Aspergillosis

What is Aspergillosis?

Aspergillus is a common, thread-like fungus that usually causes infections in people with weakened immune systems or existing lung diseases. In nature, this fungus feeds off of dead material and multiplies asexually by making conidia, tiny spore-like structures. Of the twenty-four types of Aspergillus that can cause disease in humans, A. fumigatus is the most common one, followed by A. terreus and A. flavus.

Even though aspergillosis is caused by the same group of fungi, its effects can vary greatly depending on the person’s immune system’s strength. In severe cases, aspergillosis can be life-threatening, as seen in severely immunocompromised individuals suffering from invasive lung aspergillosis or invasive rhinosinusitis. On the other hand, in people with strong immune systems, small aspergillomas (small ball-like collections of fungus in the lungs) are generally not urgent and can be monitored with periodic imaging.

Aspergillosis affects the bronchopulmonary system (lungs and associated parts) in three main ways: invasive aspergillosis, chronic aspergillosis, and allergic aspergillosis. While these infections result from inhaling the fungi’s conidia, not everyone who breathes in these spores gets sick, thanks to the immune response led by immune cells known as neutrophils. If untreated, the invasive type of aspergillosis can be deadly in nearly all cases. If invasive aspergillosis is suspected, a comprehensive examination is needed, but treatment should start as soon as possible to lower the risk of serious illness and death.

What Causes Aspergillosis?

The way you get infected with aspergillosis and the reason largely depend on the type of disease.

For lung problems, you can get pulmonary aspergillosis from breathing in Aspergillus spores, which are everywhere, both indoors and outdoors. The number of spores can be higher where the soil is disturbed. With conditions like invasive pulmonary aspergillosis (IPA) and invasive bronchial aspergillosis (IBA), the main problem is a weak immune system allowing the fungus to grow and spread. In chronic pulmonary aspergillosis, the fungus can stick around and grow in lungs that have been damaged, like from a disease such as tuberculosis. On the other hand, with allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS), the main issue is an allergic response to breathing in the fungus. The allergen involved in ABPA is almost always A. fumigatus.

When it comes to rhinosinusitis, you can contract it by breathing in Aspergillus spores through the nose. This is more common in those who have serious immune deficiencies. However, a more chronic form can occur in people with normal immune systems and is often caused by A. flavus.

With regards to cerebral infections, Aspergillus can get to the brain either through the bloodstream in the case of widespread infection or by spreading directly from nearby areas, such as the inner ear or sinuses.

Fungal endophthalmitis can be caused by Aspergillus after cataract surgery. The fungus often causes keratitis in people who wear contact lenses or have other things that damage the cornea, which raises the chance of infection.

In the case of osteomyelitis, Aspergillus can get into the bone during a widespread infection in people with serious immunodeficiency or through direct contact, like from drug use or after surgery.

As for skin infections, entry points could be through venous catheters, by way of skin conditions, or after an injury. Burns provide an easy way for Aspergillus to get in. This type of fungus has increasingly been identified as a cause of nail infections, with the fungus getting into the nail after an injury, in people with weakened immune systems, or when nails come in contact with soil.

Widespread infections usually start from one of the above infections in someone whose immune system is weak. The fungus often spreads from the lungs. The growing fungus can get into the bloodstream by pushing through the cells lining blood vessels. Endocarditis is rare; it’s usually seen in people who have had recent heart surgery or are seriously immunosuppressed with a widespread disease. Gastrointestinal aspergillosis can also occur, with the spores being swallowed. This is often due to a very weak immune system and a pre-existing condition causing inflammation in the mouth.

In the past, it’s been difficult to pinpoint the exact species causing a disease, leading to them being grouped together. But today, molecular diagnostics help to identify the species more accurately. Aspergillus fumigatus is usually thought to be the cause of about 90% of serious aspergillosis, but more recent studies suggested it makes up a smaller percentage, though it’s still the most common.

Risk Factors and Frequency for Aspergillosis

Invasive aspergillosis primarily affects people with weakened immune systems. This can include individuals with AIDS, various types of cancer, those who have received organ transplants, or are on long-term medications like corticosteroids. Specifically, this condition is most commonly seen in people who have had a type of transplant called a hematopoietic stem-cell transplant. However, it can also affect people with underlying lung conditions such as chronic obstructive pulmonary disease (COPD) or asthma.

• It is estimated that around 250,000 cases of invasive aspergillosis occur globally each year.
• The condition has been linked to severe influenza and, more recently, severe COVID-19.
• Between 2004 and 2013, the number of hospitalized patients with invasive aspergillosis increased by 44%.
• Transplant patients are seeing an increase in its incidence, as transplants become more common and easily accessible.

The chronic form of aspergillosis, on the other hand, usually affects those with existing lung diseases. These can include conditions like chronic obstructive lung disease, tuberculosis, asthma, lung cancer, and sarcoidosis. A particular type of aspergillosis, called allergic bronchopulmonary aspergillosis, is mainly found in people with asthma and cystic fibrosis.

• People working in construction, farming industries, and wastewater treatment plants may face an increased risk due to constant exposure at work.
• Smoking marijuana contaminated with the fungus can also increase the risk of infection.
• There have been reported cases of Aspergillus infections originating from hospital showers and healthcare facilities that are under construction.

Signs and Symptoms of Aspergillosis

When dealing with a suspected Aspergillus infection, it’s crucial that doctors conduct a thorough medical history check and physical examination. Understanding a patient’s risk factors for the disease is key. This includes asking about any exposure to substances that weaken the immune system, including chemotherapy drugs, steroids, and other immune suppressing medications. Additionally, learning about any history of cancer or treatments for it, such as use of ibrutinib, fludarabine, venetoclax, or CAR-T therapy, is important.

It’s also necessary to inquire about any organ transplants performed and any complications that arose afterwards. Details about any history of lung disease, along with potential environmental exposures like construction work, gardening, or wastewater treatment work should also be considered. Lastly, doctors should deeply investigate a patient’s ongoing and past health issues to assess if the patient has a weakened immune system and is therefore more at risk.

The condition is usually present in very sick individuals who have compromised immune systems. It can also occur in extremely ill patients with pre-existing lung conditions. Early symptoms of the lung infection variant commonly include fever, worsening shortness of breath, increased sputum production, coughing up blood, and chest pain. It’s important to note that severely immune-compromised individuals may not display a fever, even though the infection could be progressing. Moreover, the symptoms may appear vague and only manifest when the disease is already advanced.

Chronic pulmonary aspergillosis mainly presents as a cough. In addition, because the disease affects the blood vessels in the lungs, around half of patients may cough up blood. This may even be the initial symptom. Other symptoms may include fever, night sweats, and weight loss.

The allergic form of the disease commonly arises as recurrent bouts of asthma, characterized by difficulty breathing and wheezing, along with a cough producing a lot of sputum with brown plugs.

In examining a patient with an Aspergillus infection, findings will wildly differ depending on which part of the body is affected. Possible signs
include sinus tenderness, nasal discharge, paleness or cell death in the oral or nasal lining or the conjunctiva (the mucous membrane that covers the front of the eye and lines the inside of the eyelids), new tooth mobility, protopsis (bulging of the eye), or anomalies in nerves coming from the brain in the case of invasive fungal rhinosinusitis. Rales (abnormal lung sounds suggestive of fluid in the lungs), rhonchi (abnormal rumbling sounds), dullness to touch, and bloody sputum or secretions from endotracheal tube may be observed in invasive pulmonary aspergillosis. In allergic bronchopulmonary aspergillosis, wheezing is often noted. Changes in the skin, such as purplish spots, scabs, or signs of meningitis can indicate widespread infection. However, a normal physical examination, doesn’t eliminate the possibility of an invasive infection.

Testing for Aspergillosis

If you’re suspected to have aspergillosis, which is a fungal infection, your doctor may recommend certain tests and evaluations due to the common presence of Aspergillus in our surroundings. Just finding Aspergillus in a sputum sample (a mixture of saliva and mucus coughed up from your respiratory tract) does not confirm the infection. Other symptoms and risk factors must be present, while some types of invasive aspergillus can have subtle symptoms.

Here are some conditions, tests, and evaluations:

1. Invasive Fungal Rhinosinusitis: If invasive fungal rhinosinusitis is suspected, an urgent evaluation by an ear-nose-throat doctor is necessary, with a possible nose-endoscopy for culture collection or other related surgeries. Imaging techniques like CT and MRI can be helpful but be aware that CT can underestimate the extent of the infection.

2. Invasive Pulmonary Aspergillosis: If you are suspected to have invasive pulmonary aspergillosis, a chest CT scan should be performed to assess the situation. If safe and practical, a bronchoscopy might be performed to inspect the respiratory tract and collect tissue for tests.

3. Biomarkers & Lab Investigations: Blood tests are helpful in diagnosing aspergillosis. For example, galactomannan is a biomarker often used in patients with blood cancer and stem cell transplant recipients. However, it has limited use in other patient populations. Also, know that blood cultures rarely test positive for Aspergillus species.

4. Chronic Pulmonary Aspergillosis: This is diagnosed based on long-term respiratory symptoms, radiologic evidence of changes in the lung, and confirmation of Aspergillus involvement through microbiology or serology.

5. Allergic Bronchopulmonary Aspergillosis (ABPA): Patients with asthma or cystic fibrosis who are suspected of having ABPA should undergo certain tests such as skin testing, chest imaging, total IgE level measurement, and a count of blood eosinophil.

6. Rare Manifestations: Pleural effusion, where excess fluid builds up in the pleural space between the lungs and the chest wall, is a rare manifestation of aspergillosis and might require a thoracentesis (a procedure to remove fluid from this space) to confirm the infection.

7. Radiology: Radiology is very important in diagnosing aspergillosis. There are certain signs and formations that can be observed on chest x-rays or CT scans, which suggest the presence of aspergillosis.

Remember, if you’re ever suspected of having aspergillosis, you should undergo the appropriate evaluations and tests to confirm the condition and determine the right path for treatment.

Treatment Options for Aspergillosis

Treatment for suspected aggressive fungal infection, known as invasive aspergillosis, should start as soon as possible due to the fast-acting nature of the condition. When deciding on an anti-fungal medication, doctors must take into account the types of Aspergillus fungi common in their region, any previous anti-fungal treatments, the specific type of Aspergillus involved (if known), and any additional health concerns of the patient, such as issues with the heart’s electrical system.

It’s important to be aware that certain types of Aspergillus fungi are naturally resistant to some anti-fungal drugs. For example, A. terreus and A. alliaceus can withstand the effects of the drug amphotericin B, and A. calidoustus is naturally resistant to a group of drugs known as azoles.

The preferred medicine in most cases is a drug called voriconazole. Doctors will need to monitor the levels of voriconazole in the body about a week after starting treatment to ensure it’s working effectively. It’s also crucial that patients are told about any potential side effects, such as skin sensitivity to sunlight. Past concerns over a higher risk of a type of skin cancer in patients treated with voriconazole seem to have been disproved by a recent study. Other treatment options Involve liposomal amphotericin B or isuvaconazole.

If voriconazole has been previously used as preventative treatment, it’s advisable to use liposomal amphotericin B until test results are available. It’s unclear whether a combination of azole and echinocandin therapy is necessary, but it has been used in particularly ill patients. Decreasing immuno-suppression, if induced by medication, or treating immuno-suppression in cases of HIV or primary immunodeficiency is also important. Treatment should last for a minimum of 6-12 weeks but may need to be extended depending on the disease severity and level of immuno-suppression. Regular chest CT scans are recommended to monitor improvement.

For patients with a slow developing form of Aspergillosis, known as chronic pulmonary aspergillosis, treatment of symptoms and loss of lung function is typically managed with oral itraconazole or voriconazole. Treatment usually lasts for at least six months, although lifelong treatment may be necessary for patients with chronic progressive disease. In severe cases, surgical resection is considered. Doctors measure treatment response by evaluating symptoms, tracking lung function, and monitoring levels of Aspergillus IgE – a type of antibody. Regular imaging scans can also measure the shrinkage of aspergillomas – fungal balls, and cavitary lesions – hollowed-out areas in the lung tissue.

Surgery to remove an aspergilloma might be necessary, especially in cases where the patient coughs up blood. Surgery is generally more effective in patients with a single lesion rather than extensive disease. For symptomatic relief, therapeutic embolization – a procedure that blocks blood supply, can be used, although this isn’t a cure. In some cases with small aspergillomas not encroaching on blood vessels, doctors can adopt a wait-and-watch approach.

Exacerbations of allergic bronchopulmonary aspergillosis are usually treated with steroids to manage the immune response and itraconazole to decrease fungal load.

What else can Aspergillosis be?

The list of conditions includes:

• Asthma
• Unusual infections caused by specific types of bacteria
• Pneumonia caused by bacteria
• A severe sinus infection that has created an abscess
• Blastomycosis, a fungal infection found in damp soil and wood
• Bronchiectasis, long-term enlargement of the airways in the lungs
• A type of lung cancer that has eaten away a section of lung tissue, forming a hole
• Cavitary polyangiitis with granulomatosis, a rare disease that causes inflammation of blood vessels in the lungs
• Coccidioidomycosis or Valley fever, a fungal infection usually acquired by breathing in dust in certain regions
• Cystic fibrosis, a genetic disease causing thick, sticky mucus in the lungs
• Eosinophilia, a high number of a specific type of white blood cell
• Eosinophilic pneumonia, a type of lung inflammation
• Histoplasmosis, a lung disease from breathing in spores of a fungus found in bat and bird droppings
• Hypersensitivity pneumonitis, inflammation of the lungs due to allergic reactions to inhaled substances
• Interstitial lung disease, a group of conditions that cause scarring of lung tissue
• Nocardiosis, a bacterial infection that can cause lung disease
• Pulmonary sarcoidosis, a disease causing small patches of red and swollen tissue in the lungs
• Tuberculosis, a bacterial infection that primarily affects the lungs

Each of these conditions may have symptoms similar to the patient’s initial complaints, and a doctor must consider them in order to arrive at an accurate diagnosis.

What to expect with Aspergillosis

People with mild allergic bronchopulmonary aspergillosis – which is a lung condition – often have a good outlook. However, if this condition isn’t discovered promptly, patients may need to take steroids for an extended time, and it could potentially lead to further lung damage.

Invasive aspergillosis – a more severe type of the disease – has a poor prognosis. Despite receiving the right antifungal treatments, about 20% of these patients do not survive six weeks post-diagnosis. If the infection spreads to the central nervous system, it is very likely to be fatal.

Possible Complications When Diagnosed with Aspergillosis

These are some of the long-term effects that could happen if health issues are not properly addressed:

• Continued wheezing, or breath sound characterized by a whistling noise
• Lung fibrosis, a condition where the lungs become scarred and breathing becomes difficult
• Hemoptysis, which is the act of coughing up blood
• Respiratory failure, a severe condition where the respiratory system fails in gas exchange
• CNS infection or infection in the central nervous system
• Endocarditis, an infection in the inner lining of the heart
• Death

Recovery from Aspergillosis

People suffering from a condition called invasive aspergillosis often have to stay in the hospital for a long time because their illness is severe.

Preventing Aspergillosis

To reduce the risk of complications from aspergillosis, a type of fungal infection, it’s important to take certain precautions for hospitalized patients who are particularly vulnerable. These measures include placing them in private rooms equipped with HEPA filters which help reduce the presence of fungi.

It’s also crucial for high-risk individuals to limit their exposure to environments with heavy amounts of fungi, such as gardens, construction sites, and places like wastewater treatment plants.

In some cases, preventive antifungal treatment can help lower the risk of fungal infections. The drugs voriconazole or posaconazole are typically recommended for patients with several risk factors. These risk factors include patients receiving long-term chemotherapy leading to low neutrophil count, recipients of allogeneic stem cell transplants (transplants from a different person), patients with severe or long-lasting graft-versus-host disease (a condition where donor cells attack the patient’s cells), recently performed lung transplants, or some solid organ transplant recipients.

For lung transplant patients who show signs of an aspergillosis infection within the first six months, or those who have increased their immunosuppressive treatment due to transplant rejection in the last three months, a course of antifungal therapy is usually recommended as a preventive measure.