Aspergillus spp

From Horse
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Aspergillosis in horses is a fungal disease caused by Aspergillus spp.

Aspergillus spp are very common in the environment, especially in moldy feed and bedding[1]. They are opportunistic pathogens and often cause disease in horses that are immunosuppressed from debilitating conditions (e.g., enterocolitis, septicemia, neoplasia, Cushing's disease, equine protozoal myeloencephalitis) or major surgery or that have been treated with immunosuppressive drugs[2][3]. They can infect internal organs and the eye (Keratomycosis).

Cause

This fungus has broad (2 to 4 µm in diameter), septate hyphae with parallel sides and acute right-angled branching. They have a propensity for vascular invasion. A definitive diagnosis can be made by culture or staining by immunohistochemistry or immunofluorescence (Fusarium spp and Pseudallescheria boydii look similar on histologic examination)[4].

Clinical signs

Infection is by inhalation of an overwhelming number of spores or by translocation of organisms across an inflamed gastrointestinal tract. Aspergillus pneumonia is almost uniformly fatal, often with no or mild respiratory signs. The two forms of Aspergillus pneumonia probably reflect the two portals of entry, with fungal proliferation and invasion of the small airways occurring secondary to inhalation, and angioinvasive aspergillosis with lesions centered around large blood vessels likely due to hematogenous infection originating from the gastrointestinal tract. In two retrospective studies of invasive pulmonary aspergillosis, 41 of 49 cases were associated with enterocolitis[5][6].

Pulmonary aspergillosis is characterized grossly by multiple nodules throughout the lungs. On histologic examination, there is often necrosis and purulent inflammation. Necrosis is due to toxin and enzyme production as well as vascular obstruction. Fungal invasion of blood vessels is common and results in vasculitis, thrombosis, infarction, and necrosis. Chronic lesions are granulomatous, with macrophages, neutrophils, and multinucleated giant cells predominating.

Diagnosis

Antemortem diagnosis of pulmonary aspergillosis is rare. In a retrospective study of 30 cases of Aspergillus pneumonia, only two cases were diagnosed or suspected antemortem. Transtracheal aspirate or bronchoalveolar lavage may not be helpful because hyphae and spores are often present extracellularly or within macrophages in aspirate and lavage from healthy animals. False-negative results can also occur. Two days before euthanasia, cytologic examination of a transtracheal wash specimen obtained from the foal in Figure 4 failed to identify Aspergillus hyphae. Serologic diagnosis has occasionally been useful9 but is often unreliable. Development of a commercial ELISA is promising[7].

Treatment

Fifty percent to 90% of humans with invasive asper­gillosis die despite treatment. For decades, amphotericin B has been the mainstay of treatment of invasive infection with Aspergillus but is associated with nephrotoxicity in about 50% of patients. Nephrotoxicity is reduced using liposomal amphotericin B. Amphotericin B colloidal dispersion is not recommended because of the risk of infusional toxicities[8].

Voriconazole, a new azole antifungal, is now considered the drug of choice in treating human aspergillosis, while caspofungin (in the new class echinocandin antifungals) shows promising results in patients with refractory infections. The pharmacokinetics of voriconazole have recently been determined in horses, with excellent absorption after oral administration and high concentrations achieved in several body fluids[9]. Voriconazole is still prohibitively expensive; therefore, oral itraconazole is currently preferred for treating aspergillosis in horses.27 In humans, the use of itraconazole has shown response rates comparable to those associated with the use of amphotericin B[10]. There is a limited number of reports of horses surviving pulmonary aspergillosis. One horse with Aspergillus pneumonia survived with amphotericin B therapy (the dose and duration were not reported).

References

  1. Guillot J, Sarfati J, de Barros M, et al (1999) Comparative study of serological tests for the diagnosis of equine aspergillosis. Vet Rec 145:348-349
  2. Blomme E, Del Piero F, La Perle KMD, et al (1998) Aspergillosis in horses: a review. Equine Vet Educ 10:86-93
  3. Sweeney CR, Habecker PL. (1999) Pulmonary aspergillosis in horses: 29 cases (1974-1997). JAVMA 214:808-811
  4. Tunev SS, Ehrhart EJ, Jensen HE, et al (1999) Necrotizing mycotic vasculitis with cerebral infarction caused by Aspergillus niger in a horse with acute typhlocolitis. Vet Pathol 36:347-351
  5. Sweeney CR, Habecker PL. (1999) Pulmonary aspergillosis in horses: 29 cases (1974-1997). JAVMA 214:808-811
  6. Slocombe RF, Slauson DO. (1988) Invasive pulmonary aspergillosis of horses: an association with acute enteritis. Vet Pathol 25:277-281
  7. Guillot J, Sarfati J, de Barros M, et al (1999) Comparative study of serological tests for the diagnosis of equine aspergillosis. Vet Rec 145:348-349
  8. Chandrasekar P. (2005) Riches usher dilemmas: antifungal therapy in invasive aspergillosis. Biology Blood Bone Transpl 11:77-84
  9. Colitz CM, Latimer FG, Cheng H, et al (2007) Pharmacokinetics of voriconazole following intravenous and oral administration and body fluid concentrations of voriconazole following repeated oral administration in horses. Am J Vet Res 68(10):1115-1121
  10. Davis JL, Salmon JH, Papich MG. (2006) Pharmacokinetics of voriconazole after oral and intravenous administration to horses. Am J Vet Res 67(6):170-175