Mucormycosis

Source: Wikipedia, the free encyclopedia.

Mucormycosis
Other namesZygomycosis,
isavuconazole, posaconazole[8]
PrognosisPoor[9]
FrequencyRare[8]

Mucormycosis, also known as black fungus,

lungs, stomach and intestines, and skin.[6]
The fatality rate is about 54%.

It is spread by spores of

immunosuppressants, and to a lesser extent in HIV/AIDS.[7][9]

Diagnosis is by

biopsy and culture, with medical imaging to help determine the extent of disease.[5] It may appear similar to aspergillosis.[17] Treatment is generally with amphotericin B and surgical debridement.[8] Preventive measures include wearing a face mask in dusty areas, avoiding contact with water-damaged buildings, and protecting the skin from exposure to soil such as when gardening or certain outdoor work.[10] It tends to progress rapidly and is fatal in about half of sinus cases and almost all cases of the widespread type.[2][18]

Mucormycosis is usually rare,

premature infants.[8] The first known case of mucormycosis was possibly the one described by Friedrich Küchenmeister in 1855.[1] The disease has been reported in natural disasters; 2004 Indian Ocean tsunami and the 2011 Joplin tornado.[20] During the COVID-19 pandemic, an association between mucormycosis and COVID-19 has been reported. This association is thought to relate to reduced immune function during the course of the illness and may also be related to glucocorticoid therapy for COVID-19.[4][21] A rise in cases was particularly noted in India.[22]

Classification

Generally, mucormycosis is classified into five main types according to the part of the body affected.[14][23] A sixth type has been described as mucormycosis of the kidney,[1] or miscellaneous, i.e., mucormycosis at other sites, although less commonly affected.[23]

Signs and symptoms

Early stages of periorbital mucormycosis

Signs and symptoms of mucormycosis depend on the location in the body of the infection.[6] Infection usually begins in the mouth or nose and enters the central nervous system via the eyes.[5]

If the fungal infection begins in the nose or sinus and extends to brain, symptoms and signs may include one-sided eye pain or

bulging, and vision may be blurred.[6][24][25]

Fever, cough, chest pain, and

difficulty breathing, or coughing up blood, can occur when the lungs are involved.[6] A stomach ache, nausea, vomiting and bleeding can occur when the gastrointestinal tract is involved.[6][26] Affected skin may appear as a dusky reddish tender patch with a darkening centre due to tissue death.[12] There may be an ulcer, and it can be very painful.[5][7][12]

Invasion of the

blood vessels can result in thrombosis and subsequent death of surrounding tissue due to a loss of blood supply.[7] Widespread (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. People with disseminated infection in the brain can develop changes in mental status or lapse into a coma.[27][28]

Cause

Mucormycosis is a

fungal infection caused by fungi in the order Mucorales.[5] In most cases it is due to an invasion of the genera Rhizopus and Mucor, common bread molds.[29] Most fatal infections are caused by Rhizopus oryzae.[17] It is less likely due to Lichtheimia, and rarely due to Apophysomyces.[30] Others include Cunninghamella, Mortierella, and Saksenaea.[5][31]

The fungal spores are present in the environment, can be found on items such as moldy bread and fruit, and are breathed in frequently, but cause disease only in some people.

branch-like filaments which invade blood vessels, causing clots to form and surrounding tissues to die.[5] Other reported causes include contaminated wound dressings.[5] Mucormycosis has been reported following the use of elastoplast and the use of tongue depressors for holding in place intravenous catheters.[5] Outbreaks have also been linked to hospital bed sheets, negative-pressure rooms, water leaks, poor ventilation, contaminated medical equipment, and building works.[32] 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.[33]

Risk factors

Predisposing factors for mucormycosis include

immunosuppressive therapy.[31][10] Other risk factors include tuberculosis (TB),[20] deferoxamine[1] and to a lesser extent HIV/AIDS.[1][7] Cases of mucormycosis in fit and healthy people are less common.[7]

Corticosteroids are commonly used in the treatment of COVID-19 and reduce damage caused by the body's own immune response to the virus. They are immunosuppressant and increase blood sugar levels in both diabetic and non-diabetic patients. It is thought that both these effects may contribute to cases of mucormycosis.[34][35][21]

Mechanism

Most people are frequently exposed to Mucorales without developing the disease.[31] Mucormycosis is generally spread by breathing in, eating food contaminated by, or getting spores of molds of the Mucorales type in an open wound.[15] It is not transmitted between people.[14]

The precise mechanism by which diabetics become susceptible is unclear. In vivo, a high sugar level alone does not permit the growth of the fungus, but acidosis alone does.[1][7] People with high sugar levels frequently have high iron levels, also known to be a risk factor for developing mucormycosis.[7] In people taking deferoxamine, the iron removed is captured by siderophores on Rhizopus species, which then use the iron to grow.[36]

Diagnosis

There is no blood test that can confirm the diagnosis.

electrolytes.[37] Endoscopic examination of the nasal passages may be needed.[37]

Imaging

MRI may also be useful.[39] Currently,[when?] MRI with gadolinium contrast is the investigation of choice in rhinoorbito-cerebral mucormycosis.[citation needed
]

Culture and biopsy

To confirm the diagnosis, biopsy samples can be cultured.[13][37] Culture from biopsy samples does not always give a result as the organism is very fragile.[17] Microscopy can usually determine the genus and sometimes the species, but may require an expert mycologist.[17] The appearance of the fungus under the microscope can vary but generally shows wide (10–20 micron), ribbon-like filaments that generally do not have septa and that—unlike in aspergillosis—branch at right angles, resembling antlers of a moose, which may be seen to be invading blood vessels.[12][37]

  • Ribbon-like hyphae which branch at 90°
    Ribbon-like hyphae which branch at 90°
  • Hyphae in blood vessel
    Hyphae in blood vessel
  • Mature sporangium of a Mucor[40]
    Mature sporangium of a Mucor[40]

Other

blood sample from an artery may be useful to assess for metabolic acidosis.[37]

Differential diagnosis

Other filamentous fungi may however look similar.

bowel obstruction, ecthyma gangrenosum, lung cancer, clot in lungs, sinusitis, tuberculosis and fusariosis.[42]

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.

antifungal drugs may be given as a preventative.[10]

Treatment

Treatment involves a combination of

antifungal drugs, surgically removing infecting tissue and correcting underlying medical problems, such as diabetic ketoacidosis.[1]

Medication

Once mucormycosis is suspected,

Isavuconazole and Posaconazole are alternatives.[20][44]

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.[26] Sometimes more than one operation is required.[31]

Other considerations

The disease must be monitored carefully for any signs of reemergence.

neutrophils to kill the fungus.[7] The efficacy of this therapy is uncertain.[32]

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.

blindness, and clotting of blood vessels in the brain or lung.[26]

As treatment usually requires extensive and often disfiguring facial surgery, the

effect on life after surviving, particularly sinus and brain involvement, is significant.[31]

Epidemiology

The true incidence and prevalence of mucormycosis may be higher than appears.[36] Mucormycosis is rare, affecting fewer than 1.7 people per million population each year in San Francisco.[8][46] It is around 80 times more prevalent in India, where it is estimated that there are around 0.14 cases per 1000 population,[19] and where its incidence has been rising.[47] Causative fungi are highly dependent on location. Apophysomyces variabilis has its highest prevalence in Asia and Lichtheimia spp. in Europe.[20] It is the third most common serious fungal infection to infect people, after aspergillosis and candidiasis.[48]

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.[19] As new immunomodulating drugs and diagnostic tests are developed, the statistics for mucormycosis have been changing.[19] In addition, the figures change as new genera and species are identified, and new risk factors reported such as tuberculosis and kidney problems.[19]

COVID-19–associated mucormycosis

  India
  Countries where COVID-associated mucormycosis has been detected as of June 2021

During the

amphotericin B deoxycholate or the liposomal form. The liposomal form cost more but it was considered "safer, more effective and [with] lesser side effects".§[51] The major obstacle of using antifungal drugs in black fungus is the lack of clinical trials.[28]

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 not witness often a case during their university time. So, the documentation available on the treatment of mucormycosis is limited. In fact, there used to be a couple of mucormycosis expert ENT surgeons for millions of people pre-pandemic. The sudden rise in mucormycosis cases has left a majority of the 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, this has led to the recurrence of mucormycosis in the patients they treated. When a highly experienced doctor in mucormycosis treats a patient even he cannot guarantee that the individual is completely cured and will not have a relapse of mucormycosis; an inexperienced ENT surgeon will definitely 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 case of mucormycosis was possibly one described by Friedrich Küchenmeister in 1855.[1] Fürbringer first described the disease in the lungs in 1876.[52] 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.[1] In 1943, its association with poorly controlled diabetes was reported in three cases with severe sinus, brain and eye involvement.[1]

In 1953,

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.[52]

Naming

Arnold Paltauf coined the term "Mycosis Mucorina" in 1885, after describing a case with systemic symptoms involving the sinus, brain and gastrointestinal tract, following which the term "mucormycosis" became popular.

Fungi. The former phylum Zygomycota included Mucorales, Entomophthorales, and others. Mucormycosis describes infections caused by fungi of the order Mucorales.[41]

COVID-19–associated mucormycosis

COVID-19 associated mucormycosis cases were reported during first and second(delta) wave, with maximum number of cases in delta wave.[11] There were no cases reported during the Omicron wave.[11] A number of cases of mucormycosis, aspergillosis, and candidiasis, linked to immunosuppressive treatment for COVID-19 were reported during the COVID-19 pandemic in India in 2020 and 2021.[4][39] 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.[21] The most common underlying medical condition was diabetes.[21] Most had been in hospital with severe breathing problems due to COVID-19, had recovered, and developed mucormycosis 10–14 days following treatment for COVID-19. Five had abnormal kidney function tests, three involved the sinus, eye and brain, three the lungs, one the gastrointestinal tract, and in one the disease was widespread.[21] In two of the seven deaths, the diagnosis of mucormycosis was made at postmortem.[21] That three had no traditional risk factors led the authors to question the use of steroids and immunosuppressive drugs.[21] Although, there were cases without diabetes or use of immunosuppressive drugs. There were cases reported even in children.[11] In May 2021, the BBC reported increased cases in India.[34] In a review of COVID-19-related eye problems, mucormycosis affecting the eyes was reported to occur up to several weeks following recovery from COVID-19.[39] It was observed that people with COVID-19 were recovering from mucormycosis a bit easily when compared to non-COVID-19 patients. This is because unlike non-COVID-19 patients with severe diabetes, cancer or HIV, the recovery time required for the main cause of immune suppression is temporary.[11]

Other countries affected included Pakistan,[54] Nepal,[55] Bangladesh,[56] Russia,[57] Uruguay,[58] Paraguay,[59] Chile,[60] Egypt,[61] Iran,[62] Brazil,[63] Iraq,[64] Mexico,[65] Honduras,[66] Argentina[67] Oman,[68] and Afghanistan.[69] One explanation for why the association has surfaced remarkably in India is high rates of COVID-19 infection and high rates of diabetes.[70] In May 2021, the Indian Council of Medical Research issued guidelines for recognising and treating COVID-19–associated mucormycosis.[71] 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.[72][73]

Society and culture

The disease has been reported in natural disasters and catastrophes;

necrotizing soft-tissue infection requiring antifungal treatment or surgical debridement in a person injured in the tornado, 2) with illness onset on or after May 22 and 3) positive fungal culture or histopathology and genetic sequencing consistent with a mucormycete. No additional cases related to that outbreak were reported after June 17. Ten people required admission to an intensive-care unit, and five died.[75][76]

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.[77][78] 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.[79] 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 on the regulation of healthcare linens.[80]

Other animals

Mucormycosis in other animals is similar, in terms of frequency and types, to that in people.[81] Cases have been described in cats, dogs, cows, horses, dolphins, bison, and seals.[81]

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Further reading

External links

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