AMR and promote best practices among One Health stakeholders.
In terms of surveillance, we have a number of fascinating things ongoing. One is our database of worldwide antimicrobial use in animals, launched in 2015. For seven years, we have been using paper-based and Excel forms to collect the information from countries. This year marks a turning point, as last September we launched a totally digitalised system to allow countries to report and use their data for their own actions. The platform will become accessible for the public in the upcoming year.
At the same time, we are initiating a similar system for the detection of falsified and sub-standard products. The keys to antimicrobial stewardship are having the right antimicrobial for the right individual, at the right time, with the right dose, and for the right period. But it is also important to have the right product, because if products are falsified or sub-standard, inoculations are not going to have any efficacy, leading eventually to resistance. We are starting a pilot experience for a global system for alerting sub-standard and falsified products.
The other initiative that we have is the estimation of the economic burden of AMR. In terms of research, we are working with our Quadripartite partners, developing a One Health research priority agenda in collaboration with many different stakeholders. The goal is to provide a roadmap of priorities that should be tackled in terms of research from the One Health perspective.
Then, in terms of capacity-building, we support the Multi-Partner Trust Fund initiative in collaboration with our Quadripartite partners and the donors, which is today funding 10 low- and middle-income countries to implement their national action plans on AMR using a One Health approach. We have learned to talk to each other at global level, and we are scaling up these efforts at local level so that the Minister of Agriculture, the Minister of Health, the Minister of Environment, and the Minister of Aquaculture in a given country can do the same to successfully implement national action plans on AMR across the sectors. Kenya, Zimbabwe, Tajikistan and Morocco are examples of countries supported through this fund.
Last but not least, a strong legal framework is necessary if countries are to take effective action in the face of health threats such as AMR In addition to providing Standards on the responsible use of antimicrobials, we also have a programme on Veterinary Legislation Support (VLSP) that helps Members recognise and address their needs for clear, comprehensive veterinary legislation.
Image Credit: Pressmaster/Shutterstock.com
Are you hopeful that with this continued awareness, education and funding surrounding AMR, we will one day see a world without AMR?
I wish I could imagine such a world, but all organisms on Earth share the same planet and we are all connected. We all adapt to our environment. Antimicrobial resistance is a natural phenomenon that microorganisms implement to evolve in a hostile, toxic environment. As soon as they see an antimicrobial agent preventing them from thriving, they are going to develop resistance. Alexander Fleming warned us all when he received his Nobel prize. With every new antimicrobial that we have developed, sooner rather than later, resistance has appeared.
A world without antimicrobial resistance is difficult to imagine. However, we can learn how to live in a world where we can use antimicrobials sustainably and reduce the burden of human, animal and plant diseases. This is what we are working on. We are working on making every actor in the animal health sector aware that we must use antimicrobials responsibly to ensure they remain available for future generations.
Sustainability can be achieved by developing new antimicrobials, but also, more importantly, by using the ones that we have today responsibly.
This is where action for prevention is really important. If we encourage hygiene, improve security at farms, and keep animals in good conditions so that they have a strong immune system, then we can fight this battle and maintain low levels of antimicrobial resistance. Antimicrobials must be used responsibly and sustainably.
With the COVID-19 pandemic reminding us that all sectors must work together to achieve scientific progress, we have seen significant advancements in recent years, especially within disease diagnostics. Are there any particular fields within animal health that you are excited to watch evolve over the coming years?
I think COVID-19 has also taught us about the power of vaccination. I hope that after the pandemic everyone will understand its importance in terms of prevention. Hopefully, it will help encourage trust and confidence in this practice.
Regarding diagnostics, I am a little biased, because I worked for 18 years in the field of diagnostics, and, as a former colleague used to say, “without diagnosis, medicine is blind”. This is true for the human health sector, but even more so for the animal health sector, which is severely impacted by the lack of diagnostic tools, particularly innovative ones. I hope that this area will be reinforced, thanks to development in human health being imparted into the animal health sector.
What is next for you and your work at WOAH? Are you involved in any exciting upcoming projects?
I have mentioned several already, but I will pick the three most exciting ones.
First, the launch of the global database on antimicrobial use in animals, called ANIMUSE.
The global burden of animal diseases is also an exciting project because it will give us an idea of the socioeconomic impact of animal diseases. I think it will help mobilise resources and ratify the importance of AMR in the animal health sector.
Finally, the revision of standards we are undertaking. We are expanding the content to other animals, not only food-producing animals, and clarifying the responsibilities of every actor to use antimicrobials responsibly. I am very confident that this will help in the field if people know who does what and how to do it properly.
About Javier Y. Marcos
Javier Y. Marcos has a solid history of working in antimicrobial resistance (AMR), with eighteen years of experience in the development and commercialisation of diagnostics tests for infectious diseases, both for human and animal health. Having graduated as a Doctor in Veterinary Medicine in 1997, he also holds a PhD in Microbiology & Molecular Biology from the Leon University, Spain.
At the end of 2021, he was appointed as Head of the AMR & Veterinary Products Department at the World Organisation for Animal Health (WOAH, founded as OIE), being accountable for the enhanced quality of veterinary medicinal products, and the coordination of actions supporting a responsible and prudent use of antimicrobials in animal health worldwide.
Thought LeadersProfessor Roberto La RagioneChair of TrusteesHumanimal Trust
In this interview, News-Medical speaks to Professor Roberto La Ragione, Chair of Trustees at Humanimal Trust, about the concept of One Medicine and how human and veterinary medicine can collaborate, share knowledge, and initiate research for the benefit of both humans and animals.
Please can you introduce yourself, tell us about your professional background, and your role at Humanimal Trust?
I am Professor Roberto La Ragione, Chair of Trustees at Humanimal Trust.
I graduated in 1995 and then studied for a postgraduate degree in veterinary microbiology at the Royal Veterinary College (University of London). In 1996, I moved to the government’s Veterinary Laboratories Agency (VLA) to undertake a Ph.D. on the pathogenesis of E. coli in poultry. Upon completing my Ph.D. studies, I commenced a post-doctoral position at Royal Holloway, University of London, studying E. coli virulence factors and vaccine development.
Since 2001, my work has focused largely on understanding the pathogenesis of zoonotic bacterial pathogens to develop control strategies. I have led several commercial, Defra, research councils (BBSRC, MRC, EPSRC, AHRC, Innovate) and EU projects in this area.
My current research interests focus on the pathogenesis of food-borne pathogens with a particular interest in Antimicrobial Resistance (AMR) and the development of intervention strategies, including vaccines, rapid diagnostic, pre, and probiotics. I have published over 190 papers in the area of host-microbe interaction, with a particular emphasis on E. coli,Salmonella, vaccines, probiotics, and AMR.
In 2005, I was appointed Head of Pathogenesis and Control at the AHVLA, and in 2010, I was appointed Professor of Veterinary Microbiology and Pathology at the University of Surrey. I gained the FRCPath in 2010, and in 2012, I was appointed the Associate Dean for Veterinary Strategy in the new School of Veterinary Medicine at the University of Surrey. In 2014, I was appointed to the position of Head of the Department of Pathology and Infectious Diseases and Director of the Veterinary Pathology Centre. In 2019 I was appointed Deputy Head of the School of Veterinary Medicine at the University of Surrey, and then in 2021, I was appointed Head of the School of Biosciences and Medicine.
I am the past president of the Med-Vet-Net Association and the Veterinary Research Club, the current Chair of Humanimal Trust, a member of the FSA ACMSF AMR sub-committee, a Trustee of the Houghton Trust, a member of the APHA Science Advisory Board and Chair of the Royal College of Pathologists Veterinary Pathology SAC. I am an Associate member of the European College of Veterinary Microbiology, and in 2020, I was awarded an Honorary Associateship of the Royal College of Veterinary Surgeons.
Humanimal Trust is a unique organization. Please could you tell us about the organization’s origin, purpose, and values?
Humanimal Trust is the only organization in the UK with the sole and specific purpose of progressing One Medicine.
It was founded in May 2014 by world-renowned orthopedic-neuro veterinary surgeon Professor Noel Fitzpatrick – otherwise known as the TV Supervet. As a vet, Noel Fitzpatrick experienced personally the deep divide between human and animal medicine and saw how unfair this was.
Image Credit: LightField Studios/Shutterstock.com
Frustrated by the lack of opportunities to share what he was learning from veterinary practice or to benefit from relevant learning from human medicine, he decided to create the platform himself. This laid the foundations for the work Humanimal Trust does today, removing barriers and seeking to close the divide between human and animal medicine.
Our five areas of work spell out I-CARE, which sums up the way we feel, our supporters feel, and we hope everybody will one day feel about One Medicine:
Influence – we care about bringing together everyone who cares about One Medicine to create a road map for change in public policy, education, and at the clinical coalface.
Collaboration – we care about creating opportunities for human and veterinary professionals and students to learn from one another (in person and virtually) by demonstrating One Medicine at work.
Awareness – we care that people should know and understand the benefits of One Medicine for humans and animals, about non-animal alternatives to laboratory models, and how much human and animal medicine can learn from one another’s clinical practice – saving time, money, and lives.
Research – we care about research – funding it, facilitating it, shouting about it – that could benefit humans and animals without using laboratory animal models.
Education – we care about learning – every child learning about the connections between humans and animals; veterinary and human medical students learning with and from one another; practitioners learning continuously from their peers.
Humanimal Trust advocates for One Medicine. What is One Medicine, when did this concept originate, and how has the understanding of it evolved in recent years?
The origins of One Medicine date back to the nineteenth century when Rudolf Virchow linked human and animal health. Sir William Osler, Dr. Calvin Schwabe, Lord Lawson Soulsby, and others have since continued to expand the One Medicine concept, identifying the connections, commonalities, and synergies between human and veterinary medicine.
It was whilst studying the history of medicine that Professor Fitzpatrick came upon a term used to describe human and veterinary medicine working with one another: One Medicine. The third edition of Dr. Calvin Schwabe’s seminal publication in 1984 of ‘Veterinary Medicine and Human Health’ which spoke of One Medicine, laid the foundation for what we now know as One Health, but in considering this text, Fitzpatrick identified a need to move away from a public health agenda to a common health agenda focusing on infectious and non-infectious diseases.
Moreover, when reviewing the three Rs (refinement, reduction, and replacement) in relation to animal use in research, it became clear that a fourth R was missing from the 3Rs principle – the principle of reciprocity so that not only do medical practitioners and allied researchers benefit, but also patients, regardless of their species.
By considering the contribution that animals can make to research by studying their lives and their responses to naturally occurring, spontaneous diseases rather than using experimental animal models in research, the use of animals in research can be significantly reduced.
One Medicine and the ‘Biology of the Future’ (Biology Week 2020)
Why is it currently the case that human and veterinary medicine are kept separate, and why would it be beneficial to change this?
Although the practice of bringing veterinary and human medical and research professionals together is thought to stimulate new and innovative research, historically, this has been challenging. A number of studies have investigated why this could be, and different levels of awareness and priorities may be one reason. A 2020 study, which surveyed vets and GPs in Australia, found that vets generally had more awareness and felt more confident in engaging in zoonoses management compared to GPs, and were also more likely to initiate cross-professional referrals.
The Trust believes that education is key to One Medicine. Only by learning about the similarities between humans and animals from the earliest stage to collaboration in the most advanced science and clinical practice will we promote change. Therefore, we must ensure that the best research, clinical practice and learning, benefiting both humans and animals, are accessible, funded, encouraged, and promoted.
A study published in 2017 by a group of scientists in The Netherlands noted that having a clear common goal (like One Medicine) can help to stimulate collaboration. The study also suggested that professional organizations could be important facilitators of collaboration in this area.
With this in mind, in 2020, the Trust launched the Humanimal Hub, a free online platform for all human and animal medical and veterinary professionals to meet, collaborate, share knowledge, and initiate research for the benefit of both humans and animals.
While still in its infancy, the Hub already has over 250 members. It provides a much-needed virtual space for connections to be made and conversations to be initiated, which the Trust actively seeks to nurture. For example, Anna Radford, a Consultant in Paediatric Surgery at Hull University NHS Trust and Leeds Children’s Hospital, was looking to collaborate with an individual or group in veterinary medicine with a specialty in problems with urinary tract or kidneys and/or antimicrobial resistance. Through the Hub, we were able to identify a suitable professional, and as a result, an interdisciplinary group has been set up to identify common urological conditions affecting both humans and companion animals.
Anna was also introduced to a diagnostics company working in the animal medical care field at the Trust’s inaugural global ‘One Medicine Symposium: Stronger Together’ in May 2021. Through them, Anna has set up a new collaboration to determine whether this diagnostic technology developed with companion animal medicine in mind could potentially also be useful to help diagnose urinary, joint, and cerebrospinal fluid infections in a busy NHS hospital setting.
Genetics & Genomics eBook
Compilation of the top interviews, articles, and news in the last year.
These are just two examples of how we know that great things can happen when animal and human health professionals and scientists come together.
Which areas of medicine do you currently focus on, and what benefits does One Medicine provide to this particular area?
I believe One Medicine has transformative potential across all areas of medicine where physiological and genetic similarities exist between humans and animals. There are five main pillars of research that the Trust currently seeks to fund, namely infection control and antimicrobial resistance; cancer; bone and joint disease; brain and spinal disease; and regenerative medicine.
In line with this, the Trust began an important collaboration with the children’s charity Action Medical Research in 2020 to help support two child-focused medical research projects. The first study, led by Professor Hall-Scraggs at University College London, focuses on juvenile idiopathic arthritis (JIA). Patients with JIA have a disease that causes inflammation of their joints. This leads to pain, joint deformity, disability, and reduced quality of life. There are newer drugs now available that suppress joint inflammation, but these are expensive and can have side effects, the most serious being life-threatening infection. Magnetic resonance imaging (MRI) scans can show inflammation of joints. By measuring inflammation in patients with juvenile idiopathic arthritis, the study could help optimize their treatment by showing how much inflammation is present and whether it changes with treatment.
Image Credit: Amir Bajric/Shutterstock.com
The second study, which is ongoing, is investigating infection prevention and its impact on antimicrobial resistance in critically ill children, led by Dr. Nazima Pathan, Lecturer in Paediatric Intensive Care at the University of Cambridge. The transferable data from both studies has real potential to help improve the lives of humans and animals with similar conditions.
Another example of research the Trust has funded concerns liquid biopsies for canine patients. This research was undertaken by Professor Joanna Morris and Dr. Tomoko Iwata at the University of Glasgow and is a great example of reciprocity whereby human and animal bladder cancer patients may benefit from this research.
Are there any particular examples of where either human or veterinary medicine has led to advances in the other?
Cancer research is perhaps the area for which One Medicine is most well-known. For example, dogs, long considered our best friends, don’t just share our lives but also risk factors for certain diseases. Many diseases also share genetic similarities between humans and dogs. Canine lymphoma, the second most common cancer in dogs, has relatively similar characteristics to human non-Hodgkin lymphoma. Around 1 in 8 golden retrievers will develop canine lymphoma, and CRUK estimates that 1 in 39 males and 1 in 51 females are at risk of being diagnosed with non-Hodgkin lymphoma. Both species need better, more effective ways to treat the disease, and clinical trials with canine veterinary patients have been helping to fast-track the development of new treatments in this area for several years.
Image Credit: Varvara Serebrova/Shutterstock.com
The US-based DISCO initiative recognizes the value of aligning veterinary and human drug development projects and explains why it can be worthwhile to include veterinary patients at an early stage in cancer drug development trials. From shortening drug development times to encouraging cross-collaboration between the disciplines for the benefit of both human and veterinary patients, the potential advantages of this approach are clearly laid out in a landmark 2019 paper, which came about from a workshop of the World Small Animal Veterinary Association’s One Health committee.
What is the one thing you wish people knew about One Medicine?
One Medicine is about human and animal healthcare advancing hand in hand, in an equitable and sustainable way, and not at the expense of an animal’s life.
How can people, both medical professionals and the general public, get involved with Humanimal Trust and support the One Medicine cause?
Human and animal medical professionals, students, and researchers can join the Humanimal Hub for free and use it as an opportunity to collaborate, share knowledge, and initiate research with other like-minded individuals. The Trust also holds an annual One Medicine Day event that brings together researchers, doctors, vets, allied healthcare professionals, and students from around the world to discuss practical ways forward for One Medicine. The year’s ‘One Medicine Day Seminar: One Medicine in Action’ talks can be found here.
There are also opportunities to join our team as a volunteer Ambassador, write articles for us, present at events or act as a moderator for the Hub.
There are many ways that members of the public interested in One Medicine can get involved too, from signing The Humanimal Pledge or organizing a Paws for a Picnic fundraiser with family and friends to leaving a gift in your will or becoming a volunteer speaker in your local community.
What is next for yourself and Humanimal Trust?
We recognize the need to present One Medicine consistently through an education lens. Our absolute priority is to improve understanding at every level – from pre-school to professional training (veterinary and medical undergraduates) and development – of the relationship between human and animal health and the need for collaboration and reciprocity of benefit to humans and animals.
With this in mind, our focus for the next twelve months is on four key areas of activity:
Focused awareness building among key audiences
Developing partnerships, networks, and collaborations
Education
Research funding, engagement, and influencing activity
To help drive this, we have appointed a new CEO, Joe Bailey, who will be joining us in November from RSPCA Assured, together with a new Trustee, Anna Radford, whom I referred to earlier. I have no doubt that their understanding of and passion for our purpose will help take Humanimal Trust to the next level.
We are expanding our Science Committee, which will strengthen our ability to draw on the best available expertise to make better-informed decisions about which research activities we prioritize for funding or support. In addition, to support the strategic development of our educational program, we have created a new role – Schools Education Manager – which will enable us to initiate the long-term development of a One Medicine curriculum.
We will soon launch our new Podcast series, which I’m very excited about. This will follow the Trust’s previous series, Humanimal Connection, but with a very different feel to it, so watch this space.
About Professor Roberto La Ragione, BSc (Hons) MSc Ph.D. FRSB CBiol FIBMS CSci AECVM FRCPath HonAssocRCVS
I am a Professor of Veterinary Microbiology and Pathology in the School of Veterinary Medicine and the Head of the School of Biosciences and Medicine at the University of Surrey. My role includes delivering and overseeing teaching and research in the School and running my own research group, which consists of vets, doctors, and scientists. My current research interests focus on Antimicrobial Resistance (AMR) and understanding the pathogenesis of zoonotic bacterial pathogens (those that can be transmitted from animals to humans and, in some cases, from humans to animals). I also have a particular interest in developing control and intervention strategies, including rapid diagnostics, vaccines and probiotics for controlling bacterial pathogens in companion and food-producing animals. I have published over 190 peer-reviewed papers in the area of microbiology and pathology.
Image Credit: dturphoto/Shutterstock
Study: fizkes/Shutterstock
Image Credit: AnaLysiSStudiO/Shutterstock
Metrics Sciences of the University of Washington. He finished his medical and doctoral training at the University of Zagreb School of Medicine (Croatia), his MPH at the London School of Hygiene and Tropical medicine of the University of London (United Kingdom), and his MBA in International Healthcare Management at the Frankfurt School of Finance & Management (Germany). He is a board-certified clinical microbiology and sexual medicine specialist, with an additional one-year training in clinical research from Harvard Medical School.
My role includes delivering and overseeing teaching and research in the School and running my own research group, which consists of vets, doctors, and scientists. My current research interests focus on Antimicrobial Resistance (AMR) and understanding the pathogenesis of zoonotic bacterial pathogens (those that can be transmitted from animals to humans and, in some cases, from humans to animals). I also have a particular interest in developing control and intervention strategies, including rapid diagnostics, vaccines and probiotics for controlling bacterial pathogens in companion and food-producing animals. I have published over 190 peer-reviewed papers in the area of microbiology and pathology.