Toxoplasmosis, caused by Toxoplasma goondi, is a gut parasite that can cause systemic disease in cats and is zoonotic to humans.
In Australia, the prevalence of Toxoplasma in human females is approximately 35-36% of women of child-bearing age. In most cases, this parasite which lives in the intestines, causes mild diarrhoea. It does not normally warrant consideration except that it is capable of causing severe disease in the unborn child. When a pregnant women is infected by this parasite, it passes the placenta and infects the foetus, causing brain damage.
Toxoplasmosis, rarely, can cause signs of myopathy, with signs of muscle weakness, reluctance to move and muscle hyperaesthesia. An association between generalized toxoplasmosis and resultant development of spontaneous hyperadrenocorticism (Cushing’s syndrome) has been reported in the cat.
The coccidian Toxoplasma gondii is an obligate intracellular parasite that can infect virtually all warm-blooded animals including humans. Members of the species Felidae, however, are the only known definitive hosts for the sexual stages of T. gondii and, thus, serve as the primary reservoir for the parasite. Numerous other species are paratenic hosts and serve as intermediate hosts required for completion of the parasite’s life cycle but in which developmental changes do not occur. In the United States, the percentage of domestic cats seropositive for T. gondii is estimated to be between 16 – 43% based on regional variances. The high serological prevalence of toxoplasmosis and its zoonotic potential underscore the importance of veterinarians’ full understanding of both the disease course and the role of domestic cats in the T. gondii life cycle.
T. gondii sporulated oocysts, bradyzoites, and tachyzoites may all cause infection. Cats, as obligate carnivores, primarily contract toxoplasmosis through ingestion of infected host tissue cysts16. As definitive hosts, cats alone can complete the enteroepithelial life cycle. Extraintestinal cycling of T. gondii occurs in cats, as well, along with all other susceptible species that serve as intermediate hosts. In cats, the enteroepithelial and extraintestinal developmental cycles may occur simultaneously.
Upon ingestion of tissue from infected hosts, proteolytic digestive enzymes degrade the tissue cysts and release the bradyzoites. These slowly dividing forms of the coccidian are capable of a sexual reproductive process called merogony that occurs only in cats. Through merogony, bradyzoites undergo repeated nuclear/cytoplasmic fission to yield microgamonts (‘male-like’) and macrogamonts (‘female-like’). Microgamonts further divide to form microgametes which are then able to fertilize the macrogamont. A protective wall encapsulates fertilized macrogamonts to form the zygote-containing oocyst. Unsporulated oocysts are non-infective and are shed into the environment from the faeces in most naïve cats, 10 days or less after tissue cyst ingestion. Oocyst sporulation to the infective form occurs approximately 1-5 days later, after exposure to ambient air and humidity. This is the period of most concern for exposure to pregnant women who may be cleaning the cat litter box. Each sporulated oocyst contains eight sporozoites that can survive in the environment for up to 18 months, and insects such as roaches and earthworms may function as transport hosts by dispersing oocysts from their initial shedding point.
There are several reasons why cats who ingest oocysts or tachyzoites develop T. gondii infections less frequently (approximately 20%) and exhibit a prolonged prepatent period when compared to those cats ingesting tissue cysts. Bradyzoites are able to serve as direct precursors to enteroepithelial cycling (and thus a shorter prepatent period) whereas oocysts or tachyzoites must first develop to the bradyzoite stage. Moreover, the decreased infection rate may be related to the fact that each tissue cyst contains a large number of bradyzoites whereas only eight sporozoites are within an oocyst. Finally, tachyzoite ingestion is less likely to result in patency as they are often destroyed by gastrointestinal digestive enzymes.
Ingested sporulated oocysts release sporozoites into the gastrointestinal tract of the host. Sporozoites enter cells of the intestine and lymph nodes where they undergo endodyogeny to form rapidly dividing tachyzoites that disseminate throughout the body through the blood and lymphatic vasculature. The tachyzoite tissue phase that develops within a host or is ingested may result in bradyzoite tissue cyst formation within the brain, skeletal muscle, and liver. These tissue cysts may persist for the life of the host, and the potential for recrudescence exists as tissue cysts rupture and release bradyzoites.2 Both ingested bradyzoites and those released through host cyst rupture are capable of asexual development to tachyzoites, thereby perpetuating the cycle.
Although there is a high seroprevalence of T. gondii infection among Felidae, clinical signs usually occur as a result of a primary infection in which an inadequate immune response failed to arrest invasive tachyzoites. Alternatively, disease may result from reactivation of subclinical infection in an immunocompromised individual with encysted bradyzoites which may then form rapidly multiplying tachyzoites. Such incidents are thought to relate directly to variables such as the age and sex of the host, presence of immunodeficient states (e.g. FeLV, FIV), concomitant stress or illness, and organism load.
Clinical illness appears to be most frequent among cats less than 2 years of age which may be due in part to an insufficient immune response by young cats. In one study involving 25 kittens experimentally infected with neonatal T. gondii infection, 3 kittens were stillborn. Among the 22 live kittens, approximately 95% exhibited proliferative interstitial pneumonia, necrotizing hepatitis, myocarditis, and skeletal myositis to the extent that euthanasia was necessary. Infected neonates also often develop central nervous system infections resulting in seizures.
Fever and weight loss are common, and systemic infection can cause anterior uveitis, chorioretinitis, central nervous dysfunction, respiratory signs and gastrointestinal disease. Myelitis has also been reported in aged cats due to toxoplasmosis.
Organism ingestion followed by initial enteroepithelial replication may lead to a self-limiting small bowel diarrhoea that occurs due to an IgA response elicited by T. gondii resulting in increased intestinal secretions. Clinical illness may progress when naïve hosts are infected or when prior infections are reactivated. Extraintestinal spread of the parasite may occur as rapid multiplication of tachyzoites within host cells results in cell rupture, promoting organism dissemination and, ultimately, tissue necrosis. Disease onset may be sudden or insidious, and clinical signs are often multiple and varied as most types host cells are vulnerable to infection. Respiratory, CNS, hepatic, pancreatic, cardiac, and ocular tissues were among the most commonly affected tissues in a group of 100 adult cats with confirmed toxoplasmosis. Associated clinical signs included dyspnoea, tachypnoea, intermittent fever, jaundice, vomiting, weight loss, hyperesthesia, shifting lame lameness, ataxia, dermatitis, and death.
Laboratory testing may detect several abnormal parameters in animals with acute systemic toxoplasmosis. A nonregenerative anaemia may be detected with a concurrent neutrophilic leukocytosis, lymphocytosis, monocytosis, and eosinophilia. The biochemical profile of cats with chronic toxoplasmosis may demonstrate hyperglobulinemia due to chronic antigenic stimulation and immune response. Hepatocellular disease may result in elevated alanine aminotransferase (ALT) enzyme activity, and muscle damage may cause an increase in aspartate aminotransferase (AST) and creatine kinase (CK) activity. Hyperbilirubinemia may occur in cats with cholangiohepatitis or hepatic lipidosis secondary to liver dysfunction.
Histologically, lesions associated with toxoplasmosis are a result of cell death secondary to intracellular replication of T. gondii. The associated inflammatory reaction is primarily composed of macrophages in adult cats and neutrophils and macrophages (pyogranulomatous), with or without a lymphoplasmacytic component, in neonates. Tissue cysts often persist in the absence of host reaction.
In the CNS, encephalitis may result from tachyzoites primarily infecting astrocytes. A resultant diffuse necrotizing and nonsuppurative lymphocytic infiltrate may develop in the brain and extend to the meninges. Necrotizing hepatitis with focal areas of coagulative lobular necrosis may be observed with the presence of few organisms. Other gross lesions include pulmonary oedema and congestion with failure of lung collapse as well as multifocal areas of firm white, yellow, or grey discoloration in the pulmonary parenchyma. Toxoplasma organisms invade type 1 and 2 pneumocytes as well as pulmonary alveolar macrophages, fibroblasts, endothelial cells, and smooth muscle cells. The subsequent proliferative reaction in alveolar walls may resemble adenomatosis. Severe lymphadenopathy may occur. Pericardial effusion is occasionally reported and likely due to organisms invading the myocardium. Intestinal lymphatic tissue invasion may result in small bowel ulcerative disease. If the muscularis is involved, occasionally a chronic necrotizing process leads to large granulomatous nodules that can impede the transport of luminal contents and possible lymphangiectasia. Ocular lesions are frequent and may cause inflammation of the retina or anterior segment (anterior uveitis) with granulomatous inflammation being the prominent cytologic feature. Placental lesions can include focal necrosis with or without foci of mineralization.
Diagnosis of clinical toxoplasmosis in cats is challenging due to the high seroprevalence of the infection among non-affected cats as well as the many potential antibody responses that may occur in disease as well as in health. Since seroconversion also occurs in the absence of clinical disease, titres should be interpreted in conjunction with clinical signs consistent with toxoplasmosis. Accordingly, the exclusion of other causes of clinical disease paired with serologic evidence (such as a four-fold increase in titre) and a positive response to appropriate therapy may be simultaneously employed in order to reach a tentative diagnosis.
Near 80% of cats are thought to develop IgM antibodies within 1-2 weeks after exposure. These antibodies may remain detectable for months to years. As a result, the presence of IgM antibody cannot reliably be used to predict recent infection and oocyst shedding. Similarly, IgG antibodies may not develop for 4-6 weeks and may peak in 2-3 weeks with some cats remaining high for several years.
T. gondii titres may be by indirect fluorescent antibody testing, modified agglutination, enzyme-linked immunosorbent antibody assays, and Sabin-Feldman serologic testing. Because many cats have T. gondii antibodies from previous exposure, it is necessary to demonstrate either a four-fold rise in IgG titres over a 2-3 week period or a single high IgM titre (> 1:64). Clinical signs may develop before seroconversion occurs in 1-2 weeks or not until after peak titers have developed. For these reasons, antibody titers may be difficult to interpret and single antibody titers are often insufficient for definitive diagnosis.
Definitive diagnosis for T. gondii is possible through identification of the organisms in body tissue or fluids. In acute illness, tachyzoites may be present in large numbers in body fluids such as abdominal and pleural effusions. Peripheral blood smears, cerebrospinal fluid (CSF), fine needle aspirates of tissues, and airway washings are less likely to provide direct organism detection. Such biologic samples can be used for bioassays in mice, tissue cultures, or PCR to demonstrate the presence of T. gondii organisms.
The treatment of choice for Toxoplasmosis is clindamycin at 8-50mg/kg in divided doses with food, for 14-28 days. If clindamycin cannot be tolerated at the recommended dose, pyrimethamine or trimethoprim may be combined with a sulfonamide for treatment. However, the risk of anti-folate drug related bone marrow suppression necessitates frequent monitoring for hematologic abnormalities. Dietary supplementation with folic acid (5mg/day) or yeast (100 mg/kg) may aide in correcting hematopoietic disruption. The prognosis for cats with toxoplasmosis is guarded, as available drugs are unable to completely eliminate the parasite and the risk for relapse of clinical disease is possible. Recurrence is particularly common in immunocompromised cats.
An estimated 30-50% of the human population is currently infected with Toxoplasma in the asymptomatic cyst form. In immunocompromised patients, the cyst form may potentially lead to serious disease. Because of the potential for disastrous outcomes in infections that occur during pregnancy, women planning to become pregnant may opt for T. gondii antibody testing. Positive antibody detection indicates previous infection and suggests that the likelihood of congenital transmission upon re-exposure to the parasite during pregnancy is limited. Conversely, antibody-negative women are at far greater risk of transmitting Toxoplasma to the fetus if they should become infected during pregnancy. This risk becomes magnified as 70 million domestic cats are kept as pets in American households, making them the most numerous in the nation among domestic companion species. Clearly, it is vital to clarify the role of cats in the transmission of Toxoplasma to humans.
The primary means by which most humans are infected with T. gondii are through oocyst-contaminated soil and eating undercooked infected meat such as lamb and pork. People who own cats are not at a significantly higher risk for T. gondii infection than those who do not. Since oocysts are highly resistant to environmental conditions, exposure can be minimized by wearing rubber gloves during contact and washing hands thoroughly after possible exposure to potentially contaminated soil. Areas such as sandboxes should be kept covered to avoid oocyst contamination. Meat should routinely be cooked to an internal temperature of 70°C (158°F) for at least 15 to 30 minutes in order to destroy tissue cysts.
Restricting the access of pet cats to hunting and disallowing the ingestion of uncooked meat may prevent cats exposure to T. gondii. When they are exposed. most healthy cats will shed oocysts only during acute infection. As the infected cat develops an immune response, oocyst shedding is halted, and the development of tachyzoites is arrested with the resultant formation of bradyzoites (slowly replicating forms of the organism) contained within tissue cysts. Cats previously unexposed to T. gondii usually begin shedding oocysts between 3 and 10 days after ingestion of infected tissue and continue shedding for 10-14 days, during which time many millions of oocysts may be produced. However, once a cat has developed an immune response, further shedding of oocysts is extremely rare. In the few cats that do re-excrete oocysts after another exposure to Toxoplasma, the number of oocysts shed is lower and may even be insufficient to transmit the parasite effectively. An antibody-negative cat, particularly a kitten, is most susceptible to infection and will shed oocysts for one to two weeks post-exposure to T. gondii. In a healthy cat, positive antibody titers are suggestive that the cat is immune, not excreting oocysts, and an unlikely source of infection.
Daily cleaning of feces from litter boxes, paired with regular disinfection of the boxes, will prevent any oocysts that are shed from sporulating to the infective form. T. goondii oocysts are highly resistant to many chemical sanitizers, and appropriately aggressive cleaning methods must be employed.
It is still recommended, however, that women who are or may become pregnant avoid cleaning the litter box.
- ↑ Dubey JP, Lappin MR. (2006) Toxoplasmosis and Neosporosis. In: Greene C, ed. Infectious Diseases of the Dog and Cat, 3rd ed. St. Louis, MO: Elsevier, pp 754-768
- ↑ Ruehlmann, DS (2010) Myopathic disorders. In August, JR (Ed): Consultations in feline internal medicine. Vol 6. Elsevier Saunders, Philadelphia. pp:603
- ↑ Spada, E et al (2010) Pituitary-dependent hyperadrenocorticism and generalized toxoplasmosis in a cat with neurological signs. JFMS 12:645-658
- ↑ Toxoplasmosis. United States Center for Disease Control, 22 Nov. 2004. <http://www.dpd.cdc.gov/dpdx/HTML/Toxoplasmosis.htm>
- ↑ Bowman, DD.(2003) Georgi’s Parasitology for Veterinarians. St. Louis, MO: Saunders. pp 100-102
- ↑ Freij BJ, Sever JL. (1991) Toxoplasmosis. Paed in Rev 12:227-236
- ↑ Lappin, MR et al (1989) Clinical feline toxoplasmosis. Serologic diagnosis and therapeutic management of 15 cases. J Vet Intern Med 3:139
- ↑ Lindsay, SA et al (2010) Myelitis due to reactivated spinal toxoplasmosis in a cat. JFMS 12:818-821
- ↑ Dubey JP, Mattix ME, Lipscomb TP. (1996) Lesions of neonatally induced toxoplasmosis in cats. Vet Pathol 33:290-295
- ↑ Montoya JG, Rosso F (2005) Diagnosis and Management of Toxoplasmosis. Clin Perinatol 32:705-726
- ↑ Dubey, JP, Speer CA, et al (1997) Oocyst-induced murine toxoplasmosis: life cycle, pathogenicity, and stage conversion in mice fed Toxoplasma gondii oocysts. J Parasitol 83:870-872
- ↑ Lindsay, DS, Blagburn, BL (1997) Feline toxoplasmosis and the importance of the Toxoplasma gondii oocyst. Compend Contin Educ Pract Vet 19:448-461
- ↑ Lindsay DS, Blagburn, BL. (1991) Coccidial Parasites of Dogs and Cats. Compend Contin Educ Pract Vet 13:759-765
- ↑ Bonametti AM, Passos JN, Da Silva EMK, and Macedo ZS. (1997) Probable transmission of acute toxoplasmosis through breast feeding. J Trop Ped 43:116
- ↑ Lappin MR. (2005) General Concepts in Zoonotic Disease Control. Vet Clin North Am Small Anim Pract 35:1-20
- ↑ Villegas EN, et al (2010) Using quantitative reverse transcriptase PCR and cell culture plaque assays to determine resistance of Toxoplasma gondii oocysts to chemical sanitizers. J Microbiol Methods Apr 9