Histoplasmosis is a fungal infection caused by Histoplasma capsulatum. Symptoms of this infection vary greatly, but the disease affects primarily the lungs. Occasionally, other organs are affected; called disseminated histoplasmosis, it can be fatal if left untreated. H. capsulatum is found in soil, often associated with decaying bat guano or bird droppings. Humans may inhale infectious spores after disrupting the soil via excavation or construction. H. capsulatum has a one to two week incubation period within human lungs before symptoms arise. The disease is common among AIDS patients due to their immunosuppression. From 1938 to 2013 in the US, 105 outbreaks were reported in a total of 26 states and Puerto Rico. In 1978 to 1979 during a large urban outbreak in which 100,000 people were exposed to the fungus in Indianapolis, victims had pericarditis, rheumatological syndromes, esophageal and vocal cord ulcers, parotitis, adrenal insufficiency, uveitis, fibrosing mediastinitis, interstitial nephritis, intestinal lymphangiectasia, and epididymitis. Histoplasmosis mimics colds, pneumonia, and the flu, and can be shed by bats in their feces.
Signs and symptoms
If symptoms of histoplasmosis infection occur, they start within 3 to 17 days after exposure; the typical time is 12–14 days. Most affected individuals have clinically silent manifestations and show no apparent ill effects. The acute phase of histoplasmosis is characterized by nonspecific respiratory symptoms, often cough or flu-like. Chest X-ray findings are normal in 40–70% of cases. Chronic histoplasmosis cases can resemble tuberculosis; disseminated histoplasmosis affects multiple organ systems and is fatal unless treated. While histoplasmosis is the most common cause of mediastinitis, this remains a relatively rare disease. Severe infections can cause hepatosplenomegaly, lymphadenopathy, and adrenal enlargement. Lesions often leave calcification nodules as they are healed. Presumed ocular histoplasmosis syndrome causes chorioretinitis, where the choroid and retina of the eyes are scarred, resulting in a loss of vision not unlike macular degeneration. Despite its name, the relationship to Histoplasma is controversial. Distinct from POHS, acute ocular histoplasmosis may rarely occur in immunodeficiency.
Complications In the absence of proper treatment, and especially in immunocompromised individuals, complications can arise. These include recurrent pneumonia, respiratory failure, fibrosing mediastinitis, superior vena cava syndrome, pulmonary vessel obstruction, and progressive fibrosis of lymph nodes. Fibrosing mediastinitis is a serious complication and can be fatal. People who smoke and people with structural lung disease have a higher probability of developing chronic cavitary histoplasmosis. After healing of lesions, hard, calcified lymph nodes can erode the walls of the airway, causing hemoptysis.
Mechanisms H. capsulatum grows in soil and material contaminated with bird or bat droppings (guano). The fungus has been found in poultry-house litter, caves, areas harboring bats, and bird roosts (particularly those of starlings). 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 a yeast. Histoplasmosis is not contagious but is contracted by inhalation of the spores from disturbed soil or guano. The inoculum is represented principally by microconidia. These are inhaled and reach the alveoli. In the alveoli, macrophages ingest these microconidia. They survive inside the phagosome. As the fungus is thermally dimorphic, these microconidia are transformed into yeast. They grow and multiply inside the phagosome. The macrophages travel in the lymphatic circulation and can spread the disease to different organs. Within the phagosome, the fungus has an absolute requirement for thiamine. Cell-mediated immunity for histoplasmosis develops within 2 weeks. If the patient has strong cellular immunity, macrophages, epithelial cells, and lymphocytes surround the organisms and contain them, and eventually calcify. In immunocompromised individuals, the organisms disseminate to different organs such as bone, spleen, liver, adrenal glands, and mucocutaneous membranes, resulting in progressive disseminated histoplasmosis. Chronic lung disease can manifest.
Diagnosis
Clinically, a wide spectrum of disease manifestations occurs, making diagnosis somewhat difficult. More severe forms include the chronic pulmonary form, often occurring in the presence of underlying pulmonary disease, and a disseminated form, which is characterized by the progressive spread of infection to extrapulmonary sites. Oral manifestations have been reported as the main complaint of the disseminated forms, leading the patient to seek treatment, whereas pulmonary symptoms in disseminated disease may be mild or even misinterpreted as flu. Histoplasmosis can be diagnosed by samples containing the fungus taken from sputum (via bronchoalveolar lavage), blood, or infected organs. It can also be diagnosed by detection of antigens in blood or urine samples by ELISA or polymerase chain reaction. Antigens can cross-react with antigens of African histoplasmosis (caused by Histoplasma duboisii), blastomycosis, coccidioidomycosis, paracoccidioidomycosis, emergomycosis, and talaromycosis infection. Histoplasmosis can also be diagnosed by a test for antibodies against Histoplasma in the blood. Histoplasma skin tests indicate whether someone has been exposed, but do not indicate whether they have the disease. Formal histoplasmosis diagnoses are often confirmed only by culturing the fungus directly. Sabouraud agar is an agar growth medium on which the fungus can be cultured. Cutaneous manifestations of disseminated disease are diverse and often present as a nondescript rash with systemic complaints. Diagnosis is best established by urine antigen testing, as blood cultures may take up to 6 weeks for diagnostic growth to occur and serum antigen testing often comes back with a false negative before 4 weeks of disseminated infection. Occasionally, the much rarer disease emergomycosis may be misdiagnosed as histoplasmosis (or vice versa) because the presentation and appearance of these diseases may be nearly identical. Emergomyces sp. are primarily found in South Africa, and occasionally in Europe and Asia, with the risk of misdiagnosis mainly being limited to South Africa.
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