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LmFungal Diseases of the Respiratory System

Histoplasmosis

Histoplasmosis is a disease caused by the fungus Histoplasma capsulatum.Histoplasma capsulatum, is usually found in soil, and often associated with decaying bird droppings, poultry house litter, caves, and areas harboring bats.Symptoms of this infection vary greatly, but the disease affects primarily the lungs. Occasionally, other organs are affected, and it can be fatal if left untreated.Histoplasmosis (also known as “Cave disease,” “Ohio valley disease,” is a disease caused by the fungus Histoplasma capsulatum.Histoplasmosis is common among AIDS patients due to their suppressed immune system.

If symptoms of histoplasmosis infection occur, they will start within 12 to 14 days.

The acute phase of histoplasmosis is characterized by non-specific respiratory symptoms, often cough or flu-like.

Chronic histoplasmosis cases can resemble tuberculosis, and disseminated histoplasmosis affects multiple organ systems and is fatal unless treated.

Positive histoplasmin skin tests occur in as many as 90% of the people living in areas where H. capsulatum is common, such as the eastern and central United States

The fungus is thermally dimorphic: in the environment it grows as a brownish mycelium, and at body temperature (37 °C in humans) it morphs into yeast.

The inoculum is represented principally by microconidia that, once inhaled into the alveolar spaces, germinate and then transform into budding yeast cells. Histoplasmosis is not contagious. It is usually a subclinical infection. The organism tends to remain alive in the scattered pulmonary calcifications; therefore, some cases are detected by emergence of serious infection when a patient becomes immunocompromised.

The disease that resembles acute pneumonia but is usually self-limited. It is most often seen in children newly exposed to H. capsulatum or in heavily exposed individuals. Erythematous skin conditions arising from antigen reactions may complicate the disease, as may myalgias, arthralgias, and rarely, arthritic conditions. Emphysema sufferers may contract chronic cavitary pulmonary histoplasmosis as a disease complication Another uncommon form of histoplasmosis is a slowly progressing condition known as granulomatous mediastinitis, in which the lymph nodes in the mediastinal cavity between the lungs become inflamed and ultimately necrotic; the swollen nodes or draining fluid may ultimately affect the bronchi, the superior vena cava, the esophagus or the pericardium. Histoplasmosis, like Blastomycosis, may disseminate haematogenously to infect internal organs and tissues, but it does so in a very low proportion of cases, and half or more of these dissemination cases involve immunocompromise.

Diagnosis

Sputum samples containing the fungus, blood, or infected organs. Detection of antigens in blood or urine samples by ELISA or PCR. A test for antibodies against Histoplasma in the blood.

Histoplasma skin tests indicate whether a person has been exposed, but do not indicate whether they have the disease.

Formal histoplasmosis diagnoses are often confirmed only by culturing the fungus directly. Diagnosis is best established by urine antigen testing . Blood cultures may take up to 6 weeks for diagnostic growth to occur.

Coccidioidomycosis

Coccidioidomycosis is a fungal disease caused by Coccidioides immitis or C. posadasii.C. immitis resides in the soil in certain parts of the southwestern United States, northern Mexico, and parts of Central and South America.Infection is caused by inhalation of the particles.The disease is usually mild, with flu-like symptoms and rashes.Coccidioidomycosis (commonly known as “Valley fever”, as well as “California fever”, “Desert rheumatism”, a fungal disease caused by Coccidioides immitis or C. posadasii.

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C. immitis is dormant during long dry spells, then develops as a mold with long filaments that break off into airborne spores when the rains come. The spores, known as arthroconidia, are swept into the air by disruption of the soil, such as occurs during construction, farming, or an earthquake.

Infection is caused by inhalation of the particles. The disease is not transmitted from person to person. The infection ordinarily resolves leaving the patient with a specific immunity to re-infection. C. immitis is a dimorphic saprophytic organism that grows as a mycelium in the soil and produces a spherule form in the host organism.The disease is usually mild, with flu-like symptoms,cough, myalgia, fever, headaches and rashes. Serious complications include severe pneumonia, lung nodules, and disseminated disease, where the fungus spreads throughout the body, causing skin ulcers, abscesses, bone lesions, severe joint pain, heart inflammation, urinary tract problems, meningitis, and often death.

Diagnosis

The fungal infection can be demonstrated by microscopic detection in body fluids, exudates, sputum and biopsy-tissue.

With specific nucleotide primers, C.immitis DNA can be amplified by PCR.

It can also be detected in cultures by morphological identification, or by using molecular probes that hybridize with C.immitis RNA.

An indirect demonstration of fungal infection can be achieved also by serologic analysis detecting fungal antigen or host antibody produced against the fungus.

Pneumocystis Pneumonia

Pneumocystis pneumonia or pneumocystosis is a form of pneumonia, caused by the yeast-like fungus Pneumocystis jirovecii.

An opportunistic infection that take advantage of certain situations—such as bacterial, viral, fungal or protozoan infections that usually do not cause disease in a healthy host, one with a healthy immune system.

Pneumocystis is commonly found in the lungs of healthy people, but being a source of opportunistic infection, it can cause a lung infection in people with a weak immune system. Pneumocystis pneumonia is especially seen in people with cancer, HIV/AIDS and the use of medications that affect the immune system.

Symptoms of Pneumocystis Pneumonia Symptoms include fever, non-productive cough (because

sputum is too viscous to become productive), shortness of breath (especially on exertion), weight loss, and night sweats. There is usually not a large amount of sputum with PCP unless the patient has an additional bacterial infection. The fungus can invade other visceral organs (such as the liver, spleen, and kidney), but only in a minority of cases.

Pneumothorax is a well-known complication of PCP . An acute history of chest pain with breathlessness and diminished breath sounds .

Diagnosis

Appearance of the chest x-ray, which shows widespread pulmonary infiltrates.

The diagnosis can be definitively confirmed by histological identification of the causative organism in sputum or bronchio-alveolar lavage (lung rinse).

Staining with toluidine blue, silver stain, periodic-acid schiff stain, or an immunofluorescence assay will show the characteristic cysts.

The cysts resemble crushed ping-pong balls and are present in aggregates of 2 to 8 (and not to be confused with Histoplasma or Cryptococcus, which typically do not form aggregates of spores or cells).

A lung biopsy would show thickened alveolar septa with eosinophilic exudate in the alveoli.

Pneumocystis infection can also be diagnosed by immunofluorescent or histochemical staining of the specimen

More recently by molecular analysis of polymerase chain reaction products comparing DNA samples.

Notably, simple molecular detection of Pneumocystis jirovecii in lung fluids does not mean that a person has Pneumocystis pneumonia. The fungus appears to be present in healthy individuals in the general population.

Blastomycosis

Blastomycosis is a fungal infection caused by the organism Blastomyces dermatitidis.

Blastomycosis (also known as“North American blastomycosis, Blastomycetic dermatitidis”

Infection occurs by inhalation of the fungus from its natural soil habitat. Once inhaled in the lungs, Blastomycosis multiply and may disseminate

through the blood and lymphatics to other organs, including the skin, bone, genitourinary tract, and brain.

Symptoms

Blastomycosis can present in one of the following ways:

A flu-like illness with fever, chills, myalgia, headache, and a nonproductive cough which resolves within days

An acute illness resembling bacterial pneumonia, with symptoms of high fever, chills, a productive cough, and pleuritic chest pain

A chronic illness that mimics tuberculosis or lung cancer, with symptoms of low-grade fever, a productive cough, night

sweats, and weight loss A fast, progressive, and severe disease that manifests as ARDS, with

fever, shortness of breath, tachypnea, hypoxemia, and diffuse pulmonary infiltrates

Skin lesions, that appear as ulcerated lesions with small pustules at the margins

Bone lytic lesions that can cause bone or joint pain. Prostatitis may be asymptomatic or may cause pain on urinating. Laryngeal involvement causes hoarseness.

The incubation period is 30 to 100 days, although infection can be asymptomatic.

Diagnosis

The diagnosis of blastomycosis can usually be confirmed by demonstration of the characteristic, broad-based budding organisms in sputum or tissues by KOH prep, cytology, or histology.

Blastomycosis is histologically associated with granulomatous nodules. Commercially available urine antigen testing appears to be quite

sensitive in suggesting the diagnosis in cases where the organism is not readily detected.

While culture of the organism remains the definitive diagnostic standard, its slow growing nature can lead to delays in treatment of up to several weeks.