Neosporosis

Species

Canine neosporosis  



Neosporosis is an important neuromuscular disease of domestic dogs world-wide. The causative parasite, Neospora caninum, cycles between canine definitive hosts and herbivore intermediate hosts, most notably cattle.  Congenital N. caninum infections occur in both cattle and dogs.

Stages

• Oocysts (environmental stages formed in canine intestinal epithelium and passed with the feces)

• Tachyzoites (rapidly dividing stages that actively invade tissues)

• Bradyzoites (slowly dividing stages that encyst within tissues)

Disease

• Clinical neosporosis is a result of the proliferation of tachyzoites within tissues leading to inflammation, granulomata formation, and necrosis.  Tachyzoites are present within many tissues, but clinical signs are most often neuromuscular.

• Disease is most severe in congenitally infected puppies.  More than one littermate will develop paralysis of rear limbs, often with hyperextension, beginning 3 to 9 weeks after birth.  Muscle atrophy and contracture become evident.  Cervical weakness and dysphagia lead to death.

• Neosporosis is often observed in dogs less than six months of age, but dogs of any age can be affected. Neosporosis in adult dogs may result from recent infection with N. caninum or recrudescence of an existing infection as a result of pregnancy or other immune-compromising condition.  Multifocal central nervous system signs or polymyositis are most commonly observed, but other manifestations reported include myocarditis, dermatitis, and pneumonia.

Prevalence

• Neosporosis is found world-wide; serologic prevalence in domestic dogs ranges from 0 – 100% depending on the country.

  
  

  • In the United States, 7% of pet dogs tested from 35 states (n=1,077) were seropositive in a 2007 study.
• Overall, serologic prevalence of N. caninum infections in clinically healthy dogs is greater than the prevalence of clinically presented dogs; sub-clinical infections are suspected.
• Free-roaming dogs, dogs residing in the presence of cattle, and breeds such as basset hounds, boxers, German shorthaired pointers, golden retrievers, greyhounds, and Labrador retrievers are more commonly seropositive.
• Serologic prevalence in dairy and beef cattle varies depending on the region of the world and whether serum or milk antibodies are assayed.

  
  

  • In the United States, 10.3-60.6% of dairy cattle (n=8,342) and 5.2-79% of beef cattle (n=4,014) were seropositive in states including California, Georgia, Maryland, Nebraska, North Dakota, and Texas in 2007.

Transmission

• Ingestion of bradyzoite-laden tissues of cattle, particularly placenta and fetal membranes, and transplacental transmission are thought to be the predominant routes of infection to dogs in nature. 
• Adult cattle become infected by ingesting sporulated oocysts, which may be present in feed and water sources or soil contaminated with dog feces. 
• Congenital infections in dogs and cattle result from the active dissemination of tachyzoites across the placenta, which may result from exogenous infection or recrudescence of a persistent infection during pregnancy.

Prepatent Period and Environmental Factors

• Environmental oocyst contamination by infected dogs is not well understood.  World-wide, very few naturally infected dogs have been documented to have detectable oocysts in feces. 
• Environmental resistance of N. caninum oocysts is presumed to be comparable to that of morphologically similar Toxoplasma gondii oocysts, which can survive for months to years in the environment. Oocysts sporulate (become infective) in the environment within 24-72 hours.  
• Experimentally, oocysts are shed in the feces of canine hosts 5 days or more after ingestion of bradyzoites. The quantity and duration of oocysts shed are highly variable.
• Encysted bradyzoites within unpreserved tissues are infective to dogs for 7 to 10 days.

Host Associations, Sites of Infection, Pathogenesis

• Neospora caninum is a coccidian with an indirect lifecycle in which canids (domestic dogs, coyotes, possibly others) are definitive hosts and several documented herbivore species (cattle, sheep, water buffalo, white-tailed deer) can serve as intermediate hosts
• Sexual stages develop in the duodenal epithelium of dogs and oocysts are produced.
• In addition to serving as definitive hosts that shed oocysts, dogs can also serve as intermediate hosts that harbor extra-intestinal stages of N. caninum.  Clinical canine neosporosis is associated with tachyzoite dissemination and intracellular reproduction, resulting in tissue destruction, inflammation, and necrosis.
• Tachyzoites and bradyzoites, asexually reproductive stages found throughout tissues of intermediate hosts, can result in repeated abortions and stillbirths among cattle.
• Bradyzoites incite little inflammation, and are typically restricted to neural and muscular tissues in persistently infected dogs.  Stress and immunocompromise can cause bradyzoites to transform back into tachyzoites, resulting in clinical disease and infection of fetuses in pregnant animals.

Diagnosis

• Diagnosis is most often presumptive based on patient history, clinical signs, and positive serology (IgM or IgG).
• Serologic assays available include IFA of CSF or serum.  A titer ≥1:50 is considered positive for exposure.  Most dogs with clinical signs have titers ≥1:200, although some may be seronegative at the time of testing.
• Definitive diagnosis is achieved by microscopically detecting tachyzoites in tissue aspirates or bradyzoites in biopsy samples of affected muscles.  However, these methods are not sensitive, as results are often negative for known infected dogs.  If present, zoites must be distinguished from those of morphologically similar Toxoplasma gondii.
• Oocysts in the feces of infected dogs are rarely detected, and must be distinguished from morphologically similar oocysts of Hammondia spp.

Treatment

• There is no approved or curative treatment for canine neosporosis.  Arrestment of clinical disease is best achieved when treatment is initiated before the occurrence of contracture or paralysis.  Dogs typically die without treatment, and some dogs die even with treatment. 
• The following treatment regimens are used to control clinical neosporosis:

  
  

  • Clindamycin (12.5-25 mg/kg PO or IM every 12 hours for 4 weeks)
  • Trimethoprim sulfadiazine (15-20 mg/kg PO every 12 hours for 4 weeks) in combination with pyrimethamine (1 mg/kg PO every 24 hours for 4 weeks)
• If observable clinical improvement is slow, treatment should be extended beyond the recommended 4 weeks until two weeks after clinical signs have plateuaed.
• All littermates of affected puppies should be treated regardless of clinical signs.
• Passive range of motion exercises and massage may be beneficial in some cases.

Prevention

• Prevent contamination of livestock feed with canine feces.
• Do not allow dogs to ingest bovine placental tissues, fetal membranes, or other raw meats.
• Do not breed bitches that have previously developed clinical neosporosis or have whelped affected pups in the past.
• Seropositive dogs should not be administered glucocorticoids or other immunosuppressive drugs.

Public Health Considerations

• Neospora caninum is not considered zoonotic.
• Seropositive humans have been documented, but no clinical cases have been identified, and the parasite has not been isolated from a human host.  Still, contact should be limited between immunocompromised individuals and known N. caninum infected animals.

Selected References

• Dubey JP and Schares G. 2011. Neosporosis in animals – The last five years. Vet Parasitol 180: 90-108.
• Dubey JP, et al., 2007. Epidemiology and Control of Neosporosis and Neospora caninum. Clin Microbiol Rev.
• Lyon C, 2010.  Update on the Diagnosis and Management of Neospora caninum Infections in Dogs.  Top Companion Anim Med 25: 170-175.
• Reichel MP, et al., 2007.  Neosporosis and hammondiosis in dogs. J Small Anim Pract 48: 308-312.