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PATHOGENIC FUNGUS INFECTIONS
In true pathogenic
fungus infections, the fungus is virulent regardless of the constitutional
adequacy of the host. True pathogenic fungi include Histoplasma,
Coccidioides, Blastomyces, and Paracoccidiodies.
- Pathogenicity is an accidental phenomenon and is not
essential to the survival or dissemination of the species involved. Most
infections are either completely asympotmatic or of very short duration and
quickly resolved. Resolution of the infection is accompanied by a strong
specific resistance to reinfection that is of long duration.
- very restricted geographic distribution of fungus
- sex, age, and race are important factors in the
statistics of pathogenic fungus infections
- pathogenic fungi exhibit a morphological transition
from a the mycelial or saprobic form to the parasitic form found in infected
tissue. Thermal dimorphism is common!
BLASTOMYCOSIS (Chicago disease; North American Blastomycosis)
Clinical forms of disease
- chronic granulomatous and suppurative (bleeding pus)
disease having a primary pulmonary stage that is frequently followed by
dissemination to other body sites (e.g., skin and bone).
- occurs in humans and dogs (also seen in horses, wild
animals, northern sea lion).
- anamorph, asexual, or imperfect form of fungus,
Blastomyces dermatitidis is the etiological agent (perfect form of this
fungus is Ajellomyces dermatitidis, an ascomycete).
- dimorphic or diphasic fungus (converts from
filamentous form to yeast form and vice versa)
- soil saprophyte (erratic distribution, grows on
decaying organic materials).
- some evidence for presence of disease in Middle
Eastern countries, Africa, India, South America.
- Discovered in 1890's by Caspar Gilchrist
- diseases acquired through inhalation of conidia
- primary cutaneous disease is rare.
- very rare are reported cases of infection by yeast
phase through (a) sexual transmission (from man to woman), (b)
person-to-person, or (c) animal to person contact.
- chronic pulmonary and disseminated disease if left
untreated is fatal
- infection more likely in middle-aged men (rapid
dissemination can occur in women during pregnancy).
- median incubation period is 45 days following
exposure to symptoms.
1. Primary Pulmonary Blastomycosis
2. Chronic cutaneous and osseus
- symptoms of disease (lungs) resembles tuberculosis,
histoplasmosis, and bacterial infections
- inhalation of conidia
- may cause ARDS - adult respiratory distress syndrome
- untreated disease is fatal
3. Systemic Blastomycosis
- lesions on the skin
- damage to the vertebrate, ribs, skull, and bones
4. Inoculation Blastomycosis
- extensive and unresolving lung disease almost always
- infected tissue in lung and other organs function as
seed for other organ systems
- urogenital tract and central nervous system (gasterointestional
involvement is rare)
5. Blastomycosis in children
(generally rare, but acute pulmonary blastomycosis has been described with some
frequency in this age group).
- result of laboratory accidents
- accidental implantation during autopsy or while
embalming patients that have died due to blastomycosis
- lesions usually on hands and fingers and these heal
spontaneously without dissemination
- disease must be differentiated form chronic
granulomatous or suppurative pulmonary disease, such as histoplasmosis,
tuberculosis, and bacterial diseases
- Blastomycosis can coexist with other lung infections.
- look at KOH preparation for presence of yeast phase
- hyphae rarely seen in diseased tissue
- yeast in B. dermatitidis resembles
Histoplasma capsulatum except for presence of a braod-base of attachment
between the bud and mother cell
- isolation and identification of fungus is best method
for diagnosis of disease
- sputum and contaminated material mixed with an
antibacterial antibiotics can be injected intraperitoneallly in mice, and
these killed 3-4 weeks later to look for presence of pus and abscesses in
the abdominal area.
- mycelial form pretty much useless for purposes of
identification. Cultures convert yeast phase at 37°C when grown on brain
heart infusion or blood agar.
- amphotericin B (side effects, chills, fever,
anorexia, headaches, nausea, vomiting, anemia, renal toxicity, (almost 100%
effective if treatment started in time.)
- Experiments with imidazoles (e.g., miconazole,
itraconazole, econazole, and ketoconazole) have shown modest success
- surgery may be useful but not until disease is under
additional information and photographs.
- chronic disease
- primary pulmonary infection often inapparent
- disseminates to form ulcerative granulomata of the
buccal (cheek and mouth), nasal and gastrointestinal mucosa.
- lymph nodes, cutaneous tissue or systemic involvement
of multiple organ system.
- disease resembles blastomycosis and
- geographically restricted to South and Central
- the only etiologic agent is Paracoccidiodes
- in culture, conidiation is similar to Blastomyces
dermatiditis; in tissue similar to Coccidioides immiits.
- once thought once to be rare, but skin tests reveal
it to be subclinical and resolved infections common in endemic regions
- skin tests positives nearly equal between the sexes,
but men between 20-50 years old are more likely to get clinically apparent
- source of infect may be soil but this has hot been
- Primary infection is PULMONARY, though
infections of the mouth and alimentary canal suggested at one time source my
have been from food, or from cleaning between teeth with grass and the
trauma caused by this action.
I. Primary benign disease
II Acute (rapidly becomes a
crisis) and chronic progressive disease
- inapparent subclinical infection
- minor lung changes (bilateral lesions) and skin test
reactivity seen in otherwise healthy people.
II Acute juvenile
paracoccidioidomycosis (relatively rare)
- Acute Form
- rare in adults
- rapid infection in lung and often fatal
- sometimes observed in immunosuppressed patients
- Progressive and chronic
- occurs in about 50% of cases
- respiratory insufficiency, dyspnea (difficulty
breathing), fever, chest pain and cough productive of sputum.
- All lobes of the lung may be affected.
- Disseminated Disease (latent
- Mucocutaneous Lymphangitic Involvement
- primary infection is often subclinical\secondary
involvement of the mouth region is most apparent present symptom
- lesions in the he mouth begin as papules or
vesicles then ulcerate
- lesions are initially painless, extensive
lesions cause distress during ingestion and chewing
- in advanced case the epiglottis and uvula are
destroyed, hard palate is perforated, and lips and tongue may become
- Gingival involvement may lead to tooth loss
- regional lymph nodes may become involved
- cutaneous infections usually extend form
- mucocutaneous area is predisposed, possibly
due to the cooling effect of air in this region which promotes
growth of the fungus.
- Extracutaneous Disease
- foci for disease in organ systems without
evidence of involvement from lungs or skin occur though uncommon
(most common organ are the adrenal)
- Generalized Disease
- lymphatic system, spleen, intestine, adrenal,
- alimentary involvement results in abdominal
pain, anorexia, diarrhea, and fever.
- rarely involved are the testes, brain ,
meninges, heart, large arteries, bones
Prognosis and Therapy
- imitates other mycoses and tuberculosis
- cases where paracoccidiomycosis and other lung
diseases were present at the same time have been reported
- Often found in patients with other disease
(malnutrition, ascariasis, etc.)
- sulfas - sulfamethoxypyridazine and sulfadimehtoxine
0.5 g following an initial dose of 1 g per day for one week - relapse is
- Amphotericin B and ketoconazole are equally effective
in treating this disease.
- Laboratory Identification sputum, biopsy material and
arterial from lesions and infected lymph nodes; cleared in 10 % KOH
- yeasts are observed
- Cells vary in size depending on age 2-30 µm or more
- narrow point of attachment of buds to mother cell
- pattern of bud formation on mother cell varies, but
often resembles a "Mickey Mouse" head or a pinwheel.
- Fungus isolated from contaminated materials at room
temperature on medium (SDA) containing antibiotics (to kill contaminating
bacteria) and cycloheximide (antifungal agent). If cultured at 37°C on
medium (blood agar), antibiotics are added but not cycloheximide. Yeast
phase is sensitive to cycloheximide (also true of Histoplasma and
- Slow growing in culture.
- conidia of mycelia form are not characteristic so
conversion to yeast phase is essential!
and http://botit.botany.wisc.edu/toms_fungi/jan2005.html for additional
information and photographs.
HISTOPLASMOSIS - DARLING'S DISEASE
- worldwide; prevalent in eastern U. S.
- dimorphic fungus Histoplasma capsulatum
- infection through inhalation of conidia
- 95 % of cases are inapparent, subclinical, or
- diagnosed by x-rays through residual areas of
pulmonary calcification and a positive histoplasmin skin test.
- chronic progressive lung disease, chronic cutaneous
or systemic disease, or an acute fulminating, rapidly fatal, systemic
- growth of fungus associate with guano and debris of
bat and birds, particularly due to the roosting habits of starlings.
Interesting Trivia: All the
European Starlings in North America descended from 100 birds released in
New York's Central Park in the early 1890s. A group dedicated to
introducing America to all the birds mentioned in Shakespeare's works
set the birds free. Today, European Starlings range from Alaska to
Florida and northern Mexico, and their population is estimated at over
200 million birds (Source:
- teleomorph is Ajellomyces capsulatus, an
- disease described by Samuel Taylor Darling, 1905, in
Panama (initial thought is was a protozoan).
- 1945 it was realized that the disease was common and
- In the U. S, estimated that 40,000,000 people have
had the disease and 200,000 new infections arise every year.
- In culture at room temperature (below 35°C) on
natural substrate, the fungus is filamentous
- white to brown in color pyriform to globose
tuberculate macroconidia and small microconidia.
- the fungus favors guano-enriched environments with
climate conidiation 68-90°F (22-29°C) and annual rainfall of 35-50 inches,
relative humidity of 67-87% or more during the growing season.
- Chief vector of spores is wind.
- birds do not appear to be infected.
- bats may carry fungus via yeast-containing ulcers in
- Histoplasmin skin test - 21941 by Van Pernis filtrate
of an asparagine glucose broth in which the mycelial stage has been growing
for 2-4 months at 25°C. Histoplasmin infected intradermal as a 1:100 to
1:1000 dilution. Induration area seen after 48 hours indicates a positive
skin test. In some parts of the U.S., by age 20, 80-90% of population show
a positive skin test.
- Epidemics are anthropurgic - associated with human
activity bulldozing, digging, etc.
- soils heavily infested can be treated by soaking it
with a 3% formalin solution
Histoplasma capsulatum is a "true pathogenic"
fungus sufficient quantity of microconidia will cause infection in the lungs of
a healthy persons inhaled.
I. Benign Infection
A. Usual Dose
- most people infections abort leaving calcifications
in the lung (and spleen). Calcifications are sometimes a remnant of
infection by other respiratory mycoses and tuberculosis, but less frequent.
- Resolution confers a certain amount of immunity and
hypersensitivity to the antigenic components of the fungus; massive
reinfection may result in a fatal acute allergic reaction
B. Heavy Dose
- Endemic Subclinical Disease
- 95% of histoplasmosis cases are asymptomatic
- Endemic Symptomatic Disease
- Ranges from mild to moderately severe - flu-like
- summer flu in children and "fungus flu" in adults
- Primary Cutaneous Histoplasmosis
- very rare
- usually a result of inadvertent infection of
contaminated material (lab accidents, during an autopsy, bat guano)
- chancriform ulcer develops lesions heal
spontaneously after several months.
II. Opportunistic Infection
- Endemic Histoplasmosis
- syndrome occurs when individuals are exposed to
large quantities of conidia Primary infection symptoms don't appear for
10-18 days during which the organisms multiplies
- fever, malaise, chill, flu-like illness
- reinfection histoplasmosis symptoms develop in
3-7 days, on multiplication of organism. Flu-like symptoms.
A. Disseminated disease(defect
in cellular immunity 50 out of 50,00 people infected each (1 in a 1000) chronic
cavity disease (structural or anatomic defect predisposes to fungal
B. Chronic Pulmonary
Histoplasmosis - associated with emphysema and exacerbated by
III. Aberrant fibrosis and
hypersensitivity disease - encapsulation of fungus in a lesion.
Fungus remains inactive but viable for years
A. Histoplasmoma - an
enlarging fibrous mass (fibrous encapsulation and calcification) that develops
around a healed primary focus of infection I the lung.
B. Mediastina Fibrosis and
- Starts out 2-4 mm in size
- expands 1-2 mm annually reaching 3-4 cm over a 10 to
20 year period
- generally stops growing and calcifies completely
- if surrounding structures are threatened surgical
removal may be required
- fusion and excessive fibrosis in which the initial
lesion is in one or several nodes in the mediastinum (i.e., septum that
divides the pleural sacs containing all the thoracic viscera except the
- several nodes may become matted together, breakdown
and becomes encapsulated to form a mass up to 10 cm in diameter.
- Mass is harmless, unless it impinges on vital
adjacent structures including the superior vena cava, the pulmonary artery,
the pulmonary veins and the bronchi.
- Histoplasmosis mimic tuberculosis, actinomycosis,
viral and bacterial pneumonia, infectious mononucleosis, malaria and others.
- Therapy most infections resolve themselves
- often bed rest and supportive measures sufficient to
- Amphotericin B is the drug of choice A total of 1-3
grams administered over a 1-2 month period - Side-effects are common and
need to be monitored. In disseminated cases, 0.6 mg per Kg of body weight
per day for six weeks.
- Ketoconazole has been curative in central nervous
system disease at a dose of 200 mg per day.
- Sometimes... surgical excision of large cavities or
granulomatous masses coupled with amphotericin B to prevent reactivation.
- Detect of organism in sputum by direct examination is
difficult. KOH procedure is usually negative.
- Sputum, biopsied tissues, sternal puncture material
staining after fixing 10 minutes in methanol on a slide and treated with
Giemsa method of staining
- yeast cells are found in macrophage and monocytes
(fungus is intracellular parasite)
- Isolation from disease tissue accomplished by growing
on Blood Agar.
- Identification accomplished by demonstrating ability
of fungus to convert at 37°C and the presence of tuberculate macroconidia in
the filamentous s form grown at room temperature.
for additional information and photographs.
Coccidioidomycosis or "Valley Fever" is a benign,
inapparent or mildly severe upper respiratory infection that usually resolves
HISTORY OF THE DISEASE
- Rarely, the disease is an acute or chronic severe
disseminating, fatal mycosis.
- Recovery from the mild forms of the disease usually
results in lifelong immunity to reinfection. Chronic pulmonary condition
or as a systemic disease involving the meninges, bones, joints, subcutaneous
and cutaneous tissues. Associated with these forms are the formation of
- Etiologic agent of Coccidioidomycosis is
- This fungus is associated with a hot, semi-arid
environment and is highly endemic to the southwestern U.S. and northern
Mexico [LOWER SONORAN LIFE ZONE]. Endemic Foci are also found in Central
America, Venezuela, Colombia, Paraguay, and Argentina.
- Most virulent of the fungal pathogens - working with
live fungus requires the use of a biological safety cabinet or hood!
- Fungus is diphasic; In sputum or tissue, this fungus
produces spherules which contain endospores. In culture the fungus produces
cottony growth of mycelium and produces chains of arthrospores, which are
barrel shaped. Mycelium grown at 37-40 C and increased levels of CO2
does not convert completely to a nonfilamentous form of growth - some
- Identification often involves infecting experimental
animals to observe spherules.
- Persons with pigmented skin appear to be more
susceptible to the disease. The link is unclear. Statistically, male
Filipinos and African Americans run the highest risk of contracting this
- Coccidioidomycosis was the fist of the severe fatal
mycoses in which an inapparent or mild form of disease was found to occur
commonly in inhabitants of its endemic region.
- Probably a relatively new disease in humans. Endemic
areas where it is found were very sparsely populated until the advent of
European explorers and the subsequent settling agricultural and ranching
populations in these regions. Indigenous populations that existed there,
such as the Yokuts of the San Joaquin valley were eliminated by exposure
the European diseases of influenza, cholera, syphilis, and smallpox. We do
not know if coccidioidomycosis existed among them.
- Domingo Escurra, a soldier from the Argentine pampas,
had recurrent tumors of the skin for fours years before entering the
University hospital in Buenos Aires in 1891. His disease was studied by
Alejandro Posadas, a student of the famous pathologist Rovert Wernicke. The
patient lived another seven years during which time the investigators noted
the progress and pathologic development of the disease. On examining
lesions, they thought causal agent was an as yet undescribed protozoan in
the order Coccidia. Posadas and Wernicke described the same patient in
separated papers published (1892) in Argentina and Germany. In 1948, Dr.
Flavio Niño found an unidentified head resembling that of the patient
described by Posadas in the anatomy museum of the medical school Further
study confirmed this was so, and therefore the specimens from the first case
of coccidioidomycosis were rediscovered after being lost for half a
century. This head and other appendages of the patient are now a featured
exhibit of the medical school museum.
- First case of coccidioidomycosis first described by
Emmet Rixford in San Joaquin Valley in 1886. Organism was named as
Coccidioides immitis, but it was thought to be a protozoan. Early
attempt to isolate the parasite were discarded because a mold developed,
which at the time was thought to be a contaminant. Ophüla and Moffitt in
1900 described this organism as being a fungus.
- In 1932, Stewart and Meyer isolated C. immitis
from soil in the San Joaquin Valley near a site where 4 Filipinos had
contracted their severe or fatal infections. Site of infection and the
presence in soil suggested strongly that portal of entry into the body was
through the lungs.
- Myrnie Gifford working in San Joaquin Valley noted
that patients with "valley fever or valley bumps" shared some symptoms and
etiologic in common with severe infections caused by C. immitis. Dickson in
1937, coined the word "coccidioidomycosis", and by 1938, Dickson and Gifford
concluded that Valley Fever were mild forms of coccidioidomycosis. The
disease was not rare, instead it was rather frequent and common within the
- Dickson, Gifford, and C. E. Smith began an extensive
study of coccidioidomycosis in the San Joaquin alley. Smith criss-crossed
the desert in an old Ford named the "Flying Chlamydospore".
- Smith developed and standardized the coccidioidin
skin test. In the 1940's, airfields were built in endemic areas in the
Valley. Smith formulated dust control methods, such as oiling roads,
planting grass, and using swimming pools rather than dusty athletic files
for recreation. The disease was discovered to be a problem in other areas
of the American Southwest.
for additional information and photographs.
Opportunistic Fungus Infections are caused by organisms that are inherently of
low virulence, and disease production depends on diminished host resistance to
infection. Common etiologic agents of opportunistic infections are
Aspergillus, Candida, Rhizopus, and Cryptococcus.
- very low inherent virulence.
- recovery from an infection does not establish a
specific immunity , and reinfection may occur if general resistance is
- there are no differences in susceptibility ascribable
to age, sex, or race
- no transition is exhibited by organism in
opportunistic fungus diseases. Fungus does not convert from one form to
LIST OF MAJOR ETIOLOGICAL OR CAUSAL AGENTS
- Candida spp.
- Cryptococcus spp.
Mycelial or Filamentous Fungi
- Zygomycetes - Mucor, Rhizopus,
- Pseudallescheria boydii
- Aspergillus spp.
- Pneumocystis carinii
Yeasts - unicellular fungal organisms that reproduce by
budding and/or simple cell division and in the their anamorph stage belong to
the form-class Blastomycetes.
- the term "yeast" has no taxonomic significance,
because yeast species may belong to one of several different phyla,
including Ascomycota, Basidiomycota or Deuteromycota
- in addition to being unicellular yeasts, may produce
a mycelium or pseudomycelium
- all yeasts are opportunistic part of the natural
mycota (endogenous and ubiquitous)
Predisposing factors to infections include:
- one of the most common diseases of humans
- primary or secondary infection involving a member of
the genus Candida
- clinical manifestations ranging from acute, subacute,
chronic to episodic
- involvement localized as in the mouth, throat, nails,
bronchi, lungs, or the gastrointestinal tract, or systemic as in septicemia,
endocarditis and meningitis
- in the USA and Canada disease is called Candidiasis;
common name in most other countries is Candidosis
- forms of candidiasis include thrush (mouth) and
- disease known since antiquity - thrush was recognized
by Hippocrates in "Epidemics"
- 1841 (Berg) and 1844 (Bennett) demonstrated the
fungal etiology of thrush
- Berg reproduced the disease in healthy babies by
- in 1853, Robin recognized that thrush could become
- vaginal candidiasis was described by Wilkinson (1849)
in a 77-year old woman
- Haussmann in 1875, demonstrated that fungus of could
be transmitted to the mouths of babies from lesions in the vagina.
Haussmann also produced vaginitis in a healthy gravid female by inoculating
Candida into her vagina
- other forms of candidiasis: subcutaneous, brain
infection, intestinal disease, onychomycosis, cutaneous disease,
endocarditis, and others were recognized over time by different people
- systemic and endocarditis that can be fatal often
associated with broad-spectrum/antibacterial antibiotics and illegal drug
- most common cause is Candida albicans, but
other species can cause it as well, C. krusei, C. tropicalis
Candidiases may be caused by:
- Extreme youth (resident mycota not yet established
thrush, diaper rash)
- Physiological changes: pregnancy steroids, endocrine
- Antibiotics therapy: these drugs wipe out
microorganisms that keep resident species of Candida in check; in
absence of competition, these yeasts flourish
- General debility and constitutional inadequacy: AIDS,
- Iatrogenic and barrier-break candidiasis insults due
to catheters, surgery, self- administered injections by drugs users
- Some factors accelerate growth and colonization of
- damage to the skin
- moist skin (folded areas of the body, fruit
picking, washing dishes), living in tropical environment, eating
excessive fruit (sugars in gut)
I. Infections Disease
- Candida albicans
- Candida albicans is a normal inhabitant of
the alimentary tract and the mucocutaneous regions
- the normal skin possesses a resident yeast mycota
but this does not include Candida albicans
- C. tropicalis
- C. krusei
- C. pseudotropicalis
- C. albicans var. stellatoida
- C. parapsilosis
- C. guilliermondii
- C. glabrata (Torulopsis glabrata)
A. Mucocutaneous involvement
1. Oral Candidiasis (thrush)
- patchy growths (which cause the peeling of membrane);
appearance of milk curds as they crumble
- common in older people, diet deficiencies, premature
babies, first sign of clinical AIDS
3. Bronchial and pulmonary (not
- Predisposing factors
- pregnant women (growth promoted by secretion of
glycogen and progesterone)
- diabetes (high sugar content in urine)
- may be sexually transmitted but rarely infects
the penis (balanitis).
- Symptoms include puritis (itchiness), erythema
(reddening of the skin), yellow milky discharge from he membranes, patches
4. Alimentary candidiasis
- difficult to diagnose because organism is common in
most chronic lung conditions
- may be present in sputum without being in the lung
- look for quantity and frequency in diagnosis
B. Cutaneous involvement
- infection resides in the esophagus, intestine and
C. Systemic involvement
- often associated with skin that is kept moist and
where abrasions occur
- interdigital - between the fingers (occupational
hazard of salad chefs, waiters, fruit canners, bartenders, etc.)
- groin, axillary regions (underarms), umbilicus
(navel), feet and nails
- bacteria may be involved in a secondary invader
- nail infections - onychomycosis
- diaper rash may be caused by a species of Candida
1. Endocarditis - heart
2. Urinary Tract
- Predisposing conditions:
- drug addicts using unclean needles
- preexisting valvular disease
- people treated with antibiotics
- intravenous infusion = gets into tubes of machine
- In one study - 59 cases were species of Candida
found after heart surgery - only 6 patients survived.
- Bladder and kidney included
- more common in women then men
- yeast can be found in urine with no obvious infection
- about half of the patients based on one study, who
died after renal transplant died from systemic fungal infections; ½ of these
were due to Candida infections
- relatively rare, probably disseminated from another
part of the body that is infected
II. Allergic Diseases
- in blood and potentially fatal patients often
predisposed through antibiotic therapy or a result of having leukemia
Treatment - dependent on form of
- Candidids - similar to the
dermatophytid reaction caused by dermatophytes
- Eczema (reddening and itching of
skin, may become crusty and scaly)
- because the infections are opportunistic it is
important to control the predisposing factors
- nystatin -first polyene antimycotic discovered
- Hazen and Brown (two women discovered this in New
York) profits turned over to Research Institute for the study of Fungal
Disease. Trade Name - Mycostatin
- produced by Streptomyces noursei
- insoluble in water, side effects not pronounced;
sensitivity may develop to antibiotics
- organism do not develop resistance (rare)
- topical application or given orally as tablets
for gastrointestinal infections
- heat instable and oxidizes in light
- fungistatic, not fungicidal
- ketoconazole taken orally can improve chronic
- amphotericin B is sometimes effective in systemic
disease but resistance may develop
- from Pfizer. Contains prescribing information.
- Serological tests are not reliable in identifying
organisms or disease
- Colonies and cultures are unpigmented (unlike
- no capsule (unlike Cryptococcus)
- pseudomycelium caused by elongating yeast cells.
- blastospores (numerous budding cells) from
pseudomycelium or yeast cells
- chlamydospores are located on the terminal end of
the pseudohyphae. Spores various in sized (8-12 mm)
- Carbohydrate assimilation tests or diagnostic kits
(e.g., Analytical Profile Index [API 20C] Yeast Identification Kit by
bioMerieux Vitek, Inc.)
for additional information and photographs.
C. neoformans - yeast-like fungus, but is unique in
that it produces a capsule (polysaccharide).
- disease caused by Cryptococcus neoformans
- the only basidiomycete that is known to be a pathogen
- fungus is found in soil, fruits, milk, bovine
mastitis, and pigeon droppings
- typically associated with pigeon roosts and guano
- alkaline, high-nitrogen, high-salt substrate.
- like Coccidioides immitis, C. neoformans
appears unable to survive or compete with other species in other
situations. Cryptococci disappear from infected debris when it is mixed
with soil. Eaten by amoebas (Acanthamoeba species)
- Filobasidiella neoformans represents the
- Cryptococcus neoformams var. neoformans
(serotype A and D) and C. neoformans var. gattii (serotype B and C)
- C. albidus and a few other species have been
isolated on rare occasions from infected patients
- Rhoda Benham clearly differentiated blastomycosis
from cryptococcosis in 1934. She showed that cutaneous European type of
cryptococcosis was caused by the same organism that produces the meningitic
form more commonly reported in America.
- pulmonary infection, rarely enters through direct
inoculation by implantation (usually enters body through lungs)
- usually causes a mild, transitory infection that is
self-healing (like histoplasmosis) - common disease
- no good skin test to tell if you have had the disease
- predisposing conditions include: severely
immunocompromised individuals (organ transplant recipients, AIDS), collagen
diseases (lupus erythematosus), drug abuse, endogenous and exogenous
debilitating conditions (Cushing's syndrome)
- disease can become chronic and last for years.
- often Cryptococcosis is the first symptom of AIDS,
emphasizing this disease as malade signal or signal disease!
- if fungus disseminates, gets into CNS (sudden and
- fungus has a predilection for the CNS, why? Fewer
inhibitory substances in serum, less likely to be attacked by macrophage,
and nitrogen and carbon source in fluids encourages growth.
- Typical signs of invasion of CNS are severe headache
- Before advent of drug therapy, this form, almost
always fatal. Amphotericin B along with 5-fluorocytosine has cut mortality
to about 6 %
- When it disseminates can also appear on skin, in
bones, and other organs. Skin lesions, if severe, can ulcerate. Commonly
confused with blastomycosis. The term blastomycosis has been used very
loosely to designate any infection in which a budding yeast cell was found.
- mount using India ink (carbon-based ink) for best
view of capsule.
- rare to see a pseudomycelium
- do not use cyclohexamide for isolation (some strains
are inhibited by as little as 1 ppm)
- another way to see capsule, inject into mouse
interperitoneally and look at peritoneal fluid
- India ink method (useful for visualizing the
organisms in macerated biopsy material, centrifuged sediment of spinal
fluid, cisternal fluid, urine, or touch slides of autopsy materials).
- use very little ink so can see capsule
- ink will not penetrate capsule, so see a clear area
which is the capsule
- ink will not kill fungus, so dispose of slides
- advisable to run a saline control slide, since India
ink can become contaminated with microorganisms or ink may change in quality
- ink particles can be seen bouncing around due to
- in culture, Cryptococcus is similar to
Candida except culture tends to be gooey or slimy and falls to bottom of
- Physiological differentiation, especially between
species of Cryptococcus is a common practice.
- Chemotherapy - amphotericin B (approx. 75 %
- 5-flourocytosine (approx. 40 % effective, used mainly
as a back up drug - inhibits protein synthesis).
- Garlic has been shown to be noted to be active
against Cryptococcus. An extract has been used as an oral and
intramuscular agent in patients with cryptoccocal meningitis.
- Forms of cryptoccocal infection have been found in
horse, dog, fox, cat, dolphin, cheetah, civet, monkey, guinea pig, ferret,
various birds, and dairy cattle.
Mycelial Fungi - opportunistic pathogens that do not convert from a filamentous
form to another phase of growth (e.g., yeast phase) when pathogenesis occurs.
- the term "zygomycosis" encompasses any human or
animal disease in which the etiologic agent is a member of the Phylum
- in humans, disease is manifested in highly stressed
or debilitated individuals
- metabolic acidosis
- in animals and some cases in humans, disease is
manifested after exposure to large quantities of a particular fungi or
spores (e.g., contaminated feed, aerosols of fungal spores).
are older names that refer to diseases
caused by phycomycetes (obsolete taxonomic designation which included
the zygomycetes, oomycetes, and chytrids). Mucormycosis referred to
diseases caused by members of the Order Mucorales in the Zygomycetes.
Conidiobolae is synonymous with
rhinofacial zygomycosis caused by Conidiobolus coronatus
which is also a parasite of insects and associated with decaying plant
Entomophthoromycosis Basidiobolae is
a chronic subcutaneous form of zygomycosis caused by Basidiobolus
ranarum or B. haptosporus. Fungus is common on decaying
vegetation, soil and in the excrement of frogs.
- General forms of Zygomycosis
Symptoms and Disease
- most acute and rapidly fatal fungal disease
- some patients die within one week after the onset of
- death rate was about 90%, but now it is about 50 %
- uncontrolled diabetes with acidosis, acidosis caused
by excessive aspirin intake, diarrhea, uremia, or leukemia, lymphoma, severe
burns, and other diseases
- incidence of zygomycosis is on the increase due to
immunosuppressant drugs, cortisone (steroids), and other drugs
- Etiologic agents include: Rhizopus arrhizus
and other species; Absidia corymbifera, Mucor spp., and
1. Rhinocerebral - most common form,
associated with uncontrolled diabetes.
- nasal and orbital infection
- invasion of larger blood vessels and arteries
- patient may go into coma and die
- Mark Tatum of
Kentucky (seen below; after surgery, with and without
survived from rhinocerebral zygomycosis in 2000. Surgery was
required to remove infected tissue. He died five years later
February 26, 2005.
2. Pulmonary and thoracic zygomycosis and
3. Intestinal and Abdominal Zygomycosis.
- surgery is necessary to save the patient - often
fatal if not treated
- heart may become invaded.
4. Chronic Rhinofacial Zygomycosis (Entomophthoromycosis
- symptoms of abdominal zygomycosis vary and depend on
the site and extent of involvement. Nonspecific abdominal pain, atypical
peptic ulcer, diarrhea, "coffee ground" hematemesis (regarding blood), and
bloody stools are recorded
- if patient dies and disease recognized upon autopsy,
with ulceration of gastric mucosa with thrombosis (blood clotting) and
- malnutrition, typhoid fever, amebic colitis.
- may include liver, pancreas and spleen.
- In autopsy - in tissue, wide non-septate hyphae
- 1950's Duke Univer. Med Center first isolated a
Rhizopus and determined it as the etiologic agent. Patient was treated
5. Chronic Subcutaneous Zygomycosis (Entomophthoromycosis
- Over 150 cases reported; Central and West Africa,
Colombia, Brazil and the Caribbean.
- Animal infections, are reported in the U.S.,
Australia and other diverse parts of the world.
- Treatment with involves use of amphotericin B, sulfa,
surgery, iodides. Some cases heal spontaneously.
- Refer to
- 250+ cases of this disease have been recorded. Most
cases have been from Uganda, Nigeria, and Indonesia, with a scattering of
cases in India, Costa Rica, Togo the Near East, Brazil, and a few reports in
the United States
- Portal of entry unknown perhaps insect or mosquito
- Basidiobolus ranarum is
associated with the dung of frogs and represents a saprophyte.
- Sporangia (AKA conidia) are
forcibly discharge. Turgor pressure created by contraction of the
elastic sporangiophore wall causes a tear in the sporangial wall lifting
the sporangium away from the dung. The sporangium and "skirt" travel
about 0.5 cm. The skirt detaches from the sporangium and the sporangium
continues to travel an additional distance of 1-2 cm. This form of
explosive "spore" dispersal has been referred to as a "two stage rocket"
form of propulsion created by the rushing of fluid out of the expelled
skirt. Momentum carries the sporangium the remaining distance.
- This fungus also produces
sporangioles (also called capilliconidia with haptor) which are sticky
and catch onto passing insects, like beetles. The fungus is thought to
re-enter the amphibian or reptiles digestive track when the animal eats
a tainted beetle. In the stomach the capilliconidia cleaves into a
number of spores. Upon voiding their excrement, the fungus mycelium
grows and produces more sporangia (AKA conidia) and sporangioles (AKA
- Disease is called
Entomophthoromycosis Basidiobolae (a form of zygomycosis in humans in
which tumor like enlargements develop in the subcutaneous tissue) was
once thought to be caused by a species other than Basidiobolus
ranarum (called Basidiobolus haptosporus). However isolates
obtained from infected tissues in humans appears to be B. ranarum
and not a distinct separate species.
Dispersal of the explosive dispersal of the sporangium; the two stage
- Refer to
for additional information.
6. Primary and chronic zygomycoses do occur.
- Burned patients, trauma to skin (wound, catheter),
surgery, contaminated bandages.
- Amphotericin B is fungistatic but successful in some
- Pathogens show variable sensitivity to imidazoles.
- not necessarily effective
- control the diabetes
- control condition which predispose the person to the
- drug of choice is amphotericin B and/or KI
Isolation in pure culture
- look at scrapings and look at long nonseptate hyphae
- aspirated material
- If you are attempting to culture do not incorporate
cyclohexamide into the medium. Fungus is sensitive to this fungicide!
- Cultures grow very fast! Aerial mycelia, and may
fill up plate within 4 or 5 days.
information and photographs.
Pseudallescheria boydii - soil/water inhabiting
fungus with worldwide distribution
- caused by Pseudallescheria boydii - soil/water
inhabiting fungus with worldwide distribution
- low virulencePseudallescheria boydii -
soil/water inhabiting fungus with worldwide distribution
- opportunistic fungus
- usually associated with Immunosuppressive drugs,
underlying disease, trauma, barrier breaks, disease, aspiration of soil,
swamp or sewer water (in drowning victims)
- pulmonary colonization (lungs)
- Pseudallescheria arthritis and osteomyelitis
(inflammation of the bone marrow).
- invasive pneumonitis
- mycotic keratitis (fungus infection of the cornea)
- endophthalmitis - inner eye infections
- endocarditis - inflammation of the endocardium
(membranes that line the cavities of the heart)
- meningitis - infection of the meninges investing the
spinal cord and the brain
- brain abscesses
- sinusitis - inflammation of the sinuses
- cutaneous and subcutaneous infection
- mycotic mycetoma - usually more common in men (3:1 to
5:1) than in women.
- Infection more common in ages 20-40.
- Chronic otitis (ear infection) almost always with
children. Chronic infection sometimes lethal
for additional information and photographs.
MYCOTIC MYCETOMA - accounts for 99 % of
- usually results from trauma or
puncture wounds to feet, legs, arms and hands (usually on the feet)
- starts out as tumor-like to
- ruptures near the surface;
infects deeper tissues including subcutaneous tissues and ligaments
(tendons, muscles and bone are usually spared)
- small particles or grains leak
out of the lesions - these represent the to yellowish microcolonies
- lesions of mycetoma seldom heal
- disease is chronic may continue
for 40-50 years
- P. boydii is resistant
to all systemically useful drugs, including amphotericin B, KI,
- ketoconazole appears to be
ineffective in clinical trials
- intravenous miconazole (9 mg
per Kg of body weight sometimes higher doses) shows promise
- surgery and removal of tumor (
if small it is encapsulate, if larger amputation my be required)
- Combining miconazole and
surgery may prove useful in effectively treating the disease.
- Lung and upper respiratory tract
- fungoma (fungus ball formation - similar to
Aspergillus fungoma and difficult to distinguish)
- conidia are often formed in tissue
- predisposing condition usually some preformed cavity
- surgery usually curative
- most lower respiratory tract infections lead to
pneumonia - which is likely to fatal, but person generally compromised
(e.g. taking steroids, AIDS etc.)
- miconazole, amphotericin B and surgery are
recommended forms of drug treatments.
INNER EYE INFECTION (Endophthalmitis)
- P. boydii less common cause of cornea
infections than Aspergillus spp. and Fusarium spp.
- associated with injury to eye, such as plant debris,
splinters, twigs, (fish scale in one fishery worker)
- amphotericin B, pimaricin, nystatin can cure disease
in some instances.
OTOMYCOSIS - chronic
infection of the ear - usually in children. Not common, most culprits for this
malady are Aspergillus niger or Scopulariopsis brevicaulis
- most infections occur in compromised patients and
similar infections can also be caused by Candida species
- penetrating trauma or surgery (exogenous) or
endogenous (from some other point with the body - e.g., from the brain).
CULTURE OF THE ETIOLOGIC AGENT
- Grows readily on Sabouraud's Dextrose Agar but my not
produce cleistothecia on rich media
- repeated transfers to deficient media induces
- Pseudallescheria boydii is homothallic
(self-fertile) and represents the teleomorph (an Ascomycete)
- The anamorph is Scedosporium apiospermum and
- In older cultures, "house mouse" gray mycelium
- Asexual conidia produce annellocondia (single) or wet
clusters of conidia called Graphium-type of conidiation "synnemata".
- disease discovered in the lungs of a jay - 1815,
originally thought to be disease of birds
- penguins in London zoo began dying from Aspergillosis.
Birds are susceptible, because this fungus is somewhat thermophilic
- mycotic abortion of sheep and cattle, pulmonary
infections of birds, and toxicosis due to ingest of grain containing fugal
- first recognized as a human disease in 1842
- in humans, Aspergillosis is more prevent in males
than females or children
- "aspergillosis" refers to a spectrum of human disease
which include, otomycosis (ear), mycotic keratitis (eye), rarely mycetoma,
cutaneous infection, pulmonary infection, allergy, systemic and fatal
- Many cases of aspergillosis coexisting with some
other debilitating disease.
- Aspergillus fumigatus
- A. niger
- A. flavus (produces aflatoxin - most potent
carcinogen known, Turkey-X disease - 1960, it was later discovered that
contaminate peanut meal fed to poultry was the culprit).
- A. amstelodami - grow under condition of low
water and this produces cleistothecia (indicating that it is an ascomycete).
2. Allergic - sensitization
- Invades lungs and bronchi - symptoms similar to TB
- necrosis, and inflammation and granules in the lung
- fungal growth in lung is mycelial
- Aspergillus spp. can be secondary invaders of any
other lung disease
- fungus can be found in sputum (Hyphae or spores)
- sometimes grows in cavities left by Cocci, Histo, and
other lung diseases
- spores may form in cavities and bronchi of lung
- found in agricultural workers, fur-cleaners, pigeon
breeders (feed squabs with mouth-eaten feed)
- Aspergilloma - "fungus ball", not found infrequently.
- occurs in bronchi and causes blockage in the lung
- fungi growing in secretions of lung
- Farmer's lung" - may involve thermophilic
actinomycete and/or Aspergillus. Extreme allergic reaction, acute or
chronic sensitization, sometimes fatal. A strong asthmatic reaction to
these function - occupational hazard around moldy grain or dirty air filters
- in addition symptoms include, chill and fever,
abnormalities in lung
- shallow breathing, livid lips, weakness, and a
- disseminated form from a primary lung infection ==>
gets through the blood system or lymphatic system, may cause infection in
the heart (endocarditis), meninges, rarely bones or gastrointestinal
- generally fatal, especially in children
- been known to enter patients who are undergoing
Identification and Diagnosis
- the orbit of the eye, in the conjunctive, eyeball, or
- Otomycosis (ear)
- nail infection - onychomycosis.
- Aspergillin Skin Tests -95% of the people with
allergic rxns, 22% with fungus balls.
- immunodiffusion tests are useful in identifying that
the patient is producing antibodies to fungus.
- difficult to identify the common saprophyte as the
cause of disease.
additional information and photographs.
- Pulmonary form ==> KI is taken orally, or NaI
- Amphotericin B is not always successful but is used
for systemic forms of this disease.
- Nystatin is useful in pulmonary forms, by inhalation
and used for localized forms that occur in the sinuses
- Allergic aspergillosis, treat the infection and
- Prednisone and other steroids are used during the
acute phase, but precautioned in chronic cases. Reduce symptoms of
bronchial plugging by mucus containing the fungus. Vigorous physiotherapy,
bronchoscopic aspiration, and lavage are recommended
- with Aspergillomas - fungus balls are removed
Pneumocytis carinii Pneumonia
Check out the following sites to get
more information on pneumonia caused by Pneumocystis carnii
- THE FOLLOWING INFORMATION ON PNEUMOCYTIS
WAS GLEANED FROM THE TEXTBOOK "INTRODUCTORY MYCOLOGY", BY C. J. ALEXOPOULOS,
C. W. MIMS, AND M. BLACKWELL, 1996. JOHN WILEY & SONS, NEW YORK, 868 PAGES.
- causal agent is Pneumocystis carinii which
results in a virulent pneumonia in immunocompromised humans, primarily those
infected with HIV
- extracellular parasite of a number of mammals,
including human beings, rats, mice, ferrets, horses, pigs, and rabbits
- the fungus binds to epithelial cells of the alveoli,
and in addition to a lung infection, it may become disseminated to other
organs and throughout the bone marrow
- pathogen first described as a protozoan from lungs of
rats in France in 1912
- recognized in humans much later (1942)
- first found in individuals who were severely
malnourished or immunocompromised after drug therapy, it was only after the
spread of HIV that the organism became widely known
- recognition of Pneumocystis as a fungus is
more recent occurrence
- fungus probably related to yeast-like ascomycetes
(sensitive to antimycotic benomyl, as are other ascomycetes and
- Ultrastructural studies of spores using electron
microscopy, observation of ascomycete-like synaptonemal complexes formed
during meiosis and DNA sequences suggest that this organism is a fungus, and
not a protozoan.
- Although the evidence currently supports that
Pneumocystis carinii is an early diverging ascomycete, the matter is not
- Pneumonocystis has not been grown in culture
- This fungus is probably air dispersed; however,
dispersal has not been observed and the dispersal stage is not known.
This web page is organized and maintained by M. Huss.
Last updated 10-19-08.