Systemic MycosesSystemic MycosesCoccidioides & Coccidioides &

ParacoccidioidesParacoccidioides

Prepared By:

Naila QamarNaila Qamar

Systemic Mycosis

These infections result from inhalation of the spores of dimorphic fungi that have their mold forms in the soil.

Within the lungs, the spores differentiate into yeasts or other specialized forms.

Most lung infections are asymptomatic and self-limited.

However, in some persons, disseminated disease develops in which the organisms grow in other organs, cause destructive lesions, and may result in death.

Infected persons do not communicate these diseases to others.

COCCIDIOIDECOCCIDIOIDEHISTOPLASMAHISTOPLASMABLASTOMYCESBLASTOMYCESPARACOCCIDIOIDESPARACOCCIDIOIDES

Systemic Mycoses

COCCIDIOIDECOCCIDIOIDE

General Characteristics

Etiological agent: Coccidiode immitis Mode Of Transmission: Inhalation; Respiratory droplet Primary site of infection- LUNGS, 90% of infection is

asymptomatic or they resolved spontaneously accompanied by high degree of specific resistance to infections

Causes dissemination to other sites Geographically restricted Dimorphic fungus

25 C- grows as filamentous mold 37C- yeast cell

COCCIDIOIDE Disease Coccidioides immitis causes coccidioidomycosis. Properties C. immitis is a dimorphic fungus that exists as a

mold in soil and as a spherule in tissue

Transmission & Epidemiology Coccidioide The fungus is endemic in arid regions of the

southwestern United States and Latin America. People who live in Central and Southern

California, Arizona, New Mexico, Western Texas, and Northern Mexico, a geographic region called the Lower Sonoran Life Zone, are often infected.

In soil, it forms hyphae with alternating arthrospores

and empty cells. Arthrospores are very light and are carried by the wind. They can be inhaled and infect the lungs.

Pathogenesis of Coccidioide

In the lungs, arthrospores form spherules that are large, have a thick, doubly refractive wall, and are filled with endospores.

Upon rupture of the wall, endospores are released and differentiate to form new spherules. The organism can spread within a person by direct

extension or via the bloodstream. Granulomatous lesions can occur in virtually any

organ but are found primarily in bones and the central nervous system (meningitis)

Dissemination from the lungs to other organs occurs in people who have a defect in cell-mediated immunity.

Pathogenesis of Coccidioide

Most people who are infected by C. immitis develop a cell-mediated (delayed hypersensitivity) immune response that restricts the growth of the organism.

One way to determine whether a person has produced adequate cell-mediated immunity to the organism is to do a skin test.

In general, a person who has a positive skin test reaction has developed sufficient immunity to prevent disseminated disease from occurring.

If, at a later time, a person's cellular immunity is suppressed by drugs or disease, disseminated disease can occur.

Clinical Findings of Coccidioide

Infection of the lungs is often asymptomatic and is evident only by a positive skin test and the presence of antibodies.

Some infected persons have an influenza like illness with fever and cough.

About. 50% have changes in the lungs (infiltrates, adenopathy, or effusions) as seen on chest x-ray.

10% develop erythema nodosum. This syndrome is called "valley fever” or "desert rheumatism"; it tends to subside spontaneously. Disseminated disease can occur in almost any organ; the meninges, bone, and skin are important

sites.

Clinical Findings of Coccidioide

The overall incidence of dissemination in persons infected with C. immitis is 1%, although the incidence in Filipinos and African Americans is 10 times higher. Women in the third trimester of pregnancy also have a markedly increased incidence of dissemination. Erythema nodosum (EN) manifests as red, tender nodules ("desert bumps") on the skin. It is a delayed (cell-mediated) hypersensitivity response to fungal antigens and thus is an indicator of a good prognosis.

Clinical Findings of Coccidioide

There are no organisms in these lesions; they are not a sign of disseminated disease. EN is not specific for coccidioidomycosis; it occurs in other granulomatous diseases, e.g, histoplasmosis, tuberculosis, and leprosy.

In infected persons, Skin testing for diagnosis of coccidioidomycosis involves the intradermal injection of a coccidioidal antigen preparation (eg, coccidioidin, spherulin). The induration of the skin is measured at 24 hours and 48 hours after the injection. An induration greater than 5 mm is considered reactive.

Skin tests become positive within 2-4 weeks of infection and remain so for years but are often negative in patients with disseminated disease.

Skin test

Laboratory Diagnosis of Coccidioide

In tissue specimens, spherules are seen microscopically. Cultures on Sabouraud's agar incubated at 25 °C show hyphae with arthrospores. (Caution: Cultures are highly infectious; precautions against inhaling arthrospores must be taken.)

Laboratory Diagnosis of Coccidioide

In serologic tests, IgM and IgG precipitins appear within 2-4 weeks of infection and then decline in subsequent months.

Complement-fixing antibodies occur at low titer initially, but the titer rises greatly if dissemination occurs

Treatment & Prevention of Coccidioide

No treatment is needed in asymptomatic or mild primary infection.

Amphotericin B (Fungizone) or itraconazole is used for persisting lung lesions or disseminated disease.

Ketoconazole is also effective in lung disease. Fluconazole is the drug of choice for meningitis. Intrathecal amphotericin B may be required and

may induce remission, but long-term results are often poor.

There are no means of prevention except avoiding travel to endemic areas.

PARACOCCIDIOIDESPARACOCCIDIOIDES

General characteristics Etiologic Agent: P. brazieliensis Central & South America & has high incidence in

Brazil, Venezuela & Colombia Natural reservoir: isolated in soil that have high

humidity & average temperature of 23 C Equal distribution among males & females, but

clinical disease is about 9X higher in males Transition of fungi from mold to yeast can be

induced in vitro by raising the temperature of 25 C to 37 C

M-17-beta- estradiol inhibits transformation of the fungi

Testosterone,corticosterone & 17 alpha estradiol had NO inhibitory on the transformation

Disease of Paracoccidioides

Paracoccidioides brasiliensis causes paracoccidioidomycosis,

also known as South American blastomycosis.

Properties of Paracoccidioides

P. brasiliensis is a dimorphic fungus that exists as a mold in soil and as a yeast in tissue.

The yeast is thick walled with multiple buds, in contrast to B. derrnatitidis, which has a single bud .

Transmission & Epidemiology of Paracoccidioides

The spores are inhaled, and early lesions occur in the lungs.

Asymptomatic infection is common. This fungus grows in the soil and is

endemic in rural Latin America. Disease occurs only in that region.

Pathogenesis & Clinical Findings of Paracoccidioides

The spores are inhaled, and early lesions occur in the lungs.

Asymptomatic infection is common. Alternatively oral mucous membrane lesions, lymph

node enlargement, and sometimes dissemination to many organs develop.

Ulceration, granulomatous infection of oral and nasal mucosa

Laboratory Diagnosis of Paracoccidioides

In pus or tissues, yeast cells with multiple buds are seen microscopically.

A specimen cultured for 2-4 weeks may grow typical organisms.

Skin tests are rarely helpful. Serologic testing shows that when significant

antibody titers (by immunodiffusion or complement fixation) are found, active disease is present

Treatment & Prevention of Paracoccidioides

The drug of choice is itraconazole taken orally for several months.

There are no means of prevention.