What is Histoplasmosis?
Histoplasma capsulatum (Hc), a type of fungus that can alter its form, is found scattered across the globe, especially in areas near river valleys. The fungus is prevalent in the United States, particularly around the Ohio and Mississippi river valleys and several states in the southeast. This fungus lives in soil, and when disturbed, its tiny spores become airborne and can be breathed in.
Often, infections caused by this fungus don’t show any symptoms. However, they can cause a form of inflammation known as granulomatous inflammation that can lead to lung disease, similar to pulmonary tuberculosis. For people with weakened immune systems, the infection – known as histoplasmosis – can spread throughout the body and potentially cause serious illness or even death.
What Causes Histoplasmosis?
In 1905, a disease expert named Samuel Darling identified a type of yeast known as H. capsulatum, which is why this organism is also referred to as Darling disease. About twenty years later, scientists found out that H. capsulatum has two forms. This fungus behaves like a yeast at body temperature, but when it’s out in room temperature conditions (at around 25 degrees Celsius), it behaves like a mold.
You can usually find H. capsulatum in damp soil, especially places where there are decaying bird or bat droppings. Bats can carry this fungus in their digestive system, and birds can carry it on their feathers. Interestingly, birds don’t get sick from H. capsulatum, possibly because their bodies are warmer (around 40 degrees Celsius). Places with lots of construction activity have had outbreaks of diseases caused by H. capsulatum, especially in areas where the fungus is commonly found.
H. capsulatum belongs to a family of fungi known as ascomycetes and has two types called “mating types”. However, in human infections, one type (known as the ‘ – ‘ type) seems to be more common, but scientists still aren’t sure why. When studied under a microscope, it’s found that H. capsulatum produces two kinds of particles called conidia. The smaller particles or microconidia (around 2 to 5 micrometers in size) are believed to cause infection by getting into the air sacs in our lungs when we breathe them in.
Fascinatingly, H. capsulatum has different forms or clades based on their genetic makeup, and these are found in different parts of the world. For example, there are two clades each in North America and South America, and others in Australia, Indonesia, Africa, and Eurasia. This is important because these clades can cause different types of infections. For instance, the North American clades do not cause skin diseases, while the South American ones do.
Once inside our bodies, the H. capsulatum particles change form and start behaving like yeast. This process, which takes from a few hours to a few days, is triggered by our body temperature. Scientists have found that three genes named Ryp1, Ryp2, and Ryp3 are critical for this transformation. These yeast particles are responsible for the infection and reproduce inside our bodies.
Risk Factors and Frequency for Histoplasmosis
Histoplasmosis is a common fungal disease in the United States, especially in the Midwest and Southeast regions. This knowledge comes from skin test surveys done back in the 1940s. From 1938 to 2013, over 100 outbreaks involving about 3000 cases were reported in 26 states and Puerto Rico. An outbreak is defined as two or more cases happening together. These outbreaks often happened around chicken coops or construction sites, with birds, bats, or their droppings present in 77% of the situations. Half of the outbreaks were linked to workplaces. In areas where histoplasmosis is common, it’s often hard to identify the exact source of infection because the symptoms can also be due to the disease reactivating itself.
Worldwide, histoplasmosis exists in specific areas within each continent. Cases have been reported from Italy in Europe, North, Central and South America, in West Africa (Congo and Zimbabwe), South Africa, Southeast Asia (India, China, Malaysia, Taiwan), and Australia. More than half of the global population potentially lives in regions where the fungus that causes histoplasmosis is endemic.
Signs and Symptoms of Histoplasmosis
Acute Pulmonary Histoplasmosis is a disease that originates in the lungs. Some people might not experience symptoms and only discover it through x-rays showing signs of granulomas, which are small areas of inflammation. These granulomas contain the growth of the fungus that causes the disease. When the body doesn’t respond in an organized way to fight off this invasion, the condition can progress into a more severe form called disseminated Histoplasmosis.
Interestingly, individuals with a disorder known as X-linked hyper-immunoglobulin M syndrome, which affects the immune response, usually end up with disseminated histoplasmosis.
Often, primary infections show no symptoms or are disregarded due to mild flu-like symptoms. When symptoms do appear, they usually include high fever, headaches, a dry cough, and chest pain. Chest pain usually occurs in the front and is likely due to enlarged lymph nodes in the region. These symptoms typically clear up within 10 days. However, some patients, particularly women, can experience joint pain and skin issues. Routine imaging scans often reveal inflammation in the lungs and swollen lymph nodes.
Some patients may develop acute pericarditis, which is inflammation of the sac-like covering around the heart. This most likely happens due to the inflammation response in the lymph nodes next to the pericardium.
People living in areas where Histoplasmosis is prevalent might experience multiple exposures to the fungus. In these instances, the disease appears more quickly, usually within three days, but doesn’t last as long. Repeated infections may result in the development of small nodules scattered throughout both lungs. The presence of a growing mass caused by continuous addition of cells trying to control the yeast often necessitates a biopsy to exclude the possibility of malignancy. If the yeast is found, treatment is typically administered for approximately three months.
Interestingly, expanded lymph nodes can tug on the airways leading to potential complications such as pneumonia and bronchiectasis. Treating such complications is usually unnecessary.
Chronic Pulmonary Histoplasmosis can occur in two forms: with cavities forming in the lungs or without cavities. Despite earlier assumptions, recent findings have debunked the belief that heavy smokers are more likely to have cavities. Women also have this form of the disease. Detailed images have shown scattered nodules, infiltrations, and swollen lymph nodes in this version of histoplasmosis. However, there usually isn’t evidence of inflammation.
For patients that have healed, approximately 20% may have recurring cavitary lesions which need to be treated again. During the healing process, recurrences don’t affect the prognosis.
Progressive disseminated histoplasmosis refers to the condition where uncontrolled growth of the organism occurs in multiple organ systems. Symptoms include fever, weight loss, significant enlargement of the liver and spleen, and issues with the blood. This can be fatal if left untreated.
Testing for Histoplasmosis
It might be hard to identify how and where a person gets exposed to the fungus that causes histoplasmosis, especially in regions where it is common. Possible exposure points include cleaning basements or attics, doing construction work, and working with soil. The disease can cause mild to severe lung problems. Some people may have a fever for no apparent reason and lose weight. They might sweat a lot at night. This disease can sometimes seem like pneumonia and can cause multiple cavities in the lungs.
Several tests are used to diagnose this condition. Blood tests can identify specific cells and proteins that tell doctors whether a person has been exposed to the fungus. It’s important to rule out similar diseases like blastomycosis and coccidioidomycosis, so tests for those are often done too. Imaging studies like X-rays can show healed spots in the lungs, spleen, or liver from past infections. Also, a complete blood count can help to assess overall health and the presence of any infection. Sometimes, doctors might perform a bronchoscopic alveolar lavage (BAL), which is a procedure where they wash a sample of cells from the lungs, to rule out other diseases. This test has more chances of being positive if there are cavities in the lungs or if the fungus has reached the large airways in the lungs.
Antibody tests are important tools for diagnosing and managing histoplasmosis, but they’re not effective in all cases. The two standard antibody tests are complement fixation and immunodiffusion assay. These tests look for specific antibodies that a patient’s immune system makes in response to the fungus. While less specific, the complement fixation test is positive in about 95% of the patients within 2 to 6 weeks of infection and can last for years. Immunodiffusion assays are more specific, but their sensitivity lies in the mid-sixties.
Latex agglutination tests are better than complement fixation and immunodiffusion but can give false positives and cannot differentiate from blastomycosis infection. Western blot and enzyme immune assays, which are highly sensitive and specific antibody tests, are also used sometimes. Moreover, the detection of a certain substance, called an antigen, may be more effective in diagnosing acute disease and also in patients whose immune system does not work well. The level of this antigen goes down as the patient’s condition improves.
However, tests can give false readings. For instance, tests can report low amounts of the antigen even when a person doesn’t have histoplasmosis. In one study, this happened in about 48% of the cases. That’s why it’s important to consider other diagnoses as well, such as tuberculosis, blastomycosis, coccidioidomycosis, and sarcoidosis, which may cause similar symptoms. Sometimes, tests can mistakenly identify other microorganisms as the histoplasma fungus.
Treatment Options for Histoplasmosis
In 2007, a group of experts on infectious diseases (known as the Infectious Disease Society, or IDSA) suggested guidelines for treating histoplasmosis—a lung infection caused by inhaling fungal spores. They advise that acute lung infections, with symptoms lasting less than four weeks, usually don’t need any treatment. However, if symptoms persist for more than four weeks, antifungal medication like itraconazole is recommended for about three months.
For patients suffering from chronic and persistent histoplasmosis without cavities or pockets in their lungs, a six-month course of medication is usually enough. But if the disease has led to the formation of cavities in the lungs, treatment may need to continue for a year.
Patients with a severe form of this disease, known as progressive disseminated histoplasmosis (PDH), generally require a more intense treatment regimen. This usually starts with two to four weeks of a strong antifungal drug, called amphotericin-B, followed by a year of itraconazole. Studies have shown that a specific type called liposomal amphotericin B often yields better outcomes.
Currently, only these particular antifungal drugs are recommended by IDSA for treating histoplasmosis. However, in certain situations, an antifungal drug called posaconazole has been used as a substitute, when standard treatments aren’t effective. Posaconazole has been used to maintain the progress after the initial treatment with either itraconazole or amphotericin B.
What else can Histoplasmosis be?
When it comes to lung diseases or conditions, the following can be taken into consideration:
- Aspiration pneumonitis and pneumonia
- Bacterial pneumonia
- Blastomycosis
- Carcinoid lung tumours
- Chlamydial pneumonia
- Coccidioidomycosis and valley fever
- Fungal pneumonia
- Legionella pneumonia
- Mediastinal cysts
- Mediastinal lymphoma
- Mycoplasma infections
- Pancoast syndrome
- Pneumococcal infections
