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are ubiquitous, free-living, saprophytic organisms;
, A. niger
, A. flavus
and A. terreus
are associated with
Pathology and Clinical features
Inhalation of Aspergillus
spores can provoke a type III hypersensitivity
reaction with fever, dyspnoea and progressive lung fibrosis
(farmer's lung). Colonization by Aspergillus
can provoke a type
I hypersensitivity reaction that results in intermittent airway
obstruction (bronchopulmonary allergic aspergillosis).
Healed tuberculosis cavities or bronchiectasis can become colonized
, creating a 'fungus ball' or aspergilloma. In
neutropenic patients, Aspergillus infection typically begins in the
lungs and may be followed by fatal disseminated disease. Rarely
the paranasal sinuses, skin, central nervous system and eye may
become infected, often with a poor prognosis.
Sputum culture is of limited value. An isolate from bronchoalveolar
lavage is diagnostic (98% specificity) but lacks
Antibody detection may confirm bronchopulmonary aspergillosis
and farmer's lung, but immunocompromised patients rarely
produce an antibody response. Enzyme immunoassay (EIA) to
detect galactomannan in serial samples is useful. Nucleic acid
amplification tests (NAATs) are a useful adjunct to diagnosis.
Treatment and Prevention
Bronchopulmonary aspergillosis requires treatment of the airway
obstruction with bronchodilators and steroids. Invasive aspergillosis
requires treatment with amphotericin B. Itraconazole has
activity against Aspergillus; voriconazole improves outcome in
pulmonary aspergillosis. Surgery may be beneficial in some cases
of pulmonary infection. Patients with farmer's lung should avoid
further exposure. Neutropenic patients should be managed in
rooms with filtered air and infection should be aggressively treated
(see Intestinal protozoa
Mucor, Rhizopus and Absidia may infect severely immunocompromised
patients. Sinus infection may spread to the eyes and brain.
Pulmonary disease may be complicated by dissemination. These
infections are difficult to treat and have a poor prognosis.
Three genera of filamentous fungi are implicated in dermatophytosis:
Epidermophyton, Microsporum and Trichophyton. Dermatophytes
are also grouped according to their reservoir and host
preference: anthrophilic (mainly human pathogens); zoophilic
(mainly infect animals); and geophilic (found in soil and able to
infect animals or humans). Anthrophilic species spread by close
contact (e.g. within families, enclosed communities). Transmission
of geophilic species is rare. Close contact with animals may give
rise to zoophilic infection (e.g. pet owners, farmers and vets).
Dermatophyte infection in the form of ringworm presents as itchy,
red, scaly, patch-like lesions that spread outwards leaving a pale,
healed centre; chronic nail infection produces discoloration and
thickening; scalp infection is often associated with hair loss and
scarring. Clinical diagnostic labels are based on the site of infection
(e.g. tinea capitis, head and scalp; tinea corporis, trunk lesions).
Lesions are rarely painful, but zoophilic species produce an
intense inflammatory reaction with pustular lesions or an inflamed
Infection of skin and hair by some species may demonstrate a
characteristic fluorescence when examined under Wood's light.
Skin scrapings, nail clippings and hair samples should be sent
dry to the laboratory. Typical branching hyphal elements may be
demonstrated by microscopy in a potassium hydroxide preparation.
Dermatophytes take up to 4 weeks at 30 �C to grow on
Sabouraud's dextrose agar.
Identification is based on colonial morphology, microscopic
appearance (lactophenol blue mount), biochemical tests and
sequencing of the 18S rRNA gene.
Dermatophyte infections may be treated topically with imidazoles
(e.g. miconazole, clotrimazole, tioconazole or amorolfine). Some
infections require oral terbinafine for several weeks.
Terbinafine inhibits squalene epoxidase with resultant accumulation
of aberrant and toxic sterols in the cell wall. It is indicated for
the oral treatment of superficial dermatophyte infections that have
failed to respond to local therapy. Reported adverse effects include
Stevens-Johnson syndrome, toxic epidermal necrolysis and hepatic
toxicity. Treatment should be continued for up to 6 weeks for skin
infections and 3 months or longer for nail infections.
Griseofulvin is active only against dermatophytes by inhibition of
fungal mitosis. Given orally, it is incorporated into the stratum
corneum or nail where it inhibits fungal invasion of new skin and
nail. Treatment must be continued until uninfected tissue grows.
It is now rarely used.
There are two polyene cyclic macrolides in clinical use, nystatin
and amphotericin B, which are active against almost all fungi.
Polyenes bind ergosterol in the fungal membrane forming a pore
that leads to leakage of the intracellular contents and cell death.
Resistance is rare.
Nystatin is used for topical treatment and the prevention of
fungal infection in immunocompromised patients. It has no value
for the treatment of dermatophyte infections. Amphotericin is
given parenterally; liposomal formulations overcome much of
the toxicity of earlier compounds enabling higher doses to be
The echinocandins act by inhibiting the synthesis of 1,3β-glucan,
a homopolysaccharide in the cell wall of many pathogenic fungi.
They are active against both Candida and Aspergillus
. New agents
in this class, which are now entering clinical use (e.g. caspofungin),
are well tolerated and offer a useful alternative for refractory