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In the market for virus prevention

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With the coronavirus pandemic still raging, scientists are trying to discover how toxic pathogens move from animals to humans. Until the global wildlife trade is regulated - or better still banned - it is unlikely that Covid-19 will be the last deadly pathogen to emerge from the natural world.

Towards the end of April, the US National Institutes of Health (NIH), a medical research centre and agency of the US Department of Health and Human Services, abruptly terminated a multi-million dollar grant that would have paid for four years of research into how coronaviruses move from bats to humans, in the part of the world where the current pandemic started.

The NIH decision came after continued suggestions from US conservative politicians and the media that the coronavirus (SARS-COV-2) had not originated in bats but had, in fact, escaped or been let loose from a laboratory in Wuhan. This was supposedly the same laboratory that employs one of the virologists who had been working on the bats project.

The offending project, a collaboration between the EcoHealth Alliance, the Wuhan Institute of Virology and others, had been ongoing for 15 years, the latter five of which had been funded by the NIH. In 2019, the grant had been renewed for five years, after outstanding peer review.

NIH staff have yet to explain why they cut the grant, other than vague references to protecting public health. However, the previous week, President Donald Trump in a press conference, when asked about the project, had commented that “we will end that grant very quickly”.

On 30 April, Trump claimed to have seen evidence that the Wuhan Institute was responsible for the outbreak. On the same day, the Office of the Director of National Intelligence announced that US intelligence agencies would be investigating the possibility of an accident in Wuhan. Several weeks earlier, the NIH had asked the EcoHealth Alliance not to send any more funding to the Wuhan Institute of Virology.

Expert consensus leans away from these sort of conspiracy theories and suggests that SARS-COV-2 is indeed a zoonotic disease that originated in bats. The nearest DNA match shows 96.2 per cent similarity with a known bat coronavirus – reported by the same Wuhan virologist who so offended the NIH.

This implies that the virus jumped to humans via another species: probably pangolins, probably in a Chinese wet market. Wet markets exist all over the world and are prevalent in China and south-east Asia. They are simply markets that sell fresh ‘wet’ food. However, there are some cases where live domestic and wild animals are kept close together in very poor conditions before they are slaughtered on site, butchered and sold.

Experts say that in such places, virulent pathogens could develop and jump between species and onto humans, but it’s not just this coronavirus that we should worry about. The United Nations reports that two-thirds of all emerging infections and diseases now come from human interaction with animals. In April 2020, a cohort of more than 200 animal welfare and conservation organisations warned the World Health Organisation (WHO) that zoonotic pathogens are responsible for over two billion cases of human illness a year and two million human deaths. Of even more concern are the pathogens we don’t yet know about, those currently circulating within a wild animal population or maturing in a live market.

In their joint statement, the cohort, which includes the Zoological Society for London, Peta and the International Fund for Animal Welfare, called on the WHO to “state the proven link” between wildlife markets and serious threats to human health, and urged it to recommend that governments should ban live animal markets and regulate the wildlife trade. The statement pointed out that it’s within WHO’s mandate to do this, either to prevent the spread of disease or to prevent species extinction.

Unfortunately, the situation with NIH, Trump and the EcoHealth Alliance shows that political leaders might still be concerned with promoting their own short-term agendas and protecting moneyed interests.

Should the wildlife trade be regulated, live animal markets shut down and future zoonotic outbreaks controlled at source, a lot of people would lose an awful lot of money.

The legal wildlife trade is worth around €100bn (£87bn) a year in the EU alone, according to a 2016 report. Illegal wildlife traffickers make between $7bn and $23bn (£5.6-18.5bn) a year globally, and in 2017 the Chinese Academy of Engineering estimated that the Chinese wildlife farming industry was worth 520 billion yuan (£60bn).

Look for the root cause of the current pandemic, then, and you’ll not find disease-ridden bats, but human behaviours. However, as the Zoological Society for London’s Professor Andrew Cunningham, a veterinary pathologist, explains, if we are to know which behaviours to change we first need to understand the risk factors for zoonotic virus spill-over. “More needs to be known about wildlife diseases and how humans and wildlife interact,” he says.

There are over 1.6 million potentially zoonotic viruses in the natural world, according to a 2018 study. Most of the viruses aren’t able to jump from animals to humans or, if they do, they can’t replicate in ways that make them dangerous to humans. So predicting the one that does, where it might be and where it might come from, is difficult.

Kate Jones, professor of ecology and biodiversity at University College London (UCL), says: “Understanding the drivers of pathogen sharing and spill-over will help us to predict and prevent these events.”

Since the start of the coronavirus outbreak, authorities in individual  countries have been employing biosurviellance technologies to track the spread of Covid-19 within their own populations – using data from hospitals, doctors’ surgeries, care homes, death records and testing facilities. In many places, health authorities are looking to upgrade their systems to enable them to better pull information from a variety of sources in the medium and long term – tacit acceptance that their system might not have been fit for purpose in the first place.

What’s missing, though, are comprehensive systems for identifying diseases in places where zoonotic spill-over is most likely – systems that public health experts all over the world can access. “We need to be conducting systematic, routine human, livestock and wildlife surveillance for both known and newly emerging pathogens in these areas,” Jones says.

The EcoHealth Alliance has been working on this over the last few years. As well as the postponed coronavirus work, the organisation has also devised a centralised online platform to enable experts around the world to collaborate on research projects into infectious disease origins.

The platform consists of an editable scientific wiki that enables comparisons of multiple emerging infectious disease (EID) events, visualisation of historical disease emergence between 1940 and 2013, and exploration of individual emergence events.

The website uses collective intelligence mechanisms to improve the accuracy of the data and features a scalable cloud architecture, dynamic maps, Application Programming Interface for analysts, and an integrated reference management system. Each EID event has a unique event page that contains a narrative abstract, tables of data, a map of the event’s location, and an interactive discussion board. The idea is to use all of this as a basis for more effective modelling of emerging diseases.

The EcoHealth Alliance has also devised a dynamic app for performing detailed analysis of text, which can locate relevant information in online news outlets, blogs and reports. The app identifies and annotates important information, visualises EID events on a timeline and a map, and links to other potentially related reports. There’s also a network analysis tool to identify the likely movements around the world of infected travellers and contaminated goods.

WHO is also suggesting, through its One Health agenda, that professionals from public health, animal health, plant health and the environment should join forces to detect, respond to, and prevent outbreaks and to implement joint responses to health threats.

The Indian government has a One Health and Zoonoses programme that it claims will identify 25 infectious disease hotspots for surveillance. Laos, Mongolia, Philippines, Bangladesh and Malaysia have also developed surveillance systems to manage infectious disease through One Health.

Difficulties with biosurveillance occur when cross-nation cooperation is required, or when the solution to a problem in one country begins in another country on the other side of the world. These days, however, what might seem like somebody else’s problem today, can easily be our problem tomorrow. Unless, of course, it becomes everybody’s problem from the start.

‘We need to improve our ability to stop new infections getting into human populations in the first place’

Professor James Wood, Cambridge University

Professor James Wood at Cambridge University’s Infectious Disease group says: “We need to improve our ability to stop new infections getting into human populations in the first place.” This of course, takes us back to the bats and the fact that we don’t yet know nearly enough about them.

There are 1,400 species of bat living on six continents, and between them they carry more viruses than any other mammal. Maybe this is because they live in huge colonies – up to 20 million animals for some species, or maybe because they fly long distances, mixing with bats in other places. Maybe it’s because there are just so many of them: one in every five mammals is a bat. No one knows for sure – which is the whole point of doing the research.

Studies show that the bats themselves often don’t develop any clinical signs of the diseases they carry, probably because flying has strengthened their immune systems. Great for the bats, but not such good news for us if a virus passes over.

Arinjay Banerjee, a microbiologist from the University of Saskatchewan, explains that, in flight, a bat’s body temperature increases to over 40°C, which resembles a fever in humans. “In humans, the fever primes the immune response to a pathogen, but it’s possible that a bat’s immune response is always primed,” he says. “As a result, viruses have evolved in bats that can withstand peaks of body temperature.”

Banerjee adds that humans are not primed to make high levels of antiviral molecules, so when we are infected our immune responses are easily overwhelmed.

Traditionally, bats have lived in the wilderness, far away from humans. As human development and agriculture moves further into these areas, more bats come into contact with humans. Like rodents, bats thrive in disrupted environments alongside humans; this much we know.

To find out more, researchers from the Zoological Society of London, the Animal Plant Health Agency and a number of universities are investigating the impact of pathogens on African fruit bats and the effect of human influences on the bats’ environment.

Researchers collect and test samples of bat blood to look for antibodies that indicate whether the animals have been previously exposed to various pathogens. Samples of tissue, urine and faeces help researchers identify the types of pathogens present.

From these, experts have created dynamic models for interactions between bats and humans. They use radio telemetry to track the movement of bats between different colonies. This work is ongoing.

The aborted EcoHealth Alliance coronavirus project had already produced genetic sequencing of two coronaviruses found in Asian bats. These are now being used to test the antiviral drug remedesivir, which has been trialled as a treatment for Covid-19. Over the next five years, researchers were planning to do more human, wildlife and lab-based studies to try and pinpoint potential virus hotspots in southern China.

ZSL’s Cunningham calls banning live animal markets “the highest priority for the protection of human health”.

UCL’s Jones thinks, however, that it would be difficult for a central authority to ban wet (and live animal) markets for local cultural and economic reasons. She would, though, like to see more stringent biosecurity measures introduced.

Even this is difficult. Many markets, particularly in poorer parts of the world, have neither the money nor the technology for these types of of biosecurity measures, though it might be possible, perhaps, to implement them in larger operations, say in farms or on ranches.

A 2015 UN biosecurity guide for live poultry markets stated that the limited availability of resources should be kept in mind when developing interventions. Also, because of limited resources, only issues that pose a clear documented public health risk should be addressed.

And this is the problem. Because no one has yet to find unequivocal proof of when, where and how SARS-COV-2 passed over to humans, it is too easy for economic and sectional interests in various parts of the world to present alternatives or scapegoats and to side-step accountability.

Even a 96.2 per cent match between the bat coronavirus and the human one still gives plenty of leeway for political leaders to frame their coronavirus responses within the context of their own political and economic agendas. But to find the necessary proof it will require continued research and funding, which in turn will require political will.

Some want WHO to take the lead. Australian Prime Minister Scott Morrison recently suggested that WHO officials should be given the same powers as UN weapons inspectors to investigate wet markets with live animals.

Then there are the 200 wildlife organisations which wrote to WHO. A week after receiving that letter, WHO publicly supported the reopening of wet markets, providing they conform to stringent food safety and hygiene standards. 

WHO director general Dr Tedros Adhanom Ghebreyesus also approved of banning the sale and trade of wildlife for food, but added that it must be individual governments, and not WHO, that enforce the bans.

While national and international leaders continue to play pass-the-parcel to see who’ll take responsibility for leading the global response against emerging infectious disease, at time of writing 252,366 people have died from the coronavirus since the outbreak began, and many more will undoubtedly follow.

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