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23/07/2024
FUNGAL DISEASES
Fungi are eukaryotic organisms that lack chlorophyll, leaves, true stems, and roots, reproduce by spores, and live as saprophytes or parasites. Typical representatives of fungi are i) Mold, a gray, green or blue soft substance that sometimes forms spots on old food, on walls or on damp clothes. ii) Yeasts are single-celled fungi, can be obligate aerobic or facultative anaerobic microorganisms, reproduce by budding and have the ability to ferment sugar to form alcohol and carbon dioxide and iii) Large mushrooms (mushrooms) are known in two forms: edible mushrooms used for food and poisonous mushrooms.
This topic is an introduction to diseases caused by molds, yeasts, and filamentous fungi (collectively called microfungi). Although many species of fungi exist in the environment, only a few are capable of causing disease. Dogs and cats can become infected by inhaling or eating them or by having wounds on their skin. Some fungi can cause disease in healthy animals, but most fungi only cause disease when the host is immunocompromised. There are two main types of fungal infections in dogs: systemic fungal infections (such as blastomycosis, histoplasmosis, coccidiomycosis, cryptococcosis...) that affect the dog's body systems and localized fungal infections (such as Malassezia, Candida, Dermatophytes...) that are commonly seen. on the dog's skin or external features.
ASPERGILLUS DISEASE
Introduce
Some species of fungi of the genus Aspergillus are the causative agents of Aspergillosis in many domestic and wild animals around the world. In dogs, the disease begins when the dog inhales mold spores. In some dogs, the spores cause an allergic reaction. In others, the spores cause infection. The two forms of aspergillosis affect dogs in different ways. Most infections are localized in the nose (nasal aspergillosis) but some dogs will also have mild to severe lung infections.
The most dangerous form of aspergillosis is systemic aspergillosis, which occurs when the infection spreads outside the lungs to other organs. Even when detected and treated early, systemic aspergillosis is often fatal.
Pathogen characteristics
Fungi of the genus Aspergillus are soft lace-like molds that grow on food that has been stored for too long. There are more than 180 species of Aspergillus fungi, and they usually do not cause disease unless the host has a compromised immune system or has a lot of exposure to the fungus. Under the microscope, Aspergillus looks like a flower, and the spores (conidia) when falling will float in the air to invade organic matter or infect the host when they fall.
Epidemiology
Aspergillus is a common fungus found in both indoor and outdoor environments. Humans and animals with weakened immune systems are more susceptible to infections and other health complications due to fungal infections. It is almost impossible to avoid inhaling some Aspergillus spores in the environment, but for people and animals with healthy immune systems, it is usually not harmful.
Aspergillus often grows on dead leaves, grain reserves, compost heaps, and other decaying vegetation. It can also be found as a mold that grows on food. Fortunately, the respiratory physical protection system and the innate immune system often limit the entry of fungi, thus preventing infection.
There are two main manifestations in dogs: sinus infections and spread to multiple organ systems. German Shepherds are very susceptible to disseminated aspergillosis, and long-muzzled dog breeds such as Dachshund, Greyhound, Collie or German Shepherd are at a higher risk of nasal sinus aspergillosis.
Pathogenesis
Aspergillus species are common in decaying soils and vegetation. More than 200 species of aspergillus are known and these organisms produce cloned spores (conidia) that are easily dispersed into the air.
The fungal conidia are inhaled and deposited in the bronchioles and alveolar spaces. Due to the abundance of mushrooms in the environment, an average person can inhale up to 200 conidia per day. In healthy individuals, conidia are eliminated by the protection of mucus or are phagocytes by alveolar macrophages. Any remaining germinating conidia are targeted by invading neutrophils that can destroy the mycelium.
Neutropenic patients and other immunocompromised patients are at risk of lung invasion leading to tissue damage, uncontrolled fungal growth, and the possibility of vascular invasion.
Pathology
Sinus (nose) aspergillosis
The disease is mainly caused by infection with Aspergillus fumigatus (A. fumigatus), although other species including A. flavus, A. niger and A. nidulans can also be isolated from specimens. Most dogs with nasal sinus aspergillus have a nasal coil bone and a visibly damaged nasal mucosa. In severe cases, destruction of the frontal bone may occur with invasion of the soft tissues around the eye socket and penetration through the cranial sieve into the central nervous system. Nasal aspergillus infection can cause the destruction of the bone rolls present in the nose and this fungus can form block-like lesions called fungal plaques. The disease is usually confined to the nasal cavity and can spread from the nose to the frontal sinuses, where it is more difficult to treat. Sometimes, the disease can affect the eyes and skull. Most cases of nasal aspergillosis appear in dogs with normal immune systems and good health.
Clinical manifestations associated with nasal sinus aspergillosis infection include purulent to purulent nasal discharge, facial discomfort, loss of pigmentation or ulcers in the nose, sneezing, and nosebleeds. Pigmentation loss is thought to be caused by toxins in secretions and is not often documented as a cause of nasal disease in dogs. A runny nose is initially one side of the nose but can then progress to two sides due to the destruction of the nasal septum.
Other signs include loss of appetite, fatigue, wheezing, and mouth breathing. In more severe cases, ocular discharge and bulging eyes may be seen. In the early stages of the disease, the discharge may be intermittent or only associated with sneezing. Nosebleeds can occur in episodes and the edges of the nostrils are often rough, inflamed and ulcerative (tissue breaks off and bleeds due to discharge, which is very uncomfortable). Sneezing and scratching the nose or face can also occur.
Diffuse aspergillosis (systemic)
Diffuse (generalized) aspergillosis is relatively rare in dogs compared to sinus form. The infection is thought to occur through the respiratory tract with bloodstream spread then to other locations, including the discs, kidneys, and iris as well as other organs. Aspergillosis is spread mainly by infection with A. tereus, A. defus and A. niger. These fungi have the ability to enter the respiratory tract and spread, then travel through the bloodstream spreading throughout the body, including the discs of the spine or kidneys. Other muscles or bones can also be affected. The disease usually takes several months to develop, and clinical signs depend on the systems that are infected by the fungus. Symptoms may include loss of appetite, weight loss, muscle atrophy, fever, weakness, lameness, tooth loss, blood in the urine, urinary accident and delirium. Most dogs infected with widespread aspergillosis are severely ill and have a poor prognosis.
Diagnose
Clinical diagnosis
Signs of nasal aspergillosis include runny nose including blood mixed with pus, nasal pain, ulcers around the nostrils, nosebleeds, sneezing, lethargy and fatigue. Diffuse aspergillosis usually takes several months to develop symptoms, dogs may limp, vomit, and urinate blood.
Laboratory Diagnostics
Aspergillus can be identified through body fluid/specimen cultures. However, since Aspergillus can be isolated from the nasal cavity of a healthy dog, a positive culture result should be supported by histopathology.
Abnormalities in blood count can include mature neutrophilia, eosinophilia, and mononucleosis, along with a lack of normal blood pigmentation.
Hyperglobulinemia, hypoalbuminemia, and hypernitrogenemia may be noted. Different levels of hypercalcemia can also occur.
Usually shows dehydration, hematuria, and purulent urination. Mycelium can occasionally be observed in urine residues (as well as in fluid aspiration from other affected areas such as lymph nodes, kidneys, pleural effusion, lungs, bones, joint fluid, and tracheal lavage).
Nasal endoscopy allows visualization of the nasal cavity and collection of biopsy samples. In addition, a direct examination of the nasal passages can reveal other causes of runny nose such as tumors or foreign bodies. An endoscope can be used for this purpose. Measure the endoscope in advance from the plane of the nose to the innermost corner of the eye to avoid penetrating the sieve plate. Dogs with nasal aspergillosis often suffer from significant loss of nasal curl bones and a lot of purulent discharge. In addition, translucent white or bluish fungal patches may be noted adhering to the mucous membrane.
Tests that can detect antibodies in serum against Aspergillus species include AGID (agar gel-immuno-diffusion test), complement fixation techniques, and ELISA. The antibodies detected with AGID vary depending on the laboratory; however, most detected antibodies to A. fumigatus, A. niger and A. flavus. This test is widely available and is probably the most commonly performed fungal serology test at this time. However, a recent study found that the sensitivity of the test was only 67% in dogs infected with sinus aspergillosis, and 1/3 of the sick dogs had negative results. The specificity of the test is at 98%, indicating that it is unlikely that a false positive result will occur. However, it is important to remember that a positive result with any serological test does not rule out the possibility of non-fungal rhinitis and there is not enough evidence to make a definitive diagnosis of sinus aspergillosis.
The EIA (Enzyme Immunoassay) or ELISA test has been used to detect galactomannan, which is a component of the cell wall of Aspergillus fungi present in serum and other body fluids such as cerebrospinal fluid or alveolar lavage. However, in a recent study, the sensitivity of this test in dogs with nasal sinus disease was only 23.5%. The poor sensitivity of the test may be due to the limited release of antigens into the dog's circulatory system.
X-rays of the nasal cavity and frontal sinuses can be helpful diagnostically, but the dog must be anesthetized during an X-ray examination to allow for proper positioning. In nasal aspergillosis, the presence of fungal plaques can be considered by nasal endoscopy and nasal x-ray to see the rate at which the fungus destroys nasal curl bone tissue in dogs infected with aspergillosis.
Tomography (CT) or magnetic resonance imaging (MRI) is more sensitive than conventional radiographs in demonstrating changes and extent of damage to the nasal curls. Diagnosing disseminated aspergillosis may be more difficult. Bone destruction images on X-ray or CT scan may be suspected of Aspergillus infection.
Histology and cytology tests can provide direct evidence of mycelium, which strongly supports the diagnosis of aspergillosis. The sensitivity of these methods is high if the samples are taken from fungal plaques but tends to be lower if the samples are collected without direct imaging. Classic histological findings associated with canine aspergillosis include ulcers and mucositis, with a predominance of lymphocytes and plasma. cell. However, these changes are non-specific and may be reported in dogs with severe primary lymphocytic rhinitis.
Granular purulentitis is also commonly observed in cytology samples. In dogs with neurological signs, cerebrospinal fluid often presents with neutrophilia.
Disease prevention and treatment
Treat
Fungal infections require prolonged treatment, and many medications for aspergillosis have toxic side effects. Advances in techniques and drugs have allowed for more successful treatment of nasal aspergillosis, but systemic aspergillosis remains challenging to treat.
Removal of lesions in the nose and side of the nose followed by topical treatment is an effective treatment for nasal aspergillosis. The majority of fungal growth is located on the surface of the affected tissues and is not easily treated with injections or oral medications. For this reason, all forms of treatment of nasal aspergillosis will involve the infusion of topical antifungal drugs into the nasal cavity and frontal sinuses, and this must be done under general anesthesia.
After anesthetizing the dog, an endotracheal tube (breathing tube) is placed into the trachea that allows the dog to inhale a mixture of anesthetic gas and oxygen. The area behind the throat is packed with sponge gauze and an inflatable balloon catheter called a Foley catheter. A 1% solution of clotrimazole or 1% bifonazole with enilconazole (a topical antifungal) is infused into the nose and frontal sinuses and the nostrils are sealed. The solution was infused and left to rest in the nose for 1 hour, during which time the dog was periodically rotated to ensure the solution was in contact with all surfaces of the sinuses. At the end of the incubation period (1 hour), the solution is aspirated or drained out through the nostrils.
This treatment method is highly effective, in most cases, the runny nose will go away within 2-4 weeks after just 1 course of treatment. If after a month there are still signs of the disease, it is recommended to carry out another course of treatment. If the infection has eroded through the bones of the nasal sinuses and entered the brain, treatment with oral antifungal drugs, such as itraconazole, fluconazole or terbinafine is required. Treatment is required for several months.
Fluconazole (2.5–10 mg/kg, divided every 12 hours) and itraconazole (5–10 mg/kg, every 24 hours) are cost-effective options. Ketoconazole (5 10 mg/kg, every 12 hours for 6–8 weeks), is cost-effective but less effective. Voriconazole (3–6 mg/kg every 24 hours) is the most effective azole antifungal drug for the treatment of aspergillosis.
The survival of dogs with disseminated aspergillosis can vary, dogs with mild illness may survive treatment for months and may relapse. Dogs that are more severely injured often do not cope with complications and die. However, systemic aspergillosis is an uncommon condition, mainly observed in female German Shepherds in middle age.
Prevention
Aspergillus spores are everywhere in the environment, and we are all in constant contact with these creatures. So standard hygiene measures, including washing hands after contact with pets and cleaning the runny nose, are sufficient to keep the risk at a negligible level.
Good general health will help ensure a healthy immune system to repel this opportunistic disease. Keeping dogs indoors can be helpful, as it will limit access to grass clippings, hay, straw, and other substances where Aspergillus fungi can be found People and pets whose immune systems are compromised by drug use, disease, or old age should avoid contact with infected animals. Birds are the most common source of infection in humans.
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Source: Nguyen Duc Hien, Nguyen Ngoc Phu Vinh, Huynh Minh Tri, Pham Minh Thu, Tran Khanh Long (2023). The disease is common in dogs. Can Tho University Press.
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