MYCORMYCOSIS.pptx

BLACK FUNGUS

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.

7. 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.

8. 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.

9. 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.

10. 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. Iron overload High-affinity iron permease (FTR1) Rhizoferrin  Calcineurin Spore coat protein 

11. 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.

12. 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 .

13. 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.

14. 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.

15. 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.

16. 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.

17. 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.

18. 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.

19. 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.

20. 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.

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

22. 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.

23. 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.

24. 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.

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

26. 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.

27. BY KEERTHANA K