Story of The Black and White Devils – Mucormycosis

Black Death
Designed by Aesha Lahiri.

You can check out the illustrative concept highlights of this blog by clicking the button below. The content is now available in three languages: English, हिंदी and বাংলা.


2019 has seen the outbreak of a pandemic that is perhaps the first and only experience of such a global threat to life for the living generations across the world. It has been a year and a half since CoViD-19 surfaced in Wuhan, China, and the world is still reeling under the pandemic threat without an extremely reliable answer. Vaccines and medical procedures have evolved like never before in such a short span of time that has been the cause of some respite. Thanks to the global scientific ventures that we can still stand strong against one of the most infectious diseases of all time. However, CoViD is not the deadliest disease that we know of. In fact, it has a considerably low mortality rate of below 10% (see, John Hopkins Coronavirus Resource Centre).

Recently, there was a rise in the number of cases of fungal infections reported in some diabetic and non-diabetic CoViD patients. Simultaneously, the media and social media platforms have been raging with the outbreak of another fungal epidemic which is deadlier than the CoViD-19 itself. These infections are reportedly caused by “black” fungus and “white” fungus.

What are “black” fungus and “white” fungus?

Let’s take a systematic and logical approach in understanding what these fungi are, their historical perspectives and their effectiveness in infecting and killing human beings.

Nomenclature and Occurrence

It is to be noted that the reported “black” fungus and “white” fungus infections are caused to two different fungi with different prevalence and deadliness. Black fungus infection is caused by members of the order Mucorales, which includes Absidia, Rhizopus, Rhizomucor, Mucor, and Cunninghamella, among others, whereas, white fungus infection is referred to the infection caused by a different fungus named Candida which is from the order Saccharomycetales.

Normally, mucor moulds are ubiquitous and are found in soil, plants, manure and decaying fruits, and can also be located inside the nose and mouth along the mucosal membrane. Candida, on the other hand, is found on the skin and inside the body without causing any harm.

Figure 1: Distinguishable morphological features of Rhizopus spp. and Candida spp. as can be observed in a histopathological section.

Historical Perspective

Black fungus was first clinically reported in 1885 by a German pathologist named Arnold Paltauf, and he described it as Mycosis Mucorina. It was caused by Absidia corymbifera. Later, R.D. Baker, an American pathologist, coined the term Mucormycosis. Following this, in 1943, Dr John E. Gregory and his team first linked the case of rhino-orbital cerebral (meaning, the sinus-bony cavity of eye-brain) mucormycosis with diabetes.

In 1947, a similar case was reported in the US, and the autopsy report was published concluding that the patient had a swollen right upper eyelid, an irregular pupil of the right eye, pale yellow fluid in the lung, uncontrolled diabetes, iron deposition in many organs including the liver, pancreas, heart and kidneys, and abundance of branched, aseptate (hyphae not compartmentalized by a septum), multinucleate and refractile hyphae of a fungus. The patient was admitted partially paralyzed and passed away within two days, despite attempts to control diabetes.

Later, the first survivor was reported by Harris in 1955. However, even after this, the diagnosis and outcome of this infection have not changed much, and it is still treated by general anti-fungal drugs. Severe cases are surgically diagnosed. However, the mortality rate is still as high as 54% despite advances in medical sciences.

Although Candida albicans was discovered in 1840 at the Paris Foundling Hospital, Candida infection was well known even in ancient Greek times as oral thrush. It was a general health concern before proper sterilization, and refrigeration techniques in food processing were developed and rose dramatically during and after the Second World War. The disease could be tackled with relative ease after the development of nystatin. Overall, Candida infections have been considered to be pretty harmless and very rarely lethal.

Pathogenicity

In Mucormycosis, the fungi can enter the body through the nose, and go on invading the sinuses, brain, eyeball orbit, gastrointestinal tract, skin, and lung in immunocompromised patients. They can even disseminate throughout the body easily through the veins.

In Candida infection, the most common sites affected are the mouth, vagina, and sometimes the gut (in case of acute infection).

So far it can be understood that “black” fungus disease is the real cause of concern and not the “white” fungus disease, despite the fact that the fungi causing the latter are more abundant in association with the human skin and the mucosal layer. Some of the media houses and social media platforms are wrongly creating a hype about the “white” fungus. However, the truth is that a white fungus disease is a form of Candidiasis, that has already been known for thousands of years.

Therefore, next up we will try to understand what we should keep in our mind with respect to the deadly “black” fungus disease.

Mucormycosis

Classification

Mucormycosis can be clinically classified based on the location and nature of the infection. According to Centres for Disease Control and Prevention (CDC), there are 5 types of Mucormycosis:

  1. Rhinocerebral (sinus and brain)
  2. Pulmonary (lung)
  3. Gastrointestinal (gut)
  4. Cutaneous (skin)
  5. Disseminated (spread to other organs)

Rhinocerebral mucormycosis is the most prevalent type. In fact, CoViD patients undergoing hospital-based treatment and usage of oxygen masks are having most cases of mucormycosis that involves the nose and the mucosal membrane inside the nose and mouth, followed by rhinocerebral mucormycosis.

Cause

Mucormycosis is very rarely pathogenic unless the person has:

  • Compromised immunity
  • Overdose of immunosuppressants like steroids (Point to ponder: Fungal cell walls contain ergosterols – steroid precursors. Does medically applied steroid have anything to do with promoting biosynthesis of the fungal cell wall?)
  • Uncontrolled diabetes (an upcoming blog on The Qrius Rhino will discuss more how Diabetes aggravates such infection-based diseases. Stay tuned!)
  • High iron levels (increased ferritins)
  • Low tissue oxygen levels
  • Low pH (skin or internal tissue)
  • Undergone surgery, transplant, usage of hospital equipment (like an oxygen mask, surgical mask, etc.) for a prolonged time without proper sterilization

Most of the cases of mucormycosis in patients who have undergone/are undergoing CoViD treatment at hospitals have either or both diabetes and corticosteroid treatment as underlying conditions.

Cure

The cure of mucormycosis varies from treatment with anti-fungal medications like amphotericin B, posaconazole, or isavuconazole to surgery in acute cases. However, whatever be the mode of treatment, stopping the intake of immunosuppressants like steroids is a general practice.

Early diagnosis is crucial based on symptoms like non-specific irritations or pain, skin lesions and swellings, yellowish nasal discharge, bleeding, disoriented vision with inflammation in the eyelid, local or major paralysis, to name the most important ones. If any/some of these symptoms appear, most importantly, after a hospital-based treatment, contacting the doctor immediately is mandatory.

Candidiasis can be treated using anti-fungal drugs like amphotericin B, terbinafine, fluconazole, 5-fluorocytosine, voriconazole and caspofungin.

Understandably, for mucormycosis, a high mortality rate makes the time of diagnosis and type of infection the critical determinants of the patient’s fate. However, it is less likely that a person with a normal and good immunity will be infected in the first place unless they have the causes as listed above.

Figure 2: Some of the clinical facts and classifications in relation to mucormycosis.

Reasons to worry?

The disease is rare. It has been seen to be rising during outbreaks of some other disease, not only now but also before. However, there should be no reason to panic. A general habit should be aimed at maintaining daily cleanliness and hygiene with regular sanitization and washing of clothes, shoes, masks, etc. A person undergoing CoViD-19 treatment/cured of the same needs to be more cautious about general hygiene and appearance of the slightest of the abovementioned symptoms.

Therefore, there is a need to be educated about the disease, its causes and symptoms, but no need to panic or worry unnecessarily. One should spread general awareness, but not unnecessary hype.

Written by Diptatanu Das (Department of Biological Sciences, IISER Kolkata)

Cover illustration by Aesha Lahiri (Department of Biological Sciences, IISER Kolkata)

See also:

References

  • Lecompte, P. M., & Meissner, W. A. (1947). Mucormycosis of the Central Nervous System Associated with Hemochromatosis: Report of a Case. The American journal of pathology23(4), 673–677.
  • Bell, S., & Mahoney, L. (2000). Mucormycosis: a case study. Critical care nurse, 20(1), 18–23.
  • Baker, R. D. (1957). MUCORMYCOSIS—A NEW DISEASE? Journal of the American Medical Association, 163(10). https://doi.org/10.1001/jama.1957.02970450007003

  • He, J., Sheng, G., Yue, H., Zhang, F., & Zhang, H.-L. (2021). Isolated pulmonary mucormycosis in an immunocompetent patient: a case report and systematic review of the literature. BMC Pulmonary Medicine, 21(1). https://doi.org/10.1186/s12890-021-01504-8

  • John, T. M., Jacob, C. N., & Kontoyiannis, D. P. (2021). When Uncontrolled Diabetes Mellitus and Severe COVID-19 Converge: The Perfect Storm for Mucormycosis. Journal of Fungi, 7(4). https://doi.org/10.3390/jof7040298

  • Kwon-Chung, K. J. (2012). Taxonomy of Fungi Causing Mucormycosis and Entomophthoramycosis (Zygomycosis) and Nomenclature of the Disease: Molecular Mycologic Perspectives. Clinical Infectious Diseases, 54(suppl_1). https://doi.org/10.1093/cid/cir864
  • Obladen, M. (2012). Thrush – Nightmare of the Foundling Hospitals. Neonatology, 101(3). https://doi.org/10.1159/000329879
  • Paltauf, A. (1885). XXV. Mycosis mucorina. In Archiv für pathologische Anatomie und Physiologie und für klinische Medicin Band 102. De Gruyter. https://doi.org/10.1515/9783112390382-025
  • Ribes, J. A., Vanover-Sams, C. L., & Baker, D. J. (2000). Zygomycetes in Human Disease. Clinical Microbiology Reviews, 13(2). https://doi.org/10.1128/CMR.13.2.236-301.2000
  • Singh, A. K., Singh, R., Joshi, S. R., & Misra, A. (2021). Mucormycosis in COVID-19: A systematic review of cases reported worldwide and in India. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. https://doi.org/10.1016/j.dsx.2021.05.019
  • Liu, X., Ma, Z., Zhang, J., & Yang, L. (2017). Antifungal Compounds against Candida Infections from Traditional Chinese Medicine. BioMed research international2017, 4614183. https://doi.org/10.1155/2017/4614183

Author: Das Diptatanu

Diptatanu is a fourth-year BS-MS student at IISER Kolkata and a KVPY fellow, majoring in biology, with a chemistry minor. He has been a part of the gold-medalist iGEM IISER Kolkata teams in 2018 and 2019, and is also associated with next year’s team. Other than having a high affinity for good food and sleep, he loves to make music and play TT, football, cricket, etc., in his free time. He prefers to do some original work and has been writing articles, blogs and composing new songs. He is currently the CEO of IISER Kolkata Campus Radio and is also one of the admins and a regular blogger of our blog page, ‘The Qrius Rhino’.

1 thought on “Story of The Black and White Devils – Mucormycosis

Leave a Reply

Your email address will not be published.