GREATER vigilance is needed to prevent the same resistance problems emerging with antiviral drugs that have threatened to destroy the efficacy of many antibacterial treatments, according to speakers at the third international One Health Congress in Amsterdam in March.
Johan Neyts, professor of virology at the University of Leuven in Belgium, told the audience that there has been remarkable growth in the numbers of effective antiviral treatments available over the past decade.
There are now 25 different compounds licensed for the treatment of the HIV virus alone. These drugs can be delivered in combinations which allow patients to control the infection by taking a single pill each day rather than the complicated cocktails of different drugs around the clock. The latter strategy can reduce compliance and so risk encouraging the emergence of resistant strains, he said.
Just as with antibacterial products, resistance problems were identified soon after the introduction of the first generation of antiviral products, such as the herpesvirus treatment acyclovir.
This was probably inevitable given the increased selection pressure for resistant mutations but the process can be accelerated by misusing these products – as with Chinese chicken farmers using the influenza treatment amantadine to control the H5N1 virus in their flocks up to 2005, he said.
Prof. Neyts insisted that antivirals should not be used to treat animals for zoonotic viruses to ensure that their efficacy is not compromised in human patients. But he was happy for veterinary colleagues to administer these drugs for other indications.
“You can treat a cat with FIV with a human drug because a cat is never going to transmit that virus to its owner.”
Indeed, with the knowledge gained from the development and use of the early antiviral products, he believed that it will be much easier to prevent resistance problems in these newer products than it has been with antibacterial drugs.
It is possible early in the development process to identify drug candidates that present a high barrier to the emergence of resistance, as it would require multiple mutations to occur together. It is also possible to pick combinations of drugs with different actions to ensure that there is no overlap in their resistance profile, he said.
There is also greater cause for confidence because of the significant differences in the biology of bacteria and viruses. The latter are unable to exchange resistant genes between different species in the same way as members of bacterial communities and there are significant differences in the DNA or RNA replication mechanisms between different viral families. So the activity of drugs developed to block these processes in any one pathogen will have no effects on unrelated viruses.
Prof. Neyts acknowledged that the likelihood of drugs being developed to treat a particular viral disease was highly dependent on the size of the potential market. The numbers of different agents licensed for use against HIV reflects the huge numbers of people exposed to that pathogen.
But there are many other disease agents which can provide a sizeable market for a commercial company, such as Dengue fever. This infects an estimated 1.5 million people a year across the globe and is a condition that has proved difficult to control with existing vaccine technologies.
Health threats
The One Health Congress, which was sponsored by Zoetis and attended by clinicians, scientists, public health policymakers and industry representatives, identified antimicrobial resistance as one of many emerging health threats for humans and animals.
Dik Mevius, a veterinarian who holds a chair in antimicrobial resistance at Utrecht University, explained how multi-drug resistant Staphylococcus aureus and different bacteria carrying the extended spectrum beta-lactamase (ESBL) gene presented a huge professional challenge to both human medical and veterinary scientists.
Bacteria expressing ESBL genes have been found in between 4 and 10% of human stool samples while in dogs the proportion is much higher, between 50 and 80%. This is probably due to the practice of owners feeding raw meat to their dogs and the widespread canine habit of coprophagy.
While surveillance of human ESBL infections shows that the problem is overwhelmingly due to the person-toperson transmission of human-adapted bacterial strains, he highlighted the potential risks from the transfer of genes from animal to human bacteria.
“If you want to solve the human problem with ESBL you need to pay attention to what is happening in livestock and the environment. This is a very complex situation,” he warned.
Despite the growing interest in the One Health concept, some speakers at the meeting believed that many in the human medical profession still fail to understand the importance of zoonotic diseases for their patients.
“Veterinarians understand the significance of these conditions and so does the medical profession in the developing world. But I am afraid that in the developed countries of the west, some of them just don’t get it,” said John Mackenzie, emeritus professor of tropical infectious diseases at Curtin University in Western Australia.
This situation wasn’t helped by the lack of sustained support for research and surveillance on zoonotic diseases from national governments and international agencies. “Four years ago, following the avian flu incident, the three international agencies – the World Health Organisation, the UN Food and Agricultural Organisation and the Office International des Epizooities – agreed to work as a partnership. They were supposed to provide leadership but nothing much has happened since then and we are still struggling,” he said.
Prof. Mackenzie welcomed the announcement at the meeting of the formation of the One Health Foundation which he hoped would provide the leadership that is currently missing.
Other speakers warned that the most important zoonotic disease problems for human patients may not have even appeared on the radar of the international agencies.
Adrian Hill, director of the Jenner Institute at Oxford University, warned that there are at least another 14 diseases found in wildlife that have the potential to cause a worse global pandemic than the Ebola virus.
That virus, apparently transmitted to humans in west Africa through the hunting and consumption of wild primates, has infected more than 20,000 people since April 2014, resulting in more than 10,000 deaths.
Professor Hill identified a range of potential new threats including the Hendra virus carried by bats and the MERS (Middle East respiratory syndrome) found in camels.
“These have all emerged in the past decade or so and have caused concern, even panic. I am asked which one we should tackle first: I have to say all of them,” he said.
