Histoplasmosis is a disease caused by a fungus called Histoplasma capsulatum. The fungus is commonly found in soil, particularly soil that contains large amounts of bird or bat droppings. When soil containing the fungus is stirred up, the fungal spores can be breathed into the lungs. For most people, a small exposure does not cause any symptoms. However, a large exposure can cause an illness called histoplasmosis. If histoplasmosis is left untreated, it can lead to severe complications and in rare cases may even be fatal.
What is histoplasmosis?
Histoplasmosis is an infection caused by the fungus Histoplasma capsulatum. This fungus lives in the environment, particularly in soil that contains large amounts of bird or bat droppings. The fungal spores can become airborne when dirt or bird/bat droppings are disturbed, and if inhaled, can cause infection. Histoplasma capsulatum is found worldwide, but is most prevalent in central and eastern states of the U.S. as well as parts of Latin America, Africa, and Asia. Areas along the Ohio and Mississippi River valleys are particularly affected.
How common is histoplasmosis?
The CDC estimates that around 60,000 new infections of histoplasmosis occur each year in the U.S. However, due to the fact that most cases are mild or asymptomatic, this number likely underestimates the true frequency. Histoplasmosis is the most common respiratory mycosis in the U.S.
How do people get infected?
People get histoplasmosis by inhaling the microscopic fungal spores from the environment. Common sources include:
- Disturbing soil contaminated with bird/bat droppings, such as during construction, excavation, farming, cleanup activities
- Handing bird/bat droppings
- Demolishing old buildings contaminated with droppings in attics/walls
- Exploring caves inhabited by bats
The fungal spores enter the lungs and an infection develops from there. Histoplasmosis is not transmitted from person to person.
Symptoms of histoplasmosis
The symptoms of histoplasmosis vary greatly and depend on the amount of exposure to the fungal spores.
Mild to moderate infection
If a relatively small number of spores are inhaled, most people have no symptoms or only mild flu-like symptoms, including:
- Fever
- Cough
- Fatigue
- Chest discomfort
- Headache
Symptoms may start 3-17 days after exposure and resolve without treatment in around 1-3 weeks.
Severe infection
With a large exposure to spores, a small proportion of people, especially infants and immunocompromised individuals, develop severe pulmonary histoplasmosis. This causes symptoms similar to pneumonia, including:
- High fever
- Cough, often with mucus or blood
- Extreme fatigue & weakness
- Chest pain
- Joint and muscle pains
- Shortness of breath
- Headaches
- Gastrointestinal symptoms
This form requires treatment and can be fatal if not treated. Even with treatment, severe pulmonary histoplasmosis has a mortality rate of around 25%.
Disseminated histoplasmosis
In a small number of severe infections, the fungus can spread from the lungs to other organs throughout the body, causing disseminated histoplasmosis. This most commonly occurs in infants and people with compromised immune systems. Symptoms are severe and include:
- Fever, chills
- Ulcerations in the mouth/GI tract
- Enlarged liver, spleen, lymph nodes
- Rash
- Jaundice
- Joint and muscle pains
Disseminated histoplasmosis is fatal if untreated. Even with antifungal treatment, there is still a high mortality rate of 20-40%.
Complications of untreated histoplasmosis
If histoplasmosis is left untreated, a number of serious and potentially life-threatening complications can occur.
Chronic pulmonary histoplasmosis
In some people, the initial lung infection does not clear and instead causes scarring and damage to lung tissue. This can lead to chronic symptoms like cough, shortness of breath, wheezing, chest pain, fatigue, and weight loss. Over months to years, lung function progressively worsens.
Acute respiratory distress syndrome (ARDS)
Severe pulmonary histoplasmosis can trigger ARDS, a condition where the lungs become severely inflamed and fill with fluid. This impairs their ability to oxygenate the blood and remove carbon dioxide. ARDS requires intensive care and ventilator support. The mortality rate is high.
Fibrosing mediastinitis
The infection can spread to lymph nodes in the center of the chest, causing abnormal scarring and narrowing of the airways or major blood vessels in that area. This is called fibrosing mediastinitis and can lead to obstruction of airways, pulmonary artery hypertension, or superior vena cava syndrome.
Disseminated infection
As described earlier, the most severe manifestation is disseminated histoplasmosis, when the infection spreads throughout the body. All major organ systems can be affected. Without treatment, disseminated histoplasmosis is almost always fatal.
Opportunistic infection
In people with weakened immune systems, especially AIDS patients, untreated histoplasmosis can lead to severe, disseminated disease. It is considered an AIDS-defining opportunistic illness in people with CD4 counts under 200 cells/mm3.
Meningitis
The fungus can also spread to the brain and spinal cord, causing granulomatous meningitis. This can lead to blindness, seizures, loss of consciousness, and death if not treated.
Adrenal insufficiency
The adrenal glands can become infected, impairing their ability to produce cortisol and aldosterone. Adrenal insufficiency is a medical emergency requiring steroid replacement therapy.
Diagnosing histoplasmosis
Histoplasmosis can be challenging to diagnose, as symptoms are non-specific and mimic those of many other respiratory conditions. Diagnostic testing is needed for confirmation:
Chest X-ray
May show lung infiltrates, nodules, cavities, or lymphadenopathy. Findings are non-specific, however.
Complete blood count (CBC)
Often shows decreased neutrophils and elevated lymphocytes, monocytes, and eosinophils.
Histoplasma antigen assay
Detects Histoplasma antigen in blood, urine, or bronchoalveolar lavage fluid. Rapid and accurate for disseminated disease. Less sensitive for milder infection.
Fungal culture
Gold standard but takes several weeks. Samples include sputum, bronchoalveolar lavage fluid, blood, bone marrow biopsy.
Biopsy
Visualizing characteristic yeast forms in tissues can confirm diagnosis. Done on samples like bone marrow, lymph nodes, skin lesions.
Molecular tests like PCR are also sometimes used. Prompt, accurate diagnosis allows timely treatment to prevent complications.
Treatment for histoplasmosis
Treatment involves antifungal medications, primarily azoles or amphotericin B. Treatment duration and medication choice depends on severity:
Mild to moderate
Often resolves without treatment. If needed, itraconazole for 6-12 weeks.
Severe acute pulmonary
Liposomal amphotericin B for 1-2 weeks until improved, followed by itraconazole for at least 1 year to prevent relapse.
Disseminated
Liposomal amphotericin B for induction followed by itraconazole long term (at least 1 year).
Central nervous system
Liposomal amphotericin B plus fluconazole or itraconazole. Must treat for at least 1 year and until cerebrospinal fluid normalizes.
Immunocompromised patients
Long term itraconazole prophylaxis to prevent infection.
Monitoring severity and clinical progress guides duration of treatment. Untreated histoplasmosis has high morbidity and mortality, so prompt and appropriate treatment is vital.
Prognosis and outcomes
With appropriate diagnosis and treatment, most cases of histoplasmosis have a good outcome. However, untreated or severe disease carries risk of serious complications or death:
- Mild pulmonary – Excellent prognosis, mortality rate <1%.
- Severe pulmonary – Mortality rate around 25% even with treatment. Higher in those with underlying lung disease.
- Disseminated – 20-40% mortality even with treatment. Greater than 90% mortality if untreated.
- CNS involvement – Fatal in over 50% of AIDS patients despite treatment. Non-AIDS mortality rate 20%.
Delays in diagnosis or inadequate treatment also worsen outcomes. Immunocompromised patients are at highest risk for severe, disseminated disease. Overall, earlier diagnosis and prompt initiation of antifungal therapy is key to preventing poor outcomes.
Prevention
Preventing exposure to the fungus is the best way to avoid infection:
- Avoid areas with heavy bird/bat guano when possible
- Wear protective gear like masks when exposure cannot be avoided
- Do not handle or disturb accumulations of bird/bat droppings
- Have airborne exposure tested before cleaning up or demolishing old buildings
- Consider prophylaxis for immunosuppressed people with heavy exposure risk
Prompt recognition and treatment of active infections aims to prevent dissemination and severe complications. Histoplasmosis skin testing can identify sensitized individuals who may benefit from prophylaxis. Overall awareness of histoplasmosis risks and prevention methods protects at-risk populations.
Conclusion
Histoplasmosis is a common fungal infection acquired by inhaling spores from the environment. Though often self-limiting, severe infections can occur, especially in those with impaired immunity. Without treatment, histoplasmosis can spread hematogenously, causing life-threatening complications like disseminated disease, meningitis, adrenal insufficiency, and opportunistic infection. Chronic lung damage, respiratory failure, fibrosing mediastinitis, and death may result. Thus, prompt diagnosis using antigen testing, culture, biopsy, and molecular methods is essential. Appropriate antifungal therapy, guided by disease severity, is crucial in preventing morbidity and mortality. Avoiding exposure, monitoring at-risk individuals, and rapidly treating infections improves outcomes in this disease. Ongoing research aims to enhance diagnosis, therapy, and prevention of histoplasmosis.
