The World Health Organization (WHO) has raised the alarm over drug-resistant fungi as it released its first-ever priority list of fungal pathogens at risk from antimicrobial resistance (AMR). Nineteen species of fungi have been identified by the global health agency as representing “the greatest threat to public health” due to their growing drug resistance.  

Meanwhile,  a new report by a civil society coalition warned that unmitigated use of anti-fungal and antibacterial drugs on crop and animal production is fueling the fires of AMR – with too little action by countries and the UN system.

Speaking to media Tuesday, Dr Haileyesus Getahun, the director of AMR Global Coordination at WHO, said that WHO had compiled a list of piority fungal pathogens to put the issue on the public agenda and identify the areas for further research and development on fungal diseases.

Underlining the need for more documentation and surveillance on the fungal infections and diseases, Dr Getahun said, “ “We want the documentation of what’s happening currently … to dictate or to guide, while waiting for the evidence to be complete, what public health actions can be taken, particularly in raising awareness around these fungal infections.” 

Of the 19 species of fungi identified as priority pathogens, four pathogens were labelled as having “critical priority”. Those include Aspergillus fumigates, which causes respiratory infections in humans.  Others are Cryptococcus neoformans, Candida auris, which can cause bloodstream infections, wound infections and ear infections, and Candida albicans (thrush).  

The WHO report highlights how common fungal infections are becoming increasingly resistant to available treatments, raising risks particularly for people with low immunity. “Populations at greatest risk of invasive fungal infections include those with cancer, HIV/AIDS, organ transplants, chronic respiratory disease, and post-primary tuberculosis infection,” the report stated. During the Covid-19 pandemic, many health agencies also reported spikes in drug-resistant bacteria in samples collected from patients. 

While bacterial antimicrobial resistance (bacterial AMR) has received increasing attention from researchers and health ministries, information and data on fungal AMR is nowhere close. This is reflected in the fact that currently there are only four classes of antifungal medicines available to treat pathogenic fungal diseases. With few more treatment candidates in the clinical pipeline, WHO has warned that drug-resistant fungal pathogens are spreading far and wide across the globe due to many factors including unchecked use of antifungal agents in agriculture and aquaculture and climate change. 

Role of azoles in fungal AMR

Meanwhile, the new report on AMR released Monday by a civil society coalition carried an even stiffer warning abou the role of agrobusiness in spurring AMR – through rampant use of antifungal, antiboitic and antiviral agents on livestock and crops.

The report was co-authored by Nicoletta Dentico of the Society for International Development and the Geneva-based AMR Think-Do Tank.

The report, Untangling Antimicrobial Resistance, highlights, in particular, the role played by the widespread use of fungicides belonging to the azole family on agricultural crops – in the process fostering more drug resistant strains of Aspergillus fumigates, one of the pathogens on WHO’s priority list as a hazard for human health.

While antifungals may be regarded as key to food security, wanton use is increasing drug resistant mutations of fungi, and thus “selective pressure on human pathogens”, especially in regions where regulations against the on the use of fungicides are weak, the SID report added. 

Aspergillus fumigates causes an “environmentally acquired respiratory illness,” with Europe reporting the highest number of cases from the fungus. A 2021-study described how Aspergillus fumigatus has been spreading in all continents across the world, except Antarctica. 

Uncontrolled release of drug-laced effluents by industry, agriculture, households and the health sector is another pathway by which AMR resistance is growing silently, but steadily – particularly in parts of the world lacking good sewage treatment systems, the report states.

Not enough data on drug-resistant fungi

Another issue faced in coming to grips with the surge of fungal AMR, is the lack of data, WHO officials said at their briefing. There are no systematic requirements for countries’ reporting on the use of antimicrobial or antifungal agents in human health or agriculture – or for reporting on AMR hotspots that emerge from overuse.  Whatever data may be collected by WHO, it is not harmonised with data collected by FAO or OIE.  Without data, it is tough to know where fungal drug resistance is growing, and what is the global burden of diseases from related deaths.

“But it doesn’t mean that it’s not a problem,” Dr Getahun pointed out. “That is why we have identified the priority pathogen list. And that is why we are actually encouraging more research, more surveillance, to understand the actual extent. Then we will be able to have appropriate estimates about global [burden].”

“Currently, fungal infections receive less than 1.5% of all infectious disease research funding. Consequently, the evidence base is weak, and most treatment guidelines are informed by limited evidence and expert opinion. Tackling the problems posed by invasive fungal disease will require increased research funding, targeted at the key priorities, new antifungal medicines and improved diagnostics,” the report added. 

While a recent Lancet study estimated that drug-resistant bacterial infections directly cause around 1.3 million deaths every year, and are associated with the deaths of some five million people every year, no such numbers are available for drug-resistant fungi. “We do need surveillance to identify the real burden and direct the public health as it is.”

Coordination between WHO, FAO, OIE and UNEP – hope or smokescreen?

Recognizing the growing AMR threats from animal production and crop cultivation, WHO in April 2022 signed a Memorandum of Understanding (MoU) with Food and Agriculture Organization of the United Nations (FAO), World Organization for Animal Health (OIE) and United Nations Environment Programme (UNEP) to collaborate on so-called One Health, approaches encouraging more judicious use of available drugs and chemical agents. 

Getahun, who is also director of the Quadripartite joint secretariat, told Health Policy Watch that under the MoU, the agencies – dubbed the Quadripartite – are working more closely together to identify those antibiotics that are critical to human and veterinary health. “[This was done] in order to ensure that these antimicrobials are not prescribed without the necessary veterinary or physiotherapy, you know, indications for plants.”

However, Getahun acknowledged that this work is in its early stages.

Speaking at the launch of the civil society report on AMR at Geneva’s South Centre, SID managing director Stefano Prato criticized the Quadripartite’s work as largely “theatrical” lacking normative teeth.  Meanwhile, veterinarians and farm extension advisors often receive huge financial incentives from encouraging farmers’ over-use of antibiotics, antivirals, antifungal agents and other drugs, driving uncontrolled use of such products.

“In many countries vets are really the ones who prescribe, earn and enjoy income and profits from the prescription of antiviral or antibiotics at the farm level,” observed Prato, who is both a veterinarian and an economist by training.”

In addition, developing countries have become locked into monoculture systems of industrial crop production, which typically require large drug and chemical applications – in order to generate cash crops for export.  Shifting out of that model to more sustainable agriculture systems that can supply more nutritious foods locally, is now extremely difficult because of their foreign debt burden, Prato said.

“Many countries that are locked into that export-driven model are also exposed to significan foreign debt… That means that they need the income and the currencies that are related to their export of commodities, because they need to repay those currencies”

“And so the conflicts of interest are so entrenched, not only at the global level but also at the national and micro level,” he said.

As for the new collaborations between WHO, FAO OIE and UNEP, Prato observed: “Without a proper governance structure, there will be no solution… it will end up being some kind of policy entertainment..theatrical red carpet solutions.”

-Updated 26 October with correction to the names of the report co-authors.

Image Credits: Flickr – UK Department for International Development, WHO, The Lancet, Creative Commons Zero, E. Fletcher/Health Policy Watch.