Mucormycosis-Definition, Causes, Symptoms & Alternative Treatments

What is Mucormycosis?

Mucormycosis is an infection caused by fungi belonging to the order Mucorales . The fungal species that are most frequently isolated from patients with Mucormycosis are Apophysomyces, Cunninghamella, Lichtheimia, Mucor, Rhizopus, and Rhizomucor. Rhizopus oryzae is the most common organism isolated from patients with mucormycosis and is responsible for ∼70% of all cases of mucormycosis. These species exist as spores and thrive in dry, humid, and arid conditions. These are transmit through the air and result in mild to severe infections in immunocompromised individuals.

Who is at Higher Risk?

People who have health problems or take medicines that lower the body’s ability to fight germs (immunity) and sickness. Certain groups of people are more likely to get mucormycosis, including people with:

  • Diabetes, especially with diabetic ketoacidosis
  • Undergoing  treatment with corticosteroids
  • Malignant hematologic disorders; Cancer
  • Organ transplant
  • Stem cell transplant
  • Neutropenia pdf icon[PDF – 2 pages] (low number of white blood cells)
  • Long-term corticosteroid use
  • Injection drug use
  • Too much iron in the body (iron overload or hemochromatosis); Patients undergoing deferoxamine therapy
  • Skin injury due to surgery, burns, or wounds
  • Prematurity and low birthweight (for neonatal gastrointestinal mucormycosis)
  • In patients receiving hemodialysis.
  • Covid Patients. Not to forget, not all people who have contracted coronavirus infection and are on treatment for COVID-19 obtain mucormycosis. Certain individuals are more prone to getting affected by the fungal infection, yet if they have any of the above pre-existing condition or any other illness  or being treated in the Intensive Care Unit i.e. ICU wing of hospitals for a prolonged interval of time.
Unfortunately, despite disfiguring surgical debridement and adjunct antifungal therapy, the overall mortality rate for mucormycosis remains >50%, and it approaches 100% among patients with disseminated disease or those with persistent neutropenia.
The exact mechanisms by which phagocytes are impaired by ketoacidosis, diabetes mellitus, and corticosteroids are yet to be determined. Furthermore, phagocyte dysfunction alone cannot explain the high incidence of mucormycosis among patients with DKA, because the incidence of mucormycosis among these patients is increased more than the incidence of infections caused by other pathogens. Therefore, Mucorales must possess unique virulence traits that enable the organism to exploit the unique state of immunosuppression and physiologic impairment seen in this subset of patients.

How does someone get mucormycosis?

People get mucormycosis through contact with fungal spores in the environment. For example, the lung or sinus forms of the infection can occur after someone inhales the spores from the air. A skin infection can occur after the fungus enters the skin through a scrape, burn, or other type of skin injury.

The skin barrier represents a host defense against cutaneous mucormycosis, as evidenced by the increased risk for developing mucormycosis in persons with disruption of this barrier. The agents of mucormycosis are typically incapable of penetrating intact skin. However, burns, traumatic disruption of the skin, and persistent maceration of skin enables the organism to penetrate into deeper tissues.
These organisms could originate from traumatic implantation of contaminated soil or water (eg, the outbreaks after natural disasters, as was seen after the tsunami in Indonesia in 2004 and after the destructive tornadoes that occurred in Joplin, Missouri, in June 2011). Contaminated surgical dressings and nonsterile adhesive tape have been shown to be the source of primary cutaneous mucormycosis.
Furthermore, mucormycosis can even be introduced through direct access, as was seen with the use of contaminated tongue depressors in neonates or the use of contaminated wooden applicators used to mix drugs given to immunocompromised patients.
These cases illustrate an alarming shift in mucormycosis cases from mainly community-acquired infections to nosocomial infections in susceptible hosts.
MurcomycosisSymptoms of Black Fungus:

In addition to constantly monitoring COVID-19 patients with the above-mentioned ailing conditions who are on treatment, doctors must also keep an eye out for these indications of mucormycosis:

  • Sinusitis, along with clogging of the nasal tract and bloody or blackish mucus emission from the nose
  • Pain on only one side of the face, cheekbones, with lack of sensation and bulging
  • Distinct blackish discolouration on the bridge of the nose
  • Prominent aching in teeth, jawbone, degrading of tooth structures
  • Hazy vision, with objects appearing blurred or in double, with eye pain
  • Abnormal blood clotting or thrombosis of tissues, along with skin injury and damage or necrosis of dermal cells
  • Further deterioration of respiratory functions, with chest pain, excess fluid build-up in lungs i.e. pleural effusion and coughing up blood or haemoptysis

There is a difference in virulence across different species belonging to the order Mucorales, which indicates an array of virulence factors, resulting in aggressive invasive disease in some species and infrequent mortality in others. The following are some of the virulence factors employed by the fungal species responsible for mucormycosis;

Virulence Factors of Mucormycosis

Iron overload: Mucoralean fungi flourish in iron-rich environments as iron is required for cell growth and development as well for different vital processes in the cell. It has been observed that the increased level of iron in the serum plays an important role in predisposing patients to mucormycosis. Fungi take up the iron from the blood by using iron permeases or chelators and reduce them from ferric to the more soluble ferrous form. The ferrous iron generated from the permeases is then captured by a protein complex made up of multicopper oxidase and a ferrous permease. The iron take-up by the fungi is essential for enhancing the growth and development of the fungi and increasing their pathogenicity.

High-affinity iron permease (FTR1) : High-affinity iron permease plays an essential role in iron uptake and transfers within the fungal species, especially in environments with a lack of iron. The FTR1 gene is highly expressed in the species during infection by Rhizopus oryzae, and the knockdown of the gene is known to reduce the virulence of the species. The permeases occur in fungi as a part of a reductive system containing redundant surface reductases involved in the reduction of ferric to the soluble ferrous form.

Rhizoferrin: Rhizoferrin is a siderophore secreted by Rhizopus as a part of the polycarboxylate family. The siderophore is responsible for the supply of iron through a receptor-mediated, energy-dependent process. However, siderophore on its own is inefficient in obtaining iron from the serum and requires the involvement of the organisms’ endogenous siderophores for virulence. In some Mucoralean fungi, the fungus utilizes xenosiderophores like deferoxamine in order to effectively obtain iron from the host.

Calcineurin: Calcineurin is calcium and calmodulin-dependent serine/threonine protein phosphate that is an essential virulence factor in the pathogenesis of Mucorales. It is involved in the transition of Mucor circinelloides from the yeast form to hyphae. The spores of the species are capable of inhibiting phagosomal maturation by macrophages, unlike the yeast cells. Calcineurin is also closely related to protein kinase A activity which is an equally important factor for the pathogenesis of M. circinelloides.

Spore Coat Protein : Spore coat protein is also a virulence factor that is found universally on the spore of all Mucorales. The protein plays an important role as invasions during the pathogenesis of mucormycosis. It also disrupts and damages immune cells and acts as a specific ligand for the GRP78 receptor.

So broadly speaking three things emerge as cause
  1. Possible infection within hospital
  2. Free iron in blood –which we discussed in D-Dimmer
  3. Virus infection and comorbidities.
So possibly best precaution 
  • keep your self safe so that you don’t need to get admitted. the way things are within hospital —lot of edges would be cut.
  • Do not let your blood coagulate —use lot of liquids, increased use of cayenne pepper, ginger, turmeric.
  • Additionally, simple preventive measures go a long way in lowering the chances of acquiring mucormycosis post COVID-19 recovery, such as:

    • Ensuring personal hygiene by bathing and scrubbing the body thoroughly, particularly after returning home from work, working out or visiting neighbours, relatives, friends

    • Wearing face masks and face shields when going to dirty polluted environments such as construction sites. Even maintaining Mask hygiene is must.

    • Making sure to don fully covered clothing of concealed shoes, long pants, long-sleeved shirts and gloves while coming in contact with soil, moss, manure, like in gardening activities

Understanding Rhizopus oryzae & Alternative Interventions by using Essential Oils:

Rhizopus oryzae is a filamentous heterothallic microfungus that occurs as a saprotroph in soil, dung, and rotting vegetation. This species is very similar to Rhizopus stolonifer, but it can be distinguished by its smaller sporangia and air-dispersed sporangiospores.
R. oryzae is used economically in the production of the enzymes, glucoamylase and lipase, in the synthesis of organic acids, and in various fermented foods. The many strains of R. oryzae produce a wide range of enzymes such as carbohydrate digesting enzymes and polymers along with a number of organic acids, ethanol and esters giving it useful properties within the food industries, bio-diesel production, and pharmaceutical industries. It is also an opportunistic pathogen of humans causing mucormycosis.
During our studies with Piper essential oils, we evaluated its activity against Rhizopus oryzae, the main agent of mucormycosis. The main compounds of seven Piper essential oils analyzed were Piper callosum—safrole (53.8%), P. aduncum—dillapiole (76.0%), P. hispidinervum—safrole (91.4%), P. marginatum—propiopiperone (13.2%), P. hispidum—γ-terpinene (30.9%), P. tuberculatum—(E)-caryophyllene (30.1%), and Piper sp.—linalool (14.6%). The minimum inhibitory concentration of Piper essential oils against R. oryzae ranged from 78.12 to >1250 μg/mL.
The best result of total inhibition of biofilm formation was obtained with Piper sp. starting from 4.88 μg/mL. Considering the bioactive potential of EOs against planktonic cells and biofilm formation of R. oryzae could be of great interest for development of antimicrobials for therapeutic use in treatment of fungal infection. ( https://www.hindawi.com/journals/cjidmm/2018/5295619/).
So, using piper oil in food makes sense. Eo’s are strong, they can be blended with edible oil of mustard /sesame /ground nut /coconut oil  and be used/consumed. Piper oil is even otherwise, is also good for human body. So increasing the  use of pepper preferably Cayenne is highly recommended in current times is suggested.

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