Introduction:
The diseases caused by fungal infections have a great impact on public health worldwide. Opportunistic fungal infections such as invasive aspergillosis caused by Aspergillus, cryptococcosis caused by Cryptococcus, pneumocystis present with pneumonia, and endemic fungi are the main fungal infections that affect the lungs of humans. Although these infections are rarely found in the target organs in healthy people, they may result in life-threatening invasive diseases in patients with an impaired immune system. These individuals include patients suffering from immunodeficiency disorders, such as cancer patients who receive chemotherapy, as well as those patients who receive immunosuppressive therapy for bone marrow or stem cell transplantation and acquired immunodeficiency syndrome (AIDS).
What Are the Pathogens Involved in Causing Fungal Infection?
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Aspergillus mold is one of the most commonly found fungal species which can sufficiently sporulate with released airborne conidia.
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The conidia in the air are so small (two to three micrometer) to reach human airways and pulmonary alveoli, causing a spectrum of diseases in atopic patients with asthma allergies and immunocompromised individuals.
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In healthy individuals, the inhaled conidia are attacked by alveolar macrophages and killed in a phagocyte oxidase-dependent reaction.
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In immunocompromised individuals, the incomplete killing of inhaled fungal conidia leads to germination and tissue invasion by fungal hyphae.
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Cryptococcosis is caused by Cryptococcus exposure to the lung after the inhalation of the airborne organism. Cryptococcus neoformans are found widely in soil and avian habitats.
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The most severe form of Cryptococcus infection is cryptococcal meningitis.
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Cryptococcus neoformans and Cryptococcus gattii disseminate from the lung to reach the brain by crossing the blood-brain barrier (BBB).
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The fungal cells penetrate the blood-brain barrier through endothelial cells on the blood vessels of the brain using a Trojan horse strategy that is involved in the transport of phagocytes.
What Are the Fungal Infections Affecting the Lungs?
Aspergillosis:
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Aspergillosis is an infection caused by a type of mold (fungus). It usually targets the respiratory system, but its signs and severity vary.
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Most strains of the mold are harmless, but a few can cause serious illness when people with underlying lung disease, asthma, or a weakened immune system inhale the fungal spores.
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In some people, the spores trigger an allergic reaction from mild to the severe form.
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The most serious form of aspergillosis is invasive aspergillosis which involves the infection’s spread to blood vessels and beyond.
What Are the Causes of Aspergillosis?
Aspergillus mold is found in decaying leaves and compost of plants, grain crops, and trees. When mold spores are inhaled, immune system cells surround and destroy them. People with weakened immune systems have fewer infection-fighting cells. This allows the spores to withstand and invade the lungs and other parts in severe cases.
What Are the Symptoms of Aspergillosis?
The infection occurs in various forms, and they are as follows:
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Allergic Reaction:
Some people with cystic fibrosis or asthma have an allergic reaction to Aspergillus mold. The signs and symptoms of allergic bronchopulmonary aspergillosis include:
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Cough with blood or mucus.
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Fever.
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Asthma.
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Aspergilloma:
Certain chronic lung diseases, such as emphysema, sarcoidosis, and tuberculosis, can cause air spaces to form in the lungs. When people with lung cavities are also infected with Aspergillus, fungus fibers may find their way into the cavities and grow into tangled masses known as aspergillomas. Aspergillomas can worsen the underlying chronic condition and cause:
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Wheezing.
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Weight loss.
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Fatigue.
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Hemoptysis (cough with blood).
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Invasive Aspergillosis:
This is the most severe form of aspergillosis. It occurs only in people whose immune system is weakened as a result of cancer chemotherapy, bone marrow transplantation, or disease of the immune system. The signs and symptoms of invasive aspergillosis include:
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Hemoptysis (spitting of blood).
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Fever and chills.
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Shortness of breath.
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Skin lesions.
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Headache or eye symptoms.
What Are the Risk Factors for Aspergillosis?
Based on the type of infection, aspergillosis can cause a variety of serious complications:
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Systemic Infection:
Invasive aspergillosis spreads rapidly and is fatal. The most serious complication of invasive aspergillosis is the spread of infection to other parts of the body, including the brain, kidney, and heart.
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Bleeding:
Both aspergillosis and invasive aspergillosis can cause severe and sometimes fatal bleeding in the lungs.
How to Diagnose?
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Respiratory Secretion (Sputum) Test:
A sample of sputum is stained with a dye and checked for the presence of Aspergillus filaments. The specimen is then placed in a culture that encourages the mold to grow to help confirm the diagnosis.
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Tissue and Blood Test:
For the skin test, a small amount of Aspergillus antigen is injected into the skin of the forearm. In the presence of antibodies to the mold, red bumps are developed at the injection site. Blood tests mark high levels of certain antibodies, indicating an allergic response.
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Biopsy:
In some cases, evaluating a sample of tissue from the lungs or sinuses under a microscope is necessary to confirm the diagnosis of invasive aspergillosis.
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Imaging Test:
A chest X-ray or computerized tomography (CT) scan reveals a fungal mass, as well as characteristic signs of allergic bronchopulmonary aspergillosis and invasive aspergillosis.
What Is the Treatment for Aspergillosis?
Simple aspergillosis usually does not need treatment; if the condition progresses, antifungal medications are recommended.
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Antifungal Medications:
These drugs are most effective and commonly prescribed. The most effective treatment is a newer antifungal drug named Voriconazole. Amphotericin B can also be used. In the case of bronchopulmonary aspergillosis, corticosteroids along with antifungal drugs are taken, which is more effective.
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Surgery:
Antifungal medications do not penetrate fungal mass well; hence it is best to choose surgical removal as the first-choice treatment when aspergilloma causes bleeding in the lungs.
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Embolization:
This method aims to stop lung bleeding caused by aspergilloma. A radiologist injects a material through a catheter that has been guided into an artery feeding lung cavity where an aspergilloma is causing blood loss. The injected material hardens, blocking the blood supply to the area and stopping the blood temporarily.
Cryptococcosis:
Cryptococcosis is a disease caused by fungi from the genus Cryptococcus that infect humans and animals through inhalation of the fungus. The lung infection that spreads to the brain causes meningoencephalitis.
What Are the Causes and Risk Factors of Cryptococcosis?
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Cryptococcosis (C. neoformans) is found commonly in bird feces. Humans and animals usually get infected from inhaling dust contaminated with bird feces.
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Cryptococcus gattii is a type of Cryptococcus that is acquired by inhalation of airborne plant material. It usually infects immunocompetent individuals and is transmitted directly into the skin and by organ transplants.
What Is the Treatment for Cryptococcosis?
Cryptococcosis is treated by antifungal medications like Amphotericin B, Flucytosine, and Fluconazole. In healthy individuals, oral antifungal therapy is usually advised with Amphotericin B for a period of six to ten weeks. At times of need, Flucytosine may be prescribed along with it for two weeks. This is then followed by administration of Fluconazole for 10 more weeks. While in the case of immunocompromised patients, intravenous administration of antifungal drugs is recommended. One another important difference in the treatment plan between immunocompromised and healthy individuals is the duration. For immunocompromised patients, the duration of treatment is relatively high with initial treatment ranging for one year which is to be followed by lifelong suppressive therapy.
Conclusion:
The identification of novel genes and pathways through screening and sequencing and further studies are still required to evaluate the host defense mechanisms against infectious fungal pathogens in the lung. Proper diagnosis and timely management of underlying conditions aid in a better prognosis in severe cases. An interprofessional team approach is required for proper diagnosis and to aid in the better management of this condition. Futuristic research on mechanisms and functional studies are needed to evaluate the host defense mechanisms against the fungal pathogens in the lungs.