Curious case of black fungus!
Adevastating and invasive fungal infection called mucormycosis, dubbed ‘ black fungus’ is spreading in India lately. It is likely being triggered by the use of steroids in severe and critically ill COVID-19 patients. Although an upsurge of mucormycosis has been reported throughout the world over the past two decades, the rise of this infection in developing countries, including India, has been phenomenal. And now due to the immuno-compromised conditions as an aftermath of the pandemic, an increasingly high incidence of mucormycosis is fast becoming a cause for concern.
Mucormycosis is a serious, but rare, fungal infection caused by a group of moulds called mucormycetes or zygomycetes. These moulds gain entry into the human body via the respiratory tract or skin, and less commonly through the gastrointestinal tract, eliciting an acute inflammatory response. Under favourable conditions such as those in immune-compromised hosts, they invade the blood vessels, causing extensive vessel thrombosis and ischaemic tissue necrosis. Most of these infections are rapidly progressive and exhibit high mortality even after active management.
The infection rarely occurs in a person with an intact immune system because macrophages phagocytise the spores. However, an immunocompromised individual is unable to mount an effective immune response against the inhaled spores; thus, germination and hyphae formation occur and infection develops.
It can affect the brain, sinus, lungs, skin and even the heart. The optic nerve may also be affected, resulting in vision loss. Pulmonary or lung mucormycosis is the most common type of mucormycosis in people with cancer and in people who have had an organ transplant or a stem cell transplant. In addition, uncontrolled diabetes mellitus is the most common underlying disease associated with mucormycosis in India.
Amongst diabetics, poorly controlled Type II diabetes is the most common risk factor for mucormycosis. As a result, rhinocerebral or sinus and brain mucormycosis is most common in people with uncontrolled diabetes and in people who have had a kidney transplant.
Studies have revealed several factors relating to the unique predisposition of diabetic patients to mucormycosis. Firstly, diabetes renders the phagocytic cells or white blood cells dysfunctional. Both neutrophils and macrophages exhibit defective killing by both oxidative and non-oxidative pathways under such conditions, although the precise mechanisms mediating these remain to be elucidated. Secondly, patients with diabetes have an acidic serum pH with elevated levels of free iron, which is a major nutrient element governing susceptibility to the infection-causing organism. In fact, a considerable number of patients are ignorant of diabetes status till they acquire mucormycosis. Other emerging risk factors of mucormycosis are pulmonary tuberculosis, chronic kidney disease and critically ill patients, as in the case of COVID-19. Additionally, isolated renal mucormycosis in an immunocompetent host is now developing as a unique clinical entity.
On the whole, the major reasons for the high prevalence of mucormycosis are the abundant presence of mucorales in the community and the hospital environment, large number of susceptible hosts especially diabetics, and the lack of regular health check-ups within the Indian population.
On the treatment front, drugs such as amphotericin B, posaconazole, and isavuconazole are active against most mucormycetes while surgical debridement or resection of infected tissue is often necessary, particularly for rhinocerebral, cutaneous, and gastrointestinal infections. First-line treatment with high-dose liposomal amphotericin B is strongly recommended, and intravenous isavuconazole and intravenous or delayed release tablet posaconazole are recommended with moderate strength.
However, the main challenge lies on the diagnostic front. Routine serologic tests for mucormycosis are currently not available, and blood tests such as betaD-glucan or Aspergillus galactomannan do not detect mucormycetes. DNA-based techniques for detection are promising but are not yet fully standardised or commercially available. Thus, there is a dire need for early diagnosis of infectious diseases in our country in order to deliver better outcomes.