Toxoplasma gondii

Synopsis

CAPC Recommends

• Cats who test positive for antibodies to Toxoplasma gondii should be considered unlikely to shed infectious oocysts; most infected cats will also remain asymptomatic.

• Remove cat feces on a daily basis from the litter box; T. gondii oocysts must develop for 1-5 days after being passed in the feces to become infectious.

• Keep cats indoors and prevent them from hunting and consuming undercooked meat.

• Particular care should be taken by pregnant women and immunocompromised individuals to avoid infection. People can become infected by ingesting infective oocysts or undercooked meat that contains encysted stages.

Species

• Toxoplasma gondii is the causative agent of toxoplasmosis, one of the most important zoonotic parasites.

Stages

• Oocysts - resistant stages for environmental transmission shed in cat feces; only produced by felid definitive hosts

• Tachyzoites - rapidly dividing tissue stages found in all vertebrate hosts

• Bradyzoites - slowly dividing, encysted tissue stages found in all warm-blooded vertebrate hosts

Toxoplasma oocysts

Toxoplasma tachyzoites

Toxoplasma gondii tachyzoites 1000X

Toxoplasma bradyzoites

Toxoplasma gondii bradyzoites 1000X

Disease

• Toxoplasmosis is a multisystemic infection characterized by granulomatous inflammation associated with tachyzoite proliferation in the tissues.

• In small animal practice, the disease is most commonly seen in immunocompromised cats and, occasionally, dogs.

• Organs and tissues commonly affected include lymph nodes, liver, lung, brain/spinal cord, and eye.

• Toxoplasmosis may cause focal or generalized lymphadenitis, encephalitis, pneumonitis, myocarditis, and retinochoroiditis.

• There may be associated fever, weight loss, and lethargy.

• Cats with clinical toxoplasmosis are unlikely to be shedding oocysts in their feces.  Disease is caused by proliferation of asexual stages extraintestinally.  Cats usually do not develop any clinical disease associated with oocyst shedding.

• Congenital infection with T. gondii can cause neurologic disease, birth defects, stillbirth, and ocular disease in other animals, particularly sheep and goats.  Congenital infection has occasionally been reported in dogs and cats.

Prevalence

• Toxoplasmosis is a common, worldwide infection affecting a large variety of mammals and birds.
• Prevalence of oocysts (fecal stage) in cats in the United States is quite low. At any point in time, approximately 1% of cats have intestinal infection and will be shedding oocysts.
  • In six surveys from different states in which more than 10 cats were included in all studies, oocyst shedding ranged from 0.0 to 6.6% (mean of 0.7%).
• Much higher prevalence of oocyst shedding has been cited from other countries, (e.g., 19% in Ethiopia, 23% in Costa Rica, 40% in Turkey, 41% in Egypt).
• The prevalence of positive antibody titers in cats in the United States ranges from 14% to 100%.
• Seroprevalence of human infection in the United States is approximately 11% in people between the ages of 6 and 49 years.

Transmission

• Cats and dogs become infected with T. gondii by ingestion of bradyzoites in mammalian or avian tissues or ingestion of sporulated oocysts from articles contaminated by feline feces (e.g., soil, water, vegetation).

• Transplacental or transmammary transfer of tachyzoites from dam to offspring also occurs, albeit rarely, in pets.

Prepatent Period and Environmental Factors

• Cats and other felids are the only species that develop patent infections with T. gondii, shedding oocysts 3-10 days following ingestion of bradyzoites in raw meat and 19-48 days following ingestion of oocysts.

• Oocysts shed by cats become infective (sporulated) in 1 to 5 days and survive for months to years in the environment.

Host Associations, Sites of Infection, Pathogenesis

• Toxoplasma gondii is a two-host coccidial organism, although cats can also be infected by the ingestion of oocysts.

• Sexual stages develop only in the intestine of felid definitive hosts (wild and domestic).

• Extraintestinal, asexual stages (tachyzoites, bradyzoites) develop in all mammalian and avian species.

• Tachyzoites divide rapidly within various cells, leading to cell death, tissue necrosis, and granulomatous inflammation.

• Following acute infection, the organism survives for extended periods in host tissues as slowly dividing bradyzoites within tissue cysts. Bradyzoites may be reactivated and transform to rapidly dividing tachyzoites upon host immunosuppression.

• Clinical disease is more severe in immunocompromised individuals, developing fetuses, and the elderly.

Diagnosis

• Non-sporulated oocysts (10 µm by 12 µm) are shed in feline feces.  The oocysts of T. gondii are morphologically indistinguishable from those of Hammondia sp. and Besnoitia sp. which may also be present in feline feces.
  • Because active shedding only occurs over a very short period (approximately 1 to 3 weeks), the great majority of infected cat feces does not contain oocysts.  Fecal flotation is not recommended as a clinical means of evaluating the infection status of an individual cat.
  • Centrifugal fecal flotation may occasionally identify oocysts in the feces of recently infected cats, but this finding has limited clinical significance because the presence of oocysts is not correlated with development of disease in the cat.
  • If a cat is shedding oocysts morphologically consistent with a diagnosis of T. gondii, the cat could be quarantined until shedding ceases (i.e., 1 to 3 weeks) if any household members are pregnant or immunocompromised.  Owners should be given this option and warned of the risk of transmission and the need for meticulous hygiene when cleaning litter boxes or other articles contaminated with cat feces during the period of shedding.
  • Cat feces containing oocysts should be disposed of in a manner that prevents exposure to humans or other animals or the environment (i.e., incinerator).
• Antibody assays
  • Serologic testing cannot accurately predict oocyst shedding status in cats and no serologic assay accurately indicates when a cat has shed T. gondii oocysts in the past.  Most cats shedding oocysts are seronegative at the time of shedding.
  • Veterinarians are encouraged to utilize antibody testing that provides a titer result rather than positive/negative, as rising titers may be more suggestive of active infection.
  • Antibody testing may be useful for determining the approximate time of acquired infection, recent or in the past.  IgM titers are associated with recent or active infection, while stable IgG titers are indicative of previous infections.
  • Very high or rising IgM or IgG titers may raise the suspicion of toxoplasmosis in feline patients with clinically compatible illnesses.
  • Antibody testing is also useful in determining susceptibility to acquiring a new T. gondii infection. Seronegative cats are susceptible, while most seropositive (IgM or IgG) cats have completed oocyst shedding and are unlikely to repeat shedding or be a source of human infection.
• Fecal PCR tests forToxoplasma gondii
  
  • Commercial assays are available for detection of Toxoplasma gondii DNA.
  • Positive tests indicate oocyst shedding in feces.
  • Nucleic acid is stable in the feces for 10 days at 4ºC.
• Fluid and Tissue PCR tests for Toxoplasma gondii
  • Several PCR assays are available for the detection of Toxoplasma gondii DNA in cerebrospinal fluid, whole blood, transtracheal wash, bronchoalveolar lavage, aqueous humor, and tissue.
• Commercial laboratories publish algorithms specific to their diagnostic tests to help interpret the results. These may be useful in determining if positive results are consistent with an active T. gondii infection.
• Diagnosis can also be achieved by examining tissue and fluid samples submitted for cytology or histopathology, however the sensitivity is low.

Treatment

• There is no approved treatment for toxoplasmosis in cats or dogs.  However, the following medications and regimens have been used successfully.
  • Clindamycin hydrochloride (10 to 12.5 mg/kg orally twice daily for 2 to 4 weeks) can be used to treat disseminated toxoplasmosis.
  • Pyrimethamine (0.25 to 0.5 mg/kg) plus a sulfonamide (30 mg/kg twice daily for 2 to 4 weeks) also can be used to treat disseminated toxoplasmosis and to reduce oocyst shedding.
  • Trimethoprim-sulfamethoxazole combination can also be used at the rate of 15 mg/kg orally every 12 hours for 4 weeks.
  • Azithromycin (10 mg/kg orally once daily for 4 weeks) has also been used to treat disseminated toxoplasmosis.
  • Ponazuril has been used to treat ocular toxoplasmosis refractory to protracted clindamycin hydrochloride therapy in a dog, however there are no reports of this regimen in cats.
• Supportive care should be provided as needed.

Prevention

• Preventing infection in cats requires eliminating opportunities for exposure.
• Prevent hunting activity by cats (e.g., keep cats indoors).
• Do not feed raw or undercooked meat or viscera to cats.
• Feed cats only commercially prepared diets.
• Because oocysts require at least 24 hours to become infective, remove fecal material from litter boxes daily. This is especially important when introducing a new cat to a household with other cats. Using disposable litter pans can help.
• Disinfecting litter boxes is very difficult because sporulated T. gondii oocysts are resistant to most household disinfectants. Cleaning with scalding water or steam is most effective, but must be done carefully to avoid burns in human caretakers.

Public Health Considerations

• Follow the recommendations for prevention of infection in cats to limit human transmission from oocysts.

• Direct contact with cats is not considered to be a risk factor for T. gondii infection in people, particularly when cats are kept indoors and fed a commercial diet.

In addition, the Centers for Disease Control and Prevention (CDC) recommend the following to prevent contracting toxoplasmosis:

• Wash hands with soap and water after exposure to soil, sand, raw meat or unwashed vegetables.
• Cook ground meat completely to an internal temperature of 160°F and all poultry to 165°F. Fish and whole cuts of meat (not including poultry) should be cooked to at least 145°F.
• Do not sample meat until it is cooked.
• Freeze meat for several days before cooking.
• Wash all cutting boards, knives, and countertops thoroughly with hot soapy water after each use.
• Wash and/or peel all fruits and vegetables before eating them.
• Do not eat raw and/or undercooked oysters, mussels, and clams.
• Do not drink unpasteurized sheep or goat’s milk
• Keep sandboxes covered when not in use to avoid fecal contamination by roaming cats.
• Wear gloves when gardening and wash hands well afterward. 
• Avoid drinking untreated water, particularly when traveling in less developed countries.

Illness is likely to be more severe in fetuses and immunosuppressed individuals.  Additional precautions for these higher risk individuals include:

• Allow only immunocompetent, nonpregnant persons to perform daily litter box cleaning.
• Adopt mature, healthy cats as new pets rather than young kittens.
• Antibody testing in cats can also help determine exposure to the parasite.

Selected References

• Dubey JP, Beattie CP. 1988. Toxoplasmosis of Animals and Man. CRC Press, 1988.  118 pp.
• Dubey JP, Jones JL.  2008. Toxoplasma gondii in humans and animals in the United States. UP 38, 1257.
• Dubey JP, Lindsay DS, Lappin MR. 2009. Toxoplasmosis and other intestinal coccidial infections in cats and dogs. Vet Clin North Am Small Anim Pract 39, 1009-1034
• Elmore SA, Jones JL, Conrad PA, Patton S, Lindsay DS, Dubey JP. 2010.  Toxoplasma gondii: epidemiology, feline clinical aspects, and prevention.  Trends Parasitol 26, 190-196.
• Swinger RL, Schmidt KA, Dubielzig RR. 2009. Keratoconjunctivitis associated with Toxoplasma gondii in a dog. Vet Ophthalmol 12, 56-60.