Fungal Infections

Just when I thought that we were done with infodumping lectures, we get another one! Maybe this is our "welcome back from study break" treat >_> Just like in the first few posts, anything in red can be found on Microbe Invader (http://microbeinvader.com/).

Descriptions of Fungal Infection

Location

Fungal infections can be described as superficial, cutaneous, subcutaneous or systemic. Superficial infections, such as dandruff and oral candidiasis, generally don't cause an immune response, but they are also very rarely fatal. Cutaneous infections, such as tinea, infect keratinised tissue. Subcutaneous infections, such as sporotrichosis, can lead to granuloma formation and cysts. Finally, systemic infections can cause severe illnesses that are often fatal, and are often caused by the more virulent fungi, including the primary pathogens Coccidioides, Histoplasma, Blastomyces and Paracoccidioides. Even opportunistic pathogens, such as Candida, may be able to cause systemic infections in the immunocompromised.

Endemic vs. Opportunistic

Fungi can also be classified as endemic or opportunistic. Endemic mycoses are caused by fungi which are not part of the normal human flora, but are acquired from environmental sources. They are often associated with outdoor activities and other specific exposures: for example, Histoplasma is associated with old buildings with bird or bat droppings, Coccidioides is associated with deserts, and Blastomyces is associated with wetlands and wooded areas. (All of those three are mainly found in North America.) Other risk factors for endemic mycoses include increasing age and decreasing cell-mediated immunity. Opportunistic mycoses, on the other hand, are caused by organisms that are often part of the normal flora, and mainly cause disease in the immunocompromised.

Morphology

Yeasts are fungi that are round and multiply by budding. Filamentous fungi grow as filaments and hyphae (chain of cells that line up nicely to form smooth "branches"), which can intertwine to form a network called a mycelium. Filamentous fungi often produce asexual spores called conidia, which are located on long chains on a conidiophore.

There are also dimorphic (or more accurately polyphenic) "yeast-like fungi" which can grow as yeasts or form chains. Some of these chains might be hyphae, and some might be pseudohyphae (kind of like hyphae, but with "constrictions" between the cells in the chain). The ability of dimorphic fungi to change shape can help with overcoming defences. Dimorphic fungi tend to be in the yeast form at body temperature, aiding in dissemination. Their filamentous form, which is more common at room temperature, helps with tissue damage and invasion.

Cell Walls

Just a quick note on cell walls: fungal cell walls are mainly made up of polysaccharides, particularly glucan, chitin and mannan. The cell wall composition changes between different species.

Virulence Factors

Just like bacteria, fungi have several virulence factors that help them to fight against their host.

Phenotypic Switching and Dimorphism

As I mentioned above, some fungi can change their morphology. Aside from dimorphic fungi, which can change between yeasts and hyphae, several different fungi can change their cell surface properties, colony appearance, and so on. For example, Candida albicans can switch from white cells to opaque cells for sexual mating.

Adhesion

Like bacteria, some fungi have adhesins, which help them to bind to host cells.

Secreted hydrolytic enzymes

Some fungi can secrete enzymes, such as proteases, lipases and phospholipases. These have a wide range of roles, from acquiring nutrition (e.g. pinching iron from RBCs), damaging tissue and overcoming the host immune system.

Biofilm

Fungi, like bacteria, can form biofilm or "slime" which provides a physical barrier from phagocytosis, lysozyme and antimicrobials.

Candida

Since Candida  (especially Candida albicans) is a relatively common fungus, let's focus on it for a little while! Candida mainly exists in yeast form, and is thus oval or round and can reproduce by budding. It is, however, polyphenic, and can form pseudohyphae when exposed to certain physiological conditions. When Candida enters tissue, it can form true hyphae, which aid in invasion and infection.

Candida is found in a lot of places, including soil, food, animals and humans (yep, it is part of our commensal flora). There are over 150 species, but only a handful cause infection, and even then they mainly only cause infections in the immunocompromised. Conditions caused by Candida include intertrigo (skin fold infection), paronychia (nail bed infection), onychomycosis (nail infection), nappy rash, oral candidiasis, vaginitis and oesophagitis.

Candida can even enter the blood, causing Candidaemia. The usual causes of candidaemia are colonisation of intravenous cannulae and contaminated injections by drug users. Invasive candidiasis can cause some pretty nasty conditions, such as endophthalmitis (inflammation of the interior of the eye), meningitis, endocarditis, pyelonephritis and osteomyelitis.

Diagnosis of Candida can be done via microscopy and culture. On agar, Candida forms smoth, creamy white colonies. In serum, Candida albicans forms germ tubes (which are basically precursors of hyphae), which differentiates it from other Candida species.

Dermatophytes

Dermatophytes are fungi that usually cause milder skin diseases, such as tinea. The main genera are Microsporum, Epidermophyton and Trichophyton. They invade the epidermis and release proteinases and keratinases, causing inflammation of the skin and keratinised tissues. Dermatophyte infections include tinea pedis ("athlete's foot"), tinea corporis ("body ringworm"), tinea cruris (infection of warm, moist creases), tinea capitis (scalp infection) and tinea unguinum (thick, crumbly and discoloured nails).

For some reason, there was a slide on pityriasis versicolor here, even though it's caused by Malassezia, which is not a dermatophyte. (I've also covered it here.)

To diagnose a dermatophyte infection, skin scrapings or nail clippings are often used. Since the fungus is most active in the advancing margin of the lesion, skin scrapings are usually done in this area.

Aspergillus

The main type of Aspergillus is Aspergillus fumigatus, which is fairly ubiquitous. Most people will inhale many A. fumigatus conidia (spores) daily without any ill effect, though the immunocompromised are a different story.

There are three main manifestations of aspergillosis: allergic bronchopulmonary aspergillosis (ABPE), aspergilloma and invasive aspergillosis. ABPE is caused by an allergic or hypersensitivity response to Aspergillus spores, and causes breathlessness and fevers. Aspergilloma is a fungal ball which grows inside a pre-existing lung cavity. Invasive aspergillosis, which is an acute or subacute infection, mainly affects the lungs and causes fever, cough and haemoptysis (coughing up blood). Invasive aspergillosis occurs mainly in transplant patients. Mortality rates are fairly high, though they are not so bad if treatment is started within 10 days of symptom commencement.

Aspergillus can be diagnosed via culture, the galactomannan assay and/or the β-D-glucan assay, though these diagnostic techniques may also need to be backed up by histological proof (i.e. looking at the tissue). Culture of Aspergillus has a high likelihood of false positives, and has only around 30% sensitivity. The galactomannan assay, which is an ELISA for a particular cell wall component of Aspergillus, has some inter-lab variability, problems with false positives and negatives, and requires serial testing (i.e. test the same patient several times over several days). The β-D-glucan assay also looks for part of the cell wall of Aspergillus, but amoxicillin-clavulanate, piperacillin-tazobactam and Streptococcus pneumoniae (which also has some β-D-glucan) can all cause false positives.

Mucormycosis

Mucormycosis is an invasive lethal mycosis caused by moulds such as Rhizopus, Rhizomucor, Mucorales and Absidia. It is a severe infection of the facial sinuses that mainly affects diabetics and the immunocompromised.

Cryptococcus

I've spoken about Cryptococcus a bit here, so now I'll go into a bit more detail! Cryptococcus neoformans is mainly associated with soil and bird poo, whereas Cryptococcus gattii is mainly associated with eucalyptus trees. It mainly causes disease in the immunocompromised, but it may also cause disease in healthy people. Cryptococcus can be diagnosed via microscopy (particularly with the India ink test), testing for cryptococcal antigen in the serum or CSF, as well as by looking at the manifestations (symptoms include meningoencephalitis, pneumonia and skin lesions).