Zygomycosis
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Zygomycosis is the broadest term to refer to infections caused by ''bread mold
fungi A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately fr ...
'' of the
zygomycota Zygomycota, or zygote fungi, is a former division or phylum of the kingdom Fungi. The members are now part of two phyla: the Mucoromycota and Zoopagomycota. Approximately 1060 species are known. They are mostly terrestrial in habitat, living ...
phylum. However, because zygomycota has been identified as
polyphyletic A polyphyletic group is an assemblage of organisms or other evolving elements that is of mixed evolutionary origin. The term is often applied to groups that share similar features known as homoplasies, which are explained as a result of conver ...
, and is not included in modern fungal classification systems, the diseases that zygomycosis can refer to are better called by their specific names:
mucormycosis Mucormycosis, also known as black fungus, is a serious fungal infection that comes under fulminant fungal sinusitis, usually in people who are immunocompromised. It is curable only when diagnosed early. Symptoms depend on where in the body the ...
(after
Mucorales The Mucorales is the largest and best studied order of zygomycete fungi. Members of this order are sometimes called pin molds. The term mucormycosis is now preferred for infections caused by molds belonging to the order Mucorales. Systematics ...
),
phycomycosis Phycomycosis is an uncommon condition of the gastrointestinal tract and skin most commonly found in dogs and horses. The condition is caused by a variety of Mold (fungus), molds and fungus, fungi, and individual forms include pythiosis, zygomycos ...
(after
Phycomycetes Phycomycetes is an obsolete polyphyletic taxon for certain fungi with aseptate hyphae. It is used in the Engler system. Asexual reproduction takes place by zoospores(motile) or by Aplanospores(non-motile).These spores are endogenously produced in ...
) and
basidiobolomycosis Basidiobolomycosis is a fungal disease caused by '' Basidiobolus ranarum''. It may appear as one or more painless firm nodules in the skin which becomes purplish with an edge that appears to be slowly growing outwards. A serious but less common t ...
(after
Basidiobolus ''Basidiobolus ranarum'' is a filamentous fungus with worldwide distribution. The fungus was first isolated by Eidam in 1886. It can saprophytically live in the intestines of mainly cold-blooded vertebrates and on decaying fruits and soil. The fu ...
). These rare yet serious and potentially life-threatening fungal infections usually affect the
face The face is the front of an animal's head that features the eyes, nose and mouth, and through which animals express many of their emotions. The face is crucial for human identity, and damage such as scarring or developmental deformities may aff ...
or oropharyngeal (nose and mouth) cavity. Zygomycosis type infections are most often caused by common fungi found in soil and decaying vegetation. While most individuals are exposed to the fungi on a regular basis, those with immune disorders (
immunocompromised Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...
) are more prone to fungal infection. These types of infections are also common after natural disasters, such as tornadoes or earthquakes, where people have open wounds that have become filled with soil or vegetative matter. The condition may affect the
gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
or the
skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different ...
, often beginning in the nose and paranasal
sinuses Paranasal sinuses are a group of four paired air-filled spaces that surround the nasal cavity. The maxillary sinuses are located under the eyes; the frontal sinuses are above the eyes; the ethmoidal sinuses are between the eyes and the spheno ...
. It is one of the most rapidly spreading fungal infections in humans. Treatment consists of prompt and intensive
antifungal drug An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as ...
therapy and
surgery Surgery ''cheirourgikē'' (composed of χείρ, "hand", and ἔργον, "work"), via la, chirurgiae, meaning "hand work". is a medical specialty that uses operative manual and instrumental techniques on a person to investigate or treat a pa ...
to remove the infected tissue.


Causes

Pathogenic zygomycosis is caused by species in two orders:
Mucorales The Mucorales is the largest and best studied order of zygomycete fungi. Members of this order are sometimes called pin molds. The term mucormycosis is now preferred for infections caused by molds belonging to the order Mucorales. Systematics ...
or
Entomophthorales The Entomophthorales are an order of fungi that were previously classified in the class Zygomycetes. A new subdivision, Entomophthoromycotina, has recently been circumscribed for them. Most species of the Entomophthorales are pathogens of ins ...
, with the former causing far more disease than the latter. These diseases are known as "mucormycosis" and "entomophthoramycosis", respectively. * Order
Mucorales The Mucorales is the largest and best studied order of zygomycete fungi. Members of this order are sometimes called pin molds. The term mucormycosis is now preferred for infections caused by molds belonging to the order Mucorales. Systematics ...
(mucormycosis) ** Family
Mucoraceae The Mucoraceae are a family of fungi of the order Mucorales, characterized by having the thallus not segmented or ramified. Pathogenic genera include '' Absidia'', '' Apophysomyces'', ''Mucor'', ''Rhizomucor'', and '' Rhizopus''. According to a ...
*** ''
Absidia ''Absidia'' is a genus of zygote fungi in the family Cunninghamellaceae. ''Absidia'' species are ubiquitous in most environments where they are often associated with warm decaying plant matter, such as compost heaps. Some species in the genus ...
'' ('' Absidia corymbifera'') *** '' Apophysomyces'' ('' Apophysomyces elegans'' and '' Apophysomyces trapeziformis'') *** ''
Mucor ''Mucor'' is a microbial genus of approximately 40 species of molds in the family Mucoraceae. Species are commonly found in soil, digestive systems, plant surfaces, some cheeses like Tomme de Savoie, rotten vegetable matter and iron oxide re ...
'' ('' Mucor indicus'') *** ''
Rhizomucor ''Rhizomucor'' is a genus of fungi in the family Lichtheimiaceae. The widespread genus contains six species. ''Rhizomucor parasiticus'', the species originally selected as the type, is now considered synonymous A synonym is a word, morpheme ...
'' (''
Rhizomucor pusillus ''Rhizomucor pusillus'' is a species of ''Rhizomucor''. It can cause disease in humans. ''R. pusillus'' is a grey mycelium fungi most commonly found in compost piles. Yellow-brown spores grow on a stalk to reproduce more fungal cells. Biology ...
'') *** ''
Rhizopus ''Rhizopus'' is a genus of common saprophytic fungi on plants and specialized parasites on animals. They are found in a wide variety of organic substances, including "mature fruits and vegetables", jellies, syrups, leather, bread, peanuts, and ...
'' (''
Rhizopus oryzae ''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 ...
'') ** Family Cunninghamellaceae *** '' Cunninghamella'' ('' Cunninghamella bertholletiae'') ** Family
Thamnidiaceae The Mucoraceae are a family of fungi of the order Mucorales, characterized by having the thallus not segmented or ramified. Pathogenic genera include '' Absidia'', ''Apophysomyces'', ''Mucor'', ''Rhizomucor'', and ''Rhizopus''. According to a ...
*** '' Cokeromyces'' ('' Cokeromyces recurvatus'') ** Family Saksenaeaceae *** '' Saksenaea'' ('' Saksenaea vasiformis'') ** Family Syncephalastraceae *** '' Syncephalastrum'' ('' Syncephalastrum racemosum'') * Order
Entomophthorales The Entomophthorales are an order of fungi that were previously classified in the class Zygomycetes. A new subdivision, Entomophthoromycotina, has recently been circumscribed for them. Most species of the Entomophthorales are pathogens of ins ...
( entomophthoramycosis) ** Family
Basidiobolaceae The Basidiobolaceae are a family of fungi in the monotypic order Basidiobolales. All fungal cells of this family are exclusively uninucleate and their relatively large nuclei contain a nucleolus, but no heterochromatin.http://zygomycetes.org/inde ...
*** ''
Basidiobolus ''Basidiobolus ranarum'' is a filamentous fungus with worldwide distribution. The fungus was first isolated by Eidam in 1886. It can saprophytically live in the intestines of mainly cold-blooded vertebrates and on decaying fruits and soil. The fu ...
'' (''
Basidiobolus ranarum ''Basidiobolus ranarum'' is a filamentous fungus with worldwide distribution. The fungus was first isolated by Eidam in 1886. It can saprophytically live in the intestines of mainly cold-blooded vertebrates and on decaying fruits and soil. The fu ...
'') ** Family Ancylistaceae *** '' Conidiobolus'' ('' Conidiobolus coronatus/ Conidiobolus incongruus'')


Epidemiology

Zygomycosis has been found in survivors of the
2004 Indian Ocean earthquake and tsunami An earthquake and a tsunami, known as the Boxing Day Tsunami and, by the scientific community, the Sumatra–Andaman earthquake, occurred at 07:58:53 local time ( UTC+7) on 26 December 2004, with an epicentre off the west coast of northern ...
and in survivors of the 2011 Joplin, Missouri tornado.


Symptoms

In the primary cutaneous form, the lesions are usually painful and necrotic, with black eschar, accompanied by a fever. Patients will usually present with a history of poorly controlled diabetes or malignancy. Myocutaneous infections may lead to amputation. Pulmonary tract infections seen with lung transplant patients, who are at high risk for fatal invasive mycoses. Rhinocerebral infection is characterized by paranasal swelling with necrotic tissues. Patient may have hemorrhagic exudates (tissue fluid from lesions tinged with blood) from the nose and eyes as the fungi penetrate through blood vessels and other anatomical structures.


Diagnosis

Diagnosis is done with potassium hydroxide (KOH) preparation in tissue. On light microscopy, there will be broad, ribbon-like septate hyphae with 90 degree angles on branches. KOH wet mount of the black eschar will show aseptate fungal hyphae with right angle branching. Periodic Acid Schiff (PAS) staining will reveal similar broad hyphae in the dermis and cutis. Fungal culture can also confirm the organism.Li H, Hwang SK, Zhou C, Du J, Zhang J. Gangrenous cutaneous mucormycosis caused by Rhizopus oryzae: a case report and review of primary cutaneous mucormycosis in China over Past 20 years. Mycopathologia. 2013 Aug;176(1-2):123-8. doi: 10.1007/s11046-013-9654-z. Epub 2013 Apr 25. . Diagnosis remains difficult due to the lack of laboratory tests as mortality remains high. In 2005, a multiplex PCR test was able to identify five species of Rhizopus and may prove useful as a screening method for visceral mucormycosis in the future.Nagao K, Ota T, Tanikawa A, Takae Y, Mori T, Udagawa S, Nishikawa T. Genetic identification and detection of human pathogenic Rhizopus species, a major mucormycosis agent, by multiplex PCR based on internal transcribed spacer region of rRNA gene. J Dermatol Sci. 2005 Jul;39(1):23-31. doi: 10.1016/j.jdermsci.2005.01.010. Epub 2005 Feb 25. . The clinical approach to diagnosis includes radiologic, where more than ten nodules and pleural effusion are associated to pulmonary forms of the disease. In CT, a reverse halo sign is noted. Direct microscopy and histopathology, and cultures remain the gold standards for diagnoses.Skiada A, Lass-Floerl C, Klimko N, Ibrahim A, Roilides E, Petrikkos G. Challenges in the diagnosis and treatment of mucormycosis. Med Mycol. 2018 Apr 1;56(suppl_1):93-101. doi: 10.1093/mmy/myx101. ; PMCID: PMC6251532. ''Zygomycophyta'' share close clinical and radiological features to Aspergillosis. Invasive procedures such as bronchial endoscopy and lung biopsy may be necessary to confirm pulmonary diagnosis are no validated indirect tests are available. Quantitative polymerase chain reaction to detect serum DNA of the pathogen shows promise.


Treatment

The condition may affect the
gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
or the
skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different ...
In non-trauma cases, it usually begins in the nose and paranasal
sinuses Paranasal sinuses are a group of four paired air-filled spaces that surround the nasal cavity. The maxillary sinuses are located under the eyes; the frontal sinuses are above the eyes; the ethmoidal sinuses are between the eyes and the spheno ...
and is one of the most rapidly spreading fungal infections in humans. Common symptoms include
thrombosis Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (th ...
and tissue
necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated diges ...
. Due to the organisms' rapid growth and invasion, zygomycosis presents with a high fatality rate. Treatment must begin immediately with debridement of the necrotic tissue plus
Amphotericin B Amphotericin B is an antifungal medication used for serious fungal infections and leishmaniasis. The fungal infections it is used to treat include mucormycosis, aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, and cryptococcosis ...
. Complete excision of the infectious tissue may be required as suspected dead tissue must be excised aggressively. Documented case of conservative surgical drainage, intravenous amphotericin B in an insulin-dependent diabetic have proven effective in sino-orbital infection. The prognosis varies vastly depending upon an individual patient's circumstances.


Other animals

The term oomycosis is used to describe
oomycete Oomycota forms a distinct phylogenetic lineage of fungus-like eukaryotic microorganisms, called oomycetes (). They are filamentous and heterotrophic, and can reproduce both sexually and asexually. Sexual reproduction of an oospore is the resul ...
infections. These are more common in animals, notably dogs and
horse The horse (''Equus ferus caballus'') is a domesticated, one-toed, hoofed mammal. It belongs to the taxonomic family Equidae and is one of two extant subspecies of ''Equus ferus''. The horse has evolved over the past 45 to 55 million yea ...
s. These are
heterokont Heterokonts are a group of protists (formally referred to as Heterokonta, Heterokontae or Heterokontophyta). The group is a major line of eukaryotes. Most are algae, ranging from the giant multicellular kelp to the unicellular diatoms, which a ...
s, not true fungi. Types include pythiosis (caused by ''
Pythium insidiosum ''Pythium insidiosum'' is a species of ''Pythium'' and a member of the class oomycota. ''Pythium insidiosum'' is mainly found in standing water and occasionally soil. Unlike most ''Pythium'' species, which are generally pathogens of terrestrial ...
'') and
lagenidiosis Lagenidiosis is a type of infectious disease. The best known species of '' Lagenidium'' is ''Lagenidium giganteum'', a parasite of ''mosquito'' larvae used in biological control of mosquitoes. The disease lagenidiosis in dogs is caused by a new spe ...
. Zygomycosis has been described in a
cat The cat (''Felis catus'') is a domestic species of small carnivorous mammal. It is the only domesticated species in the family Felidae and is commonly referred to as the domestic cat or house cat to distinguish it from the wild members of ...
, where fungal infection of the tracheobronchus led to respiratory disease requiring
euthanasia Euthanasia (from el, εὐθανασία 'good death': εὖ, ''eu'' 'well, good' + θάνατος, ''thanatos'' 'death') is the practice of intentionally ending life to eliminate pain and suffering. Different countries have different eut ...
.


References


External links

{{Mycoses Animal fungal diseases Dog diseases Horse diseases Mycosis-related cutaneous conditions Parasitic fungi Sheep and goat diseases