Histoplasmosis is a fungal infection caused by the organism Histoplasma capsulatum (H. capsulatum). The infection is usually mild and asymptomatic, but in approximately 5% of cases it causes a sudden, short-term (up to 10 days), flu-like respiratory illness. In very rare cases (1% to 5%) it can produce serious syndromes that progress rapidly and may result in death. Because of the similarity in symptoms, histoplasmosis is sometimes mistaken for tuberculosis. Approximately 500,000 people are exposed to H. capsulatum annually in the United States.

Most cases of histoplasmosis produce no symptoms or symptoms that are extremely mild. Signs and symptoms that occur in rare cases include the following:

• Acute, flu-like infection – includes fever, chills, cough, chest pain, and headache 
• Chronic lung infection – develops gradually over weeks to months and produces a progressive, worsening cough, weight loss, night sweats, and possibly, shortness of breath 

When the disease spreads throughout the body and affects many organ systems, a person may experience fever, chills, weight loss, enlarged liver and spleen, swollen lymph nodes, ulcers in the mouth, stomach ulcers that may bleed, infection of heart valves, meningitis (inflammation of the membranes of the brain and spinal cord), anemia, and elevated calcium levels.

The primary cause of histoplasmosis is exposure to the organism H. capsulatum, which is found primarily in mild climates worldwide. More people living in the Ohio and Mississippi river valleys of the United States have been infected with H. capsulatum than anywhere else in the world. H. capsulatum grows in moist soil that is rich in nitrogen or in areas contaminated with bird or bat droppings, such as attics, barns, caves, and city parks. The spores of H. capsulatum are inhaled into the lungs and transformed into the yeast form of the fungus. The yeast multiply in lung cells, but usually do not spread to other parts of the body in individuals with healthy immune systems. In those with weakened immune systems, the yeast may spread to the lymph nodes, liver, spleen, bone marrow, adrenal glands, and gastrointestinal tract.

The risk factors for histoplasmosis include:

• Exposure to soil contaminated with bird and bat droppings 
• Residence in areas where histoplasmosis is prevalent 
• Construction-related activities, such as bulldozing or demolition, that disturb contaminated soil 
• Conditions that suppress the immune system, including AIDS, corticosteroid therapy, organ transplantation, and chemotherapy 
• Lung disease 
• Spelunking (exploring caves) 
• Male gender – males are four times more likely than women to become infected
• Very young or very old age 
• Cigarette smoking 

Because most cases of histoplasmosis produce no symptoms, the condition can be difficult to diagnose. In addition to a physical exam, a physician may perform the following tests to confirm the diagnosis:

• Blood test 
• Mucus test 
• Urine test 
• Chest X ray 

The best solution to the problem of histoplasmosis is to avoid exposure to H. capsulatum, the organism that causes the infection. The following steps may help prevent the infection:

• Wear masks or respirators when exposed to areas contaminated by bird or bat droppings 
• Spray contaminated areas with 3% formalin (this will kill the fungus) 

Mild cases of histoplasmosis usually require minimal treatment, such as bed rest and analgesics (pain medication). More serious cases of histoplasmosis, with symptoms that include a high fever, respiratory distress, loss of appetite, and malaise, are treated with antifungal medications (medications that inhibit the growth of fungi). While complementary and alternative therapies have not been widely studied for their use in the treatment of histoplasmosis, preliminary studies suggest that garlic may enhance the therapeutic effects of some medications.

Medications used to treat histoplasmosis inhibit the growth of fungi in the body. These medications are often used in severe cases when the infection has spread to various organs and tissues throughout the body.

• Amphotericin B (intravenous)
• Intraconazole (oral) 
• Ketoconazole (oral) 

Surgery is only necessary in rare cases when serious complications associated with the infection arise. Some surgical procedures include:

• Laser photocoagulation – procedure used to prevent visual impairment when infection spreads to the eyes 

• Surgical resection – procedure used to remove heart valves infected with H. capsulatum 

N-acetylcysteine

Although N-acetylcysteine (NAC) has yet to be investigated in scientific studies, some researchers theorize that this supplement may be effective in treating lung infections such as histoplasmosis. Laboratory studies indicate that N-acetylecysteine may scavenge free radicals (damaging molecules) in lung tissue, but its effectiveness in humans has yet to be established.

Garlic (Allium sativum)

Laboratory studies indicate that extracts of garlic (Allium sativum) may inhibit the growth of H. capsulatum. Studies also suggest that garlic may enhance the therapeutic effects of amphotericin B, a medication commonly used to treat histoplasmosis. These findings suggest that individuals with weakened immune systems who are required to take high doses of amphotericin B to treat histoplasmosis may benefit from a shorter treatment period at a lower dose with garlic supplementation. Further studies are needed however, to conclusively determine what role, if any, garlic may have in the treatment of histoplasmosis.

A trained herbalist may also recommend the following antifungal herbs to treat histoplasmosis:

• Grapefruit seed extract 
• Bromelain (Ananas comosus) 

The medications used to treat histoplasmosis may interact adversely with the antihistamine medications terfenadine and astemizole, possibly producing abnormal heart rhythms.

Individuals with histoplasmosis should also avoid supplementation with vitamin D and calcium; case reports suggest that they may worsen the condition and promote the spread of infection throughout the body.

Fortunately, serious complications associated with histoplasmosis are extremely rare. These complications may include:

• Formation of fibrous tissue in the lining of the chest wall cavity, which may compress the esophagus, heart, or lungs, affecting their ability to function properly 
• Enlargement of lymph nodes – may constrict airway, esophagus, or large blood vessels in the chest region 
• Scar tissue in the lungs 
• Blindness – may occur if infection spreads to the eyes

Many cases of histoplasmosis are mild and resolve in 10 days without treatment. Occasionally, however, symptoms may persist for several weeks. In the most severe cases, particularly when the infection spreads to various organs throughout the body, long-term therapy with antifungal medications may be necessary. If left untreated, however, such severe cases generally result in death. Individuals who contract histoplasmosis in areas where infection is prevalent may experience a second infection – even after adequate treatment – but the second infection is usually milder than the first. Relapse is more likely in those with weakened immune systems, although it can happen in individuals with healthy immune systems as well. In general, however, histoplasmosis produces no long-term complications and is rarely fatal.

Bennett JE. Histoplasmosis. In: Fauci AS, Braunwald E, Isselbacher KJ, et al, eds. Harrison's Principles of Internal Medicine. 14th ed. New York, NY: McGraw Hill; 1998:1150-1151.

Blumenthal M, ed. Herbal Medicine: Expanded Commission E Monographs. Newton, Mass: Integrative Medicine Communications; 2000:33-35.

Bradsher RW. Histoplasmosis and blastomycosis. Clin Infect Dis. 1996;22(suppl 2):S102-S111.

Conces DJ Jr. Histoplasmosis. Semin Roentgenol. 1996;31(1):14-27.

Davies SF. Histoplasmosis: update 1989. Semin Respir Infect. 1990;5(2):93-104.

Davis LE, Shen J, Royer RE. In vitro synergism of concentrated Allium sativum extract and amphotericin B against Cryptococcus neoformans. Planta Med. 1994;60(6):546-549.

Fliermans CB. Inhibition of Histoplasma capsulatum by garlic. Mycopathol Mycol Appl. 1973;50(3):227-231.

Goldman L, Bennett JC. Cecil Textbook of Medicine. 21st ed. Philadelphia, Pa: W.B. Saunders; 2000:1860-1862.

Gorbach SL, et al. Infectious Diseases. 2nd ed. Philadelphia, Pa: W.B. Saunders; 1998:2335-2341.

Gurney JW, Conces DJ. Pulmonary histoplasmosis. Radiology. 1996;199(2):297-306.

Hay RJ. Histoplasmosis. Semin Dermatol. 1993;12(4):310-314.

Hiltbrand JB, McGuirt WF. Oropharyngeal histoplasmosis. South Med J. 1990;83(2):227-231.

Howell JM, et al. Emergency Medicine. Vol 1. Philadelphia, Pa: W.B. Saunders; 1998:424, 430-431, 436.

Kelly GS. Clinical applications of N-acetylcysteine. Altern Med Rev. 1998;3(2):114-127.

Laurent T, Markert M, Feihl F, Schaller MD, Perret C. Oxidant-antioxidant balance in granulocytes during ARDS. Effect of N-acetylcysteine. Chest. 1996;109(1):163-166.

Mandell GL, et al. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 5th ed. Philadelphia, Pa: Churchill Livingstone; 2000:2718-2731.

McMillan TA, Lashkari K. Ocular histoplasmosis. Int Ophthalmol Clin. 1996;36(3):179-186.

Murray JJ, Heim CR. Hypercalcemia in disseminated histoplasmosis. Aggravation by vitamin D. Am J Med. 1985;78(5):881-884.

Murray PR, et al. Medical Microbiology. 3rd ed. St. Louis, Mo: Mosby; 1998:577-581.

Rubin SA, Winer-Muram HT. Thoracic histoplasmosis. J Thorac Imaging. 1992;7(4):39-50.

Sataloff RT, Wilborn A, Prestipino A, Hawkshaw M, Heuer RJ, Cohn J. Histoplasmosis of the larynx. Am J Otolaryngol. 1993;14(3):199-205.

Shulman ST, et al. The Biologic and Clinical Basis of Infectious Diseases. 5th ed. Philadelphia, Pa: W.B. Saunders Company; 1997:176-179.

Tierney LM Jr, et al. Current Medical Diagnosis and Treatment 2000. New York, NY: Lange Medical Books/McGraw-Hill; 2000:854-855,1464-1465.

Walsh TJ, Gonzalez C, Lyman CA, Chanock SJ, Pizzo PA. Invasive fungal infections in children: recent advances in diagnosis and treatment. Adv Pediatr Infect Dis. 1996;11:187-290.

Wheat J. Histoplasmosis: recognition and treatment. Clin Infect Dis. 1994;19(suppl 1):S19-S27.