Agents of Opportunistic Mycoses

- The types of disease caused by a fungi are as varied as species because a given fungus can help multiple clinical
presentation
o Surgical wounds are ideal points of inoculation, allowing saprobes to become opportunistic agents of
disease
 Saprobes are an organism usually referring to a fungus that feeds on dead or decaying organic
matter
o Skin and nail bed infections as well as severe respiratory infections can be caused by a variety of fungi in
patients with AIDS
- This fungi are found worldwide, it’s often associated with decaying vegetation

Mucorales

- Belong to kingdom fungi and order Mucorales

- An order of perfect fungi on the class Zygomycetes which is made up of bread molds and related fungi
- It causes mucormycosis in humans
- It’s the largest and best studied order of zygomycetes fungi
- Members of this order are sometimes called pin molds

Mucorales
Cunninghamella - Genera of mucorales
- Cunninghamella spp. can be recovered from the sinuses or other organs during
disseminated disease
- Found worldwide and common in the environment; human beings are easily
infected
- Sporangiophore are erect meaning very straight, branching into several vesicles that
bear the sporangium and can be covered with long pines pines?
- Rapidly growing zygomycetes that form cotton colony that’s initially white becomes
gray with age
Lichtheimia - Have a predilection for vascular invasion, causing thrombosis and necrosis of the
tissues
o Predilection is natural liking there’s a tendency to do or to be attracted to
something or in an infection or affinity. Meaning, this type of fungus really
wanted to be in vascular invasion
o That’s why the blood vessels, it will now cause thrombosis and necrosis
o If there’s necrosis, there’s now trouble in circulatory system
- Usually found in diabetic patients suffering from ketoacidosis
o Accumulation of ketone bodies which results in metabolic acidosis
o Often associated with uncontrolled diabetes mellitus
o Ketones are breakdown product formed during the catabolism of fatty acids
o Catabolism is a breakdown of complex molecules in living organisms to form
simpler ones together with the residue of energy
- The infection usually begins in the sinuses, where conidia are inhaled and take up
residence
o From the sinuses, infection rapidly spreads to the orbits, face, palets (top
part of the inside of the mouth), and brains
o Orbits are the socket of the eye
- Known as rhinocerebral zygomycosis
- Other signs of infections have been noted in cancer patient to include cutaneous,
subcutaneous and systemic disease and will result to opportunistic
 - Found worldwide and is often associated with soil/decomposing organic matter
- Hyphae are broad and sigmoid? like with few septations, erects sporangioosphores,
solitary or in groups
- Colonies are woolly, grow rapidly
- Colony color is initially white becoming gray to gray-brown with age

Mucor - Mucor spp. have been implicated in rhinocerebral zygomycosis in addition to

disseminated disease
- Commonly isolated from the environment worldwide
- The rhizoids are typical of mucoralis are absent in mucor
- Growing rapid and form cottony dirty-white colonies that become mousy brown to
grayish (differentiate)

Rhizopus - Spp. are the most common Mucorales causing human disease
- Typically involved in diabetic patients with ketoacidosis, presenting rhinocerebral
mucormycosis
- Are extremely refractory to treatment and maybe recovered from almost any
source
Refractory: difficult to treat
- Worldwide, decaying vegetation
- Erect sporangiosphore, terminated by black sporangia and sporangiospore
- Rapidly growing, woolly colonies that covered the entire face of the culture medium
- Colonies are initially white but become gray to brown with age
Syncephalastrum - Syncephalastrum is rarely implicated in human disease but has been documented in
cutaneous infections
- This fungus is found in the soil and decaying vegetation
- Erect sporangiosphores are noted
- Care should be taken when viewing because it is sometimes confused with
Aspergillus on initial examination
- Colonies are initially white and become gray with age
- Growth rate is rapid with colonies covering the entire surface agar

SEPTATE AND HYALINE

SAPROPHYTES

Aspergillus - Second most isolated fungus after Candida spp. Aspergillus fumigates is the specie
most commonly isolated
- Other pathogenic spp. include A. flavus, A. terreus, and A. niger
- Causes neutropenia; single most predictive factor for developing Aspergillosis
Most frequent cause of disease in bone marrow transplant recipient in addition to
other cancer and transplantation pX
- The infection is initiated following to the inhalation of fungal conidia in the lung air
spaces
- Conidia germinate and invade the tissues
- Colonies is derived from the conidia
- Colors range from black to white and include yellow brown green, gray-pink beige
and white
 - Most known pathogen in this group forms from green to tan colony
- The pathogenic type of Aspergillus will produce green to tan colored colonies
Aspergillosis
Description: a disease caused by Aspergillus. A common mold (a type of fungus)
that lives indoors and outdoors. Most people breathe in aspergillus spores every
day without getting sick

Location: aspergillus lives in the environment

Laboratory diagnosis
Healthcare providers should consider your medical history, risk factors, symptoms,
physical examinations and lab tests when diagnosing aspergillosis. You may need:

1. Imaging tests such as a chest x-ray or a CT scan of your lungs or other parts of
the body depending on the location of the suspected infection.
2. If your healthcare provider suspects that you have an aspergillus infection in
your lungs, he/she might collect a sample of fluid from your respiratory system
to send to a laboratory
3. Healthcare providers may also perform a tissue biopsy, in which a small sample
of affected tissue is analyzed in a laboratory for evidence of aspergillus under a
microscope or in a fungal culture.
4. A blood test can help diagnose invasive aspergillosis early in people who have
severely weakened immune systems

Beauveria - Beauveria bassiana is a rare human isolate, uncommonly associated with keratitis
o Keratitis is an inflammation of cornea, the transparent membrane that
covers the colored part of the eye which is iris and pupil
- This fungus is a known insect pathogen and is found worldwide on vegetation and
in the soil

Chrysosporium - A rare cause of Chrysosporium spp. have been recovered form nails and skin
lesions
- They are found in the environment worldwide
Fusarium - Spp. are frequently seen in mycotic keratitis
- Last 2006 there was an outbreak infecting the eye because they wore contact
lenses solution
- Easily recovered in blood culture systems
Geotrichum - Has been implicated in pulmonary disease in immunocompromised patients
Paecilomyces - Rarely cause infection, most reports of disease involve chronic fungal sinusitis
- Ubiquitous in nature
- Can be recovered worldwide
Scopulariopsis - Commonly isolated from nail specimens and have been implicated in pulmonary
disease in immunocompromised patients
- This fungus is recovered from the environment worldwide
Trichoderma - Are an emerging pathogen in the immunocompromised host that can cause a range
infections, including pulmonary and skin infections
 - This isolate is readily recovered from the environment worldwide

SEPTATE AND
PHAEOID (dark)
SAPROPHYTES
Alternaria - Although can be recovered from almost any source, they are primarily
implicated in chronic fungal sinusitis
- Patients often misdiagnosed and treated for an extended period of time for
bacterial sinusitis
- Found worldwide on grasses and leaves
- They have been implicated to a tomato rot and are readily recovered from
the environment from air _ place
Aureobasidium - Infections are rare but can be traced to contaminated dialysis lines and other
similar devices
- The organisms may be recovered from blood, tissues, and abscesses
Chaetomium - Infections by this organisms have been reported in the brains of patients
with central nervous disease
- Several of these patients have been identified as intravenous drug abusers
- In Europe and western countries it was very often
- Because of punctured vein, easy to penetrate
- Found in the environment and have a predilection for cellulose product
Cellulose products are polysaccharide of glucose that constitute the chief
part of the cell walls of the plants
- They are known to devastate printed literature and library holdings and have
been associated with indoor air quality problems
- Bookworm hahaha

Cladosporium - Primarily recovered as laboratory contaminants

- Infections are typically confined to the sinuses or following traumatic
inoculation
- Known to be ubiquitous in nature and can be recovered from almost any
location in the world (char)
Culvularia - Isolated are usually implicated in chronic sinusitis in immunocompetent
patients
- Found worldwide
- This fungus is frequently recovered from grass, leaves and decaying
vegetation
Phoma - Disease caused is usually secondary to a traumatic inoculation
- Traumatic inoculation: traumatic wound. Like soldiers
Pithomyces - Is a diseased caused is usually secondary to traumatic inoculation
Ulocladium - Are sometimes implicated in subcutaneous infections, usually following
traumatic inoculation
AGENTS OF YEAST INFECTIONS
- Molds and yeasts are different morphologically but, some are used in identifying yeasts
- Macroscopic characteristics include color and colony texture
- The color of a yeast colony ranges from white to cream or tan, with few species forming pink –to-
salmon-colored colonies
- Some yeast isolates referred to as to phaeiods (brown/darkly pigmented)

Candida

- Are commonly present as normal biota of the mucosa, skin, and digestive tract, and vagina
- They are also the most notorious agents of yeasts
- Clinical disease ranges from superficial skin infections to disseminated disease
- C. albicans currently reigns as the premier cause of yeast infection in the world
4th most common cause of blood-borne infection in the USA accounting for 10-15% all hospital-
acquired septicemias
- One of the most widely recognized manifestations infection is thrush
- Thrush is also recognized as an indicator of immunosuppression (individuals infected with HIV, those
receiving prolonged antibacterial therapy, other chemotherapeutic agents)
- Thrush manifest as a serious infection capable of dissemination

- Candida glabrata
Probably the 2nd most common candida spp. to cause disease and may account 21% of all urinary yeast
isolates
Infections associated tend to be aggressive and difficult to treat with traditional anti-fungal therapy

Other notable species:

- C. krusei
- C. tropicalis
- C. parapsilosis : has become a major cause of outbreaks of nosocomial infections

Location: vagina

Description

- Extreme itching in the vaginal area. Soreness and redness in the vaginal area

Transmission

- Candida normally live as a normal flora in the human body

- Sexual intercourse
Laboratory diagnosis

- Pelvic examination
- A small amount of the vaginal discharge is examined using a microscope. This is called wet mount KOH
test
- Sometimes, a culture is taken when the infection does not get better with treatment or comes back
many times (relapse)

Candidiasis is a fungal infection due to any type of Candida (a type of yeast).

- When it affects the mouth, it is commonly called thrush

Signs and symptoms include:

- White patches on the tongue or other areas of the mouth and throat
- Other symptoms include: soreness and problems swallowing

When it affects the vagina, it is commonly called a yeast infection

Signs and symptoms:

- Genital itching
- Burning
- Sometimes a white cottage cheese-like” discharge
- Less commonly the penis may be affected, resulting in itchiness

Cryptococcus

- Are important causes of meningitis, pulmonary disease, and septicemia

- C. neoformans, the most notable pathogen in this genus, has become a major cause of opportunistic
infection in patients with AIDS
- The organisms is commonly found in soil contaminated with pigeon droppings and is most likely
acquired by inhalation

Cryptococcosis

Location –brain

Information of disease:

- It’s chronic, subacute to acute pulmonary, systemic or meningitic disease

- Initiated by the inhalation of basidiospores and or desiccated yeast cells of C. neoformans
- Primary pulmonary infections have no diagnostic symptoms and are usually subclinical
- On the dissemination, the fungus usually shows a predilection for the CNS, however skin, bones, and
other visceral organs may also become involved
Lab test

Specimen:

- CSF, biopsy tissue, sputum, bronchial washing, pus, blood, urine

C. gatti is an emerging pathogen, particularly in the Pacific Northwest of the United States

- Infections caused are similar to those caused by C. neoformans, targeting primarily compromised patients

Rhodotorula

- Are noted for their bright salmon-pink color

- They are closely related to the Cryptococci because they bear a capsule and are urease-positive
- Some species are also nitrate-positive
- They are not common agents of disease but have been known to cause opportunistic infections

Pneumocystis infection:

- Can inhabit the lungs of many mammals

- P. carinii was originally classified with protozoa, but nucleic acid sequencing showed conclusively that
the organism is a fungus
- Is the spp. most commonly found in rats
- P. jirovecii is the spp. most often recovered from humans

Pneumocystis pneumonia PCP is a serious illness caused by infection with the fungus P. jirovecii (carrinii). It is
one of the most common opportunistic infections in people with HIV/AIDS

It can also occur in patients being treated for malignancies, bone marrow transplant and other severe
immunocompromised states.

Blastomyces dermatitidis

 Blastomycosis is most prevalent in middle-aged men, as are other systemic mycoses,

presumably because occupational and recreational exposure to soil is often greater among men.
 Although patients with primary infection may exhibit flulike symptoms, most are asymptomatic and
cannot accurately define the time of onset.
 When the primary disease fails to resolve, pulmonary disease may ensue, with cough, weight
loss, chest pain, and fever.
 Progressive pulmonary or invasive disease may follow, resulting in ulcerative lesions of skin and
bone.
 In the immunocompromised patient, multiple organ systems may be involved, and the course may
be rapidly fatal.
 Blastomycosis is also known as Gilchrist disease, North American blastomycosis, and Chicago
disease.
 The teleomorph or sexual form of B. dermatitidis is named Ajellomyces dermatitidis. It occurs only
in rigidly controlled environments by mating of isolates with tester strains to produce gymnothecia
containing ascospores.
 This teleomorph does not occur in the routine laboratory because the species is heterothallic,
requiring two mating strains to produce the sexual form.

Laboratory Diagnosis

 Examination of tissue or purulent material in cutaneous skin lesions may reveal large, spherical,
refractile yeast cells, 8 to 15 µm in diameter, with a double- contoured wall and buds connected
by a broad base.
 KOH (10%), or calcofluor white (a fluorescent dye), may be used to enhance the detection of the
yeast cells.
 In the mold phase, conidia are borne on short lateral branches that are ovoid to dumbbell shaped
and range in diameter from 2 to 10 µm.
 Because they resemble a variety of other fungi, the microconidia are not diagnostic.

 In culture at 22° C, the organism can produce a variety of colony morphologies—white, tan, or
brown—and may be fluffy to glabrous.
 When grown at 37° C on suitable media, B. dermatitidis produces characteristic, broad-based,
budding yeast cells.

 The mycelial phase of the systemic dimorphic fungi—B. dermatitidis, B. gilchristii, Cocccidioides
immitis, Cocccidioides posadasii, Histoplasma capsulatum, and Paracoccidioides brasiliensis—
requires confirmatory identification, typically by DNA probe and DNA sequencing. Because of low
sensitivity and specificity, antigen detection methods are generally not used.
 Frequently, raised areas, termed spicules, are seen in the centers of the colonies.

Coccidioides Species
 Coccidioides spp. are probably the most virulent of all human mycotic agents. Two very similar
species that infect humans are C. immitis and C. posadasii.
 The inhalation of only a few arthroconidia produces primary coccidioidomycosis.
 Allergy can manifest itself as toxic erythema. Erythema nodosum (desert bumps), Erythema
multiforme (valley fever), and Arthritis (desert rheumatism).

 Primary disease usually resolves without therapy and confers a strong, specific immunity to
reinfection, which is detected by the coccidioidin skin test.
 In symptomatic patients, fever, respiratory distress, cough, anorexia, headache, malaise, and
myalgia can be present for 6 weeks or longer. The disease might then progress to secondary
coccidioidomycosis, which can include nodules, cavitary lung disease, and/or progressive
pulmonary disease. Single-system or multisystem dissemination follows in about 1% of this
population.

 Filipinos and blacks run the highest risk of dissemination, with meningeal involvement being a
common result of disseminated disease.
 The sex distribution (9:1) ratio for clinically apparent disease has been reported to favor males.
 Coccidioides spp. reside in a narrow ecologic niche known as the Lower Sonoran life zone, which
is characterized by low rainfall and semi-arid conditions.
 Highly endemic areas include the San Joaquin Valley of California, the Maricopa and Pima
counties of Arizona, and southwestern Texas.
 Because they are morphologically identical, geographic location is required to differentiate, C.
immitis encountered in the San Joaquin Valley region of California and C. posadasii is found in
the desert areas of the Southwest United States, Mexico, and South America.

Laboratory Diagnosis

 Direct smear examination of secretions may reveal the spherules containing the endospores.
 Caution must be exercised when diagnosis is made by histopathologic means only.
 Small, empty spherules may resemble the yeast cells of B. dermatitidis
 ; and the endospores can be confused with the cells of C. neoformans, H. capsulatum, and P.
brasiliensis.
 Direct antigen detection methods are limited.

 Microscopic examination of the culture shows fertile hyphae arising at right angles to the
vegetative hyphae, producing alternating (separated by a disjunctor cell) hyaline arthroconidia.
 When released, conidia have an annular frill at both ends.
 As the culture ages, the vegetative hyphae also fragment into arthroconidia.
 Although Coccidioides spp. do not readily convert to the spherule stage at 37° C in the laboratory,
they produce a variety of mold morphologies at 22° C.

 Initial growth, which occurs within 3 to 4 days, is white to gray, moist, and glabrous.
 Colonies rapidly develop abundant aerial mycelia, and the colony appears to enlarge in a circular
bloom.
 Mature colonies usually turn tan to brown to lavender in color.
Histoplasma capsulatum

 Histoplasmosis is acquired by the inhalation of the microconidia of Histoplasma capsulatum.

 The microconidia are phagocytized by macrophages in the pulmonary parenchyma.
 In the host with intact immune defenses, the infection is limited and is usually asymptomatic, with
the only sequelae being areas of calcification in the lungs, liver, and spleen.
 With heavy exposure, however, acute pulmonary disease can occur.
 In the mild form of the disease, viable organisms remain in the host, quiescent for years, and are
the presumed source of reactivation in individuals with abrogated immune systems.
 In immunocompromised individuals, H. capsulatum can cause a progressive and potentially fatal
disseminated disease.

 Chronic pulmonary histoplasmosis in patients with chronic obstructive pulmonary disease (COPD)
can also occur.
 Other various manifestations of the disease include mediastinitis (swelling and and initiation in
the mediastinum) , pericarditis (inflammation of the two layers of the thin sac-like membranes that
surrounds the heart) ,and mucocutaneous lesions.

 H. capsulatum causes histoplasmosis, also known as reticuloendothelial cytomycosis, cave

disease, spelunker's disease, and Darling disease. Histoplasmosis occurs worldwide.
 This organism resides in soil with a high nitrogen content, particularly in areas heavily
contaminated with bat and bird guano.

Laboratory Diagnosis.

 Careful examination of direct smear preparations of specimens for histoplasmosis frequently

reveals the small yeast cells of H. capsulatum, particularly in infections seen in immunodeficient
hosts.
 Smears are stained with Giemsa or Wright stain, the yeast cells are commonly seen within
monocytes and macrophages, occurring in significant numbers, as shown in.
 Small cells, when found in tissue, resemble the blastoconidia of Candida glabrata, but they can
be differentiated by fluorescent antibody (FA) techniques or culture.

 Conversion of the mold form to the yeast form, using BHI agar incubated at 37° C, is confirmatory
for H. capsulatum.
 Direct antigen detection and serologic procedures for the diagnosis of histoplasmosis might be
adjuncts to culture methods.
 Using EIA methods, H. capsulatum antigen can be detected from serum, CSF, and urine with a
sensitivity of about 95%.
 Other assays include complement fixation, immunodiffusion, and latex agglutination to detect
circulating antibody, along with FA microscopy to detect viable or nonviable fungal elements in
tissue sections.

Paracoccidioides brasiliensis

 Although the primary route of infection for Paracoccidioides brasiliensis is pulmonary.

 Infection is usually unapparent and asymptomatic, subsequent dissemination leads to the
formation of ulcerative granulomatous lesions of the buccal, nasal, and occasionally
gastrointestinal mucosa.
 A concomitant striking lymph node involvement is also evident.
 It has a rather narrow range of temperature tolerance, as evidenced by its predilection for growth
in cooler areas of the body (nasal and oropharyngeal), dissemination to other organs, particularly
the adrenals, occurs with compromised host defenses.

 P. brasiliensis is the causative agent of paracoccidioidomycosis (South American blastomycosis,

Brazilian blastomycosis, Lutz-Splendore-Almeida disease, paracoccidioidal granuloma), a
chronic, progressive fungal disease endemic to Central and South America.
 Geographic areas of highest incidence are typically humid, high-rainfall areas, with acidic soil
conditions.

Laboratory Diagnosis.

 Direct microscopic examination of cutaneous and mucosal lesions demonstrates the

characteristic yeast cells.
 The typical budding yeast with multipolar budding at the periphery, resembling a mariner's wheel.
 Many buds of various sizes can occur, or there may be only a few buds, giving the appearance of
a so-called Mickey Mouse cap to the yeast cell.
 It also produces a variety of mold morphologies when grown at 22° C.
 Flat colonies are glabrous to leathery, wrinkled to folded, floccose to velvety, and pink to beige to
brown with a yellowish-brown reverse, resembling those of B. dermatitidis.
 On BHI-blood agar, at 37° C, the mycelial phase rapidly converts to the yeast phase.

Talaromyces (Penicillium) marneffei

 Talaromyces (Penicillium) marneffei is unique among the Talaromyces spp., being dimorphic.
 It is the only true pathogen in the genus. T. marneffei is a common cause of systemic infection in
immunocompromised patients who have visited the endemic region of Southeast Asia.

 This includes patients with AIDS, hematologic malignancies, or autoimmune disease and patients
undergoing organ transplantations. Infections are usually disseminated, with multiple organ
involvement.
 The fungus can be isolated from cutaneous lesions, which are frequently present in infected
individuals. Disseminated disease is typically fatal.

Laboratory Diagnosis.

 The yeastlike cells of T. marneffei can be detected in Wright-stained smears from skin lesions or
biopsy specimens.
 The cells resemble those of H. capsulatum, oval to cylindric, and may have a cross- wall.
 The mold form has sparse green aerial and reddish-brown vegetative hyphae and produces a red
diffusible pigment.
 Polymerase chain reaction (PCR) tests have been described for identification confirmation.
 Serologic assays have been shown to be important in early diagnosis; however, they are not
commercially available.

Agents of Systemic Mycoses

 Organisms that cause classic systemic fungal diseases have historically been categorized
together because they share several characteristics, such as mode of transmission, dimorphism,
and systemic dissemination.
 Although the term systemic generally refers to the organisms described here, it must be
understood that any fungus, in an immunocompromised host, has the potential to become
invasive and disseminate to sites far removed from the portal of entry.
 Spherule - thick walled spherical structure enclosing endospores and occuring in parasitic forms
of fungus of the genus Coccydiodes.
 Conversion to the yeast or spherule form occurs when it is incubated at 35° to 37° C on enriched
media with increased concentration of CO2.
 The morphology of the systemic dimorphic at 22° C.