The drugged macaque lying in the bed of a pick-up truck in Thailand’s Khao Yai national park is an unwitting but potentially crucial sentinel for the next pandemic.
Thai veterinarians are taking vials of blood and swabs from the anaesthetised animal, to be screened for known and new pathogens that could infect people.
“Even though we are dealing with wildlife, our work is for human beings,” says Supaporn Wacharapluesadee, a field virologist based in Bangkok, observing a collection of the samples she will later analyse. “It is a hard battle to win — but we hope to stay one step ahead of the diseases.”
The prone primate is one small part of the stuttering global hunt for “Disease X” — an as yet unknown pathogen that could cause the next pandemic. There is a high chance this microbe will be a zoonosis, or disease that can pass from animals to humans.
The lethal dangers were put into stark focus this week by the worsening US bird flu outbreak, which claimed its first human fatality after spreading to livestock and poultry across the nation.
Zoonotic diseases have high potential to cause pandemics in the future as they have in the past — including, very probably, Covid-19. All seven of the priority known pathogens identified by the international Coalition for Epidemic Preparedness Innovations (Cepi) on its website are zoonotic, including Mers, Ebola and Lassa Fever. Many zoonotic diseases have no vaccines or effective treatments.
The risk of transmission is high in environments such as the popular tourist spot of Khao Yai, where visitors often come close to wild creatures. It is rising due to trends such as human population spread and animal behavioural shifts related to rising global temperatures.
Zoonotic diseases pose a “significant threat to global health security”, says Maria Van Kerkhove, director of the World Health Organization’s department of epidemic and pandemic preparedness and prevention.
“It is estimated that three out of four emerging or re-emerging infectious pathogens are zoonotic,” she says. “Drivers such as climate change can accelerate the risk of spillover of pathogens from animals to humans.”
The zoonotic menace is growing in severity. Even beyond bird flu, the last year alone has seen several high-profile outbreaks. Mpox, the virus formerly known as monkeypox that causes rashes and lesions, spread to more than a dozen countries in Africa. Rwanda suffered an outbreak of Marburg viral disease, a haemorrhagic fever similar to Ebola.
Cepi is working with the WHO to improve international understanding of dangerous microbe “families”, many of which are zoonotic. But Cepi has warned of “dark spaces” in knowledge, particularly in biodiverse countries that lack the resources to do disease monitoring and comprehensive research.
The zoonotic story is emblematic of troubled efforts to prevent another global pandemic, almost five years since the WHO declared the last one.
The millions of deaths and trillions of dollars of economic disruption caused by Covid triggered international moves to prevent a repeat. But a WHO-brokered initiative to agree an international pandemic treaty foundered last year. A new deadline for the accord is set for May 2025, by when President Donald Trump may have resumed efforts to fulfil his long-held goal of pulling the US out of the UN health body.
Amid this disunity, many scientists and policymakers say the world needs to step up a co-ordinated response to the risks.
“The earlier we can detect and act on such threats, the greater the chance we can stop an outbreak in its early stages,” says Richard Hatchett, Cepi’s chief executive. “The alternative to making such investments is more and larger epidemics — and an increased risk of pandemics.”
Zoonotic diseases, which range from notorious afflictions to little-publicised potential killers, are not easy to detect, track or prevent.
They include centuries-old threats such as rabies from dog bites, plague from rat fleas and some forms of malaria via mosquitoes. Among the lesser-known diseases is the ulcer-causing soil fungus Sporothrix brasiliensis, which infects cats who can then transmit it to humans via bites, scratches or wounds.
Zoonotic diseases can also spread through indirect contact, such as through water contaminated with animal faeces containing the gastroenteritis bacteria Campylobacter. The Nipah virus behind deadly outbreaks in south and south-east Asia since the late 1990s can be picked up from palm sap infected with fruit bat saliva or excreta. The bacterium that causes anthrax, a source of potentially lethal skin, respiratory and intestinal infections, is carried by herbivores such as cows and can persist in the environment for decades.
Once these ailments make their way to human populations, they are hard to eradicate. Five existing zoonotic diseases threaten to cause 12 times as many human deaths in 2050 as in 2020, according to a study published in November 2023. Researchers examined the Ebola and Marburg viruses, the haemorrhagic fever-causing Machupo pathogen, Nipah and Sars-Cov-1 — a genetic forebear of the Covid-19 virus. Animal-to-human spillover events were more numerous, longer lasting and more lethal, the paper found.
“Early detection and intervention is crucial to limit potential human and economic losses from zoonotic diseases,” says Nita Madhav, senior director of Ginkgo Biosecurity, the company that led the research and works with governments on early warning monitoring of pandemics. “But there is persistent under-investment in this critical infrastructure.”
Zoonotic diseases have emerged at an escalating rate since the middle of the last century, according to studies. They appear most frequently in South America, central Africa and south-east Asia. A high-risk area is wet markets that sell fresh produce — including, in some cases, wild mammals and birds.
Many scientists believe that the origins of Covid-19 in Wuhan, China, were zoonotic, although some observers still suspect it originated from a laboratory accident. Researchers who analysed samples taken from a Wuhan market in early 2020 pointed last year to raccoon dogs, civets and bamboo rats as possible sources for the virus. The WHO said last month that it was a “moral and scientific imperative” for China to offer the data and access needed to confirm how the pandemic started.
The growth in the numbers of zoonotic diseases highlights how human activities have strained the natural world and our relationship with it. We live closer to animals, impinging on their habitats. More intensive farming raises the risk of proliferation among domesticated animal populations. Rising global temperatures due to climate change have increased the range of disease vectors such as ticks and promote the growth of some pathogens. Transmission of dengue by mosquitoes rose 12 per cent between 1951-60 and 2012-21, according to a 2023 paper.
“Our world is changing,” says Jaspreet Turner, research lead in infectious diseases at Wellcome, the charitable foundation. “Increased global movement, urbanisation and climate change are creating the perfect storm to allow zoonotic diseases like dengue to thrive.”
Domesticated animals can also play a big role in spreading zoonotic diseases, as the present US outbreak of H5N1 bird flu shows. The pathogen has now been detected in dairy cows in 16 states and poultry in all 50, according to US Centers for Disease Control and Prevention data.
No H5N1 person-to-person transmission has yet been established in the US outbreak, but the risk of it grows each day.
Researchers fear H5N1 could adapt to become more infectious to humans. Or it could encounter another flu virus and undergo what is known as a “reassortment” of genetic material with it. If the resulting new pathogen is more transmissible between humans, it could trigger an epidemic or even a pandemic. Each day that passes with a zoonotic disease in wide circulation in animal populations is a roll of the dice, hoping that we stay lucky.
The US had shown a troubling lack of transparency over the H5N1 surge, argues Ayoade Alakija, a global vaccine specialist.
“If this had been China, the whole world would be up in arms and talking about a China virus, but because it’s the US there’s a deathly silence,” says Alakija, chair of Find, a Swiss-based NGO that pushes for equitable global access to diagnostics.
The free flow of information is essential to tracking zoonotic diseases, because so much uncertainty still surrounds how they originate and spread. Scientists have been surprised by what they have learnt about mpox, which was first identified in captive primates in 1958.
In 2023, researchers suggested mpox may have been circulating in humans and interacting with their immune systems as long ago as 2016. This overturned assumptions that significant transmission among people happened only at the time of the international health emergency for the disease declared in 2022.
Experts are still learning how different types of animals may incubate and disseminate zoonotic diseases. In 2021, researchers determined that several crucial genes in the immune systems of certain carnivores do not function. This raised the possibility that the animals could carry pathogens asymptomatically, allowing them to mutate undetected into potent zoonotic threats.
These fears had led Denmark to cull millions of mink in late 2020, as the pandemic raged. The government ordered the massacre of the carnivores because of alarm over Covid outbreaks and the emergence of new virus variants on fur farms.
But the evolution of zoonotic diseases often remains mysterious. There are many “super, super important” things that “we don’t know that we should know”, says Clare Bryant, a veterinarian and professor of innate immunity at Cambridge university.
“There is this pipeline between wild animals, domestic animals and then the spillover into humans,” says Bryant, the senior author on the carnivore research. “The bird flu alone illustrates that really beautifully — and scarily.”
Governments and researchers are making efforts to fill the gaps in knowledge of emerging zoonotic threats.
One such campaign is under way in Thailand, a potential crucible for zoonoses. The country is subtropical, rich in flora and fauna and borders four other countries: Myanmar, Laos, Cambodia and Malaysia.
A joint venture between the US and Thai armies based in Bangkok is monitoring livestock in border regions of the country. The Walter Reed Army Institute of Research-Armed Forces Research Institute of Medical Sciences has for decades studied infectious diseases that menace troops — and civilian populations.
Thai army veterinarians take samples from humans, swine and birds, as well as wastewater, animal faeces and areas where creatures spend time. Swabs are analysed for influenza genetic material. The blood is tested for antibodies to zoonotic influenza A viruses, which would suggest previous exposure (or vaccination). Should the pathogen itself be discovered, it would be sequenced and the data shared with public health authorities as appropriate.
The work is less of a needle in a haystack search than it might appear, argues Lieutenant Colonel Erin Ball, a Bangkok-based US Army veterinary pathologist.
The populations selected for testing are in border areas where there are many movements of humans and animals, plus “backyard” farms where people live right next to domesticated creatures. Testing these species, particularly poultry, waterfowl and swine that are known carriers of the zoonotic influenza A virus, can offer a vital time advantage. It should enable earlier responses to disease outbreaks than would be possible through only testing people when they fall sick.
“You have to approach it in an intelligent, targeted and very deliberate way,” Ball says. “If you are just doing testing in humans, you may be too late. You end up more in a reactive situation — and less in a proactive, preventive situation.”
The relative ease of genetic sequencing enabled by technological advances is a “game-changer” in the hunt for new pathogens, says Ball. The influenza monitoring project is small, but Ball argues there is a case for expanding it — and to widen the limited international sharing of information on emerging zoonotic threats.
“The old method of everybody holding on to their discovery or their data — I think that we need to move away from that and all work together,” she says. “We should have learnt that from Covid, among other things.”
Systems for collecting and sharing information on zoonotic threats remain fragmented. The WHO opened a pandemic and epidemic intelligence hub in Berlin in 2021. A Global Preparedness Monitoring Board set up after the Ebola crisis of 2014 to 2016 issues assessments of threats, including zoonoses.
A Global Early Warning System uses the expertise of the WHO, the UN’s Food and Agriculture Organization (FAO) and the World Organisation for Animal Health to monitor and disseminate data about zoonotic diseases.
During the pandemic, it co-ordinated a risk assessment for transmission of Covid in fur farms. And it monitors other diseases, such as Rift Valley fever, a viral infection that can be deadly to livestock and humans.
But, despite these achievements, the FAO admits the work is hampered by structural problems. These include patchy data from remote areas and a reluctance by some countries to share information, for political or economic reasons.
The WHO has issued guidance on reducing zoonosis risks in wet markets. It and other international organisations have called for measures to reduce contact with live animals.
Surveillance beyond directly sampling animals includes testing wastewater, which has helped reveal the spread of bird flu in the US. Hospital emergency rooms provide another window into the emergence of acute new diseases. Networks of community health volunteers, like those that exist in Thailand, can be additional valuable early warning stations.
In a world of limited resources and growing disease threats, the best answer is likely to involve targeting resources at what models suggest are the biggest potential hazard areas.
“Ideally we would have great surveillance globally, but that’s somewhat unrealistic,” says Jacqueline Buchanan, lead biorisk analyst at Airfinity, the health data provider. “So you could try to find the most at-risk species and the areas where spillover is most likely to happen. We’re looking at areas where we already see an elevated incidence of disease in humans — and lots of interactions with animals.”
Back in the Thai national park, the virologist Supaporn reflects on how uneven the fight against zoonotic diseases remains.
Her main research focus is bats, but funding has been stop-start as health experts disagree over whether this kind of surveillance is the best use of resources. During her research trips, she runs public education sessions, warning local people against eating fruit nibbled by the flying mammals.
The zoonotic conundrum is a main reason why it is now an alarming global health cliché that the next pandemic is a question of when, not if. The Khao Yai monkeys have not yet revealed a threat, but one day they — or some other creature somewhere else — may. The macaques now come out of the forest more to scavenge for food, increasing the chances of a deadly interspecies mingling of microbes.
“Monkeys don’t have vaccines,” Supaporn says. “So if they are comfortable around humans, it’s dangerous for us — and for them.”
Additional reporting by David Pilling in London
