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Eleven years ago, my colleagues and I estimated that about 2 million people around the world were dying from fungal infections annually. My latest estimate puts the figure today at nearly double that: around 3.8 million deaths.
To put this in perspective, it accounts for around 6.8% of total global deaths. Coronary heart disease is probably responsible for 16% of the world’s total deaths, followed by stroke at 11%. Smoke-related lung disease (COPD) comprises 6% of total deaths, with fungal infection being responsible for about one-third of these 3,228,000 deaths.
Other comparative global death statistics put pneumonia at 2,600,000 (some fungal) and tuberculosis at 1,208,000 (of which mostly undiagnosed fungal disease probably comprises 340,000 deaths).
To arrive at these estimates – published in Lancet Infectious Diseases – I made a judgment about the proportion of fungal cases actually diagnosed and treated, and those that are missed. While fungal disease diagnostics have improved greatly in the last ten to 15 years, both access to and actual usage of these tests is limited – and not only in low-income countries.
For example, South Africa has an enviable diagnostic service for fungal (cryptococcal) meningitis and bloodstream fungal infection (Candida), but has no diagnostics for infections caused by another very common fungus, Aspergillus. These gaps contribute substantially to unnecessary deaths. In particular, timely diagnosis of severe Aspergillus infections, ideally within 48 hours, could save millions of lives each year.
The most important lethal fungi are Aspergillus fumigatus and Aspergillus flavus, which cause lung infections. Among the people affected are those with lung diseases, such as asthma, TB and lung cancer, but also people with leukaemia, those who have had an organ transplant and those in intensive care.
Many of these people die because their doctor does not recognise that they have fungal disease – or they recognise it too late. But also, many of the deaths are down to slow or absent diagnostic testing and a lack of effective antifungal drugs. Tests based on fungal cultures only identify about a third of people who actually have a fungal infection.
Unfortunately, as with antibiotic resistance, antifungal resistance is a growing problem too. Spraying crops with certain types of fungicides is greatly increasing resistance rates to a group of antifungal drugs, known as azoles.
Candida infections are one cause of sepsis and are found in the bloodstream. They are also linked to diabetes or renal failure – or both – and can also take hold after major surgery or trauma. This fungus is a normal part of the gut microbiome, but when we are very ill, it travels across the gut wall into the bloodstream.
With over 1.5 million people affected globally by life-threatening Candida infection, and nearly 1 million deaths annually, we urgently need better diagnostics tests. Current blood culture tests only pick up 40% of life-threatening Candida infections.
About 50% of the approximately 600,000 deaths from Aids are attributable to fungal infections. There are major efforts globally to eradicate cryptococcal meningitis as a cause of death, partly led by the US Centers for Disease Control and Prevention and the World Health Organization.
Also in Aids, much more work is required on histoplasmosis in Africa and south-east Asia, using the better tests. Too many of these patients are misdiagnosed with TB, or have a dual infection with TB, without the lethal Histoplasma infection being recognised or treated.
Black fungus
The world’s first large-scale outbreak of mucormycosis followed COVID in India – the so-called black fungus. The fungi causing mucormycosis block off tissue blood supply causing dead tissue, hence the popular name “black fungus”.
In 2012, my colleagues and I estimated about 10,000 cases of mucormycosis globally. The COVID pandemic in India led to at least 51,000 reported cases – a massive increase attributable to factors including excess steroid usage for COVID (too high a dose and for too long) and poorly controlled diabetes.
Aspergillus and Candida infections were also much more common in COVID patients in intensive care around the world. Indeed the COVID spike in fungal disease was not taken into account in assembling these newly published incidence and mortality figures from the fungal disease, so they could be even higher.
Double whammy
People admitted to intensive care with influenza also have a high incidence of life-threatening Aspergillus infection, doubling the risk of death, even if Aspergillus is diagnosed. Indeed, doctors and scientists are fearful of a double whammy epidemic of fungal infections and influenza or another respiratory virus.
There is also a strong association between fungal allergy and severe, or poorly controlled, asthma.
Asthma is common and increasingly problematic as people get older. People with fungal asthma usually need several medications and endure flare-ups, emergency room visits and hospitalisations.
Despite all the efforts to control asthma, an estimated 461,000 people die from it each year or with it as a component of their final illness, worldwide.
Fungal diseases are here to stay. We are surrounded by them, and they live in our guts and on our skin.
There are no vaccines for fungi. Severe fungal disease strikes when people are already ill, with only a few exceptions in healthy people and in those living or working in mouldy homes or work environments. That is why accurate and timely diagnosis is desperately needed, and why we need to take fungi very seriously.
Dr Denning and family hold Founder shares in F2G Ltd, a University of Manchester spin-out antifungal discovery company, and share options in TFF Pharma. He acts or has recently acted as a consultant to Pulmatrix, Pulmocide, Biosergen, TFF Pharmaceuticals, Rostra Therapeutics, Mucpharma PTY and Lifemine Therapeutics. In the last 3 years, he has been paid for talks on behalf of Mundipharma, BioRad, Basilea, Gilead, Avir and Pfizer. He has been involved in multiple guideline groups, primarily focussed on diagnostics and aspergillosis. He was the founder of Global Action For Fungal Infections in 2013, and was its unpaid Chief Executive until 2023.
