Histoplasmosis: Cause, Types and Complications

Histoplasmosis is a is primarily a disease of reticuloendothelial system caused by an intracellular  and  dimorphic fungus Histoplasma capsulatum, which has been isolated from the soil which appears to be the source of infection for human beings. Symptoms vary greatly, but the disease mainly affects the lungs and occasionally other organs which may be fatal if left untreated.

Histoplasmosis: Cause, Types and  Complications

Histoplasmosis is very common among people living with AIDS. This is due to their compromised immune system. In immunocompetent individuals, past infection results in partial protection against disease if reinfected.

What is the causative agent of Histoplasmosis?

Histoplasmosis is a disease caused by a dimorphic fungus Histoplasma capsulatum, it is present in the tissues in yeast form (that measures 2–4 m in diameter) and in filamentous mold form in the cultures and in the soil (dimorphic). The perfect form of Histoplasma capsulatum is called Emmonsiella capsulate or Ajellomyces capsulatum.

Clinical Features of Histoplasmosis

Histoplasmosis is asymptomatic for 90-95 percent of most cases. It is expressed primarily by a positive histoplasmin skin test and also by lung calcification that can be observed by X-ray. Other common clinical manifestations includes:

  • Acute Pulmonary Histoplasmosis

The onset is similar to influenza with an incubation period which varies from 3 to 14 days and manifests as a general malaise with fever, chills, profuse sweating, sore throat, chest pain, cough and dyspnoea.

  • Chronic Progressive Pulmonary Type

This is a variation of acute form. It is a primary form that persists latent for a long time and then slowly presents the same symptoms as the acute disease but with haemoptysis and apical and sub apical cavities in a more pronounced infection

  • Disseminated Histoplasmosis

This form may occur at any age, but is most commonly seen in children under two years of age and elderly adults. The forecast is poor. Variable fever, anorexia, weight loss, general condition deterioration, anaemia, leukopenia, hepatosplenomegaly and multiple adenopathy are reported.

  • Cutaneous, Subcutaneous and Mucocutaneous Type

As a rule, skin and mucous membrane lesions are secondary and may occur in one of the forms described above. These usually occur as petechial or ecchymotic purpura, usually in the abdomen and chest.

Mode of Transmission of Histoplasmosis

  • Adult males are affected more often than females, but there are no sex-related differences in children.
  • The soil, which forms the fungal reservoir, is the source of infection.
  • Transfer from man to man or from animal to man is unknown.
  • In most cases, infection is caused by inhalation of spores (conidia and mycelial fragments) from contaminated soil.
  • When inhaled, it is accumulated in lung alveoli and conversion occurs intracellularly within the macrophages from the mycelial to pathogenic yeast form.
  • Within the macrophages, the yeast multiplies in about 15–18 hours. In spite of fusion with lysosomes, multiplication continues within phagosomes. This may be due to yeasts producing certain proteins that inhibit lysosomal protease activity.
  • Host protection against the fungus is a key component of cell-mediated immunity.
  • T lymphocytes are necessary to reduce the severity of the infection.
  • Histoplasma species that remained latent in healed granulomas may be reactivated in people with impaired cell-mediated immunity, resulting in histoplasmosis.

Laboratory Diagnosis of Histoplasma capsulatum

  • For laboratory examination, specimens such as peripheral blood, sternal bone marrow, sputum, skin lesion biopsy tissue, mucous membranes, lymph node, or autopsy tissue should be placed in sterile containers.
  • Smears can be made from blood, bone marrow, sputum, or other moist specimens directly.

Microscopic examination of Histoplasma capsulatum

  • Thick and thin smears should be made from peripheral blood, sternal bone marrow or other appropriate infected material and stained with Giemsa or Wright stain.
  • Under the microscope, the fungus appears in the polymorphonuclear cells as small oval yeast, 1 to 5 μm in diameter.
  • Fluorescent antibody technique was found to be useful in the diagnosis of histoplasmosis in tissues.

Cutural Response of Histoplasma capsulatum

  • Since Histoplasma capsulatum is dimorphic, infected material is inoculated in brain heart infusion (BHI) agar with cycloheximide and chloramphenicol and incubated at 25 ° C. Another set of antibiotic-free BHI agar with 6 percent blood is inoculated and incubated at 37 ° C. Cultures are examined for up to 3 weeks of incubation.
  • Slides prepared from cultures grown at room temperature (37° C) produces produces mycelial, cottony colonies characterized by thin, branching, septate hyphae that produce tubercular macroconidia and microconidia. The macroconidia are thick-walled spherical spores with a diameter of 8–20 m and a finger-like projection. This is the diagnostic form of Histoplasma capsulatum.
  • Microconidia are smaller, thin-walled spores and are the infectious form of the fungus.
  • Slide prepared from cultures grown at 25 °C produces the parasitic or tissue phase of the fungus (yeast) that measures 2–4 m in diameter. Yeast phase should be cultivated at room temperature in order to verify the conversion to the mycelial phase and the formation of chlamydospores.

Immunological Diagnosis of Histoplasmosis

The histoplasmin skin test, similar to the tuberculin test, is significant in epidemiological studies. However, a negative intracutaneous reaction that is positive is evidence of a new infection.

Treatment of Histoplasmosis

  • Amphotericin B is the drug of choice for treatment of disseminated disease.
  • Fluconazole is often recommended for meningitis due to its better penetration of the cerebrospinal fluid (CSF).
  • Asymptomatic or mild condition needs no treatment.

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