Nations are recognizing ‘the shared risk of public health emergencies and future pandemics.’ (Patrick Assalé/Unsplash)

Health horizons: The future of outbreak prevention and deadly fungal infections

 

The best way to deal with a pandemic is to stop it from happening in the first place, but preventing major outbreaks will require better surveillance and early warning systems, the 2023 GESDA Science Breakthrough Radar® tells us. Pandemic preparedness and international health regulations to deal with public emergencies dominated much of the World Health Assembly’s annual deliberations until June 1 at the UN in Geneva.

By John Heilprin

June 19, 2024

A key research challenge is to understand how disease outbreaks happen, and, ultimately, to gain the ability to predict them. That’s why scientists say it’s crucial to study each disease in the multiple species that it infects and to track the disease as it moves from one species to another, while gathering genomic data that will allow the outbreaks to be traced back to their sources, which could then be monitored.

This information can then be harnessed to predict outbreaks and to rapidly detect them when they occur. Better surveillance and early-warning systems are essential and it will be important to develop cheap, effective and easy-to-use rapid testing tools, ideally able to detect several pathogens with one test. This will be particularly relevant in communities where human and animal populations are in regular close contact.

That’s according to the 2023 GESDA Science Breakthrough Radar®, which anticipates some of the key drivers behind emerging diseases will be “tamed” within the next five years. Our preventative strategies will be most effective if we approach human health in more social-ecological terms, according to scientists who collaborated on the Radar. For instance, changing animal husbandry practices will slow down the reshuffling of pathogen genetics and reduce the chances of generating new zoonotic diseases.

One framework for this is the One Health approach to sustainably balance and optimize the health of people, animals and ecosystems. It will be integrated into mainstream medicine and public health over the next decade, the Radar forecasts, and early warning systems for pandemics will be available 25 years from now.

Another framework, called Planetary Health, was formally launched by the Rockefeller Foundation and The Lancet in 2015.  It draws on the concept of “planetary boundaries” that should confine human activity. The exact definitions of these concepts are not fully agreed upon, and it is not clear which provides the better framework.

Bibliometric analyses suggest that researchers focusing on one or the other tend to emphasise different topics. However, there is also a clear complementarity, and the overarching concept is widely agreed to be a desirable framing for the future of public health. There also is an urgent need to redevelop and modernise public health systems in the face of the threat from infectious disease.

In many developed countries there has been considerable focus on developing essential pharmaceutical and hospital treatments. These are only part of the picture, however, since many countries have poor capabilities for testing and contact tracing, and their welfare systems do not provide adequate support for containment measures such as self-isolation. Better ventilation and air filtration systems could both reduce the spread of airborne viruses like SARS-CoV-2 and help fight air pollution.

Pandemic preparedness and international health regulations to deal with public emergencies dominated much of the World Health Assembly’s annual deliberations that ended on June 1 at the UN in Geneva. The UN health agency’s governing body approved new amendments to the International Health Regulations, known as IHR, which took effect in 2007 and are legally binding on 196 countries.

 

A new category of ‘pandemic emergency’

 

The assembly, which governs the 194-nation World Health Organization, added a new category for when a “pandemic emergency” exists to trigger international collaboration. A pandemic emergency is a communicable disease that poses a high risk of crossing borders, overrunning health systems and substantially disrupting the economy and society. The amendments require greater solidarity and equity in sharing medical products and financing, and call for the establishment of a committee to ensure the IHR are followed and the creation of national panels to provide coordination.

“The experience of epidemics and pandemics, from Ebola and Zika to COVID-19 and MPOX, showed us where we needed better public health surveillance, response and preparedness mechanisms,” said Dr. Ashley Bloomfield, a New Zealand official who oversaw the IHR amendments.

WHO Director-General Tedros Adhanom Ghebreyesus said the IHR amendments should help countries improve their ability to deal with future infectious disease outbreaks and pandemics by strengthening their disease surveillance and information sharing.

“This is built on a commitment to equity, an understanding that health threats do not recognize national borders, and that preparedness is a collective endeavor,” he said. “The decision to conclude the pandemic agreement within the next year demonstrates how strongly and urgently countries want it, because the next pandemic is a matter of when, not if.”

Nations also agreed to extend the more than two years of pandemic treaty talks by up to a year “at the latest.” The talks were mired by divisions between wealthy and poorer countries over equity issues on the sharing of vaccines, treatments and diagnostic tools. If the talks succeed, the proposed treaty is to be presented for adoption at the 2025 World Health Assembly. The aim of the treaty is to ensure there is far greater collaboration during the next pandemic than there was during the COVID-19 pandemic.

Fungal pandemic preparedness

 

Fungi have a staggering impact on human health. Of an estimated 6 million species of fungi, more than 200 are closely associated with humans, the Radar tells us. They may live on us harmlessly, form part of our microbiome or, as pathogens, cause infectious and sometimes lethal diseases. These pathogens (including Candida, Aspergillus, and Cryptococcus species) currently infect billions of people worldwide and cause more than 1.5 million deaths per year — on a par with prominent bacterial and protozoan pathogens, such as those that cause tuberculosis and malaria.

Fungi are a serious threat to global food security. Crop-destroying fungi have been a threat to humanity since the agricultural revolution. Diseases caused by fungi and oomycetes have led to the starvation of populations, ruination of economies, and decimation of landscapes. Such diseases have been increasing in severity since the mid-20th century; emerging fungal diseases now pose an unprecedented threat to global food security and ecosystem health, by causing epidemics in staple crops that feed billions and producing toxins that contaminate food supplies and cause cancer.

The future will bring new variants of old foes, movement of old adversaries to new areas, and entirely new fungal diseases. Further, there is alarmingly open scope for fungi and their toxins to be deployed as biological weapons.

Fungi cause rapid species extinctions and loss of biodiversity. It is unlikely that there is a single animal on the planet that has not been parasitised by fungi, and animals are also subject to novel and re-emerging diseases. Several fungal species have recently become notorious for causing emerging infectious diseases which have led to massive die-offs, population declines and, in some cases, species extinctions.

Yet fungal infections are widely unrecognized and there’s little surveillance data. “People die more with fungal infections than malaria and it is same with tuberculosis,” Anuradha Chowdhary, a Professor in the Department of Medical Mycology at Vallabhbhai Patel Chest Institute, University of Delhi, India, told the 2023 GESDA Summit. “The most important cause of death of fungal infection is under-diagnosis.”

Billions of people on the planet suffer from skin infections, dental cavities and headaches caused by fungi, according to Chowdhary, while tens of millions of infants and hundreds of millions of women are affected by other types of common fungal infections. “Not only dry skin and mucosal infections, but we have a lot of allergies. We have chronic fungal infections when we have a change of weather because fungi are present and the spores are present in the environment,” she said.

 

Professor Anuradha Chowdhary explains the complexity of the fungal kingdom at the 2023 GESDA Summit (©GESDA/von Loebell)

Where the science and diplomacy can take us

The 2023 GESDA Science Breakthrough Radar®, distilling the insights of 1,500 scientists from more than 70 countries, tells us the past century has seen enormous progress against some diseases, with the mortality associated with a few diseases — malaria, for instance — falling dramatically. However, infectious diseases remain a major threat. The current disease load is only a part of the problem. New diseases are continually emerging, with COVID-19 being the most dramatic recent example, as humans come into contact with novel pathogens and global transport networks facilitate their rapid spread. Environmental degradation is a potential contributor to this emergence through human infiltration and destruction of natural habitats for increased trading of wildlife and intensive livestock farming, among other activities.

The findings in the 2023 Science Breakthrough Radar®

Based on the Radar, here’s where we stand in several important areas:

3.7 Infectious Diseases

Warming temperatures and other climatic shifts are forecast to move vector organisms, such as mosquitoes and ticks, into new regions. This will intensify disease pressure on communities that are already struggling with other stressors. Thawing of Arctic permafrost due to climate change represents another potential source of new and dangerous diseases.

Given the difficulty of addressing these underlying factors in the short term, our overall aim should be to move from treating and managing disease outbreaks to preventing or at least detecting spillover events early, and containing them. There are many specialized areas of infectious disease science — such as accelerated vaccine development, and genetic sequencing in pursuit of vector control technologies — in which considerable progress remains to be made.

The tantalizing prospect of preventing future pandemics before they take hold will entail tackling infectious diseases in their broader context as part of a social-ecological system: for example, understanding when diseases are likely to spread from wild animals to humans as a result of environmental changes that are, in turn, influenced by social, economic and political trends; or understanding when socioeconomic conditions promote the spread of infections such as cholera.

Radar, page 162

3.7.2 Zoonotic disease

The COVID-19 pandemic demonstrated once again the risk from zoonoses: diseases that move from animals to humans. More zoonotic diseases will surely emerge in the coming decades due to human-animal contact, but it is unclear where such zoonotic outbreaks are most likely to happen.

Pathogens can come from wild species — as with SARS-CoV-2, which originated in bats — or from domestic animals, as with MERS, which came from camels. While researchers have devised risk maps showing regions of the world where the risk is highest, in practice the high-risk areas are too large to be practicably managed, so it is vital that we create more finely-grained maps.

Anticipation in a nutshell

5-year horizon: One Health comes closer
10-year horizon: Risk maps developed
25-year horizon: Rabies eliminated

Radar, page 165

3.7.3 Vector control

Around 80% of the world’s population is at risk from infection by viruses or parasites transmitted by vector organisms like mosquitoes, ticks and fleas. These vectors transmit the disease directly into a person’s body, often by biting them. Gaining a measure of control over these vectors could have significant benefits for global health.

A number of emerging tools can directly control vector organisms. For example, altering the gut microbiome of mosquitos or tsetse flies can make it impossible for them to host the parasites responsible for disease development in humans. Similarly, genetically modified Aedes aegypti mosquitoes have been released carrying a gene that kills females in the larval stage.

The mosquitoes carry a range of diseases including Zika, but it is hoped that the female-lethal gene will spread and cause the population to dwindle, reducing transmission of the pathogens. Previously, trials have used mosquitoes infected with Wolbachia bacteria, which have successfully reduced the transmission of dengue.

5-year horizon: Success in mosquito control
10-year horizon: Synthetic biology harnessed
25-year horizon: Vector microbiomes put to work

Radar, page 166

3.7.4 Outbreak prevention

Our preventative strategies will be most effective if we approach human health in more social-ecological terms. For instance, changing animal husbandry practices will slow down the reshuffling of pathogen genetics and reduce the chances of generating new zoonotic diseases.

Alongside this, there is an urgent need to redevelop and modernize public health systems in the face of the threat from infectious disease.
In many developed countries there has been considerable focus on developing pharmaceutical and hospital treatments. But while these are obviously essential, they are only part of the picture.

For example, many countries have poor capabilities for testing and contact tracing, and their welfare systems do not provide adequate support for containment measures such as self-isolation. In addition, a combination of better ventilation and air filtration systems can reduce the spread of airborne viruses like SARS-CoV-2 and reduce the enormous harm from air pollution into the bargain.

5-year horizon: Drivers of disease emergence are tamed
10-year horizon: Public health systems strengthened
25-year horizon: Early warning system established

Radar, page 167

Invited Contribution: Fungal Pandemics

It may not attract much attention in everyday life, but the fungal kingdom has a remarkable breadth and depth of impact on human and environmental wellbeing. Fungi are integral to health, agriculture, biodiversity, ecology, manufacturing and biomedicine. They are the earth’s pre-eminent degraders of organic matter, are among the best-characterized model systems for biomedical research and produce enzymes crucial for fermentation, food production, bioremediation and biofuel production.

Fungi have also made invaluable contributions to medicine: they produce a phenomenal diversity of chemicals that we have found uses for as antibiotics, immunosuppressants that make organ transplants possible and drugs that reduce the risk of heart disease. But while there is still much to be learned about the potential benefits of fungi, they also have detrimental aspects that need to be addressed.

Novel infectious diseases caused by fungi are on the increase all over the world, just as they are for other microbes (such as zoonotic viruses) — but fungi are responsible for an increasing proportion of emerging disease alerts across humans, plants, and animals, possibly because as eukaryotes they are more closely related to their host animals and plants than bacteria or viruses are, and thus more difficult to treat.

Radar, page 172