The forgotten superbug: Is it time to bring fungal infections out of the dark?

4th August 2020

They kill more than a million and cause misery to billions every year. Yet despite this, fungal infections are all often treated as the poor relation of other, more ‘glamorous’ microorganisms...

Cryptococcal meningitis, caused by fungal species Cryptococcus neoformans and C. gattii, causes 20 times more deaths than meningitis caused by the bacterium Neisseria meningitidis but receives less than a quarter of the research funding. This disparity is just one of many disparities between funding for fungal diseases and other diseases highlighted by Rodrigues and Albuquerque in their 2018 paper in PLOS Neglected Tropical Diseases [1]. In fact, fungal diseases combined affect billions of people globally and result in an estimated 1.5 million deaths each year, yet from 1997-2010 only 2% of the UK’s £2.6 billion research budget for infectious diseases was spent on medical mycology [2]. By comparison, during the same time period 13.3% of this budget was spent on researching malaria (405,000 deaths in 2018 [3]), 5.7% on tuberculosis (1.5 million deaths in 2018 [4]), 3.1% on influenza (estimated 389,000 annual deaths [5]) and 2.3% on hepatitis C (estimated 700,000 annual deaths [6]) [7].  In 2014, a Medical Research Council (MRC) strategic review found that only 1% of grant applications between 2007 and 2012 involved fungal research [8].

In addition to a lack of funding, fungal diseases suffer from a lack of treatment options. There are currently only four classes of antifungal drugs approved for clinical practice [9]- compared to 20 classes of antibiotics [10] and 13 functional groups of antivirals [11] – with only one class developed in the past 30 years [12]. Furthermore, fungi are rapidly evolving resistance to commonly used fungicide drugs resulting in a growing threat to human health and food security [13].

However, the situation is improving! In 2015, the Aberdeen Fungal Group received a Wellcome Trust Strategic Award (WTSA) worth £5.1 million and has since established the Medical Mycology and Fungal Immunology (MMFI) consortium involving 12 UK universities. Also in 2015, the World Health Organisation (WHO) added three antifungal drugs to its List of Essential Medicines and has since included antifungal resistance surveillance in its Global Antimicrobial Resistance Surveillance System (GLASS) [14]. Recently, substantial progress has occurred towards developing new antifungals, with at least 11 antifungals in phase 1 and 2 clinical trials [15]. The Public Health England (PHE) Mycology Reference Laboratory has seen a nearly 4-fold increase in the number of clinical samples being sent to them for diagnosis of fungal infections in 2019-2020 compared to 2009-2010. Charities such as Global Action Fund for Fungal Infections (GAFFI) and Fungal Infection Trust, as well as patient support groups such as The Aspergillosis Trust, continue to raise awareness of fungal infections and publicise disparities in diagnosis and treatments.

As the global population rises, so will the impact of fungal diseases – on our health and on our food chain. We face the challenges of global trade and travel facilitating movement of fungal pathogens and the potential for global warming selecting for fungi that are able to grow at mammalian body temperatures [16]. As our medical knowledge grows so does our population of ageing and immunocompromised individuals, who are most at risk of developing serious fungal diseases. We need to be prepared to meet these challenges with increased awareness of fungal diseases – amongst policy makers, medical practitioners, scientists and the public – better teaching of medical mycology and greater funding for mycological research and antifungal drug development.

Jenny Shelton, PhD student on the Science and Solutions for a Changing Planet DTP at Imperial College London.Researching drug-resistant Aspergillus fumigatus in the environment and its implications for human health. Supervised by Professor Matthew Fisher at ICL and Dr Andrew Singer at UK Centre for Ecology & Hydrology. @jenmgshe

[1]      M. L. Rodrigues and P. C. Albuquerque, “Searching for a change: The need for increased support for public health and research on fungal diseases,” PLoS Negl. Trop. Dis., vol. 12, no. 6, pp. 1–5, 2018.
[2]      N. A. R. Gow et al., “Strategic Research Funding: A Success Story for Medical Mycology,” Trends Microbiol., vol. 26, no. 10, pp. 811–813, 2018.
[3]      WHO, World Malaria Report. Colombia, vol. 23. 2011.
[4]      WHO, “Global Tuberculosis Report,” 2019.
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[8]      MRC, “Strategic review of fungal disease research in the UK – Meeting report,” Mrc, vol. 1, no. 1, pp. 1–11, 2014.
[9]      S. C. A. Chen and T. C. Sorrell, “Antifungal agents,” Encycl. Microbiol., vol. 187, no. 7, pp. 140–159, 2019.
[10]    A. R. Coates, G. Halls, and Y. Hu, “Novel classes of antibiotics or more of the same?,” Br. J. Pharmacol., vol. 163, no. 1, pp. 184–194, 2011.
[11]    E. de Clercq and D. C. E., “Approved antiviral drugs over the past 50 years. ,” Clin. Microbiol. Rev. , vol. 29, no. 3, pp. 695–747, 2016.
[12]    T. Roemer and D. J. Krysan, “Antifungal Drug Development: Challenges, Unmet Clinical Needs, and New Approaches,” Cold Spring Harb Perspect Med, vol. 4, p. a019703, 2014.
[13]    M. C. Fisher, N. J. Hawkins, D. Sanglard, and S. J. Gurr, “Worldwide emergence of resistance to antifungal drugs challenges human health and food security,” Science (80-. )., vol. 360, pp. 739–742, 2018.
[14]    A. Chakrabarti, “‘Medical Mycology’ – a new section in the Journal of Medical Microbiology,” J. Med. Microbiol., vol. 68, no. 12, pp. 1697–1698, 2019.
[15]    J. R. Perfect, “The antifungal pipeline: A reality check,” Nat. Rev. Drug Discov., vol. 16, no. 9, pp. 603–616, 2017.
[16]    M. A. Garcia-Solache and A. Casadevall, “Global warming will bring new fungal diseases for mammals,” MBio, vol. 1, no. 1, pp. 1–3, 2010.
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