Structure, Pathogenesis, Lab Diagnosis of Histoplasma capsulatum

Histoplasma capsulatum

Histoplasma capsulatumis a dimorphic fungus. Diseases caused byC.neoformansis commonly called cryptococcosis . It is an intracellular parasite. Its natural habitat is soil enriched with birds dropping. Birds are not infected however bats and other domestic animals may get infected with the organism.

• Disease caused by H. capsulatum is known as histoplasmosis.
• Reports of histopathology in acute histoplasmosis are rare.
• A case of fulminating acute histoplasmosis is described in which Histoplasma capsulatum was identified in a transbronchial biopsy.
• The yeast forms observed were of a typical size, but they were present within the alveoli.
• No tissue granulomata were noted.
• This unusual morphology is in sharp contrast to the classic description of the organism in tissues and presented diagnostic difficulties.
• Hematogenous dissemination is considered to be an important part of the pathogenesis of the disease, but it is rarely documented during the symptomatic phase of acute histoplasmosis.
• The observations stress the importance of obtaining culture material from extrapulmonary sites early in the course of acute histoplasmosis when a specific diagnosis is necessary.

Morphology

H. capsulatum is dimorphic fungi i.e. it grows well in soil and artificial culture media at 25-30° C as septate mycelium as an intracellular yeast in animal tissue. The yeast phase can also be seen on artificial culture media like Blood Agar when incubated at body temperature i.e. 37°C. In culture, asexual spores, Large round typically thick walled tuberculate macroconidia (8-14 mm in diameter) and smaller elliptical, smooth thin walled conidia(2-4mm in diameter).

H.capsulatum is a dimorphic fungus responsible for a wide range of clinical presentations, from asymptomatic infection or a mild influenza-like illness to disseminated sepsis.

Virulence factors and pathogenesis

The outer layer of H. capsulatum yeast cells displays several surface molecules that are involved in their internalization (various phagocytes and several carbohydrate-linked structures) which are intimately linked to fungal pathogenesis and virulence

1.Ability to survive phagolysosome

When an organism is inhaled, conidia or hyphae fragments are taken up by alveolar macrophages. Inside the macrophages, they behave as facultative intracellular organism i.e. they can survive and produce alkaline substance such as bicarbonates and ammonia that raise that pH and thereby inactivate the degradative enzymes of phagolysosome.

2.Dimorphism

Dimorphism is the ability of an organism to show two different morphological characteristics at two different thermal conditions. H.capsulatum forms mycelia when to growing at a temperature of 25-30°C while yeast forms are seen at body temperature i.e. 37°C.

The life cycle of Histoplasma capsulate

• H. capsulatum resides in the soil or decaying organic matter during the free-living mycelial stages.
• It produces fruiting bodies in two form i.e. of microconidia (2-5 µm) and macroconidia (5-18 µm).
• When people inhaled the microconidia, it reaches to the lower respiratory tract.
• Primary fungal infection also can occur by ingestion of the organism, but not been studied experimentally.
• The incubation period is about 2 weeks and during which the microconidia convert to the yeast phase and replicate by budding.
• These yeasts are subsequently phagocytosed by macrophages.
• The fungal infection either eliminated or the organism continues to reproduce intracellularly and disseminates throughout the body.

Transmission

• Histoplasmosis is not transmitted person to person except when a transplant patient has contracted histoplasmosis from a transplanted organ.
• The large majority of cases occur when people inhale fungal mycelia and spores, usually from a source where the fungus growth is enhanced.
• Such sources are a bat or chicken coops, bird droppings,bird houses, bird roosts, or soil contaminated with such droppings.
• Unfortunately, H. capsulatum can survive in soil for years and if the soil becomes airborne (dust), inhalation of H. capsulatum-contaminated dust may lead to histoplasmosis

Diseases caused byHistoplasma capsulatum

Diseases caused byH.capsulatumare commonly called histoplasmosis. Histoplasmosis may occur in different forms.

• An infection caused by a fungus Histoplasma is called histoplasmosis.
• The fungus lives in the environment, particularly in soil that contains large amounts of bird or bat droppings.
• When people breathe fungal spores from the air they can get histoplasmosis.
• Although most people who breathe in the spores don’t get sick, those who do may have a fever, cough, and fatigue.
• Many people who get histoplasmosis will get better with their defence mechanism.
• But in some people, such as those who have weakened immune systems, the infection can become severe.

1.Acute pulmonary histoplasmosis

It is acute pneumonia or influenza-like infection of lungs. In most case, the disease is self-limiting and symptoms like a fever and nonproductive cough are seen with such infections.

2.Chronic pulmonary histoplasmosis

About 95% of case of histoplasmosis are asymptomatic and self-limiting. However, a chronic pulmonary infection may occur sometimes. Clinical feature of chronic pulmonary infection resemble closely to that of pulmonary TB i.e. in the case of chronic pulmonary histoplasmosis, cavities are seen in the lungs.

3.Other disseminated diseases

The organism sometimes may get disseminated in various parts or organs of the body. Dissemination occurs through the reticule endothelial system with the primary site of dissemination being the lymph nodes, liver, spleen and bone marrow. Infection of the kidneys or meninges is also possible sometimes.

Lab diagnosis

Specimens: sputum, blood, bone marrow, aspirates or biopsy materials from various sites of lesions.

• Direct microscopy

Smears of septum or pus are stained with wright or Giemsa stains and examined microscopicallyH.capsulatumappears as small, oval yeast cells of 2-4 mm in diameter packed within macrophages. Blood and bone marrow smears may also be positive particularly in AIDS patients.

When facilities for fluorescence microscopy are available the yeast can also be seen in a calcofluor white preparation.

• Culture

H.capsulatumis a dimorphic fungus so it can grow in artificial media at 25-30°C as well as at 37°C. specimens when infusion agar with cycloheximide and chloromphenicol and incubated at 25C for 2-6 days, the samples yield white cottony mycelium. Small thin walled, smooth, round microconidia and characteristics large, round, spiny or tubercle macroconidia are also produced. At 37°C yeast phase of this dimorphic fungus induces.

• Histoplasmin skin test

Histoplasmin is a culture filtrate antigen of mycelial phase of this fungus. The antigen is injected intradermally. The test is similar to induration is checked after 72 hrs.

Prevention

There is no vaccine for H. capsulatum infection. In fact, there are no means of prevention except avoiding exposure in areas of endemic infection.

Treatment

No theory is needed in asymptomatic or mild primary infections. With progressive lungs lesions, oral itraconazole is beneficial. In disseminated diseases, amphotericin B is a treatment of choice. In meningitis, fluconazole is often used because it penetrates the spinal fluid well. Oral itraconazole is used to treat pulmonary or disseminated diseases as well as for chronic suppression in AIDS patients.

REFERENCE

D, Grenwood, Slack RCB, and Peutherer J. Medical Microbiology. Dunclude Livingstone: ELBS, 2001.

Cheesbrough, M.Medical Laboratory Manual for Tropical Countries.Vol 2. ELBS London, 2007.

Tille, P.Diagnostic Microbiology.13th. Elsevier, 2014.