Scientifically Speaking | Mucormycosis is only the tip of the fungal iceberg
The explosion of cases of mucormycosis that India has experienced in the past few months is unprecedented for any fungal disease. Many hospitals went from admitting one or two patients a month prior to the pandemic, to over 500 cases at once
Mucormycosis is a debilitating and often fatal disease that requires aggressive treatment with antifungal drugs such as amphotericin B. The infection spreads rapidly, often through blood vessels, after vulnerable people inhale fungal spores. Invasion of tissues of the face, nose, eyes, and brain can occur. As tissues die, they turn black. Even with treatment, fungal invasion into tissues can cause blindness and disfigurement. Fortunately, the causative fungi do not spread from person to person.
The explosion of cases of mucormycosis that India has experienced in the past few months alongside the second wave of the Covid-19 pandemic is unprecedented for any fungal disease. Many hospitals went from admitting one or two patients a month with mucormycosis prior to the pandemic, to over 500 cases at once. Special wards to treat patients were set up. By the end of June, India had reported nearly 41,000 cases.
Moulds that cause the fungal infection mucormycosis (often erroneously called “black fungus”) are pervasive. You and I breathe in spores of these fungi every day. Yet, most people have immune systems that can clear them without symptoms.
What contributed to this crisis in the midst of the Covid-19 pandemic? Speaking at the Joint General Session on “Emerging Pathogens” at the World Microbe Forum held last month, microbiologist Ilan Schwartz of the University of Alberta noted that while much remains unknown, an “unholy trinity” of factors precipitated the mucormycosis crisis in India. A plethora of Covid-19 cases during the second wave, poorly controlled diabetes in many patients, and indiscriminate use of steroids such as dexamethasone led to the sharp spike. Steroids are useful in patients requiring oxygen, but as Schwartz noted, they reduce immunity to fungal infections and can worsen diabetes.
Even before the pandemic, India experienced a higher baseline of mucormycosis compared to many other countries due to its tropical climate. India also has a large population with poorly controlled diabetes. In the fourth edition of the Textbook of Medical Microbiology published in 2018, Jagdish Chander foreshadowed the calamity that would befall India (even if he had no inkling of the Covid-19 pandemic). He wrote that an “upsurge in the number of diabetics has really changed the entire scenario more of less like an epidemic… Mucormycosis is going to destroy India shortly, in a couple of years.”
Mucormycosis is not the only concern; other fungal infections are resurging. Many new fungal diseases are also emerging. Certainly, better detection of infections explains some (but not all) of the cases. Candidiasis was not common before the 1950s. Many other fungal diseases were rare until HIV/AIDS and immunosuppressive treatments became common. Overall, we are witnessing an alarming trend.
Deadly fungal infections were thought to only occur in people with weak immune systems, the elderly, and those battling other infections at the same time. But there is accumulating evidence that external factors such as global travel are increasing their prevalence. And over the past decade, microbiologist Arturo Casadevall of the Johns Hopkins Bloomberg School of Public Health has gathered evidence for a hypothesis involving another culprit — the climate crisis.
A few years ago, Casadevall wondered why only a few hundred of the roughly 1.5 million fungal species cause diseases in mammals (including humans). For comparison, insects are susceptible to around 50,000 fungal species. Among vertebrates, cold-blooded animals such as amphibians are particularly prone to fungal infections. He found that the comfort zone in which most fungi grow in the environment is cooler than the core temperatures of most mammals.
Based on this research, Casadevall proposed an elegant hypothesis that mammals evolved stable and warm core temperatures as a firewall against environmental germs such as fungi. Among fungal species, there are only a few variants that can tolerate warm mammalian core temperatures. This thermal gap has protected us.
But on the flipside, with global temperatures rising, heat tolerant variants are expected to flourish. As the difference between environmental temperatures and body temperature diminishes, we may face fungi that have the potential to cause new diseases in humans.
In fact, this may already be happening. Candida auris is a fungal species that has caused hundreds of deadly outbreaks worldwide. No one on the planet knew of its existence before 2009. Today, it is highly prevalent in India. And in 2011 and 2012, cases of C. auris exploded almost simultaneously on three continents.
C. auris can grow at temperatures higher that those suitable for most fungi. And it may have become tolerant of higher temperatures only recently. Unlike mucormycosis and most other fungal infections, it is contagious. To make matters worse, C. auris is incredibly difficult to remove from surfaces, and many strains are resistant to known antifungal drugs. This fungus represents “a perfect storm” of a new pathogen that can wreak havoc in humans.
Writing in the journal mBio in 2019, Casadevall and colleagues hypothesized “that C. auris may be the first example of a fungal species that has jumped the thermal barrier due to adapting to global warming,” In March of this year, a team led by Anuradha Chowdhary of the Vallabhbhai Patel Chest Institute at the University of Delhi published the discovery of C. auris strains from a salt marsh and a sandy beach in the Andaman Islands in mBio. In this scheme, heat-tolerant fungi infected animals that encountered then in the environment, and then spread through people to hospitals in urban areas. While this data does not prove that the climate crisis precipitated the jump of this fungus to humans, it provides evidence of an environmental reservoir— a necessary step in Casadevall’s hypothesis.
If thr climate crisis selects fungal strains that thrive in the higher core temperatures of humans, the rise of fungal diseases is all but certain. Unfortunately, the mucormycosis epidemic is only the tip of the iceberg.
Anirban Mahapatra, a microbiologist by training, is the author of COVID-19: Separating Fact From Fiction
The views expressed are personal