Invasive fungal infections - The new threat | DW Documentary

Key Concepts

• Invasive Fungal Infections: Fungal infections that spread from their initial site of infection into deeper tissues or organs, potentially becoming life-threatening.
• Fungal Spores: Microscopic reproductive units of fungi that can be inhaled, ingested, or enter the body through wounds, leading to infection.
• Immunocompromised Individuals: People with weakened immune systems (due to diseases like diabetes, cancer, transplants, or treatments like cortisone) are at higher risk of invasive fungal infections.
• Antifungal Resistance: The ability of fungi to develop immunity to antifungal medications, making treatment increasingly difficult.
• Cryptococcus gattii: A specific fungus that caused outbreaks on Vancouver Island, affecting both animals and healthy humans.
• Candida auris: A multidrug-resistant fungus that has emerged as a significant global health threat, particularly in healthcare settings.
• Fungicides: Chemical agents used in agriculture to control fungal diseases in crops.
• Monoculture: The practice of growing a single crop species over a large area, which can make it vulnerable to widespread fungal infections.
• Mixed Cropping: The practice of growing multiple crop species together, which can enhance crop resilience and reduce the need for fungicides.
• Azoles: A class of antifungal medications commonly used in human medicine and also found in agricultural fungicides.

Invasive Fungal Infections: A Growing Global Threat

This video explores the escalating danger posed by invasive fungal infections, highlighting their impact on human health, agriculture, and the environment. It emphasizes the challenges in combating these infections due to the fungi's adaptability and the growing ineffectiveness of current treatments.

Case Study: Dogan Eskicirak's Battle with Invasive Fungal Infection

The video opens with the harrowing case of Dogan Eskicirak, who contracted an invasive fungal infection that spread into his head. His treatment at Cologne University Hospital involved aggressive infusions, which, while showing signs of success after nine months, took a severe toll on his liver and kidneys. This case illustrates the insidious nature of these infections, often initially unrecognized and underestimated, leading to significant spread and prolonged, debilitating treatment. Dr. Oliver Cornely, an expert in the field, explains the critical proximity of the fungus to the brain, underscoring the high-risk treatment decisions made to save the patient's life, prioritizing the brain's integrity over potentially recoverable organs like the kidneys and liver.

The Pervasive Nature and Spread of Fungi

Fungi are ubiquitous, found wherever organic matter decomposes, such as in compost or forests. Their fine spores, released into the air, can enter the human body through various routes:

• Open wounds: Leading to bloodstream infections.
• Inhalation: Settling in sinuses and growing into tissues, often reaching the lungs.
• Lungs: If unchecked, they can reach blood vessels, spreading throughout the body and clogging organs, ultimately interrupting blood flow and preventing medication delivery.

Globally, at least 2.5 million people die annually from fungal infections. While essential for decomposition and nutrient cycling, their presence within the human body can be dangerous.

Vancouver Island Outbreak: Cryptococcus gattii and Healthy Individuals

A significant case study presented is the outbreak of Cryptococcus gattii on Vancouver Island, Canada, in the early 2000s. This fungus, normally not problematic for healthy individuals, caused severe illnesses and deaths in both animals and humans. Dr. Murray Fyfe's research team discovered that many infected individuals had competent immune systems, challenging the long-held belief that only immunocompromised people were at risk. Ken James, a healthy individual, experienced severe headaches, night sweats, and fatigue, later diagnosed with a Cryptococcus gattii lung infection. The source was traced to spores dispersed from Douglas fir trees. Between 1999 and 2007, over 200 people fell ill, and 19 died, demonstrating the potential of fungi to affect healthy populations and the importance of early detection and treatment.

The Challenge of Antifungal Resistance

A critical issue highlighted is the growing resistance of fungi to antifungal medications. In Cologne's microbiology lab, Dr. Cornely and lab head Anna Dudakova demonstrate how fungal pathogens are tested against various drugs. Petri dishes show fungal colonies growing around effective drugs, while resistance is indicated by fungi growing directly on drug-infused test strips. This resistance is a significant problem, as standard medications become ineffective, leading to treatment failure and patient deterioration.

The Environmental Origin of Antifungal Resistance

Researchers at Wageningen University in the Netherlands, led by geneticist Eveline Snelders and environmental geneticist Sijmen Schoustra, uncovered a shocking link between agricultural practices and antifungal resistance. They found that a mold resistant to hospital-used drugs was present in patients, yet these patients had never been treated with antifungals. Their investigation revealed that the source of resistance was not the hospital but agricultural fungicides.

• Mechanism of Resistance: The drugs used to treat human fungal infections are chemically identical or belong to the same chemical group as fungicides used in agriculture. When plant waste treated with these fungicides (e.g., from strawberries, potatoes, flower bulbs) is composted, the fungicides contaminate the compost. Fungi exposed to these fungicides in the environment develop resistance.
• Environmental Hotspots: Resistant fungal spores are released into the air, and their concentration is significantly higher (up to 20 times) in areas where large amounts of green waste from intensively sprayed fields are composted, particularly regions with greenhouses and fields growing strawberries and potatoes. Flower bulbs treated with fungicides also contribute to this issue.

This discovery was initially met with disbelief but was later confirmed by widespread testing across the Netherlands.

Fungal Threats in Agriculture and the Need for Sustainable Practices

Botanist Eva Stukenbrock explains the significant impact of fungi on agriculture, with global harvests losing at least 20% annually due to fungal infestations. Fungicides, while seemingly indispensable, are becoming less effective.

• Pesticide Use: At an experimental farm in Kiel, farmer Jill Jensen demonstrates the difference between treated and untreated barley plants, showing significantly smaller ears in the untreated, fungus-infested plants.
• Resistance in Fields: Outside the research farm, sprayed fields show yellow and brown spots on leaves, indicating fungal penetration and reduced photosynthetic capacity, leading to smaller yields.
• Integrated Pest Management: The Hohenschulen experimental farm employs a strategy of combating fungi with a range of precisely formulated, synergistic substances. The idea is that if fungi are resistant to one fungicide, another in the blend will be effective. However, this elaborate process is not widely adopted.
• Monoculture Vulnerability: Eva Stukenbrock highlights the vulnerability of monocultures, where genetically identical plants are grown. If one plant is infected, the entire field is susceptible.
• Mixed Cropping Solution: In contrast, growing different crop varieties together (mixed cropping) makes it harder for fungi to spread, as they must overcome the defenses of multiple species. Denmark has already adopted this practice for over half of its wheat growth, reporting no yield loss and a 30-40% reduction in disease, thus decreasing the need for fungicides. This approach is seen as a crucial step towards reducing fungicide use and saving costs.

The Limited Arsenal of Antifungal Medications

In Cologne's hospital pharmacy, Andrea Liekweg shows that while there are many medications, the number of effective antifungal agents is limited, with a heavy reliance on the "azole" group. The intensive use of azoles in agriculture, in kilogram and liter quantities, compared to milligram or milliliter quantities in human medicine, accelerates resistance development. If fungi like Aspergillus develop resistance to azoles, the options for treatment become severely limited, with only a few unapproved or unevaluated drugs remaining.

Emerging Threats: Chytric Fungus and Candida Auris

The video also touches upon other invasive fungal threats:

• Chytric Fungus (Bsal): Affecting amphibians, this invasive fungus from Asia causes devastating skin lesions in native species like salamanders and newts, leading to secondary infections and death.
• Candida Auris: A multidrug-resistant fungus that emerged in Japan in 2009 and has spread globally, causing severe infections, particularly in healthcare settings. It is difficult to control, resistant to most medications, and has led to significant outbreaks in hospitals, such as in Valencia, Spain. The LA FE University Hospital experienced major outbreaks where the fungus spread rapidly, was resistant to disinfectants, and had a high mortality rate. It took two years of stringent measures, including isolation, new disinfection protocols, and a cocktail of medications, to control the spread.

Preparedness and Future Challenges

Oliver Kurzai at the National Reference Center for Invasive Fungal Infections in Germany reports around 80 cases of Candida auris in Germany in 2023, but acknowledges that the true figure is unknown due to the lack of a general reporting requirement. Climate change is also a concern, as rising temperatures could allow fungi to adapt and infect humans more frequently, potentially leading to more invasive fungal species emerging.

Conclusion and Call to Action

The video concludes by emphasizing the urgent need for a rapid and comprehensive response to the growing threat of invasive fungi. The current chemical arsenal is inadequate, and new drug substances are desperately needed. However, the widespread use of these substances in agriculture must be managed to prevent rapid resistance development. The video advocates for a realization that invasive fungi exploit vulnerabilities, such as agricultural monocultures, and calls for more intelligent farming methods and reduced pesticide use. Ultimately, averting the threat requires seizing every opportunity to develop and implement effective strategies.