Feline toxoplasmosis

Introduction

The intracellular protozoan parasite Toxoplasma gondii can infect the majority of vertebrate animal species, and although felids serve as its sole definitive host, it is being increasingly recognized as a major threat in many ecosystems. Ingestion of the parasite by either the definitive or an intermediate host will typically culminate in either a chronic subclinical or asymptomatic infection; in susceptible or non-immunocompetent subjects, however, toxoplasmosis may lead to abortion and reproductive failure, or even organ failure and death 1. Nowadays toxoplasmosis is found worldwide; the prevalence of oocyst shedding varies from 0.7-41% of cats at any given time, depending on the country in question. In the USA the prevalence of positive T. gondii antibody titers in cats ranges from 14-100% 2. Whilst many humans are also infected (for example, approximately 40 million in the USA), most are asymptomatic, but some, especially those that are immunocompromised, may suffer from associated ocular or neurological problems 3.

Toxoplasma gondii life cycle

Toxoplasma gondii has a complex lifecycle, requiring a definitive host and an intermediate host to complete sexual and asexual cycles respectively (Figure 1). The parasite exists in 3 distinct forms – tachyzoite, bradyzoite, and sporozoite (in oocyst), all of which can be infectious to humans. Tachyzoites constitute the rapidly dividing asexual stage of the parasite, and may be found in the tissues of any vertebrate host. Bradyzoites are also ubiquitous and will also be found in host tissues, but this life stage divides slowly and is encysted.

Cats, the definitive host of T. gondii, become infected through ingestion of tissue cysts, for example when hunting and eating prey (Figure 2) or sporulated or infective oocysts (from soil, water, or plants contaminated with feline feces). The parasite can reproduce sexually in this species, and cats infected by bradyzoites or oocysts will begin to shed oocysts in their own feces 3-10 or 19-48 days following ingestion, respectively, and may continue to shed for up to 2 weeks (Figure 3) 2,4. Oocysts sporulate and become infective 1-5 days following excretion, and are extremely resistant in the environment. 

The main methods through which humans are infected with T. gondii include ingestion of undercooked meat containing parasitic cysts, or ingestion of oocysts through fecal contamination of food, hands, etc. 4,5.

Clinical signs of feline toxoplasmosis

Toxoplasmosis can be difficult to identify in cats, as most infections are asymptomatic; if clinical signs are present, fever, anorexia, and lethargy are most frequently seen. Intracellular growth of the organism results in direct cytopathic effects, with cellular inflammation and necrosis, so other more specific signs depend on the location of tachyzoites in the body (Figures 4-6); these may include ocular changes, neurological signs, pneumonia, and jaundice 4. Feline leukemia virus, feline immunodeficiency virus, neoplasia, and administration of immunosuppressive drugs (especially cyclosporin) are all risk factors for the development of clinical disease. Acute infections, especially in kittens, are usually fatal 6.

Diagnosis

Reliable diagnosis of toxoplasmosis can be problematic. Hematological abnormalities noted in affected cats may include non-regenerative anemia, leukocytosis, lymphocytosis, monocytosis, and eosinophilia. Severe infections can also cause leukopenia; in particular, neutropenia with a degenerative left shift. Changes in serum biochemistry and urinary values will depend on the organs involved 6.

As a diagnostic tool, detection of T. gondii oocysts in the feces as a stand-alone test is not recommended due to the short shedding period of feline hosts, as well as the microscopic similarity of T. gondii oocysts to other parasites 4,7. Furthermore, identification of oocysts in the feces does not correlate with development of clinical disease in cats 2. Instead, serologic testing is recommended for definitive ante-mortem diagnosis, and high IgM titers (> 1:256) are generally compatible with recent T. gondii infection. Alternatively, paired IgG titers (taken 2-4 weeks apart) can be used, although interpretation of results can be complex (Table 1) 1,2. Some cats may also suffer from chronic T. gondii infection, whereby tissue cysts rupture and re-release bradyzoites into the circulation; such episodes may or may not be associated with excretion of oocysts, depending on the immune status of the animal in question 8.

Testing healthy cats for T. gondii antibodies is not recommended 6, as serologic testing is not an accurate predictor of oocyst shedding in cats, and most cats when actively shedding oocysts are actually seronegative at the time 2.

Table 1. Interpretation of T. gondii IgG serology results 6.

Treatment and prognosis

There is no licensed treatment for feline toxoplasmosis, but for acute or disseminated cases clindamycin is the drug of choice (10-12.5 mg/kg PO q12h for up to 4 weeks), accompanied by appropriate supportive care 6. For reduction of oocyst shedding, pyrimethamine (0.25-0.5 mg/kg PO q12h for up to 4 weeks) or sulfonamides (15-30 mg/kg PO q12h for up to 4 weeks) can be administered, and will generally prove beneficial during the acute phase of infection, but are rarely effective at clearing infection. Trimethoprim-sulfonamide combination treatments are an alternative option (15 mg/kg PO q12h for 4 weeks) 2, and anti-coccidial drugs (e.g., toltrazuril, ponazuril) may also be considered. Of note, no treatments have proven significantly effective during the bradyzoite stage of infection 1.

A number of factors affect the prognosis for cats that display clinical signs of toxoplasmosis; these include the systems/organs affected (Figures 7 and 8), and the time between infection and the beginning of treatment. Generally, if clinical signs improve within 2-3 days after starting therapy, prognosis is more favorable, but toxoplasmosis infection affecting the lungs or liver carries a poor prognosis 4.

Zoonotic implications

Humans are at risk for T. gondii infection through ingestion of oocyst-contaminated food or water, tissue cysts in contaminated undercooked meat, or from blood transfusions, organ transplantation, or congenital infection. Most infections are asymptomatic, although occasional cases of fever, lymphadenopathy, and malaise have been reported. However, T. gondii represents a serious risk for the fetus during human pregnancy; congenital toxoplasmosis can cause severe ocular and/or neurological damage when tachyzoites migrate transplacentally to reach the fetus 1. Although generally born without symptoms, these individuals can suffer from severe vision impairment, seizures, or other neurological issues later in life 9. Furthermore, immunocompromised individuals of any age are at risk of developing symptomatic toxoplasmosis, often involving the brain, lungs, and/or other vital organs 5.

It is being increasingly reported that Toxoplasma oocysts are contaminating soil and groundwater worldwide. A review of 22 studies concluded that this is a serious cause for concern, with run-off from infected cat feces polluting bodies of water to a considerable degree 3. Contamination of the ocean has led to infection and death of various marine mammals, including seals, whales, dolphins, and sea otters 10,11. Drinking water is also at risk; cat litter being flushed down toilets has contributed to a number of outbreaks of human toxoplasmosis in various countries 12,13.

Oocysts are remarkably robust, and are able to survive and remain infective for years, even in suboptimal conditions 14. Furthermore, it is likely that very few oocysts are required to successfully infect a human; studies in pigs demonstrated that one oocyst was sufficient to induce infection 15. As such, taking steps to responsibly dispose of cat feces is crucial.

Contrary to popular belief, it has been determined that direct contact with cats is not a significant risk factor for human infection with Toxoplasma gondii 16. However, daily litter box cleaning in and of itself is an easy strategy to prevent infection (Figure 9) – oocysts require at least 24 hours to become infective 4, and (where possible) keeping cats indoors will also help. Veterinarians must play a critical role in educating clients on steps to take to mitigate the risks related to T. gondii infection, both in cats and in general (Table 2).

Table 2. Strategies to mitigate zoonotic risk from T. gondii infection 1,2,3,4.

Conclusion

Toxoplasma gondii is a common parasitic infection in cats but is often asymptomatic, although acute or disseminated infections may affect the eyes, brain or other systems, with clindamycin being the preferred treatment. Conclusive diagnosis requires either IgM or paired IgG titer serology. As a zoonotic disease, toxoplasmosis is especially dangerous for pregnant or immunocompromised individuals, but cat ownership is not a significant risk for human infection; rather, ingestion of oocyst-contaminated food or water, or tissue cysts in undercooked meat, are a much more real threat. Fecal contamination of soil and water also presents a serious health risk. Simple hygiene strategies can prevent transmission of T. gondii and, for cat owners, keeping their pets indoors (if possible) and daily cleaning of the litter box greatly mitigates the zoonotic risk.