Wednesday, December 14, 2011

Blastomyces dermatitidis: A review of a deadly disease from a small spore

Amongst the pristine beauty of the northern end of the Mississippi and the Great Lakes lies a deadly yeast that is responsible for infecting more dogs in the Midwest than any other fungus. Blastomyces dermatitidis is the causative agent of the disease Blastomycosis, which can infect lungs, eyes, lymph nodes, bone, CNS, and skin. Even after administration of an antifungal, mortality rate is conservatively 40% (Brömel et al 2005). The clinical signs of this infection are common symptoms to most diseases. Dogs have a fever, they lose weight, stop eating and have low energy, and therefore many owners do not think to get their pet immediately treated. If the fungus is not treated within its early stages, a more rigorous and expensive treatment must be performed for close to a half of a year. In addition to the shear amount of medication needed to rid the animal of the fungus, the antifungal itraconizole costs $3,717, which is three times more then the antifungal used to treat other less serious infections (Mazepa 2011). Because of the lack of insurance, cost can determine whether or not an animal is treated. Without medication, a dog will undoubting succumb to the infection.
Blastomyces dermatitidis exist as a branching fungal hyphae when found in nature. It typically resides in rotting wood, mud, sand and animal wastes near a body of water (Brömel et al 2005). Many infections are diagnosed shortly after the owners take trips with their dog up north to camp or hunt. Infection occurs when a dog inhales spores produced by the fungi’s sexual cycle, so therefore it’s not surprising that the dogs that are infected are typical hunting dogs; a large, intact, male dogs. The germination of the spore, known as conidita, is caused by the rapid change in temperature when entering the body of a dog (Brömel et al 2005). Within the dog, the newly formed yeast triggers an immunological and inflammatory response in which the phagocytes and complement proteins bind B. dermatitidis in attempts to destroy it. Interestingly, B. dermatididis show better growth within the macrophages and other phagocytes then outside the cell. Giles et al. discovered that this enhanced growth was aided by the release of a canine soluble factor, which increases adherence to the walls of the macrophages. Although the factor that enhances cell growth is unknown, the adherence of the yeast to the macrophages protects B. dermatitidis from being degraded by the phagocytes. In addition to the resistance of host macrophages, B. dermatitidis produces melanin. This virulence factor makes the yeast less susceptible to antifungals such as amphotericin and fluconazole. Fortunately, itraconizole is not affected by the presence of melanin (Mazepa 2011).
Early diagnosis of Blastomycosis is pivotal due to the fungus’ ability to become systemic quickly, which can drastically affect the chance of survival.  Because the yeast is carried within the host’s macrophages, the immune system spreads B. dermatitidis and infects other areas of the body such as the skin and eyes. Serosanguineous (blood and pus) drainage can occur from the lesions, which appear on the nose, face, back and nail bed of the animal (Greene 2006). When Blastomycosis infects the eyes, excess of blood vessels, constriction of the eye, and watery swollen cornea are clinical signs. Severe infections can cause the lens of the eye to rupture, consequently resulting in the removal of the eye (Brömel et al 2005).
The two most severe forms of Blastomycosis are infection of the lungs and the central nervous system. Blastomycosis is most commonly seen within the lungs because it is the initial site of germination. Severe pulmonary infections result in a 50% mortality rate within the first seven days of treatment. If the infection spreads to the CNS, very few survive (Greene 2006). An acute pulmonary infection can be seen in an X-ray in which the lungs look cloudy and opaque from the plaques of yeast living amongst the cells.  But to truly know if the patient has Blastomycosis and not a less serious infection, the veterinarian has to see the yeast itself.
The different strategies in diagnosing Blastomycosis depend on site of infection. Tracheal washes are a common procedure to obtain an appropriate sample within animals with a pulmonary infection. The protocol of a wash consists of syringe placed down the trachea and sterile saline coats the tissue surface. The saline then is quickly collected with the syringe and can be analyzed for budding yeast. Recently, a urine test has been a tool to be able to diagnose Blastomycosis. The urine is screened for antibodies against the B. dermatitidis yeast but unfortunately, this is not a perfect screening because it has been known to cause false negatives. Additionally, antigen testing can be done by drawing blood and isolating the serum to identifying the antigen. This test is much more reliable, however it is more difficult and time consuming to perform (Greene 2006).
Treatment for Blastomycosis consists of administering an antifungal medication until there are no signs of the yeast. Sterilizing an animal of B. dermatitidis is largely a waiting game. Itraconizole is the most effective drug to treat the infection because it rids the animal of the yeast the quickest (an average of 138 days). Other antifungals such as fluconazole are just as affective however the average time to do this is significantly longer due to the yeast’s production of melanin. When comparing costs, itraconizole is three times more expensive then the fluconazole. However, regardless of price, it may be more effective to treat the patient with an antifungal that can destroy cells faster and are not affected by the melanin (Mazepa 2011).
B. dermatitidis infects Midwestern dogs more than any other fungus and without affordable and effective treatments many die from Blastomycosis. Because there is largely no means of prevention, finding an accessible cure and reliable ways to diagnose patients is pivotal in the fight against the disease. Researching this organism could assist scientists in finding an effective cure which would save the lives of many pets in our own state.


Works Cited:
Brömel, Catharina, and Jane E Sykes. 2005. “Epidemiology, diagnosis, and treatment of blastomycosis in dogs and cats.” Clinical Techniques in Small Animal Practice 20 (4) (November): 233-239.

Giles S, Klein B, Czuprynski C: The effect of canine macrophages on the adherence and growth of Blastomyces dermatitidis yeast: Evidence of a soluble factor that enhances the growth of B. dermatitidis yeast. Microb
Pathog 27:395-405, 1999

Greene, Craig E. 2006. Infectious diseases of the dog and cat. Saunders Elsevier, March 29.

Mazepa, A. S.W, L. A Trepanier, and D. S Foy. 2011. “Retrospective Comparison of the Efficacy of Fluconazole or Itraconazole for the Treatment of Systemic Blastomycosis in Dogs.” Journal of Veterinary Internal Medicine 25 (3) (May 1): 440-445.

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