Somali International University

Faculty of Medicine and Health Sciences

Department of General Medicine and Surgery

Systemic Mycosis

Mr. Mohamed Yusuf Abdi

Master Degree in Microbiology and Immunology

 General features
• Systemic mycosis cause a disease in healthy persons, but the most serious disease still
occurs in immunocompromised persons, such as patients with HIV/AIDS, have a
greatly increased risk of serious infection.
• Most species are dimorphic.
• None is transmitted from human to human.
• Clinical manifestations closely resemble those seen in tuberculosis.
• Entry into the host is by inhalation of airborne spores, which germinate in the lungs.
• Most infections are asymptomatic or mild and resolve without treatment.
• These are the include histoplasmosis, blastomycosis, coccidioidomycosis and
paracoccidioidomycosis.
Histoplasmosis
 Histoplasmosis
• Histoplasmosis is an intracellular infection of the reticuloendothelial system caused by the
dimorphic fungus Histoplasma capsulatum.
• In nature, H.capsulatum grows as a mold in association with soil and avian habitats.
• The primary site of infection is the lungs following inhalation of the conidia from the environment.
• Most infections are asymptomatic.
• Some infected persons develop pulmonary disease which resembles tuberculosis.
• Histoplasmosis occur worldwide however, most cases occur in the United States.
• African histoplasmosis, caused by H.duboisii, is endemic to central and western Africa, the majority
of cases have been reported from Nigeria. The ecology of the var. duboisii is not well-known, but it
has been found in bat caves.
 Pathogenesis

• After inhalation, the conidia develop into yeast cells and are engulfed by
alveolar macrophages, where they are able to replicate.
• The yeast form of H. capsulatum is uniquely able to survive within the
phagolysosomes of macrophages through several mechanisms, including the
ability to resist killing and to modulate the intraphagosomal pH.
• Within macrophages, the yeasts may disseminate to reticuloendothelial
tissues such as the liver, spleen, bone marrow, and lymph nodes.
• In over 95% of cases, the resulting cell-mediated immune response leads to
the secretion of cytokines that activate macrophages to inhibit the
intracellular growth of the yeasts.
• Finally, after several weeks, specific T-cell immunity develops, macrophages
become activated, and then killing of the organism ensues. At this point,
long-lasting immunity to H. capsulatum occurs.
 Clinical Manifestations

• The extent of disease is determined both by the immune response of the host and
the number of conidia that are inhaled.
• A healthy individual can develop severe life-threatening pulmonary infection if a
large number of conidia are inhaled.
• However, because dissemination is the rule, latent infection probably persists for
an lifetime and reactivation can result if the host becomes immunosuppressed.
• Reinfection histoplasmosis is usually less severe than primary infection because
there is residual immunity induced by the initial episode.
 Pulmonary Histoplasmosis
Acute Pulmonary Histoplasmosis :
• The usual result of exposure of a normal host to H. capsulatum is asymptomatic infection.
• Acute pulmonary histoplasmosis is most often manifested as a self-limited illness usually
presents as a non-specific flu-like illness characterized by dry cough, fever, chest pain,
loss of appetite and fatigue.
• A few patients present with an aseptic arthritis or arthralgia.
• On radiographic examination, most patients will have lymphadenopathy and pulmonary
nodules.
• These symptoms resolve spontaneously without therapy, and the granulomatous nodules in
the lungs or other sites heal.
Chronic pulmonary histoplasmosis :
• Occurs most often in men and is usually a reactivation process or with underlying
chronic obstructive pulmonary disease.
• The clinical manifestations include fatigue, fever, night sweats, chronic cough,
sputum production, hemoptysis, dyspnea, and weight loss.
• This reactivation is usually precipitated by pulmonary damage.
• The clinical picture- closely resembles tuberculosis.
• The differential diagnosis of chronic pulmonary histoplasmosis also includes
mycobacterial infections, blastomycosis, sporotrichosis, and coccidioidomycosis.
 Disseminated Histoplasmosis

• Disseminated infection occurs most often in old age and infancy, or in

individuals with impaired immune responses.
• The reticuloendothelial system is especially apt to be involved, with
lymphadenopathy, enlarged spleen and liver, high fever, anemia, and a high
mortality rate without antifungal therapy.
• Mucocutaneous ulcers of the nose, mouth, tongue, and intestine can occur.
• The yeasts may be present in macrophages in the blood, liver, spleen, and
bone marrow.
 African Histoplasmosis

• Bone and skin are the two major organs affected.

• Multiple papular lesions often develop on the face and trunk .
• Osteomyelitis occurs in about 30% of patients with African histoplasmosis
• The lesions are often painless.
• The infection may spread into contiguous joints causing arthritis.
• The infection is not life-threatening.
 Laboratory Diagnosis

• The definitive diagnostic test for histoplasmosis is growth of H. capsulatum from tissue or body fluids.
• Specimens for culture include sputum, urine, scrapings from superfcial lesions, bone marrow aspirates,
and buffy coat blood cells.

• In microscopic examination, a small ovoid cells may be observed within macrophages in histologic
sections stained with fungal stains (eg, Gomori methenamine silver, periodic acid-Schiff, or calcofluor
white) or in Giemsa-stained smears of bone marrow or blood.

• Specimens are cultured in glucosecysteine blood agar at 37°C and on Sabouraud’s agar.
• In serology, antibodies to histoplasmin or the yeast cells become positive within 2–5 weeks after infection.
• All patients with disseminated histoplasmosis have a positive test for antigen in the serum or urine.
• The histoplasmin skin test becomes positive soon after infection and remains positive for years.
 Treatment and Prevention

• Most patients infected with H. capsulatum are asymptomatic or have mild, self-
limited disease and, thus, do not need treatment with an antifungal agent.
• Itraconazole is the treatment for mild to moderate infection.
• In disseminated disease, systemic treatment with amphotericin B is often curative.
• Workers should wear a respirator when dismantling known bird or bat roosts or
chicken coops, refurbishing old structures that are found to have provided roosts
for bats or birds, and moving large quantities of soil in areas known to be highly
endemic for H. capsulatum.
Blastomycosis
 Blastomycosis

• Blastomycosis is a chronic infection of the lungs which may spread to other tissues,
particularly skin, bone and genitourinary tract.
• The disease has been called North American blastomycosis, also endemic in Africa.
• Soil is considered to be the source of infection, which is acquired by inhalation.
• The disease often occurs in individuals with an outdoor occupation, such as
construction or farming, or recreational interest, such as hunting, fishing or boating.
• Blastomycosis is more commonly seen in adults than children.
• More men than women are affected.
 Pathogenesis and Clinical Findings

• Human infection is initiated in the lungs.

• Acute lower respiratory infections (fever, malaise, cough, night sweats, sputum
production, chest pain and myalgias).
• Patients can also present with chronic pneumonia.
• When dissemination occurs, skin lesions on exposed surfaces are most common.
• The cutaneous disease is usually on the skin of the face or other exposed parts of
the body.
• Fewer than 10% of chronic infections have brain involvement.
• The involvement of the reticuloendothelial system and adrenal glands is
uncommon.
 Laboratory Diagnosis

• Specimens: Sputum or pus, exudates, urine and biopsy lesions.

• Microcopic examination: Potassium hydroxide (10%) mount of specimens may
show characteristic thick-walled yeast cells with a single broad based bud.
• Culture: Sabouraud’s dextrose agar or enriched blood agar at 30°C within 2 weeks.
• Serology: Antibodies can be measured by complement fixation (CF) test, and
enzyme immunoassay (EIA).
• Histopathology
 Treatment

• Some patients with blastomycosis recover spontaneously without specific

antifungal therapy just as occurs in the majority of cases of histoplasmosis.
• Severe cases of blastomycosis are treated with amphotericin B.
• In patients with confined lesions, a 6-month course of itraconazole is very
effective.
Coccidioidomycosis
 Coccidioidomycosis

• This is primarily an infection of the lungs.

• Coccidioidomycosis is endemic in well-circumscribed semiarid regions of the
south western United States, Central America, and South America.
• Infection is usually self-limited, and dissemination is rare but always serious,
and it may be fatal.
• Human infection has been associated with building construction, landscaping,
and farming.
• Risk factors for severe pulmonary disease include older age and diabetes
mellitus, both of which are associated with alterations in host immunological
response and smoking.
 Pathogenesis and Clinical Findings

• Inhalation of conidia leads to A primary infection that is asymptomatic in 60% of

individuals.
• The other 40% of individuals develop a self-limited influenza like illness with fever,
malaise, cough, arthralgia, and headache.
• This condition is called valley fever, san joaquin valley fever, or desert rheumatism.
• After 1–2 weeks, about 15% of these patients develop hypersensitivity reactions.
• Less than 1% of persons infected develop secondary or disseminated coccidioidomycosis,
which is often debilitating and life-threatening.
 Laboratory Diagnosis

• Specimens: Sputum, pus and biopsy material.

• Microscopic Examination: Diagnosis may be made by microscopic
examination of specimens.
• Culture: Specimen is inoculated on SDA medium in the test tube and incubated
at 25–30°C.
• The conidia are highly infectious.
• Serological tests: agglutination test.
 Treatment

• In most persons, symptomatic primary infection is self limited and

requires only supportive treatment.
• Itraconazole may reduce the symptoms.
• Patients who have severe disease require treatment with amphotericin
B, which is administered intravenously.
• The disease is not communicable from person to person.
Paracoccidioidomycosis
 Paracoccidioidomycosis

• Disease is confined to south America, it is called ‘south American

blastomycosis’
• This is a chronic granulomatous disease of the skin, mucosa, lymph nodes
and internal organs.
• It is caused by paracoccidioides brasiliensis, a dimorphic fungus.
• P. Brasiliensis is a soil-inhabiting fungus.
 Clinical manifestations

• Little is known of the pathogenesis of paracoccidioidomycosis, although the route of

infection is believed to be inhalation.
• In most cases the primary infection is asymptomatic.
• Paracoccidioidomycosis is a pleomorphic disease that may affect any organ or system
and resemble other conditions, thus making diagnosis difficult in many patients.
• All patients complain of constitutional symptoms such as malaise, weight loss, asthenia,
and sometimes fever.
• Hematogenous route to mucosa of the nose, mouth and the gastrointestinal tract, skin,
lymphatic system, and the internal organs producing chronic granulomatous reaction.
 Laboratory diagnosis

• Specimens: Sputum or pus, crusts and biopsies from granulomatous lesions.

• Microscopy of sputum or pus, crusts and biopsies from granulomatous lesions
usually reveals numerous yeast cells.
• Culture: P. brasiliensis grows in the mycelial phase in culture at 25–30°C, and
in the yeast phase in tissue or at 37°C. Blood agar (without cycloheximide) and
incubation at 37°C is recommended for isolation of the yeast phase (tissue form).
Mycelial (mold) phase of the fungus develops on SDA incubated at 25–30°C.
• Histopathology: Tissue sections should be stained with H and E, PAS and
GMS.
 Treatment

• Oral itraconazole is the drug of choice for the treatment (6 months).

• Oral ketoconazole is almost as effective ( 6-18 months).
• AmphotericinB remains a useful drug for the management of severe
or refractory paracoccidioidomycosis. ( 4-8 weeks ).
Thank You
Properties Fungi Bacteria

Nucleus    

Cytoplasm    

Cytoplasmic    
membrane

Cell wall    

Metabolism    
 Features Actinomycetoma Eumycetoma

Etiological agent    

Progression of the disease    

Destruction    

Bone involvement    

Gram stain    

Culture media    

Treatment