The document provides information on mucormycosis or black fungus disease. It discusses what mucormycosis is, the fungi that cause it, risk factors, symptoms, types (rhinocerebral, pulmonary, gastrointestinal, cutaneous, disseminated), treatment which involves controlling underlying conditions, antifungal medication like amphotericin B, and sometimes surgery, and prevention measures like controlling diabetes and limiting environmental exposure to fungal spores. Mucormycosis is a serious fungal infection caused by exposure to fungal spores that can affect the sinuses, lungs or other organs and has a high mortality rate, especially in immunocompromised individuals.

1. MUCORMYCOSIS/BLACK FUNGUS
DISEASE

2. WHAT IS MUCORMYCOSIS ?
Mucormycosis is an infection caused by several species of
filamentous molds belonging to the order Mucorales.
The infections usually occur in immunocompromised individuals
with one or more underlying conditions.
The fungi responsible for these infections are found in different
environmental niches like soil, decaying vegetables, bread, and
even dust.
Some of the risk factors associated with mucormycosis include
conditions like uncontrolled diabetes mellitus, bone marrow
transplant, neutropenia, trauma, burns, and hematologic
disorders.

3. CONTD..
Studies related to mucormycosis have increased over the years due to
the severity of these infections, with a high rate of mortality.
Some of the species belonging to the order Mucorales are Rhizopus,
Mucor, Rhizomucor, Apophysomyces, etc. Rhizopus is the most
common species associated with mucormycosis, closely followed by
Mucor and Lichtheimia.
The infections can be characterized by different clinical
manifestations depending on the site of infection and the severity.
Mucormycosis has also been associated with molds from the order
Entomophthorales; however, these infections are not angioinvasive
and do not disseminate. Such molds result in chronic subcutaneous
infections even in immunocompetent hosts.

4. TAXONOMY
Kingdom: Fungi
Division: Zygomycota
Class: Mucormycotina
Order: Mucorales
Family: Mucoraceae
Genus: Mucor

5. HABITAT
The fungal species belonging to the order Mucorales can be found
throughout the environment in different sources ranging from soil to
vegetables.
Even though these species are ubiquitous in distribution, they are
predominantly saprobic soil organisms.
The fungi can be commonly found in soil than in air as these exist in
the form of spores in order to protect themselves as well as to assist
the process of dispersal. The occurrence thus is more prevalent in
tropical areas.
The dispersal and occurrence of these species are more common
during summer than in winter as the fungal spores thrive in dry and
arid conditions.

6. CONTD..
Besides, some of these fungi can also occur in decaying matter
like decaying vegetables and fruits as these are good sources of
carbohydrates that are essential for the growth and survival of
the species.
Mucoralean fungi usually reproduce anamorphically via non-
motile sporangiospores released from different sporangia.
Some of the Mucoralean fungi can also occur as parasites of
plants, fungi, and animals, resulting in different forms of
diseases.

8. ETIOLOGY
 The fungal species that are most frequently isolated from patients
with Mucormycosis are Apophysomyces, Cunninghamella,
Lichtheimia, Mucor, Rhizopus, and Rhizomucor.
 The etiology of these infections differs considerably in different
countries, but Rhizopus spp is the most common cause of these
infections in most parts of the world.
 These species exist as spores and thrive in dry, humid, and arid
conditions. These transmit through the air and result in mild to severe
infections in immunocompromised individuals.
 The species present in the order Mucorales display only a small
number of distinguishable morphological characteristics that can be
used to distinguish between themselves.

9. CONTD..
 Most of these species are differentiated based on characteristics
like structure, size, and shape of the sporangia, color and state of the
spores, and the mycelium.
 The Mucoralean fungi are defined by usually abundant and rapidly
growing mycelium and other anamorph structures.
 The mycelium is unsepted or irregularly septed, and the anamorphic
sporangiospores produce multi-spored sporangia.
 Structures like chlamydospores, arthrospores, and yeast cells are rare in
these species. The sporangia consist of the variously shaped columella.
 Some species might exhibit appendages that enable them to switch
between the filamentous multicellular state and the yeast-like state.

10. MODE OF TRANSMISSION
• Mucormycosis is acquired by immunocompromised individuals, mostly
by the inhalation of fungal spores from the environment.
• The primary mode of transmission of Mucorales is the inhalation of
sporangiospores. Other modes of transmission include ingestion of the
spore or inoculation of conidia from wounds or trauma.
• Nosocomial outbreaks of infections can also occur; however, these are
quite rare. Nosocomial infections are associated with contaminated
bandages, medical equipment, and ventilation.
• The mode of transmission of the fungi from one individual to the other
depends on the site of infection and the severity of infection.
• Rhinocerebral mucormycosis transmits mostly via the inhalation of
spores or droplets, whereas cutaneous mucormycosis transmits via
close personal contact.

11. VIRULENCE FACTORS
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.
a. Iron overload
b. High-affinity iron permease (FTR1)
c. Rhizoferrin
d. Calcineurin
e. Spore coat protein

12. PATHOGENESIS OF
MYCORMYCOSIS
The pathogenesis of mucormycosis begins with the inhalation or
ingestion of spores from the environment.
The entry of the spores into healthy individuals results in
phagocytosis of the spores with the help of polymorphonuclear
phagocytes.
The persistence of the fungi and their growth is facilitated by defects
in the phagocytic activity of the immune cells.
Conditions like hyperglycemia and acidosis affect chemotaxis and
phagocytic killing by the immune cells.
 Fungi like Rhizopus secrete the enzyme ketone reductase that
supports the growth of fungi in acidic and glucose-rich environments
like ketoacidosis.

13. The increased virulence in the fungal species results in inherent
resistance in these species to human phagocytes.
Similarly, iron metabolism also plays an important role in the
pathogenesis of mucormycosis. Different factors in the fungal
species like the iron permeases, rhizoferrin, etc., help in the
transition of ferric into soluble ferrous.
The presence of iron in the serum further supports the growth and
survival of the species in the human body.
The fungi then slowly make their way into the bloodstream by
invading blood vessels with resultant thrombosis and tissue
necrosis.
The host-pathogen interaction further results in extensive
angioinvasion with ischemic necrosis and tissue damage.
The movement of the organisms through endothelial cells and the
extracellular matrix is the most critical step in the pathogenesis of
fungal species like R. Oryzae.

15. TYPES
Rhinocerebral (Sinus and Brain) mucormycosis:
Rhinocerebral mucormycosis is a condition caused by filamentous fungi of
the order Mucorales, which affect organs like the paranasal sinuses, nose,
and brain.
The disease is most acute, but it can become chronic as the fungus grows
rapidly and aggressively.
Rhinocerebral mucormycosis is the most common form of mucormycosis,
and the prevalence of the infections depends on the occurrence of the
different high-risk populations.
The infection begins in the nasal cavity and slowly moves to the adjacent
paranasal sinuses. The fungi then attached themselves to the surface of the
sinus and began reproducing as the humid condition of the nose facilitates
growth and invasion of the organism.
The initial condition of the infection is associated with the formation of the
fungal ball in the maxillary sinus with no bone erosion.

16. The condition proliferates further depending on the duration of
infection, host immunity, and severity of the condition.
The progression of the diseases continues as a result of different
virulence factors. It is initiated by the invasion of blood vessels and
damage to the endothelial cells resulting in ischemia and tissue
necrosis.
The invasion of the brain and orbits of the brain is the result of the
invasion of the sphenopalatine and internal maxillary arteries.
Rhinocerebral mucormycosis occurs more commonly in diabetic
patients with diabetic ketoacidosis and hyperglycemia.
The early diagnosis of the infection is impeded by the nonspecific
symptoms of the disease. Commonly observed symptoms include one-
sided headache behind the eyes and lethargy.
It is then followed by facial pain, numbness, nasal discharge, and
sinusitis, along with convulsions, altered mental condition, and gait.

17. Pulmonary (Lung) mucormycosis:
Pulmonary mucormycosis is an uncommon form of mucormycosis but
can result in life-threatening opportunistic infections.
It is the second most common mucormycosis infection accounting for
about 25% of total mucormycosis infections.
The infection is more frequent in immunocompromised patients with
transplants and hematological malignancies.
Pulmonary mucormycosis has a high mortality rate of 40-70%,
especially in cases with rapid local progression and angioinvasion.
The infection proceeds from the entry of the organism via inhalation.
The organism reaches the lung spaces where it adheres to the
endothelial cells to result in tissue damage.
The extent of damage and progression of the infection depends on the
immune status of the individual and the underlying conditions.

18. Gastrointestinal mucormycosis:
Gastrointestinal mucormycosis is very rare and is observed only
in about 2 to 11% of the total cases of mucormycosis.
The organs involved in the infection are the stomach and
intestine, but in some cases, the infection can spread to other
regions of the intestinal tract.
The infections are mostly mild, but in some cases, these can be
fatal. The infection begins with the ingestion of spores with food
or other substances that finally make way into the
gastrointestinal tract.
Aggressive antifungal treatments and medical therapy with
surgeries can be used as a method of treatment.

19. Cutaneous (Skin) mucormycosis:
Cutaneous mucormycosis is also a form of mucormycosis either as a
localized infection or dissemination disease.
Cutaneous mucormycosis results from the entry of the pathogen
through trauma or cuts on the skin as a result of surgery, natural
disaster, or inoculation of soil and other contaminated sources.
The infection can spread quite rapidly on the skin to inner layers like
the subcutaneous layer, fascia, and bone.
The predominant species involved in cutaneous mucormycosis
are Apophysomyces and Saksenaea, both of which are common soil
saprophytes.
Cutaneous mucormycosis can be classified as primary and secondary
mucormycosis, where the primary infections include infections where
the organism infects the individual via direct inoculation. Secondary
mucormycosis involves the dissemination of organisms from other
locations, commonly a rhinocerebral infection.

20. The most commonly affected areas in the case of cutaneous
mucormycosis are legs and arms, including other rare cases in the
scalp, face, back, thorax, breast, neck, and groin.
Primary infections are characterized by lesions that are indurated
plaques that eventually become erythematous.
Other manifestations include tender nodules, swollen and scaly
plaques with purpuric lesions.
Primary infections can be nosocomial infections, in which case the
erythema and tenderness rapidly progress to necrosis.
Secondary infections result from the spread of rhinocerebral infection,
and these are more common than primary infections.
The infection begins with sinusitis which then progresses with the
formation of a necrotic eschar.
Other symptoms include fever, periorbital cellulitis, edema, and
proptosis with later intracranial involvement.

21. Disseminated mucormycosis
Disseminated mucormycosis is the rarest form of mucormycosis that is usually
only observed in neutropenic patients with hematologic tumors or post-
transplant patients.
The high rate of dissemination associated with mucormycosis is due to the
tendency of invading endothelial cells within the vascular system.
Dissemination of infections can occur in organs like the lung, pancreas, brain,
and spleen, which mild to severe infections in all or some of the regions.
The condition only occurs in severely immunocompromised individuals who
have received deferoxamine.
The symptoms and presentations associated with disseminated mucormycosis
consist of nonspecific manifestations which result in delayed diagnosis and
further invasion.
The direct inoculation of the fungi is a common mode of transmission where
the fungi can infect cutaneous, subcutaneous, fat muscles, and skeletal tissues.

22. HOW MYCORMYCOSIS SPREAD?
Mucormycosis starts as a skin infection in the air pockets
behind our eyes, nose, cheekbones, and in the spaces
between our eyes and teeth. It then spreads to the skin,
lungs, and possibly the brain. It causes nose
discoloration or blackening, blurred or double vision,
chest pain, breathing problems, and bloody coughing.

23. SYMPTOMS
rhinocerebral (sinus and brain) mucormycosis include:
I. One-sided facial swelling
II. Headache
III. Nasal or sinus congestion
IV. Black lesions on nasal bridge or upper inside of mouth that quickly
become more severe
V. Fever
pulmonary (lung) mucormycosis include:
I. Fever
II. Cough
III. Chest pain
IV. Shortness of breath

24. Cutaneous (skin) mucormycosis can look like blisters or ulcers,
and the infected area may turn black. Other symptoms include
pain, warmth, excessive redness, or swelling around a wound.
gastrointestinal mucormycosis include:
• Abdominal pain
• Nausea and vomiting
• Gastrointestinal bleeding
Disseminated mucormycosis typically occurs in people who are
already sick from other medical conditions, so it can be difficult to
know which symptoms are related to mucormycosis. Patients with
disseminated infection in the brain can develop mental status
changes or coma.

25. TREATMENT
The successful treatment of mucormycosis is based on a multi-step
approach which requires reversal of underlying conditions, early
administration of antifungal agents at optimal dosages, and removal of
all infected tissues.
In patients with uncontrolled diabetes and suspected mucormycosis,
rapid correction of metabolic abnormalities is a must.
The use of corticosteroids and other immunosuppressive drugs should be
tapered to the lowest dose possible.
The success of the treatment of mucormycosis depends on the early
diagnosis of the disease with prompt initiation of therapeutic
interventions.
Mucorales can be resistant to most antifungal agents like voriconazole,
but Amphotericin B is the most effective drug for most Mucorales.

26. The medicinal therapy has to be introduced immediately once the
infection is suspected due to the potential for the rapid spread of the
infection.
The optimal dose for these antifungal drugs is still in question; however,
some guidelines have been proposed to provide the appropriate dose and
concentration of these drugs.
The prevalence of intravenous and tablet forms of these drugs has
increased bioavailability and drug exposure.
Other forms of treatment include surgeries when needed. Removal of not
just the necrotic tissues but also surrounding infected healthy tissues
might be required.
Surgery is often required in rhinocerebral mucormycosis and soft tissue
infections. Surgeries might also be helpful in the single localized
pulmonary lesion.
Other forms of medical therapy include the use of hyperbaric oxygen to
prepare a more oxygen-rich environment and the administration of
cytokines along with antifungal agents.

27. PREVENTION AND CONTROL
MEASURES
1) The high mortality rate of these infections indicates the need for early
intervention with immunocompromised individuals.
2) It is important that the patients are aware of the infections and their
presentations so that they can make an early visit to the hospital.
3) Prevention and control of these infections are based on the early
diagnosis of the disease and the maintenance of a proper immune
system.
4) Individuals at risk with different underlying conditions should be careful
about any possible symptoms and other conditions.
5) It has been recommended that the patients take appropriate drugs
assigned for their underlying conditions in order to maintain their
health.
6) The control of the disease can also be made by the use of masks in areas
that might contain the spores the causative agents.

28. How Mucormysosis is related to COVID-19, Why corona
patients are at more risk of Black Fungal Infection ?
 Mucormycosis has been increasingly observed as a form of secondary
fungal infection in COVID 19 patients.
 The most common form of mucormycosis in COVID 19 patients is
pulmonary mucormycosis, closely followed by rhinocerebral
mucormycosis.
 The incidence of mucormycosis with COVID 19 isn’t unusual as the
disease tends to affect the immune status of the patients, resulting in
increased chances of mucormycosis.
 Similarly, glucocorticoids and remdesivir are some of the only drugs
that have been beneficial in COVID 19; however, the use of
glucocorticoids can increase the risk of secondary infections.
 The use of concurrent immunomodulatory drugs and the immune
dysregulation as a result of the viral infection further add to the
increased risk of the infections.

29. BY
KEERTHANA K