Mucormycosis

Generally, mucormycosis is classified into five main types according to the part of the body affected. A sixth type has been described as mucormycosis of the kidney, or miscellaneous, i.e., mucormycosis at other sites, although less commonly affected. • Sinuses and brain (rhinocerebral); most common in people with poorly controlled diabetes and in people who have had a kidney transplant. • Lungs (pulmonary); the most common type of mucormycosis in people with cancer and in people who have had an organ transplant or a stem cell transplant. • Stomach and intestine (gastrointestinal); more common among young, premature, and low birth weight infants, who have had antibiotics, surgery, or medications that lower the body's ability to fight infection. • Skin (cutaneous); after a burn, or another skin injury, in people with leukaemia, poorly-controlled diabetes, graft-versus-host disease, HIV and intravenous drug use. • Widespread (disseminated); when the infection spreads to other organs via the blood. ==Signs and symptoms==

Signs and symptoms of mucormycosis depend on the location of the infection in the body. The face may look swollen on one side, with rapidly progressing "black lesions" across the nose or upper inside of mouth. One eye may look swollen and bulging, and vision may be blurred. Fever, cough, chest pain, and difficulty breathing, or coughing up blood, can occur when the lungs are involved. Affected skin may appear as a dusky reddish tender patch with a darkening centre due to tissue death. There may be an ulcer, and it can be very painful. ==Cause==

Mucormycosis is a fungal infection caused by fungi in the order Mucorales. Most fatal infections are caused by Rhizopus oryzae. It is less likely due to Lichtheimia, and rarely due to Apophysomyces. Others include Cunninghamella, Mortierella, and Saksenaea. The fungal spores are present in the environment. Once inside the body, the fungus grows branch-like filaments which invade blood vessels, causing clots to form and surrounding tissues to die. One hypothesis suggests that the spread of fungal spores in India could be due to fumes generated from the burning of Mucorales-rich biomass, like cow dung and crop stubble. Risk factors Predisposing factors for mucormycosis include immune deficiencies, a low neutrophil count, and metabolic acidosis. ==Mechanism==

Most people are frequently exposed to Mucorales without developing the disease. Mucormycosis is generally spread by breathing in, eating food contaminated by, or getting spores of molds of the Mucorales type in an open wound. It is not transmitted between people. The precise mechanism by which people with diabetes mellitus become susceptible is unclear. In vivo, a high sugar level alone does not permit the growth of the fungus, but acidosis alone does. People with high sugar levels frequently have high iron levels, also known to be a risk factor for developing mucormycosis. In people taking deferoxamine, the iron removed is captured by siderophores on Rhizopus species, which then use the iron to grow. ==Diagnosis==

No blood test can confirm the diagnosis. Signs on chest CT scans, such as nodules, cavities, halo signs, pleural effusion and wedge-shaped shadows, showing invasion of blood vessels, may suggest a fungal infection, but do not confirm mucormycosis. Culture from biopsy samples does not always give a result as the organism is very fragile. Other Matrix-assisted laser desorption/ionization may be used to identify the species. ==Prevention==

Preventive measures include wearing a face mask in dusty areas, washing hands, avoiding direct contact with water-damaged buildings, and protecting skin, feet, and hands where there is exposure to soil or manure, such as gardening or certain outdoor work. In high-risk groups, such as organ transplant patients, antifungal drugs may be given as a preventative. ==Treatment==

Treatment involves a combination of antifungal drugs, surgically removing infecting tissue, and correcting underlying medical problems, such as diabetic ketoacidosis. It may need to be continued for longer. Surgery Surgery can be very drastic, and, in some cases of disease involving the nasal cavity and the brain, removal of infected brain tissue may be required. Removal of the palate, nasal cavity, or eye structures can be very disfiguring. Treatment also requires correcting sugar levels and improving neutrophil counts. Hyperbaric oxygen may be considered as an adjunctive therapy because higher oxygen pressure increases the ability of neutrophils to kill the fungus. The efficacy of this therapy is uncertain. == Prognosis ==

It tends to progress rapidly and is fatal in about half of sinus cases, two-thirds of lung cases, and almost all cases of the widespread type. Skin involvement carries the lowest mortality rate of around 15%. Possible complications of mucormycosis include the partial loss of neurological function, blindness, and clotting of blood vessels in the brain or lung. As treatment usually requires extensive and often disfiguring facial surgery, the effect on life after surviving, particularly sinus and brain involvement, is significant. ==Epidemiology==

The true incidence and prevalence of mucormycosis may be higher than appears. Mucormycosis is rare, affecting fewer than 1.7 people per million population each year in San Francisco. It is around 80 times more prevalent in India, where in 2020 it was estimated that there were around 0.14 cases per 1000 population, Causative fungi are highly dependent on location. Apophysomyces variabilis has its highest prevalence in Asia and Lichtheimia in Europe. Diabetes is the main underlying disease in low and middle-income countries, whereas blood cancers and organ transplantation are the more common underlying problems in developed countries. Due to its rapidly growing number of cases some Indian state governments have declared it an epidemic. One treatment was a daily injection for eight weeks of anti-fungal intravenous injection of amphotericin B which was in short supply. The injection could be standard amphotericin B deoxycholate or the liposomal form. The liposomal form cost more but it was considered "safer, more effective and [with] lesser side effects". The major obstacle of using antifungal drugs in black fungus is the lack of clinical trials. Recurrence of mucormycosis during COVID-19 second wave in India Pre-COVID mucormycosis was a very rare infection, even in India. It is so rare that an ENT (ear, nose, throat) doctor would often not witness a case during their education. So, the documentation available on the treatment of mucormycosis is limited. There used to be a few mucormycosis expert ENT surgeons for millions of people before the pandemic. The sudden rise in mucormycosis cases has left a majority of ENT doctors with no option but to accept mucormycosis cases, as the expert doctors were very much occupied, and the patient would die if left untreated. The majority of the ENT doctors had to manage with minimal or no experience on mucormycosis, which has led to the recurrence of mucormycosis in the patients they treated. When a highly experienced doctor in mucormycosis treats a patient even if he cannot guarantee that the individual is completely cured and will not have a relapse of mucormycosis; an inexperienced ENT surgeon will have a high number of patients with recurrence due to which there were many recurrent cases of mucormycosis although it did not get the limelight of media or the Indian Government. ==History==

The first described case of mucormycosis was possibly one described by Friedrich Küchenmeister in 1855. Fürbringer first described the disease in the lungs in 1876. In 1884, Lichtheim established the development of the disease in rabbits and described two species; Mucor corymbifera and Mucor rhizopodiformis, later known as Lichtheimia and Rhizopus, respectively. Until the latter half of the 20th century, the only available treatment was potassium iodide. In a review of cases involving the lungs diagnosed following flexible bronchoscopy between 1970 and 2000, survival was found to be better in those who received combined surgery and medical treatment, mostly with amphotericin B. COVID-19–associated mucormycosis COVID-19-associated mucormycosis cases were reported during the first and second(delta) waves, with the maximum number of cases in the delta wave. One review in early 2021 relating to the association of mucormycosis and COVID-19 reported eight cases of mucormycosis; three from the U.S., two from India, and one case each from Brazil, Italy, and the UK. In May 2021, the BBC reported increased cases in India. Nepal, Bangladesh, Russia, Uruguay, Paraguay, Chile, Egypt, Iran, Brazil, Iraq, Mexico, Honduras, Argentina Oman, and Afghanistan. One explanation for why the association has surfaced remarkably in India is high rates of COVID-19 infection and high rates of diabetes. In May 2021, the Indian Council of Medical Research issued guidelines for recognising and treating COVID-19–associated mucormycosis. In India, as of 28 June 2021, over 40,845 people have been confirmed to have mucormycosis, and 3,129 have died. From these cases, 85.5% (34,940) had a history of being infected with SARS-CoV-2 and 52.69% (21,523) were on steroids, also 64.11% (26,187) had diabetes. ==Society and culture==

The disease has been reported in natural disasters and catastrophes; 2004 Indian Ocean tsunami and the 2011 Missouri tornado. The first international congress on mucormycosis was held in Chicago in 2010, set up by the Hank Schueuler 41 & 9 Foundation, which was established in 2008 for the research of children with leukaemia and fungal infections. In 2014, details of a lethal mucormycosis outbreak that occurred in 2008 emerged after television and newspaper reports responded to an article in a pediatric medical journal. Contaminated hospital linen was found to be spreading the infection. A 2018 study found many freshly laundered hospital linens delivered to U.S. transplant hospitals were contaminated with Mucorales. Another study attributed an outbreak of hospital-acquired mucormycosis to a laundry facility supplying linens contaminated with Mucorales. The outbreak stopped when major changes were made at the laundry facility. The authors raised concerns about the regulation of healthcare linens. ==Other animals==

Mucormycosis in other animals is similar, in terms of frequency and types, to that in people. Cases have been described in cats, dogs, cows, horses, dolphins, bison, and seals. == References ==