Fungal diseases

Question 1

What are the typical features of fungi?

Answer 1

These are large and complex organisms when compared to bacteria, they are eukaryotes and can from multi-cellualr, functionally differentiated structure
The cells contain cell walls but no chloroplasts
They are tolerant to salt, acid and sugar (which inhibit bacterial growth)
30% of the 100,000 species cause fungal diseases known as mycoses

Question 2

What is the thallus?

Answer 2

This is the vegetative non-reproductive body of a fungus this can be unicellular (as in yeast) or multicellular (mould)

Question 3

What are the features of the thallus of mould?

Answer 3

This is multicellular and composed of branched and tubular filaments called hyphae which are filamentous branching tubular structures which have septa (cross walls), they may also intertwine and form a tangled mass called a mycelium
Some fungi may be dimorphic in response to environmental conditions where they have both yeast like and mould like thalli

Question 4

How does histoplasma capsulatum cause disease?

Answer 4

This is an example of how fungi which are dimorphic can be particularly important as direct fungal pathogens
This fungus grows as a mould at ambient temperature at a yeast at 37 degrees
It causes a respiratory diseas known as histoplasmosis

Question 5

How do fungi acquire nutrients?

Answer 5

Through absorption where the thalli secrete digestive enzymes which breakdown large macromolecules allowing them to absorb the nutrients
Fungi which derive nutrients from living organisms have modified hyphae which penetrate the tissue of the human host

Question 6

Who do unicellular fungi reproduce/

Answer 6

Through asexual budding
Candida Albicans is unusual in this as the buds will remain attached to each other as well as to the parent cell forming a pseudohyphae which are capable of penetrating inter-cellular gaps allowing it to invade human tissues

Question 7

How do multicellular fungi reproduce?

Answer 7

These from asexual spores, though they may reproduce sexually by forming haploid cells

Question 8

How is fungal infection in human tissues detected?

Answer 8

This doesn’t typically use H and E stain as it is not a specialized fungal stain, instead the periodic acid Schiff stain is used to outline fungal cell walls is typically used however the gomori methenamine silver stain may also be used to stain non-viable fungal thalli

Question 9

Why are diseases caused by fungal infections less common than those caused by bacterial infactions?

Answer 9

Normal body temperature of 37 degrees typically arrests the growth of fungi (with the exception of dimorphic fungi) as well as cellular immunity typically limiting infection

Question 10

What are dermatophytes?

Answer 10

These are fungi that are part of the normal flora of the skin causing superficial infection of the keratinised layer of the epidermis, they can colonise this surface due to the lower temperature and the ability to produce proteinase enzymes
They use keratin as a nutrient and are the only fungi which depend on human infection for survival and dissemination

Question 11

What is the role of dematophytes in disease?

Answer 11

these fungi are primary fungal pathogens as they can produce disease on routine exposure, fungi which cause superficial human disease include
Trichophyton, microsporum and epidermophyton
Trichophyton rubrum is the most widely distributed dermatophyte of man and causes chronic infections of skin, nails, hair and scalp
Epidermophyton floccosum cannot infect hair and microsporum is a frequent cause of ringworm in humans with cats and dogs being the main source of infection

Question 12

What type of disease is caused by dermatophytes?

Answer 12

These typically cause minor illness with localised infection in the skin, hair and nails including the most common infection of atheltes foot/ringworm and onchyomycosis (infection of the nail)
These fungi do not invade living tissue and only colonize the keratinized strtum corneum of the epidemis with the hyphae being confined to the non viable keratinised layer however both the fungus and its metabolic products can induce an inflammatory reaction in the host observed as mild lymphocytic inflammatory infiltrate in the dermis

Question 13

What are the opportunistic fungal infections?

Answer 13

Candidiasis, Aspergillosis, Mucormycosis, Rhinocerebral mucromycosis and mycotoxicosis

Question 14

What is candidiasis?

Answer 14

Candida albicans is a yeast typically confined to the oropharynx, GI tract and vagina through the actions of mechanical barriers, cellular immunity and competition by other microflora
However these defences may become compromised through the actions of maceration, alteration in normal microflora and immunodeficiency leading to opportunistic infection of muco-cutaneous sites with candida albicans causing intertrigo, nappy rash, vulvo-vaginitis and oral thrush
In severe cases there may be systemic candidiasis where it enters the body via ulceration or iatrogenic means with the urinary tract being a common site of entry

Question 15

What is maceration/

Answer 15

Softening and destruction of the keratinised layer of the skin usually due to excessive moisture

Question 16

What is aspergillosis?

Answer 16

Aspergillus is a fungus that is extremely common in the environment and grows on decaying vegetation, inhalation of the spores (conidia) can cause illness in three ways
An allergic reaction (allergic bronchopulmonary aspergillosis
As colonization and growth in an old heald lung cavity from a previous disease producing a fungus ball (aspergilloma)
As an invasive infection with pneumonia that is spread to other parts of the body by the blood stream

Question 17

What does exposure to aspergillus spores most commonly cause?

Answer 17

Hypersesnitvity aspergillosis which may be an underlying cause of asthma symptoms in some individuals
Ball like masses of hyphae (aspergilloma) germinate and colonize TB cavities in the warm moist lung this is not invasive and may be asymptomatic

Question 18

What is acute invasive pulmonary aspergillosis/

Answer 18

This is a very serious condition but is relatively rare the early symptoms are pneumonia like illness however as the spores germinate in the alveoli the hyphae spread through the lung parenchyma and blood vessels casuing haemorrhage and necrosis of the alveolar pneumocytes and capillaries, the fungus produces proteolytic enzymes which inhibit coagulation and cause thrombosis resulting in lung infarcts
Hyphal fragments may also disseminate through the blood to other distal sites resulting in systemic invasive aspergillosis which is often fatal as ti leads to abscesses in the brain an kidney etc

Question 19

What is mucormycosis?

Answer 19

This is a disease caused by fungi such as rhizopus, mucor and absidia (zygomycetes) which are ubiquitous to our environment and the small spores which are released into the air means that humans are constantly exposed
These fungi are capable of causing severe necrotising invasive opportunistic infections but these will occur exclusively in patients with an underlying illness such as diabetes, starvation, severe burns, i.v. drug abuse, leukaemia and lymphoma, immunosuppressive therapy and major trauma
The disease has three forms rhinocerebral, pulmonary and subcutaneous

Question 20

Why are patients with uncontrolled diabetes at considerable risk to mucromycosis?

Answer 20

Normal serum inhibits the growth of these fungi but serum from diabetics where ketoacidosis is present stimulates the growth of these fungi

Question 21

What is rhinocerebral mucromycosis?

Answer 21

Following inhalation of zygomycete spores the nasal sinuses become infected where the fungus proliferates and invades the surrounding tissue including the facial soft tissue, nerves and blood vessels
The palate/nose is covered with a cotton like crust and the underlying tissue is friable and haemorrhagic
The hyphae grow into arteries, embolize and cause subsequent necrosis of the surrounding tissue causing rapidly progressive septic infarction
Extension into the brain results in fatal necrotising hemorrhagic encephalitis where there is considerable facial pain, headaches, cranial nerve dysfunction and persistent change in mental function, other symptoms include blood stained nasal discharge, eye pain and bulging with a discoloured eye and fixed pupil

Question 22

What is subcutaneous mucromycosis?

Answer 22

This is an invasive mycosis which can occur following a sever burn injury, the lesions of this vary considerably in morphology including plaques, pustules, ulcerations, deep abscesses and ragged necrotic patches

Question 23

What other fungal infection does pulmonary mucromycosis resemble?

Answer 23

Pulmonary aspergillosis

Question 24

What is mycotoxicosis?

Answer 24

This is a condition which can be the consequence of not only a fungal infection but also an allergic reaction to the fungus or toxicosis where the fungus itself is not the pathogen and the disease is a result of toxic fungal products
Fungal metabolites are chemically diverse organic, non-volatile, low molecular weight compounds capable of contaminating food and the environment

Question 25

What is the classical example of a fungal metabolite contamination?

Answer 25

Contamination of Rye with claviceps purprea which results in gangrenous ergotism

Question 26

What are the classes of mycotoxins?

Answer 26

Aflatoxin, Ochratoxin, Fumosin, Zearlenone which are produced by common moulds and associated with a wide range of effects on multiple organs including liver cancer, nephrotoxicity and immunosuppression

Question 27

What is stachybotrys chartarum?

Answer 27

This is a greenish black mould which grows on material with a high cellulose and low nitrogen content such as decaying hay, straw, grains but also fibreboard, gypsum doad, parer and dust
It requires constant moisture, higher than that of other fungi these conditions cause it to be associated with excessive humidity due to water leaks, condensation, water infiltration and flooding
Environmental exposure to this may be associated with mycotoxicosis

Question 28

What are the features of stachybotrys spores/

Answer 28

These are relatively large and covered slime, only becoming airborne when dry and disturbed, the fungus however is not a direct pathogen and the spores are not likely to reach the lower airway however the fungus does produce multiple mycotoxins

Question 29

What occurs in contamination of feed with Stachybotrys chartarum?

Answer 29

In animals this is known as stchybotryotoxicosis and handling of this grain may lead to skin and mucosal irritation causing respiratory symptoms suchas bloody rhitits and cough

Question 30

What might the growth of stachybotyrs in homes be associated with?

Answer 30

Toxic building syndrome which can cause reare effects of idiopathic pulmonary haemorrhage in infants

Question 31

Why is a causal link between disease and stachybotrys difficult to prove?

Answer 31

Moulds are common in buildings and homes growing where there is moisture with common indoor moulds including cladosporium, penicillium, aspergillus, alternaria as well as the less common stachbotrys chartarum
As well as the fact that many of the symptoms overlap with other pathogens found in these conditions although experimentally toxins from fungi found in the damp houses can cause inflammatory changes in the lungs