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Lecture 9 Systemic Infection Part 2

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37 views22 pages

Lecture 9 Systemic Infection Part 2

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maznhsyn435
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© © All Rights Reserved
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Systemic Mycoses part 2

Lec. 9

Dr. Nadhira Shaban Salih


Systemic mycoses
Coccidioidomycosis

• Coccidioidomycosis is fungal infection of respiratory system of human


and a wide variety of animal.

• Coccidioidomycosis is caused by inhalation of airborne spore of two


dimorphic, soil-borne, fungi Coccidioides immitis and C. posadasii.

• Coccidioides immitis (typically found in California) and Coccidioides


posadasii (typically found outside California).

• Endemic in semiarid desert soils of Southwestern USA, northwestern


Mexico and some parts of central and south America.
Coccidioidomycosis
The term coccidia is actually derived from
their tissue (parasitic) phase resembling
protozoa belonging to the genus Coccidia
that cause coccidiosis in domestic fowl and Spherule
rabbits.

As Coccidioides species are soil- dwelling


dimorphic fungi, the grow as white fluffy
filamentous molds in soil and as spherule at
body temperature. The hypha form may
rarely be found in human tissue
Clinical Manifesta-on
• Most of coccidioidal infection is self limiting and take place
in healthy individual.

• However, in few cases may develop progressive and even


fatal disease.
CT image of the lung
• Types of coccidioidomycosis: -

1. Pulmonary coccidioidomycosis

• The infection acquired through inhalation of arthroconidia


and average incubation time is about two weeks.

• Most of the cases are asymptomatic. However,


symptomatic pulmonary infection presents with acute flu
like symptoms such as headache, fever, cough, rash,
malaise and myalgia, which usually self- limiting.
Clinical Manifestation
2. Disseminated coccidioidomycosis

• The disseminated is defined as coccidioidal


disease that spread beyond pulmonary infection
and it occurs in 1% of infected individual with
coccidioidomycosis.

• The dissemination is through hematogenous


rout. The most common site is skin, bone and
brain.

• The coccidioidomycosis characterized by


numerous small “millet seed’ granulomas
throughout the lung and other organs.
Clinical Manifestation
3. Chronic coccoidioidal meningitis
• The disease can disseminate widely into meninges as chronic
meningitis, occur in one-third to one-half of all patient with
dissemination.

• Meningitis usually involve the basilar portion of the brain where thick
opaque membrane is formed, that obstructs flow of cerebrospinal
fluid.
Pathogenesis of coccidioidomycosis
• Lung is the usual portal of entry of this fungus and is the most commonly infected
organ.

• The infec6on occurs following inhala6on of arthroconidia of mycelial form of


Coccidioides species or reac6va6on of latent infec6on in immunocompromised
pa6ents.

• The cell wall of arthroconidia is an6-phagocy6c as it inhibit phygocytosis.

• In the host the arthroconidia swell to form think-walled spherules, which enlarge in
size and develop endospores.

• The mature spherules mechanically rupture, releasing endospore that spread locally
and disseminated to extra-pulmonary site.

• The spherules and endospores provide major barriers to host defense as spherules
are too large to be engulfed by phagocytes.
Life cycle of Coccidioides. Coccidioides spp. alternate between
saprobic (mycelia) (left) and parasitic (spherules) (right).hbtededx
Laboratory diagnosis
1. Specimens
• Sputum, pus and biopsy.

2. Direct microscopic examination

• Yeast form

• Appears as a spherule (15- 75μm in diameter)

• Thick double walled refractile wall filled with


endospores.

• Mycelial form

• Pseudohyphae occasionally found, which


fragments into arthrospores- highly infectious.
Laboratory diagnosis
3. Culture
• SDA or BHI agar with cycloheximide and
chloramphenicol

• Incubate at 37 C
̊ and 25 C
̊ for 4-5 days.

• the colony is moist and smooth at beginning


but rapidly become suede-like to downy
greyish white with tan to brown underside.

• The culture of Coccidioides species differ from


other dimorphic fungi because under standard
laboratory condiIon grow as mold at 37 C
̊ and
25 C
̊ .
Laboratory diagnosis
4. Skin test
• At present there are two sources of antigen are available and used for

serological test. These are mycelial phase (coccidiodin) and spherule phase
(Spherulin).

• The skin test is done by intradermal inoculation of coccidioidin antigen.

• positive test (5mm induration within 48 hrs).

• Endemic areas test not useful, because it does not distinguish between the
present and past infection.
Treatment
• Options

• Antifungal drugs (such as fluconazole, itraconazole and


ketoconazole, as well as amphotericin B)
• Surgical excision/debridement

• Some cases may resolve without treatment

• Lifetime treatment may be necessary

• E.g., HIV-1 infected patients with low CD4 cell counts.

Center for Food Security and Public Health, Iowa


State University, 2013
Paracoccidioidomycosis
• South American Blastomycosis or Brazilian blastomycosis

• Paracoccidiodomycosis is subacute , acute or chronic granulomatous systemic


fungal infection. characterized by formation of suppurative lesions in any part of
the body with a marked predilection for the lungs and skin.

• It involved primary lungs and subsequently disseminates to various mucosal


surfaces, skin, lymph nodes and occasionally to internal organs in otherwise
healthy individual.

• Causative agent: thermally dimorphic fungi Paracoccidioides braziliensis and


Paracoccidioides lutizii.

• Distribution:
• endemic in Latin America, esp. Brazil
• Imported cases are diagnosed in north America, Europe and Asia.
Types of paracoccidioidomycosis based on anatomic site of
infec2on
1. Pulmonary form Gilchrist disease, Chicago disease

• Asymptomatic.

• Dissemination is by hematogenous route.

2. Mucocutaneous form

• Cooler areas of body such as nasal and oropharyngeal.

• Ulcerative lesions seen in mouth, on lips, tongue and conjunctiva

3. Lymphatic Paracoccidioidomycosis

• Cervical lymphadenopathy and can spread to other lymph node .

4. Disseminated

• Seen in Immunocompromised patients.

• Disease spreads to other organs specially adrenals


Types of paracoccidioidomycosis based on duration of infection
1. Acute/ subacute form (Juvenile Type)

• Pa#ent present with acute/ subacute onset of disease.

• Less common and accounts for about 5% cases.

• Usually affect young adults and has rapidly progressive course with high mortality
rate.

• Characterized by involvement of re#culoendothelial system and found equally in


both sex.

2. Quiescent or Sequelae (Latent form)

• Paracoccidioidomycosis can either be eliminated or further progress once


established, thereby, leading to forma#on of quiescent or latent foci in a manner
dependent on bath fungal and host factors.
Types of paracoccidioidomycosis based on duration of infection
3. Chronic form (Adult Type)

• This form of disease is long lasting with slow onset and gradual change in general
conditions.

• This form divided into two sub-types: Unifocal (affect only one organ or system) and
Multifocal (affect more than one organ or system).

• Most common types and affect predominantly male of age 30 years or more.

• The chronic form results from reactivation of Quiescent lung lesions, Then
disseminated to other part of the body.
Clinical features
• The clinical manifestations of paracoccidioidomycosis range from an
asymptomatic infection to disease process with either acute or chronic
form.

• The acute form is characterized by involvement of reticuloendothelial


system and equally affect both sex.

• The chronic form shows predominantly pulmonary and/ or


mucocutaneous involvement and its prevalent in adult male.
Laboratory Diagnosis
1. Samples:
• sputum, pus, biopsy, bronchoalveolar lavage, csf

2. Direct Examination: -

• In direct examination appears as yeast, which characterized as:

• Yeast forms with multiple buds encircling mother cell.

• Mariner’s wheel or pilot’ wheel or mickey mouse cap appearance

• 15-30 μm

• Narrow based budding


Laboratory Diagnosis
1. Culture: -

• Media : SDA, BHI agar, Blood Agar

• Two media inoculated and incubated- one at 25°C and


one at 37°C.

• Slow growth- 6 weeks at 25°C

• Colony on medium at 25°C- Fluffy and tan coloured

• LPCB- septate hyphae which are sterile (no conidia)

• Colony on medium at 37°C white to Cream coloured,


wrinkle and rough to pasty in appearance.

• LPCB- mariner’s wheel


Treatment
• Itraconazole, fluconazole with
amphotericin B and ketoconazole

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