Histoplasmosis

Histoplasmosis is a fungal infection caused by Histoplasma capsulatum.^[2][3] Symptoms of this infection vary greatly, but the disease affects primarily the lungs.^[4] 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

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

While histoplasmosis is the most common cause of mediastinitis, this remains a relatively rare disease. Severe infections can cause hepatosplenomegaly, lymphadenopathy, and adrenal enlargement.^[4] Lesions often left calcification nodules as they are healed.^[12]

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.^[13][14] Distinct from POHS, acute ocular histoplasmosis may rarely occur in immunodeficiency.^[15][16]

Complications

In absence of proper treatment and especially in

After healing of lesions, hard, calcified lymph nodes can erode the walls of the airway, causing hemoptysis.^[17]

Mechanisms

H. capsulatum grows in soil and material contaminated with bird or bat droppings (

Within the phagosome, the fungus has an absolute requirement for thiamine.^[19] 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.^[20]

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 may be divided into these types:[23]^{: 316–317}

• Primary pulmonary histoplasmosis
• Progressive disseminated histoplasmosis
• Primary cutaneous histoplasmosis
• African histoplasmosis

• 
  Histopathology of Histoplasma capsulatum,

  histiocytes

  .
• 
  Histopathology of Histoplasma capsulatum,

  GMS stain

  , showing narrow budding yeast
• 
  Histoplasma capsulatum var. duboisii, methenamine silver stain
• 
  Macroconida form of Histoplasma capsulatum

Prevention

Testing or decontaminating most sites that may be contaminated with H. capsulatum is impractical, but the sources below list environments where histoplasmosis is common, and precautions to reduce a person's risk of exposure, in the three parts of the world where the disease is prevalent. Precautions common to all geographical locations would be to avoid accumulations of bird or bat droppings.^{[citation needed]}

The US National Institute for Occupational Safety and Health provides information on work practices and personal protective equipment that may reduce the risk of infection.^[24]

A review paper includes information on locations in which Histoplasma has been found in Africa (in chicken runs, on bats, in the caves bats inhabit, and in soil), and a thorough reference list including English, French, and Spanish language references.^[25]

Treatment

In the majority of

Liposomal preparations of amphotericin B are more effective than deoxycholate preparations. The liposomal preparation is preferred in patients who might be at risk of nephrotoxicity, although all preparations of amphotericin B have risk of nephrotoxicity. Individuals taking amphotericin B are monitored for renal function.[28] Liposomal amphotericin B is better at treating people with progressive disseminated Histoplasmosis and underlying HIV when compared to deoxycholate amphotericin B. Meanwhile, fluconazole performs poorly when compared to other azoles.^[29]

Treatment with itraconazole must continue for at least a year in severe cases,^[30] while in acute pulmonary Histoplasmosis, 6 to 12 weeks treatment is sufficient. Alternatives to itraconazole are posaconazole, voriconazole, and fluconazole. Individuals taking itraconazole are monitored for hepatic function.^{[citation needed]}

Prognosis

About 90% of patients with normal immune systems regain health without any intervention. Less than 5% need serious treatments.^{[citation needed]}

Epidemiology

H. capsulatum is found throughout the world. It is endemic in certain areas of the United States, particularly in states bordering the Ohio River valley and the lower Mississippi River. The humidity and acidity patterns of soil are associated with endemicity. Bird and bat droppings in soil promote the growth of Histoplasma. Contact with such soil aerosolizes the microconidia, which can infect humans. It is also common in caves in Southern and East Africa. 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.^[4]

In Canada, the

In non-endemic countries, 40-50% of histoplasmosis cases are diagnosed in immunocompromised patients (HIV/AIDS, transplanted patients, cancer patients).[35]

Histoplasmosis in Workplaces

H. capsulatum is commonly found across the United States. The fungus can grow in any materials corrupted with bird and bat droppings, but particularly manifests in soils.

These occurrences emphasize the importance of protective measures for workers. The CDC advises that those who work in potentially hazardous environments reduce their exposure as much as possible following the Hierarchy of hazard controls.^[37] They recommend that any build up of bird and bat droppings should be avoided if possible, but if it is unpreventable various engineering, administrative controls and personal protective equipment can be implemented in the workplace.^[40] The CDC also suggests that workplaces should be responsible for administrative controls such as developing a safety plan, posting notice of the risk of exposure, disposing of any potentially contaminated materials, and providing proper education on the dangers associated with histoplasma.^[37] Adequate personal protective equipment includes a respirator, hooded coveralls, shoe coverings, gloves, and eye protection.^[40]

History

Histoplasma was discovered in 1905 by

• Johnny Cash included a reference to the disease, even correctly noting its source in bird droppings, in the song "Beans for Breakfast".^[43]
• Bob Dylan was hospitalized due to histoplasmosis in 1997, causing the cancellation of concerts in the United Kingdom and Switzerland.^[44]
• In
  episode 21 of season three of the television series House M.D., a patient was diagnosed with histoplasmosis.^{[citation needed}
  ]
• In episode five of season one of the television series Dexter, Vince Masuka gets worried about getting histoplasmosis from the dust in the air and the hair of the rats.^{[citation needed]}
• In episode 5 of season 5 of Monsters Inside Me, "There's a Worm Crawling In My What?" (aired November 13, 2014), a video game programmer, Cody Fry was infected with the disease. He survived his initial bout with disease up to the premiere of the episode, but unfortunately, would die from the illness less than a year after the episode premiered, on October 23, 2015.^[45]
• In the
  Call The Midwife's 9th season, a character is diagnosed with the disease after initial confusion regarding whether his symptoms were more indicative of tuberculosis. He contracts it from the droppings of pet pigeons he keeps in his home.^{[citation needed}
  ]