All you need to know about Aspergillosis.
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What is Aspergillosis?
Aspergillosis, a mould species that is present all over the world, is a fungal infection caused by Aspergillus. More than 180 different Aspergillus species have been identified and more are still being identified. These moulds are usually harmless. Any types, however, can cause a range of human diseases, ranging from basic allergic reactions to invasive diseases that are life-threatening. This category of diseases is commonly referred to as aspergillosis and is classified roughly into three categories: allergic, chronic and invasive. There are many different types, including allergic bronchopulmonary aspergillosis, allergic sinusitis of Aspergillus, invasive aspergillosis, aspergillosis of the scalp, and chronic pulmonary aspergillosis. Aspergillosis rarely occurs in healthy individuals; without any complications, most people breathe in these spores every day. Infection is much more likely to occur in people who have an underlying disorder such as asthma, cystic fibrosis, and prior lung disease, or who have been taking corticosteroid medicines for a long period of time, or in people who have a compromised immune system, including people with low levels of neutrophils, a type of white blood cell that helps the body combat infection and heal When prone persons breathe in (inhale) Aspergillus spores, aspergillosis occurs in most cases. Aspergillosis can not be spread from one human to another and is not infectious.
What causes Aspergillosis?
A fungal infection caused by some forms of mould is aspergillosis. They are present in nature (ubiquitous) and, like rotting plants, can be found in the soil and decaying organic matter. They can be found indoors, especially in ducts for heating or cooling or in insulation. There are about 180 species of Aspergillus, but there are only about 40 known to be infected with human disease.
Though they are widely present in nature, these moulds typically do not cause problems. We all inhale the spores of the mould every day, however, healthy people will expel them from the lungs promptly. However, they can cause serious, even life-threatening, infections in some individuals, such as people with a damaged or compromised immune system. Through breathing in mould spores, most individuals develop this infection. Less commonly, as spores reach the body from a cut or open wound, the infection may occur.
Among patients who have asthma or cystic fibrosis, allergic bronchopulmonary aspergillosis is more likely to occur. People who have had a previous lung condition, like tuberculosis or chronic obstructive pulmonary disease (COPD), or a condition that may damage the lungs, such as sarcoidosis, are more likely to experience symptoms of chronic pulmonary aspergillosis. In addition, patients who have had lung surgery in the past can also develop recurrent pulmonary aspergilloses, such as pneumothorax or lung cancer.
Invasive aspergillosis is more likely to occur in patients with a compromised immune system, including people with reduced levels of neutrophils (neutropenia), which are white blood cells that help combat infection and obtain broad-spectrum antibiotics; people undergoing chemotherapy, or people receiving drugs that inhibit immune system function (immunosuppressive drugs). Neutropenia can be seen in cancer, particularly blood (hematologic) cancers, and immunosuppressive drugs can be used. Few rare diseases can also cause reduced neutrophil activity and susceptibility to Aspergillus, such as chronic granulomatous disease.
The highest prevalence of invasive aspergillosis is in individuals who have recently undergone hematopoietic stem cell transplantation (HSCT). In the bone marrow, hematopoietic stem cells are located which are cells that gradually grow into red blood cells, white blood cells, and platelets. A transplant requires washing out and replacing the original bone marrow with bone marrow from a healthy donor. In order to better combat rejection, infected people must take immunosuppressive medications, although this will leave them more vulnerable to infection, like mucormycosis infection. There may also be a chance of contracting this infection in people taking immunosuppressive medications for other causes, such as receiving an organ transplant.
Other conditions can raise the risk of developing aspergillosis include late-stage HIV/AIDS individuals; the use of infected medical devices near or in open wounds; the long-term use of highly potent anti-inflammatory corticosteroids; and severe injury involving burns or other skin damage.
Some researchers have indicated that in the development of aspergillosis, genetics can play a role. Researchers speculate that certain people may be more likely to experience an Aspergillus infection from some genes. This is alluded to as possessing a ‘genetic predisposition’ to an illness arising. Any study has shown that in some persons, genes that play a part in innate immune functions could be implicated in developing chronic pulmonary aspergillosis. For allergic bronchopulmonary aspergillosis, genetic causes have also been studied, and this type of infection is assumed to arise from many factors arising together (e.g. genetic, immunologic, environmental). Study is ongoing to establish the role of genetics in the growth of different types of aspergillosis.
For a couple of unique forms of Aspergillus, researchers have mapped the genome. A genome is an organism’s full genetic makeup, and researchers expect that these genomes will lead them to new avenues for therapy and to a deeper understanding of the various variations between the different Aspergillus organisms.
What are the types of Aspergillosis?
- Allergic bronchopulmonary aspergillosis (ABPA): Occurs when Aspergillus causes inflammation in the lungs and allergy symptoms such as coughing and wheezing, but doesn’t cause an infection.
- Allergic Aspergillus sinusitis: Occurs when Aspergillus causes inflammation in the sinuses and symptoms of a sinus infection (drainage, stuffiness, headache) but doesn’t cause an infection.
- Azole-Resistant Aspergillus fumigatus: Occurs when one species of Aspergillus, A. fumigatus, becomes resistant to certain medicines used to treat it. Patients with resistant infections might not get better with treatment.
- Aspergilloma: Occurs when a ball of Aspergillus grows in the lungs or sinuses, but usually does not spread to other parts of the body. Aspergilloma is also called a “fungus ball.”
- Chronic pulmonary aspergillosis: Occurs when Aspergillus infection causes cavities in the lungs, and can be a long-term (3 months or more) condition. One or more fungal balls (aspergillomas) may also be present in the lungs.
- Invasive aspergillosis: Occurs when Aspergillus causes a serious infection, and usually affects people who have weakened immune systems, such as people who have had an organ transplant or a stem cell transplant. Invasive aspergillosis most commonly affects the lungs, but it can also spread to other parts of the body.
- Cutaneous (skin) aspergillosis: Occurs when Aspergillus enters the body through a break in the skin (for example, after surgery or a burn wound) and causes infection, usually in people who have weakened immune systems. Cutaneous aspergillosis can also occur if invasive aspergillosis spreads to the skin from somewhere else in the body, such as the lungs.
What are the symptoms of Aspergillosis?
The different types of aspergillosis can cause different symptoms.
The symptoms of allergic bronchopulmonary aspergillosis (ABPA) are similar to asthma symptoms, including:
- Shortness of breath
- Fever (in rare cases)
Symptoms of allergic Aspergillus sinusitis include:
- Runny nose
- Reduced ability to smell
Symptoms of an aspergilloma (“fungus ball”) include:
- Coughing up blood
- Shortness of breath
Symptoms of chronic pulmonary aspergillosis include:
- Weight loss
- Coughing up blood
- Shortness of breath
Fever is a common symptom of invasive aspergillosis.
Invasive aspergillosis usually occurs in people who are already sick from other medical conditions, so it can be difficult to know which symptoms are related to an Aspergillus infection.
However, the symptoms of invasive aspergillosis in the lungs include:
- Chest pain
- Coughing up blood
- Shortness of breath
- Other symptoms can develop if the infection spreads from the lungs to other parts of the body.
Contact your healthcare provider if you have symptoms that you think are related to any form of aspergillosis.
What are the risk factors of Aspergillosis?
Depending on your physical health and the level of your exposure to mould, your chance of contracting aspergillosis varies. In general, these factors make you more vulnerable to infection:
An immune system that is compromised.
After undergoing transplant surgery, particularly bone marrow or stem cell transplants, people taking immune-suppressing drugs or people who have some blood cancers are at the greatest risk of invasive aspergillosis. People can also be at greater risk in the latter stages of AIDS.
Low amount of White Blood Cells.
There are reduced numbers of white cells in patients who have had chemotherapy, an organ transplant or leukaemia, making them more vulnerable to invasive aspergillosis. Chronic granulomatous disease, a hereditary condition that affects the cells of the immune system, is also present.
Cavities in the lungs.
There is a greater chance of forming aspergillomas in individuals who have air gaps (cavities) in their lungs.
Cystic fibrosis or asthma.
People with asthma and cystic fibrosis are more likely to have an allergic reaction to aspergillus mould, especially those whose lung conditions are long-standing or difficult to manage.
Therapy of long-term corticosteroids.
Depending on the underlying condition being treated and what other medicines are being used, long-term use of corticosteroids can raise the risk of opportunistic infections.
What are the complications of Aspergillosis?
Aspergillosis can cause a number of serious complications, depending on the form of infection:
Serious, and often fatal, bleeding in your lungs will result from both aspergillosis and invasive aspergillosis.
Spreading the infection to other areas of the body, especially your brain, heart and kidneys, is the most dangerous complication of invasive aspergillosis. Invasive aspergillosis is quickly spreading and may be fatal.
How is Aspergillosis diagnosed?
A diagnosis of aspergillosis is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests such as bronchoscopy with biopsy, x-rays, antigen skin tests, tissue culture or blood tests. Allergic bronchopulmonary aspergillosis should be suspected in individuals with difficult to control asthma or cystic fibrosis.
Clinical Testing and Workup
Doctors will take samples of affected tissue and a special doctor called a pathologist will study the tissue for changes caused by disease (histopathology). This can show the presence of mould. Samples can include fluid from the respiratory system of mucus coughed up from the lungs (sputum) if lung infection is suspected. Respiratory fluid can be obtained through a procedure called bronchoalveolar lavage or BAL. During BAL, a narrow tube (bronchoscope) is slid down the windpipe into the lungs and a sterile solution is passed through the tube washing out (lavaging) cells. This fluid is collected and then the tube is removed, allowing the cells to be studied.
Surgical removal (biopsy) of affected lung tissue can also be performed. In order to obtain a lung sample, physicians may recommend a bronchoscopy or percutaneous needle biopsy. During a bronchoscopy, a physician inserts a bronchoscope through the mouth and down an affected individual’s throat and obtains a sample of tissue to be analyzed (biopsy). During a percutaneous needle biopsy, a needle is passed through the skin and inserted directly into the lungs to remove a tissue sample. A biopsy may not always be feasible due to the risk of complications such as bleeding.
Along with histopathologic examination, a tissue sample can also be taken and used for a fungal culture. A fungal culture is a procedure in which a sample of affected tissue is taken and sent to a laboratory and any fungus or similar organism discovered in the tissue is given time to grow. This test can determine the presence and type of fungal infection. The advantage of this test is that it allows us to know which antifungal medications are active against the infection. However, sometimes a fungal culture does not reveal a fungal infection despite the presence of an infection. Thus, a negative result of a fungal culture does not rule out aspergillosis.
An Aspergillus antigen skin test can be used to screen for allergic bronchopulmonary aspergillosis. During this test, a physician will inject a needle into a specific area of the body. If the area becomes inflamed or irritated within 48–72 hours, the person has been exposed to the Aspergillus fungus. Alternatively, a blood test (Aspergillus specific IgE) can be used if the skin test is not available. If the test is positive, then an additional test (total IgE) is required to make the diagnosis of allergic bronchopulmonary aspergillosis).
A physician may also perform a blood test to determine whether any aspergillosis antibodies are present. Antibodies, also known as immunoglobulins, are specialized proteins produced by the body to combat invading microorganisms, toxins, or other foreign substances. Blood tests can also reveal galactomannan or beta-d-glucan, which are substances found in the cell wall of Aspergillus. These tests, called assays, can be performed on certain people at risk of infection. The galactomannan assay test can also be performed on fluid obtained from the lungs (BAL fluid). When either of these tests is positive, this is indicative of invasive aspergillosis. These tests can also be positive for chronic pulmonary aspergillosis, although a blood galactomannan test is usually negative for this form of aspergillosis. The beta-d-glucan test is also often positive in other conditions, so it is not very specific for Aspergillosis.
X-rays of the chest are taken to detect characteristic findings such as the presence of an aspergilloma in a lung cavity or the buildup of Aspergillus fungi in the lungs. More advanced imaging techniques such as computerized tomography (CT) scanning may be used to determine the exact location and extent of infection. A CT scan can reveal an aspergilloma or findings that are suggestive of allergic bronchopulmonary aspergillosis or invasive aspergillosis. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. A CT scan may be taken of the lungs, sinuses, or other areas of the body.
What is the treatment for Aspergillosis?
Aspergillosis treatments vary with the type of disease. Possible treatments include:
- Observation. There is always no need for care for plain, single aspergillomas, and drugs are typically not effective in treating these masses of fungi. Instead, chest X-rays can simply be carefully watched for aspergillomas that don’t cause symptoms. Then antifungal drugs may be prescribed if the disease persists.
- Oral corticosteroids. The aim of treating allergic bronchopulmonary aspergillosis is to prevent the deterioration of existing asthma or cystic fibrosis. Oral corticosteroids are the safest way to achieve this. For allergic bronchopulmonary aspergillosis, antifungal drugs alone are not helpful, but they can be paired with corticosteroids to reduce the dosage of steroids and boost the function of the lungs.
- Antifungal medications. For invasive pulmonary aspergillosis, these medications are the standard therapy. A newer antifungal medication, voriconazole, is the most effective therapy. Another alternative is amphotericin B.
- Both antifungal medications, including damage to the kidneys and liver, may have significant side effects. Often popular are reactions between antifungal drugs and other medicines.
- Surgery. Since antifungal antibiotics do not so easily reach an aspergilloma, when an aspergilloma causes bleeding in the lungs, surgery to remove the fungal mass is the first-choice procedure.
- Embolization. This treatment prevents any aspergilloma-induced lung bleeding. Via a catheter that has been directed into an artery feeding a lung cavity where an aspergilloma is causing blood loss, a radiologist injects a substance. The substance inserted hardens, restricting the area’s blood flow and preventing the bleeding. This medication succeeds momentarily, but it is possible that the bleeding will resume again.
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