October 25, 2022

expert reaction to report published by the WHO about fungi: ‘WHO fungal priority pathogens list to guide research, development and public health action’

The World Health Organisation (WHO) have published a report highlighting the first-ever list of fungal ‘priority pathogens’ cataloguing the 19 fungi that represent the greatest threat to public health.

Prof Darius Armstrong-James, Clinical Professor of Infectious Diseases and Medical Mycology, and Director of Imperial Network of Excellence in Fungal Science, said:

“This is an incredibly important step forward for advocacy for fungal diseases, which will enable the public health, medical and scientific community to focus efforts on fighting these high-mortality, difficult to treat, increasingly drug resistant infections.

Is this a good quality report?

“Yes.

Are the conclusions backed up by solid data?

“Yes.

How does this work fit with the existing evidence?

“The report is a fair reflection of current evidence, I full endorse its findings.

Is it significant the WHO have done a report on fungi – why now?

“Fungal diseases have become increasingly problematic, in particular we have seen major issues with secondary respiratory mould infections in the context of the COVID pandemic leading to greatly increased mortality, and because we have witnessed the emergence of new outbreaks of antifungal drug resistance, with Candida auris and Aspergillus fumigatus a particular concern.

Have fungi just become more important/dangerous, or have they always been and it has only just been recognised?

“All four of the critical fungal pathogen group identified by WHO primarily attack people with underlying chronic disease or immunocompromise, which are expanding groups.  In addition, it is notable that fungal disease is generally underappreciated by the wider public, for instance in the HIV-AIDS pandemic, it is not widely known that fungi were in fact the major cause of death as opportunistic infections.

Are these fungi dangerous everywhere or only in certain places/populations?

“As discussed above, fungi cause issues mainly in the weak and vulnerable.  The epidemic is therefore largely unseen by the general public, the war against fungi being fought mainly in hospitals, but this does not diminish the threat.

Have the authors accounted for confounders?  Are there important limitations to be aware of?

“I don’t think so, quite the reverse, this is an important step forward for an area of infectious diseases that has been relatively neglected for too long.

What are the implications in the real world?  Is there any overspeculation?

“The hope is that by backing this area, WHO can enable momentum to drive forward the pragmatic advances needed to grow the very real and growing threat from fungal diseases.”

Dr Neil Stone, Consultant in Infectious Diseases and Microbiology, and Lead for Fungal Infection, Hospital for Tropical Diseases, University College London Hospitals, said:

“This is a timely and important report which addresses the critical threat of fungal disease.

In 2017 WHO published a list of priority pathogens to be tackled regarding the growing threat of antimicrobial resistance, however failed to include any fungi, despite the fact that fungal infections cause hundreds of thousands of deaths per year, from diseased such as Cryptococcosis – a fungal meningitis.

“Finally the threat of fungal infection has been raised as a priority issue which is long overdue.

“Fungal infections have always been a threat but historically have been grossly neglected when it comes to public awareness and clinical research funding.  Funding for fungal research attracts a tiny fraction as compared to diseases with comparative annual mortality such as Malaria or Tuberculosis.

“As a result, diagnosis and treatment of fungal disease remains far behind that of bacterial disease.

“They are also undoubtedly a growing threat for the following reasons:

• Increased geographical range of these infections is occurring due to climate change;
• Multidrug resistant fungi such as Candida auris – an ultra drug resistant yeast which has caused major outbreaks worldwide – is on the increase, and has caused intensive care units to be shut down because of uncontrollable outbreaks;
• Increased numbers of immune suppressed patients who are at greatest risk of these infections;
• Critical lack of therapeutic options for those who need treatment.

“This is an overdue and critically important report which can serve as a catalyst to boost much needed research for this neglected group of diseases.  It is a robust and widely consulted document with a broad consensus from experts in the field.”

Prof Paul Hunter, Professor in Medicine, UEA, said:

“The World Health Organization has now published its “fungal priority pathogens list to guide research, development and public health action”.  This is the outcome of a fairly extensive consultative process using an external expert advisory group and in depth reviews of the relevant literature.  The fungal diseases were ranked according to several criteria including the global burden of disease, cases fatality rates, and whether the disease was global or limited to a few regions.  The timing of this report is opportune as we are learning that serious fungal infections are being seen in patients with covid https://www.nature.com/articles/s41564-022-01172-2.

“The highest rank “Critical group” include four fungi with a global distribution:

• Cryptococcus neoformans, an infection that tends to affect people with immune deficiency such as HIV, or cancer.  It can cause meningitis and we do occasionally see outbreaks in hospital such as the one at Queen Elizabeth University Hospital in Glasgow in 2019 where a 10-year-old boy and a 73-year-old woman died.  The source of the infection was thought to be pigeon droppings.
• Candida auris, is an emerging fungal infection that also causes infections primarily in people with weakened immunity.  It was first identified in a Tokyo hospital in 2009 and since then has caused hospital outbreaks around the world.  The big concern about this yeast is that it is often resistant to commonly used antifungal drugs and can also be difficult to distinguish from other yeast that are sensitive to antifungals leading to ineffective treatment.
• Aspergillus fumigatus is a common mould that is widespread in the environment in people’s homes and outdoors.  We probably breath in the spores from this fungus most days.  It tends to cause lung problems often in people with some existing lung problem and can cause an asthma like illness, pulmonary fibrosis or a non-cancerous tumour.
• Candida albicans was the subject of my doctoral thesis back in the 1980s.  It is the principal cause of thrush which is a common and unpleasant illness.  However, in people with weakened immune systems can cause a range of severe diseases including meningitis and septicaemia.  There have been a number of hospital outbreaks including ones in special care baby units that led to fatalities.

“The second tier of fungal pathogens include several fungi that are perhaps even more dangerous to the infected person but are geographically restricted.  For example:

• Histoplasma can be life threatening even in otherwise apparently healthy people, though again tends to affect people with weakened immunity more.  It is acquired by breathing in airborne fungal spores.  Geographically it tends to be restricted to mid Western and south Eastern United States, central and south America, though cases have been reported worldwide.
• eumycetoma is a fungal disease usually of the feet and can cause severe disfiguration and disability.  It primarily occurs in tropical and sub-tropical countries, especially in people who do not wear shoes.
• Mucomycosis (Mucorales), is another very serious infection, that has a mortality rate of about 50%.  It is a mould that can be inhaled and can cause systemic infections particularly in people with weakened immune systems or even in previously healthy people after severe injury.

“This prioritisation of fungal diseases by the WHO is an important development.  Fungal infections are very common globally and severe fungal infections can be very difficult to treat.  It is certainly the case that medical mycological research and expertise needs to be developed in many countries.  It would be a shame, however, if this list focused attention solely on the top four fungal disease as all of these fungi are causing severe, and at times disfiguring and debilitating disease.  We do need to develop research and skills in those under-resourced countries where disease like eumycetoma may be locally common and a cause of significant health problems.”

Prof Jon Cohen, Emeritus Professor of Infectious Diseases, Brighton & Sussex Medical School, said:

“This report from WHO, the first of its kind dealing with fungi that cause human disease, is very welcome.  While the problems associated with bacteria, especially resistance to antibiotics, have become well known, and of course viruses such as COVID have claimed huge public attention, serious infections caused by fungi have received far less attention.  They are less common than other types of infection but can cause extremely serious disease or death, and there are frequently far fewer treatment options.

“The choice of which fungi to include, and whether to grade them as priority or of lesser importance, is tricky and inevitably there will be some disagreements about the ranking.  Some fungi, such as Aspergillus, usually only cause disease in people whose immunity is reduced, for example after HIV/AIDS or organ transplantation.  Others such as Coccidioides, can infect otherwise healthy people but only occur in very restricted geographic areas.  Quite how best to “rank” or weigh up these differences is a little arbitrary.

“But in the end these distinctions are less important than the fact that this kind of recognition for fungi will rightly bring them out of the shadows and encourage much greater awareness, increase diagnosis, and importantly, stimulate research.  The number of drugs to treat fungi is much more limited than the case with bacteria, and fungi too are developing resistance to these drugs.  The WHO should be congratulated for this important initiative.”

Report ‘WHO fungal priority pathogens list to guide research, development and public health action’ was published by the World Health Organization on Tuesday 25 October 2022.

https://www.who.int/news/item/25-10-2022-who-releases-first-ever-list-of-health-threatening-fungi

https://www.who.int/publications/i/item/9789240060241

Declared interests

Prof Darius Armstrong-James: “I have received industrial research funding and have share options in Pulmocide, a antifungal pharmaceutical company.”

Dr Neil Stone: “I have no conflict of interest to declare.”

Prof Jon Cohen: “I have no conflicts to declare.”

For all other experts, no reply to our request for DOIs was received.