Histoplasma
Histoplasma is a genus of fungi that includes several species responsible for the disease known as histoplasmosis. This fungus is commonly found in soil that is contaminated with bird or bat droppings, predominantly in specific regions such as the Ohio, Tennessee, Missouri, and Mississippi River basins in the United States, as well as tropical areas of Central and South America, eastern Asia, and parts of Africa. Histoplasma exhibits thermally dimorphic characteristics, meaning it changes form depending on temperature—growing as a mold in cooler soil and as a yeast at body temperature.
When inhaled, Histoplasma spores can lead to respiratory infections, with many individuals experiencing no symptoms. However, some may develop acute pulmonary histoplasmosis, which can present flu-like symptoms. Severe cases can lead to complications affecting the lungs, lymph nodes, and other organ systems, particularly in immunocompromised or elderly patients. Diagnosis typically involves laboratory testing, including cultures and blood tests, while treatment options range from antifungal medications to steroids, depending on the severity of the infection. In more complex cases, such as ocular histoplasmosis, specialized treatments may be required to address complications.
Histoplasma
- TRANSMISSION ROUTE: Inhalation
Definition
Histoplasma is a diverse genus of fungi containing multiple species that are the causative agent of the disease histoplasmosis.
![Micrograph showing Histoplasmosis in a granuloma. Liver biopsy. Periodic acid-Schiff diastase (PAS-D) stain. By Nephron (Own work) [CC-BY-SA-3.0 (creativecommons.org/licenses/by-sa/3.0) or GFDL (www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons 94416940-89287.jpg](https://imageserver.ebscohost.com/img/embimages/ers/sp/embedded/94416940-89287.jpg?ephost1=dGJyMNHX8kSepq84xNvgOLCmsE2epq5Srqa4SK6WxWXS)
![Micrograph showing histoplasmosis in a granuloma. Liver biopsy. Gomori's Methenamine Silver (GMS) stain. Histoplasma = clumps of black circles. Granuloma = large circle with big clumps of histoplasma in it. By Nephron (Own work) [CC-BY-SA-3.0 (creativecommons.org/licenses/by-sa/3.0) or GFDL (www.gnu.org/copyleft/fdl.html)], via Wikimedia Commons 94416940-89288.jpg](https://imageserver.ebscohost.com/img/embimages/ers/sp/embedded/94416940-89288.jpg?ephost1=dGJyMNHX8kSepq84xNvgOLCmsE2epq5Srqa4SK6WxWXS)
Natural Habitat and Features
The species H. capsulatum includes multiple varieties. H. c. var. capsulatum was once the term for the New World variety that causes histoplasmosis involving primarily the pulmonary and reticuloendothelial systems. However, research has led to a reclassification of Histoplasma species. What was previously known as H. capsulatum var. capsulatum is now recognized as multiple species, including H. capsulatum sensu stricto, H. mississippiense, and H. suramericanum. Each is associated with infections in different geographical regions. Another species, H. c. var. duboisii, the cause of African histoplasmosis, usually involves infections of the bones and skin.
Histoplasma is a naturally occurring fungus that is generally found in soil contaminated with either bird or bat droppings. It is endemic to the Ohio, Tennessee, Missouri, and Mississippi River basins of the United States. The fungus is also found in tropical areas of Central America, South America, eastern Asia, Australia, and eastern and Central Africa, often in caves that contain bat guano (feces).
Histoplasma is a thermally dimorphic fungus, which means that it has two morphs, or forms, depending upon the temperature at which it grows. At temperatures of approximately 77° Fahrenheit (25° Celsius), an average soil temperature, it grows in mold form. Colonies at this temperature grow slowly and have a granular to cottony texture and a whitish color that turns buff brown as the fungus ages. Once within a human host, growing at a normal body temperature of 98.6° F (37° C), ovoid, cream-colored budding yeast cells are formed. While within soil, the hyphae, or fungal strands, are septate and hyaline. Conidiophores, the spore-bearing portions of the fungus, grow at right angles to the parent colony, and both macroconidia and microconidia are present. The macroconidia are unicellular, large, tuberculate, thick-walled structures. These macroconidia are also called tuberculate chlamydospores or macro aleurioconidia. Histoplasma microconidia are unicellular and round and possess either rough or smooth walls.
Histoplasma grows best in moist, acidic soil conditions such as those found in caves, poultry houses, and silos serving as bird roosts. The fungus can contaminate soil for years, and spores can be inhaled when the soil is disturbed.
Pathogenicity and Clinical Significance
When spores of H. capsulatum from contaminated soil are inhaled, they lodge in the lungs. In the alveoli of the lungs, macrophages of the immune system attack the fungal spores and transport them to the lymph nodes of the chest. Inflammation, scarring, and calcification can then occur in the lungs. The majority of people who contract histoplasmosis, however, have no symptoms, but for some, an acute pulmonary phase of the disease occurs. Symptoms of acute pulmonary symptomatic histoplasmosis infection start within three to seventeen days of initial exposure. This phase is characterized by cold or flulike symptoms and may last two weeks or longer. Fever, periodic sweats, muscle aches, a dry cough, chest pain, and loss of appetite often occur.
Rare but serious complications of acute phase infection include enlargement of the lymph nodes of the chest, causing esophageal or airway obstruction, and making swallowing and breathing extremely difficult. Fibrosing mediastinitis, severe scarring of the lymph nodes in the chest, may also cause chest pain and breathlessness and can be life-threatening. Pericarditis (inflammation of the pericardial sac around the heart), meningitis (inflammation of the meninges and cerebrospinal fluid of the brain and spinal cord), and arthritis are all severe complications of acute histoplasmosis cases. Adrenal insufficiency may also occur if adrenal glands are destroyed by the fungus.
Chronic pulmonary cases of histoplasmosis symptomatically mimic tuberculosis. These cases usually occur in patients who already have a lung disease, such as emphysema. Disseminated or systemic cases of histoplasmosis affect multiple organ systems and can prove fatal to elderly or immunocompromised persons. Liver and spleen enlargement, Addison’s disease, meningitis, pericarditis, and pneumonia may all result from disseminated histoplasmosis.
Ocular histoplasmosis damages the retina, resulting in scar tissue that can lead to leakage and subsequent vision loss. In cases of African histoplasmosis, skin lesions and osteolytic lesions, particularly in the skull, ribs, and vertebrae, frequently develop. Also common is fever and lymph node enlargement.
Fungal samples from sputum, blood, and infected organs can be cultured in the laboratory for a definitive diagnosis of histoplasmosis. However, this process may take as long as four weeks, so it is not the diagnostic tool of choice for suspected cases of disseminated histoplasmosis. Blood samples may reveal antigens or antibodies against Histoplasma; antigens may also be present in the urine of infected persons. If a person has been infected in the past with Histoplasma, blood tests can give false-positive results, which may mask a different type of infection.
Fungal stain tests can be conducted on tissue samples, but because other fungi resemble H. capsulatum, a misdiagnosis is possible with this technique. Chest X-rays, computed tomography (CT) scans, and bronchoscopies may also be useful in assisting with a definitive diagnosis.
Drug Susceptibility
Treatment with amphotericin B for one to two weeks is standard for severe cases of acute pulmonary symptomatic histoplasmosis. Steroid treatment with drugs such as methylprednisolone may follow liposomal amphotericin B once patients are stabilized. Treatment with itraconazole may continue for up to one year following serious cases. Other antifungal drugs, such as fluconazole and ketoconazole, may occasionally be used. Posaconazole and voriconazole are alternatives that have shown effectiveness.
For chronic pulmonary histoplasmosis cases that involve cavitary lesions within the lungs, treatment includes long-term itraconazole use and surgical intervention. Ocular histoplasmosis treatment requires steroids. Presumed Ocular Histoplasmosis Syndrome (POHS) is considered a long-term complication and may be treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections or photodynamic therapy.
Bibliography
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“Histoplasmosis.” Cleveland Clinic, 8 Mar. 2023, my.clevelandclinic.org/health/diseases/24811-histoplasmosis. Accessed 22 Nov. 2024.
Hospenthal, D. R., and H. J. Becker. "Update on Therapy for Histoplasmosis." Infectious Medicine, vol. 26, 2009, pp. 121-124.
Kauffman, C. A. "Histoplasmosis: A Clinical and Laboratory Update." Clinical Microbiology Reviews, vol. 20, no. 1, 2007, pp. 115-132.
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Shoham, Shmuel. "Histoplasma Capsulatum." Johns Hopkins Medicine, 13 July 2024, www.hopkinsguides.com/hopkins/view/Johns‗Hopkins‗ABX‗Guide/540273/all/Histoplasma‗capsulatum. Accessed 22 Nov. 2024.