Spillover events are when a pathogen from animals infects people. They have been responsible for every virus pandemic since the beginning of the 20th century. A August 2021 analysis of the four century history of disease outbreaks shows that the likelihood of pandemics increasing by severalfold could be due to human-caused environmental changes.

The likelihood of spillover could therefore be significantly reduced for as little as US$20 billion annually. This amount is needed to reduce global deforestation and protect wildlife from emerging diseases. It also helps to regulate wildlife trade and improve the ability of farmed animals to detect and manage infectious diseases.

This is a modest investment when compared to the billions of dollars and lives lost in the COVID-19 epidemic. It is also less than one-tenth the annual economic productivity lost due to viral diseases that have spread from animals since 1918.

Many international efforts to prevent future outbreaks of disease, prompted by COVID-19, fail to prioritise the prevention of spread. The Independent Panel for Pandemic Preparedness and Response was established by the World Health Organization (WHO). In order to prevent another pandemic, the panel was established in September 2020. The 86-page report, which was released in May last year, mentions wildlife twice and deforestation once.

We call on the three international endeavors that are currently being developed to place spillover prevention at the center of each.

First, the G20 group representing the 20 largest economies in the world agreed to create a global pandemic fund last month. If realized, this could provide funding at levels that infectious-disease experts have been recommending for decades — around $5 per person per year globally (see go.nature.com/3yjitwx). The World Health Assembly (WHA), which is the WHO’s decision-making body, is currently discussing a global agreement to reduce pandemics. Parties to the Convention on Biological Diversity are currently negotiating a draft framework for biodiversity conservation, the post-2020 global biodiversity frame.

These three international initiatives could help foster a more global proactive approach to infectious disease prevention if they are done in the right manner. This chance to address the major factors driving disease outbreaks and many of them also contribute to climate change or biodiversity loss, might not be available again until there is another pandemic.

There are more chances for humans and animals to come into contact with each other, such as when wildlife is traded or forests are cut for farming, mining, or roads. This is because infected animals are more likely to shed viruses when they are kept in poor conditions or are not properly fed.

Research from ecology, genetics and epidemiology has shown that four actions are the best ways to reduce spillover risk.

Protecting tropical and subtropical forest must be the first step. Numerous studies have shown that changing the land use, especially in tropical and subtropical forest areas, could be the biggest driver of emerging infectious disease of zoonotic origin worldwide. Wildlife that is able to survive forest clearing or degradation often includes species that can live with humans and are capable of carrying pathogens that could infect them. Because their forest habitat is almost completely cleared, bats infected with Nipah virus, which can cause death in 40-75%, now roost near high populations of humans in Bangladesh.

Climate change is also being driven by the loss of forests. This could lead to spillover as animals like bats are forced out of areas that have become unhospitable and into areas that are more suitable for them7.

As long as there’s enough political will and the resources, forests can still be protected. The 70% reduction of deforestation in Amazon between 2004-12 was a result of better monitoring, law enforcement, and financial incentives for farmers. (Deforestation rates have increased sharply since Jair Bolsonaro’s presidency in 2019 due to changes in environmental legislation. They began rising in 2013 because of these changes.

Second, live wild animals must not be traded or sold on commercial markets.

This would be in line with the WHO and other international organizations’ call in 2021 to countries to temporarily suspend trade in wild live animals and close markets that sell such animals. These are not new ideas. China has banned the sale and consumption of terrestrial wildlife as a result of COVID-19. Gabon also prohibits the sale of certain mammal types as food on its markets.

Restrictions on urban and periurban trade and markets must not be infringed on the rights and needs Indigenous peoples and local communities. These peoples often depend on wildlife for their food security, livelihoods, and cultural practices. In many countries, such as Brazil, Canada, and the United States, there are already rules that vary according to the community.

Biosecurity must also be improved in dealing with farmed animals. This could include improved veterinary care, increased surveillance for animal diseases, better feeding and housing, and quarantines that limit the spread of pathogens.

Afraid of being infected by pathogens and spreading them to others increases the risk for farmed animals. Nearly 80% of livestock pathogens are capable of infecting multiple host species, including humans.

Fourth, especially in areas where infectious diseases are at high risk, it is important to improve people’s economic security and their health.

Poor health, such as uncontrolled HIV infection or malnutrition, can make people more vulnerable to zoonotic pathogens. Pathogens can also mutate, especially in immunosuppressed people.

Some communities, especially in rural areas, use natural resources to generate income or produce commodities that bring them in contact with wildlife and wildlife by-products. For example, in Bangladesh date palm sap is collected in pots attached on to palm trees. They can be contaminated by bat-related bodily substances. An investigation in 2016 found that this practice was linked to 14 Nipah viruses infections in humans, which caused 8 deaths11.

It is vital to provide communities with education and tools that reduce the chance of harm. In the Bangladesh case, tools could be as simple as pot covers that prevent contamination of date sap.

It is possible to help the environment and people by providing education opportunities, as well as health-care services, and training in alternative livelihood skills such organic agriculture. Health in Harmony, a non-governmental organization based in Portland, Oregon has invested in community-designed intervention in Indonesian Borneo. These interventions contributed to a 90% decrease in households who were dependent on illegal logging as their main source of income during 2007-17. This led to a 70% decrease in the loss of local rainforests. The programme’s catchment region saw a 67% drop in infant mortality12.

These systems-oriented interventions need to be better understood and scaled up.

These strategies would help reduce dependence on containment measures such as human disease surveillance and contact tracing, lockdowns and vaccines. These interventions are vital, but they can be costly and too late to implement. In short, they are not sufficient when used in isolation to combat emerging infectious diseases.

The COVID-19 pandemic exposed the limitations of reactive measures, especially in this age of disinformation and growing populism. For example, despite the US federal government spending more than $3.7 trillion on its pandemic response as of the end of March, nearly one million people in the United States — or around one in 330 — have died from COVID-19 (see go.nature.com/39jtdfh and go.nature.com/38urqvc). Globally, between 15 million and 21 million lives are estimated to have been lost during the COVID-19 pandemic beyond what would be expected under non-pandemic conditions (known as excess deaths; see Nature https://doi.org/htd6; 2022). And a 2021 model indicates that, by 2025, $157 billion will have been spent on COVID-19 vaccines alone (see go.nature.com/3jqds76).

Spillover prevention is also a way to protect people, domestic animals, and wildlife from harm. It’s more equitable than containment. In Africa, for example, 21% have received at least one dose of COVID-19 vaccines in the 18 months that have passed since their availability. In the United States and Canada, the figure is nearly 80% (see go.nature.com/3vrdpfo). Pfizer’s total drug sales increased from $43 billion to $72 billion in 2020, largely due to its COVID-19 vaccine. This is the most-sold drug of 202113.

Finally, spillover prevention actions, which are not contained, also help to prevent the spread of zoonotic diseases from animals to humans. Because selection pressures vary across species, these jumps could be a source of new variants capable of evading existing immunity. Researchers have suggested that there was spillback in the development of Omicron SARS-CoV-2 (see Nature 602, 26-28 and 2022).

The US President Joe Biden’s administration and two international panels, one established by the WHO in 2020 and the other by the G20 in 2021 respectively, have issued guidance over the past year on how to combat pandemics. All of the recommendations have acknowledged that spillover is the main cause of new infectious diseases. It is unclear how this risk can be reduced. A PubMed search for spike protein in SARS-CoV-2 returns thousands of papers. However, only a few studies examine coronavirus dynamics among bats. This is where SARS-CoV-2 likely originated14.

For many reasons, spillover prevention might be overlooked. Biomedical researchers and funders might overlook upstream animals and environmental sources of pathogens because they are complex systems. Research into these systems does not usually yield tangible, profitable outputs. People working in biomedical science and public health have little training in ecology, wildlife biology and conservation.

It is becoming more common to recognize the importance of cross-sectoral cooperation. There has been a lot of support for the “One Health” approach, which is an integrated view of health that acknowledges the links between humans, animals, and the environment. However, it has not been translated into actions to prevent pandemics.

It can take years to see the benefits of spillover prevention, as opposed to weeks or months for containment measures. It can be difficult to quantify spillover prevention’s benefits, regardless of how long it takes. However, there is no risk of an outbreak if the measures are successful. Preventing a disaster is counter-productive to political, social and individual tendencies to wait until it happens before taking action.

There are new opportunities to change this mindset with the global pandemic fund and WHA pandemic agreements, and the post 2020 global biodiversity framework. They offer new chances to put in place a coordinated global effort that reduces the risk of pandemic-related spillovers and to prepare for the worst.

A global fund for pandemics is the first step to ensure that spillover prevention evidence is put into practice. Spillover prevention funding should not be incorporated into existing conservation funds or drawn from any other funding streams.

Investing should be directed to areas and practices that are most at risk from spillover, such as the Amazon Basin and Central Africa in southeast Asia. These areas are at high risk of spillover, and it is important to reduce deforestation to help mitigate climate change. Conservation is also severely underfunded. Natural solutions, such as conservation, restoration, and improved management forests, wetlands, and grasslands, represent more than one third of the climate mitigation required by 2030 to stabilize global warming below 2 degrees Celsius15. These approaches still receive less than 2 percent of global climate mitigation funds16. (Energy systems receive over half.)

The global fund for pandemics should not be backed by decision-makers who assume existing funds can handle the risk of spillover. Despite the economic downturn that COVID-19 triggered, the 2020 loss of primary tropical forests was 12% more than it was in 2019. This highlights the threat forest ecosystems continue to face.

To ensure that efforts to reduce spillover risk are sustained over the long-term, funding must be maintained.

Charles Michel, president of the European Council in 2020, demanded a treaty that would allow for a more coordinated response to pandemics and major epidemics around the world. More than 20 world leaders echoed this call last year. The WHA began negotiations to negotiate a treaty (or other international instrument) that would “strengthen pandemic preventive, preparedness and response”.

Multilateral agreements could be a way to ensure more equitable international action in the area of medical supplies, scientific knowledge, and therapeutics transfer. It could address some of the limitations currently placed on the WHO and clarify the conditions under which countries must notify other governments of a possible disease threat. Many of the International Health Regulations’ shortcomings were exposed by the COVID-19 pandemic. This legal framework outlines the rights and obligations of countries in relation to handling public-health emergencies and other emergency situations that may cross national borders.

We ask negotiators for priority in the WHA pandemic deal to include the four measures to prevent spillover. It could, for example, require countries to develop national pandemic action plans that include closing or strictly regulating wildlife markets and reducing deforestation. To evaluate the progress made in implementing the agreement, a reporting mechanism must be established. This could draw on the experience of existing schemes such as the WHO Joint External Evaluation process, which assesses countries’ ability to manage public-health risk, and the verification regime under the Chemical Weapons Convention.

The WHA agreement should include commitments to increase pathogen surveillance at the interfaces between humans and domesticated animals. This includes US mink farms, Asian wet markets, and areas of high deforestation. While surveillance will not prevent spread, it can help to detect and control zoonotic epidemics earlier and better understand the causes. Investing in medical care for animals and people in emerging infectious diseases hotspots would make disease surveillance more effective.

The sixth mass extinction is upon us, and the destruction of biodiversity can also lead to the spread of infectious diseases. Pandemics and epidemics that result from the exploitation and misuse of nature can cause further conservation setbacks, including economic loss and staff shortages, which could impact management of protected areas. Infective pathogens can also be passed to other animals, decimating populations. In 2002-03, for example, a virus called Ebola in the Republic of Congo killed approximately 5,000 gorillas19.

The Convention on Biological Diversity is currently negotiating a global biodiversity framework. However, it fails to address the negative feedback loop between environmental degradation and wildlife exploitation. Pandemics were not mentioned in the first draft. Although spillover prevention text was suggested in March, it has not been agreed upon.

This omission is due to the siloing and dissimilarities in expertise and disciplines. As the WHA pandemic agreements relied on specialists from the health sector, the Convention on Biological Diversity informs specialists in conservation and environmental science.

The environment-health connection must be reflected in the global biodiversity framework that will be adopted at the Conference of the Parties later in the year. This requires that spillover prevention must be explicitly included in all texts relating to wildlife exploitation and nature’s contributions. This is a key component of the convention’s ability to reach its goals in conservation and sustainable resource use.

Reacting to a catastrophe does not have to be the norm. Preventive healthcare for chronic diseases is a popular option in many countries. This is due to its obvious economic and health benefits. One example is that for every 1,000 people who are screened with colonoscopies, or any other method20, there are many colorectal cancer deaths. Preventive measures are not a substitute for treating disease when it occurs.

Leaders must immediately adopt this approach to pandemics, given all the stressors currently being placed on the biosphere and the adverse implications it has for human health.