Toxoplasma gondii is one of the most prevalent parasites infecting warm-blooded vertebrates. Only cats complete the coccidian life cycle and pass environmentally resistant oocysts in feces. Dogs can pass oocysts in feces after the ingestion of feline feces but cannot produce oocysts. Sporozoites develop in oocysts after 1 to 5 days of exposure to oxygen and appropriate environmental temperature and humidity. Tachyzoites disseminate in blood or lymph during active infection and replicate intracellularly rapidly until the cell is destroyed. Bradyzoites are the slowly dividing, persistent, tissue stage that form in the extraintestinal tissues of infected hosts as immune responses attenuate tachyzoite replication. Tissue cysts form readily in the CNS, muscles, and visceral organs. Infection of warm-blooded vertebrates occurs following ingestion of any of the 3 life stages of the organism or transplacentally. Most cats are not coprophagic and so are infected most commonly by ingesting T. gondii bradyzoites during carnivorous feeding; oocysts are shed in feces from 3 to 21 days. Sporulated oocysts can survive in the environment for months to years and are resistant to most disinfectants. Bradyzoites may persist in tissues for the life of the host. Approximately 30% to 40% of cats and people and 20% of the dogs in the United States are seropositive and so presumed to be infected. Prior to 1988, many of the dogs diagnosed with toxoplasmosis based on histologic evaluation were truly infected with Neospora caninum.

Clinical disease associated with the intestinal phase of infection is rare. Approximately 10 to 20% of experimentally inoculated cats develop self-limiting, small bowel diarrhea after primary oral inoculation with T. gondii tissue cysts. Detection of T. gondii oocysts in feces is rarely reported in studies of naturally exposed cats with diarrhea.

Death in dogs and cats can develop from overwhelming intracellular replication of tachyzoites following primary infection; hepatic, pulmonary, CNS, and pancreatic tissues are commonly involved. Transplacentally or lactationally infected kittens develop the most severe signs of extraintestinal toxoplasmosis and generally die of pulmonary or hepatic disease.

Common clinical findings in cats with disseminated toxoplasmosis include depression, anorexia, fever followed by hypothermia, peritoneal effusion, icterus, and dyspnea. If a host with chronic toxoplasmosis is immunosuppressed, bradyzoites in tissue cysts can replicate rapidly and disseminate again as tachyzoites. Disseminated toxoplasmosis has been documented in cats concurrently infected with feline leukemia, feline immunodeficiency, feline infectious peritonitis virus, and following renal transplantation.

Chronic toxoplasmosis occurs in some dogs and cats. Toxoplasma gondii infection should be on the differential diagnoses list for cats with anterior or posterior uveitis, fever, muscle hyperesthesia, weight loss, anorexia, seizures, ataxia, icterus, diarrhea, and pancreatitis. Based on results of T. gondii-specific aqueous humor antibody and polymerase chain reaction studies, toxoplasmosis appears to be a common infectious cause of uveitis in cats. Kittens infected transplacentally or lactationally commonly develop ocular disease. Immune complex formation and deposition in tissues and delayed hypersensitivity reactions may be involved in chronic, subfatal clinical toxoplasmosis. Since none of the anti-Toxoplasma drugs totally clear the body of the organism, recurrence of disease is common.

In dogs, respiratory, gastrointestinal, or neuromuscular infection resulting in fever, vomiting, diarrhea, dyspnea, and icterus are most common and occur most frequently in immune suppressed dogs like those with canine distemper virus infection or those receiving cyclosporine to prevent rejection of a transplanted kidney. Neurologic signs are dependent on the location of the primary lesions and include ataxia, seizures, tremors, cranial nerve deficits, paresis, and paralysis. Dogs with myositis present with weakness, stiff gait, or muscle wasting. Rapid progression to tetraparesis and paralysis with lower motor neuron dysfunction can occur. Some dogs with suspected neuromuscular toxoplasmosis probably had neosporosis. Myocardial infection resulting in ventricular arrhythmias occurs in some infected dogs. Dyspnea, vomiting, or diarrhea occur in dogs with polysystemic disease. Retinitis, anterior uveitis, iridocyclitis, and optic neuritis occur in some dogs with toxoplasmosis, but are less common than in the cat.

Dogs or cats with clinical toxoplasmosis can have a variety of clinicopathological and radiographic abnormalities but none document the disease. Nonregenerative anemia, neutrophilic leukocytosis, lymphocytosis, monocytosis, neutropenia, eosinophilia, proteinuria, bilirubinuria, as well as increases in serum proteins and bilirubin concentration, and creatinine kinase, alanine aminotransferase, alkaline phosphatase, and lipase activities occur in some. Pulmonary toxoplasmosis most commonly causes diffuse interstitial to alveolar patterns or pleural effusion. Cerebrospinal fluid protein concentrations and cell counts are often higher than normal. The predominant white blood cells in CSF are small mononuclear cells, but neutrophils also are commonly found.

The antemortem definitive diagnosis of toxoplasmosis can be made if the organism is demonstrated; however, this is uncommon. Bradyzoites or tachyzoites are rarely detected in tissues, effusions, bronchoalveolar lavage fluids, aqueous humor, or CSF. Detection of 10 X 12 µ oocysts in feces in cats with diarrhea suggests toxoplasmosis but is not definitive since Besnoitia and Hammondia infections of cats produce morphologically similar oocysts.

Toxoplasma gondii-specific antibodies (dogs or cats), antigens (cats), immune complexes (cats), and DNA (cats) can be detected in the blood of normal animals, as well as in those with clinical signs of disease, so it is impossible to make an antemortem diagnosis of clinical toxoplasmosis based on these tests alone. Of the serum tests, IgM correlates the best with clinical toxoplasmosis since this antibody class is rarely detected in serum of healthy animals. The antemortem diagnosis of clinical toxoplasmosis can be tentatively based on the combination of:

 Demonstration of antibodies in serum which documents exposure to T. gondii

 Demonstration of an IgM titer >1:64 or a four-fold or greater increase in IgG titer which Suggests recent or active infection

 Clinical signs of disease referable to toxoplasmosis

 Exclusion of other common causes of the clinical syndrome

 Positive response to appropriate treatment.

Some animals with clinical toxoplasmosis will have reached their maximal IgG titer or will have undergone antibody class shift from IgM to IgG by the time they are serologically evaluated, so the failure to document an increasing IgG titer or a positive IgM titer does not exclude the diagnosis of clinical toxoplasmosis. Since some healthy animals have extremely high serum antibody titers and some clinically ill animals have low serum antibody titers, the magnitude of titer is relatively unimportant in the clinical diagnosis of toxoplasmosis. Because the organism cannot be cleared from the body, most animals will be antibody-positive for life, so there is little use for repeating serum antibody titers after clinical disease has resolved.

The combination of aqueous humor or CSF T. gondii -specific antibody detection and organism DNA detection by PCR is the most accurate way to diagnose ocular or CNS toxoplasmosis in cats. While Toxoplasma gondii -specific IgA, IgG, and organism DNA can be detected in aqueous humor and CSF of both normal and clinically ill cats, T. gondii-specific IgM has only been detected in the aqueous humor or CSF of clinically ill cats and so may be the best indicator of clinical disease. Since T. gondii DNA can be detected in blood of healthy cats, positive PCR results do not correlate to clinical disease.

Supportive care should be instituted as needed. Clindamycin hydrochloride (10 mg/kg, PO, q12hr), trimethoprim-sulfonamide combination (15 mg/kg, PO, q12hr), and azithromycin (10mg/kg, PO, q24hr) for at least 28 days have been used most frequently by the author for the treatment of clinical toxoplasmosis. Pyrimethamine combined with sulfa drugs is effective for the treatment of human toxoplasmosis, but commonly results in toxicity in cats. Cats or dogs with uveitis should be topical, oral, or parenteral glucocorticoids to avoid secondary glaucoma and lens luxations. Toxoplasma gondii seropositive animals with uveitis that are otherwise normal can be treated with topical glucocorticoids alone unless the uveitis is recurrent or persistent. In these situations, administration of a drug with anti-T. gondii activity may be beneficial.

Toxoplasma gondii is a significant zoonosis. Primary infection of mothers during gestation can lead to clinical toxoplasmosis in the fetus; stillbirth, CNS disease, and ocular disease are common clinical manifestations. Primary infection in immunocompetent individuals results in self-limiting fever, malaise, and lymphadenopathy. As T-helper cells counts decline, approximately 10% of people with AIDS develop toxoplasmic encephalitis from activation of bradyzoites in tissue cysts. People most commonly acquire toxoplasmosis by ingesting sporulated oocysts, tissue cysts, or transplacentally. To prevent toxoplasmosis, avoid eating undercooked meats or ingesting sporulated oocysts. While owning a pet cat was epidemiologically associated with acquiring toxoplasmosis in one study of pregnant women, touching individual cats is probably not a common way to acquire toxoplasmosis for the following reasons.

 Cats generally only shed oocysts for days to several weeks following primary inoculation.

 Repeat oocyst shedding is rare, even in cats receiving glucocorticoids, or in those infected with FIV or FeLV.

 Cats with toxoplasmosis inoculated with tissue cysts 16 months after primary inoculation did not shed oocysts.

 Cats are very fastidious and usually do not allow feces to remain on their skin for time periods long enough to lead to oocyst sporulation; the organism was not isolated from the fur of cats shedding millions of oocysts 7 days previously.

 Increased risk of acquired toxoplasmosis was not associated with cat ownership in HIV-infected people or in veterinary health care providers.

If infection is suspected on fecal examination, the oocyst shedding period can be shortened by administration of clindamycin (25-50 mg/kg, daily, PO), sulfonamides (100 mg/kg, daily, PO), or pyrimethamine (2.0 mg/kg, daily PO). Since humans are not commonly infected with T. gondii from contact with individual cats, testing healthy cats for toxoplasmosis is not recommended. There is no serologic assay that accurately predicts when a cat shed T. gondii oocysts in the past and most cats that are shedding oocysts are seronegative. Most seropositive cats have completed the oocyst shedding period and are unlikely to repeat shedding; most seronegative cats would shed the organism if infected. If an owner is concerned that they may have toxoplasmosis, they should see their doctor for testing. The risk of acquiring toxoplasmosis can be lessened by avoided sporulated oocysts and tissue cysts in undercooked meat.

References

1.  Baril L, Ancelle T, Goulet V, et al. Risk factors for Toxoplasma infection in pregnancy: a case-control study in France. Scand J Infect Dis 1999;31:305.

2.  Bernstein L, Gregory CR, Aronson LR, et al. Acute toxoplasmosis following renal transplantation in three cats and a dog. J Am Vet Med Assoc 1999;215:1123.

3.  Brownlee L, Sellon RK. Diagnosis of naturally occurring toxoplasmosis by bronchoalveolar lavage in a cat. J Am Anim Hosp Assoc 2001;37:251.

4.  Burney DP, Spilker M, McReynolds L, et al. Detection of Toxoplasma gondii parasitemia in experimentally inoculated cats. J Parasitol 1999;5:947.

5.  Davidson MG. Toxoplasmosis. Vet Clin North Am Small Anim Pract 2000;30:1051.

6.  Dubey JP. Duration of immunity to shedding Toxoplasma gondii oocysts by cats. J Parasitol 1995;81:410.

7.  Dubey JP, Carpenter JL, Speer CA, et al. Newly recognized fatal protozoan disease of dogs. J Am Vet Med Assoc 1988;-192:1269.

8.  Dubey JP, Carpenter JL. Histologically confirmed clinical toxoplasmosis in cats: 100 cases (1952-1990). J Am Vet Med Assoc 1993;203:1556.

9.  Dubey JP, Carpenter JL, Topper MJ, et al. Fatal toxoplasmosis in dogs. J Am Anim Hosp Assoc 1989;25:659.

10. Dubey JP, Carpenter JL . Neonatal toxoplasmosis in littermate cats. J Am Vet Med Assoc 1993;203:1546.

11. Dubey JP, Johnstone I. Fatal neonatal toxoplasmosis in cats. J Am Anim Hosp Assoc 1982;18:461.

12. Dubey JP, Lappin MR. Toxoplasmosis and neosporosis. In: Greene CE, ed. Infectious Diseases of the Dog and Cat, 2nd ed. Philadelphia: W.B. Saunders, 1998;493.

13. Hass JA, Shell L, Saunders G. Neurological manifestations of toxoplasmosis: a literature review and case summary. J Am Anim Hosp Assoc 1989;25:253.

14. Lappin MR. Feline toxoplasmosis: interpretation of diagnostic test results. Seminars Vet Med Surg 1996;11:154.

15. Lappin MR, Burney DP, Dow SW, et al. Polymerase chain reaction for the detection of Toxoplasma gondii in aqueous humor of cats. Am J Vet Res 1996;57:1589.

16. Lappin MR, Dawe DL, Lindl PA, et al. The effect of glucocorticoid administration on oocyst shedding, serology, and cell-mediated immune responses of cats with recent or chronic toxoplasmosis. J Am Anim Hosp Assoc 1992;27:625.

17. Lappin MR, George JW, Pedersen NC, et al. Primary and secondary Toxoplasma gondii infection in normal and feline immunodeficiency virus-infected cats. J Parasitol 1996;82:733.

18. Lappin MR, Greene CE, Winston S, et al. Clinical feline toxoplasmosis: serologic diagnosis and therapeutic management of 15 cases. J Vet Int Med 1989;3:139.

19. Lindsay DS, Dubey JP, Butler JM, et al. Mechanical transmission of Toxoplasma gondii oocysts by dogs. Vet Parasitol 1997;73:27.

20. Powell CC, Lappin MR. Clinical ocular toxoplasmosis in neonatal kittens. Vet Ophthalmol 2001;4:87.

21. Wallace MR, Rossetti RJ, Olson PE. Cats and toxoplasmosis risk in HIV-infected adults. J Am Med Assoc 1993;269:76.