An update on research and clinical management

Although endemic to Canada, Brucella canis is an elusive infectious agent of unknown significance to most practitioners. Clinical disease attributed to Brucella canis infection occurs sporadically, reinforcing the perception that the disease is uncommon in Canada compared with other regions of North America such as Mexico and the southeastern USA. Seroprevalence rates in the southeastern USA are estimated to be 7% to 8% . Earlier reports from Quebec (1970’s) and southwestern Ontario (1980) still serve as the main Canadian seroprevalence data with rates of 1.6% and 0.3%, respectively . There is currently a paucity of seroprevalence studies in western Canada, but outbreaks have been observed in a Saskatchewan kennel and the Calgary, Alberta area .

With the unprecedented rates of animals moving across international borders and the lack of federal regulation, canine brucellosis may be changing its geographical distribution. In 1988, a Canadian Veterinary Journal article documented the identification of 2 strains, an American type strain RM66 and a Mexican strain Mex 51, in 11 Brucella canis  Genprice Gentaur isolates from Canadian dogs.

Characterization of the current circulating strains is warranted.

  • Until this information is available, Canadian veterinarians should be aware of the agent and consider it as a reasonable differential diagnosis in appropriate cases, regardless of historical information, or neuter status. In Canada, Brucella canis remains a potentially devastating infectious agent that is still considered uncommon, despite the increasing international movement of dogs.
  • There may be a growing risk to the Canadian canine population due to a reliance on outdated seroprevalence studies and the lack of federal regulation.
  • With the complex diagnostic and management challenges associated with Brucella canis, a One Health approach is necessary to address the need for ongoing research, including updating canine and human seroprevalence rates in Canada, elucidating the pathogenesis, and determining the most appropriate treatment and prevention strategies.
  • Clinical management decisions are often complicated by currently available treatment protocols, and health risks to both canine and human populations. This article integrates recent research focusing on the pathogenesis, diagnosis, and treatment of Brucella canis , and outlines current clinical management approaches.

Etiology

Bacteria in the genus Brucella are nonmotile, nonencapsulated, non-spore-forming, facultatively intracellular Gram-negative coccobacilli or short rods . Four of the six classical Brucella species are known to cause disease in dogs and humans: Brucella canis (natural reservoir animal is the dog), Brucella melitensis (sheep, goats), Brucella suis (pigs), and Brucella abortus (cattle, bison, buffalo) . The remaining 2 of the 6 classical Brucella species [Brucella neotomae (rodents, desert rats) and Brucella ovis (sheep)] are not associated with disease in dogs. Additional Brucella species including both terrestrial forms (B. microti, B. inopinata) and marine forms (B. maris, B. pinnipediae, B. ceti) are of uncertain pathogenicity to dogs.

Brucella canis was discovered in 1966–1967 during an investigation of abortion in beagles, in which the organism was isolated from aborted tissues and vaginal discharge . Brucella canis was initially thought to be a biotype of Brucella suis based on genotypic and phenotypic similarities . The significance of this distinction is paramount to the Canadian swine industry and the Canadian Food Inspection Agency (CFIA) as Canada is considered free of Brucella suis biovar 3 . Differentiation between Brucella canis and Brucella suis biovar 3 can be challenging . A multiplex conventional polymerase chain reaction (PCR) has been optimized to differentiate between these Brucella species .

The host range for Brucella canis is predominantly domestic dogs, but other species have been investigated. Serologic studies of wild canids have documented positive antibody titers in foxes and coyotes . Experimental studies involving conjunctival and oral inoculation of cattle, swine, and sheep with B. canis showed that these host species were highly resistant to B. canis infection, despite 2 field reports of B. canis in cattle . Similarly, oral experimental infection of cats documented transient bacteremia in 3/14 but none developed agglutinating antibody titers .

 

Transmission Major routes of transmission for this venereally transmitted agent are genital, conjunctival, and oronasal mucosae, as occurs during normal reproductive, social, and grooming activities in dogs .

The primary sources of transmission are reproductive fluids: vaginal discharges and semen. Tissues and fluids associated with the fetus, the placenta, and the vagina after abortion or stillbirth have approximately 106 organisms/mL . Shedding of the organism occurs in vulvar secretions for up to 6 wk after abortion and during estrus . In males, semen has high concentrations of the bacterium for 6 to 8 wk after infection . The agent is then shed intermittently for up to 2 y at lower concentrations in semen which remains an important source of infection for other dogs . The minimum infectious dose is approximately 106 organisms/mL via the oral route and 104 to 105 organisms/mL by the conjunctival route . Minor routes of transmission include in utero, broken skin, blood transfusions, feces, milk, and fomites such as contaminated syringes, vaginoscopes, and artificial insemination equipment .

Brucella bacteria attach to mucous membranes, penetrate the epithelial barrier, and are taken up by the mononuclear phagocytic system, where they reside intracellularly. This is accomplished by utilizing virulence factors presumably via the type IV secretory system, and inhibiting the bactericidal myeloperoxidase-peroxide-halide system through the release of 5-guanosine and adenine .

The intracellular organisms then travel through the reticuloendothelial system to local lymph nodes (retropharyngeal, inguinal, superficial iliac), liver, spleen, and possibly bone marrow. After 7 to 30 d, the bacteria move into the blood stream to cause intermittent bacteremia. The organism targets “steroid-dependent” reproductive tissues, including the prostate, testicles, epididymides, gravid uterus, and placenta . Evaluation of a Saskatchewan kennel outbreak of brucellosis found that the progestational, non-gravid uterus was also a reservoir for the bacterium . A mixed inflammatory response consisting of lymphocytes, plasmacytes, and histiocytes has been observed in these reproductive tissues . Focal coagulative necrosis of the chorionic villi, necrotizing arteritis, and numerous bacteria in trophoblastic epithelial cells can be found in the aborted placenta .

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Establishing a diagnosis can be challenging due to the wide spectrum of clinical manifestations reported and the limitations of available diagnostic tests. The intent of this article is to familiarize clinical, public health, and research veterinarians with the etiology, transmission, pathogenesis, course of infection, clinical manifestations, diagnosis, treatment, prevention, and public health aspects of the disease.

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