A hamburger not quite cooked enough; a farm worker in contact with livestock; a mosquito bite; a cat scratching its owner; a dog walker going through a field being grazed by sheep and picking up a tick – all these events have the potential, even if sometimes very remote, to lead to serious human infection.
And sometimes, a chance event will mean that an animal infection spills over to humans for the first time. The COVID-19 pandemic highlighted, perhaps more than any other disease outbreak, the consequences of pathogens, such as viruses or bacteria, crossing animal species, including into humans (what we call zoonotic diseases), and the impact they can have if they are then able to spread between their new human hosts. Following the end of the COVID-19 global emergency, we face multiple reminders of just how unpredictable emerging infections can be.
Predicting which pathogen might pose the next significant threat is extremely challenging.
No room for complacency
Marc-Alain Widdowson, who leads the High Threat Pathogens team in WHO’s Health Emergencies Programme, makes it clear that we need to seriously consider new potential transmission routes and do all we can to prevent diseases from becoming endemic to new areas.
“Animal and human interactions have increased significantly over the last few decades, making it much more likely that a pathogen could spread into new animal and human populations, and areas far from where it originated.”
“We also have to remember that when pathogens transmit in new species or in new ways, they have more opportunities to adapt and mutate as time goes on – potentially becoming more efficient at transmitting between animals or humans. A single event, such as a spillover into a new species, can be enough to enable wider spread,” he continues.
What drives pathogens to spill over?
There are several drivers for this. Firstly, some infections are not that specific to any one species; many bacteria are not exclusive and are essentially self-sufficient in that they do not require much interaction with host cells to multiply. Take anthrax, as an example: it is present everywhere and can survive for years in soil. It is infectious and fatal to herbivores especially, but can also affect carnivores, birds and – of course – humans. So, if you prepare or eat meat from an anthrax affected cow, you may well get anthrax.
Secondly, the world’s burgeoning population is clearing and farming more natural areas, displacing wild animals into inhabited areas. Displacement of fruit bats by deforestation in Indonesia, for example, has been linked with Nipah virus outbreaks in nearby areas.
Thirdly, man’s impact on the world is leading to the decline and extinction of many animal species, reducing biodiversity. This means that pathogens are being concentrated in animal reservoirs of fewer, more common species.
Fourth, the global wildlife trade means that different animal species from different ecosystems are brought together and share viruses that had previously been localized.
Fifth, climate change will result in a wider geographical range of vectors and pathogens.
Lastly, there is the simple fact that pathogens are always mutating.
New routes of transmission
Prior to 2022, mpox was a disease endemic to central and west Africa and found mainly in small mammal populations. Occasional human mpox cases were usually caused by animal bites or eating infected meat.
But something changed.
In summer 2022, new cases were being detected around the world, including in Europe, in people with no travel history to Africa. The virus was now spreading widely through sexual contact, primarily through men who have sex with men (MSM) with multiple sexual partners – a mode of transmission that had never previously been proven, and so was rarely suspected.
Another recent example came in spring 2024, when the United States declared that highly pathogenic avian influenza (H5N1) had been found in dairy cattle and raw milk. Again, up until this point there was little evidence to suggest that cows could be transmitters of avian influenza.
It was discovered that cows’ udders are covered with bird-like receptors, rendering them prone to infection. It is plausible that a cow had laid down in some infected bird droppings or rubbed against contaminated milking equipment and become infected. There have now been 3 separate introductions into the US dairy herd, and, in March 2025, health authorities in the United Kingdom reported the first-ever case of a sheep becoming infected by H5N1. Quite how it picked up the virus still remains a mystery.
Vigilance needed
While it is true that we have seen some very concerning disease outbreaks over the last few years, the viruses behind them are often essentially unchanged. The mpox virus strain that infected MSM in Europe and elsewhere is essentially the same as seen in non-sexually transmitted mpox in west Africa. Likewise, the avian influenza being found in cows is the same as that found in wild birds and poultry.
So far, there have been no reports of human-to-human transmission of H5N1 in the USA, with the small numbers of people infected by the virus mainly being as a result of working directly with animals on livestock farms. Worldwide, there have been fewer than 1000 human cases of H5N1 since 2003, although almost half of these resulted in deaths. Thankfully, the mortality rate has significantly reduced in the more recent outbreaks.
However, the fact that we have had so many recent introductions of H5N1 into cow herds and poultry farms highlights how vulnerable our food supply is to this and other strains of the influenza A virus.
Since October 2024, we have also seen sporadic importations of a new strain of mpox into the European Region. So far, the numbers have been very small and it seems the virus has not chanced upon an effective way to spread further; onward spread has been limited to just 2 reports of household transmission in the United Kingdom and Germany, where children have also become infected.
Rapid action is needed when dealing with every new imported case, as we risk the danger that the virus could be finding new pathways and new types of human hosts if we are not vigilant in detecting and isolating cases as we find them.
The work of WHO and others in preventing and managing zoonotic disease threats
WHO works with national governments, academia, nongovernmental and philanthropic organizations, and regional and international partners to prevent and manage zoonotic threats and their public health, social and economic impacts.
“Human health, animal health and environmental health are not separate issues – they are One Health. Collaboration and coordination across sectors, stakeholders and national border is an absolute necessity,” says Peter Sousa Hoejskov, Technical Officer for Food Safety and Zoonotic Diseases in WHO’s Health Emergencies Programme. “When we protect animals and ecosystems, we protect ourselves,” he emphasizes.
WHO also helps develop and promote practical, evidence-based and cost-effective tools and mechanisms for strengthening zoonotic disease prevention and control – including for surveillance and risk assessment, coordinated outbreak investigation and response, and multisectoral coordination using the One Health approach.
WHO collaborates with the Food and Agriculture Organization of the United Nations (FAO), the World Organisation for Animal Health (WOAH) and the United Nations Environment Programme (UNEP) on promoting the One Health approach to pandemic prevention, preparedness and response – including through the Global Early Warning System for health threats and emerging risks at the human-animal-ecosystems interface (GLEWS+).
This article was amended on 27 May 2025 to clarify some of the points raised and to reflect the fact that the next zoonotic disease threats could be caused by a range of different pathogens, not just viruses.