Mucormycosis: time to address this deadly fungal infection

Mucormycosis, a severe and often fatal invasive fungal infection, has entered public consciousness in response to an outbreak of cases in India. Thousands of cases of mucormycosis have been reported in the wake of India's second wave of COVID-19 cases, bringing worldwide attention to this deadly yet neglected disease. Mucormycosis is caused by ubiquitous environmental moulds with a global distribution, including the Rhizopus, Apophysomyces, Mucor, and Lichtheimia species. Although generally harmless to an immunocompetent host, the infection can be deadly in patients with an impaired immune system, such as in those with haematological malignancies or poorly controlled diabetes, or in individuals receiving steroids or other immunosuppressants. Structural breaches, such as traumatic cutaneous inoculation, can also lead to mucormycosis. Infection manifests as a rapidly developing, angioinvasive infection, with rhino–orbital–cerebral and pulmonary manifestations the most common forms of disease. Although prevalent worldwide, mucormycosis is much more common in India: even before the COVID-19 pandemic, the incidence of mucormycosis in India was as much as 70 times higher than the global average.1Prakash H Chakrabarti A Epidemiology of mucormycosis in India.Microorganisms. 2021; 9: 523Crossref PubMed Scopus (24) Google Scholar The scale of the current epidemic is difficult to overstate. According to an Indian Government minister, on May 25, 2021, alone, there were reported to be over 11 700 patients receiving care for mucormycosis.2@DVSadanandGowda https://twitter.com/DVSadanandGowda/status/1397438818899296259Date: May 26, 2021Date accessed: June 9, 2021Google Scholar Some hospitals have opened dedicated mucormycosis wards. The reason for the sharp increase in cases in India is not entirely clear; however, it is likely to have resulted from a combination of factors. Such factors include widespread use (and misuse) of steroids, even for mild COVID-19; poorly controlled diabetes, which is unmasked or exacerbated by COVID-19 itself (with scarce capacity for glucose monitoring in overburdened hospital wards); and, possibly, mucosal damage from the virus. Additional hypotheses that need investigation include factors related to the host, pathogen (heightened prevalence and virulence of Mucorales strains in India), or the antecedent SARS-CoV-2 infection (with an increased risk imposed by variants predominating in India [ie, the Delta variant]). Despite the ubiquitous and deadly nature of fungal infections, the field of mycology has suffered from inadequate investment in research into diagnosis and therapies over many decades. Research funding dedicated to fungal disease pales in comparison with the study of bacterial, viral, or even parasitic infection,3Rodrigues ML Albuquerque PC Searching for a change: the need for increased support for public health and research on fungal diseases.PLoS Negl Trop Dis. 2018; 12e0006479Crossref PubMed Scopus (24) Google Scholar despite the fact that 1 billion people worldwide have a fungal infection at any one time, and that fungal diseases claim an estimated 1·5 million lives per year.4Bongomin F Gago S Oladele RO Denning DW Global and multi-national prevalence of fungal diseases-estimate precision.J Fungi (Basel). 2017; 3: 57Crossref PubMed Scopus (625) Google Scholar As a result of this chronic neglect, the medical profession has been left with a scarcity of tools to diagnose and treat mucormycosis. Mortality is unacceptably high, reaching 80% in some case series.5Roden MM Zaoutis TE Buchanan WL et al.Epidemiology and outcome of zygomycosis: a review of 929 reported cases.Clin Infect Dis. 2005; 41: 634-653Crossref PubMed Scopus (1576) Google Scholar Prompt diagnosis is crucial because treatment initiation is time-critical due to the rapid progression of the infection, yet this is hampered by the paucity of diagnostic tests available. Diagnosis is based on histology and tissue culture, which can be invasive, slow, and insensitive. There is no serology test or serum biomarker available to enable early diagnosis. Molecular methods are in development, but are not generally available.6Millon L Scherer E Rocchi S Bellanger AP Molecular strategies to diagnose mucormycosis.J Fungi (Basel). 2019; 5: 24Crossref Scopus (25) Google Scholar Even after a diagnosis is made, management is challenging. Surgical debridement of infected and necrotic tissue is essential to give the patient any chance of survival; however, this can lead to visual loss, severe disfigurement, or both. Many patients cannot access or afford effective antifungal therapy, which comprises another important pillar of management.7Cornely OA Alastruey-Izquierdo A Arenz D et al.Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium.Lancet Infect Dis. 2019; 19: e405-e421Summary Full Text Full Text PDF PubMed Scopus (203) Google Scholar The mainstay of antifungal treatment is amphotericin B, a nephrotoxic polyene antifungal in use since 1958. Liposomal formulations, preferred because of reduced toxicity, are often prohibitively expensive or simply unavailable in many resource-limited settings. The few alternatives, such as posaconazole and isavuconazole, are out of reach for much of the world due to cost and availability. The mucormycosis epidemic in India has brought into sharp focus the seriousness of fungal infections and the relatively poor state of the science on their prevention, diagnosis, and management. Dubbed the so-called black fungus in popular media (due to the black and necrotic tissue seen in sufferers, rather than the mould itself), there is an unprecedented focus on this deadly infection.8Biswas S Mucormycosis: the ‘black fungus’ maiming Covid patients in India.https://www.bbc.co.uk/news/world-asia-india-57027829Date: May 9, 2021Date accessed: June 9, 2021Google Scholar This increased awareness is an opportunity to stimulate action to address the numerous areas of urgent need in the advancement of managing this condition. Beyond uncovering risk factors that might be contributing to the current epidemic, priorities must include the development of rapid, reliable, and non-invasive or minimally-invasive diagnostics for mucormycosis, access to existing treatments, and the improvement of therapeutic strategies. Crisis brings opportunity, and the time for action on mucormycosis is now. We declare no competing interests.