Toxoplasma gondii

Toxoplasma gondii is a zoonotic intracellular apicomplexan protozoan parasite of mammals and birds that occurs around the world, including in Canada. Prevalence of infection varies with location, host species and, in many instances, host age. Infection with T. gondii is much more common than is clinical disease. The life cycle is indirect. The only definitive hosts are domestic and free-ranging felids in which the parasite undergoes asexual and then sexual reproduction in the enterocytes of the small intestine (similar to Eimeria), resulting in the production of unsporulated oocysts, which leave the host in the faeces. In the environment (in a few days in ideal conditions) these oocysts sporulate and become infective - each contains four sporozoites in each of two sporocysts. If a felid ingests these sporulated oocysts, the sprozoites are released and can initiate parasite development in the enterocytes. Thus T. gondii can complete its life cycle using only felids. If sporulated oocysts are ingested by a non-felid (intermediate) host, or by a felid, the sporozoites can invade the intestinal wall, enter blood and lymph cells and, dividing rapidly as tachyzoites, spread throughout the body. Some of these tachyzoites come to rest in tissues, form a tissue cyst around them and divide slowly as bradyzoites. Tachyzoites and tissue cysts containing bradyzoites in mammalian and avian tissues, along with sporulated oocysts in the environment, are all infective for hosts. In some host species, notably people, sheep and cats, congenital (prenatal) infection of foetuses can also occur, with a risk of abortion, stillbirth and neonatal disease in the offspring.

Toxoplasma gondii is a major cause of abortion in sheep and goats and a threat to marsupials, New World primates and marine mammals. Toxoplasma gondii is also a significant human pathogen around the world. In the United States it is a common cause of ocular disease, and worldwide it is a problem in people with compromised immune systems. In people and in animals recent evidence suggests that subclinical infections with T. gondii might influence mental development in the young as well as behaviour in all age groups.

NOTE: Identical information on T. gondii is included in the text for all the host species and for zoonoses. Information on the effects of the parasite on each host is included in the Pathology and Clinical Signs section.

Phylum: Apicomplexa
Class: Conoidasida
Subclass: Coccidiasina
Order: Eucoccidiorida
Suborder: Eimeriorina

Toxoplasma gondii, the cause of toxoplasmosis in people, animals and birds, is an apicomplexan protozoan related to the coccidians Eimeria and Isospora, with which it shares many biological features. Recently several distinct strains of T. gondii have been identified which differ in geographic distribution and perhaps some important biological features.  The methodologies for strain discrimination, the number of strains, and their defining characteristics, all remain topics of active debate among parasitologists and molecular biologists. 

In its mammalian and avian hosts hosts Toxoplasma gondii is an intracellular parasite.  Several life cycle stages can be visualized using standard microscopy in various organs and tissues: a) tachyzoites (tissues of any host); b) tissue cysts (tissues of any host); c) bradyzoites within the tissue cysts (tissues of any host); d) meronts, gametocytes and gamonts (enterocytes of felids); and e) ocysts (feces of felids).

 

Tachyzoites of T. gondii are crescent-shaped, measuring approximately 6 µm by 2 µm, with a central nucleus and a pointed anterior and a blunt posterior end. Details of the internal structures are not visible by light microscopy. Tachyzoites are normally located within cells, but sometimes in histological sections they appear to be extracellular, and may appear singly or, less commonly, in small groups.

Tissue cysts of T. gondii occur in a variety of organs and tissues, particularly the central nervous system and skeletal musculature, and are round to oval, with a greater dimension of up to 100 µm. The cyst wall is thin, measuring less than 0.5 µm thick. Tissue cysts of T. gondii can contain from a few to hundreds of bradyzoites. The basic structure of tissue cysts, including the bradyzoites, can be seen by light microscopy.

Bradyzoites of T. gondii occur within the tissue cysts. They are very similar in structure to tachyzoites, except that the nucleus is usually posterior. Details of the internal structures are not visible by light microscopy.

 

Meronts, gametocytes and gamonts of T. gondii are basically similar in structure to the same stages in the related organisms Eimeria and Isospora.

Oocysts of T. gondii are approximately spherical, measure 10 to 12 µm in diameter, and have a smooth, thin shell. When passed in feces they contain one or two cells, and when sporulated (a process that takes a few days under ideal conditions), each contains two sporocysts, each with four sporozoites. Oocysts of T. gondii are very difficult or impossible to distinguish microscopically from those of the Hammondia and Isospora species infecting cats.

Surveys and case reports from around the world have demonstrated serological and other evidence of Toxoplasma gondii infection in a wide range of mammals and birds.   In some regions of Canada Toxoplasma is a significant problem in sheep as a cause of abortion, and across the country the parasite is an occasional cause of disease in other host species, including people. 

Toxoplasma gondii requires felids (domestic or free-ranging) as definitive hosts. Only in these hosts can the parasite undergo asexual (merogony) and then sexual (gametogony) reproduction in the epithelial cells of the small intestine. In this phase of the life cycle is very similar to that of Eimeria. Sexual reproduction results in oocysts, which pass in the feces.  Oocyst production is higher in young kittens than in adult cats, and following the ingestion of tissue cysts rather than oocysts, and ingestion of tissue cysts by felids is twice as likely to result in oocyst production than is tachyzoite or oocyst ingestion.  Also, most cats will excrete oocysts only for a few weeks following infection, and only when first infected.  A few cats, however, will continue to produce low numbers of oocysts and serve as "carriers".  To become infective for another host these oocysts must sporulate - four sporozoites develop within each of two sporocysts within each oocyst. Under ideal conditions sporulation takes a few days.

If a felid host ingests sporulated oocysts the sporozoites can invade and develop in the enterocytes of the small intestine, as described above. Alternatively, if the oocysts are ingested by a felid, or by any other species of host, the sporozoites can enter the intestinal wall, then blood and lymph cells, begin to divide rapidly as tachyzoites, and are distributed throughout the body. Once in the tissues, tachyzoite division slows and they give rise to tissue cysts containing bradyzoites, which divide slowly. Tissue cysts are most commonly located in the central nervous system, including the eyes, and in skeletal and cardiac muscle. These tissue cysts can persist in an animal or person for years, often without adverse effect, and eventually they die. Under some circumstances, however, for example immunosuppression, parasite division in the cysts can be accelerated and the resulting tachyzoites released and distributed throughout the body.  In cats, and in some other hosts including sheep and people, Toxoplasma can be transmitted from a female to her foetuses prenatally.  The parasite has also been transmitted between people by blood transfusion or organ transplantation..

Infections with Toxoplasma can occur following the ingestion by definitive or intermediate hosts of tachyzoites, tissue cysts with bradyzoites, or sporulated oocysts. In the definitive hosts the pre-patent period for T. gondii varies depending on the life cycle stage ingested: 3 to 10 days for bradyzoites, and approximately three weeks for oocysts and tachyzoites. 

Life Cycle: Toxoplasma gondii

The three major means of T. gondii transmission are: a) oocysts in the feces of cats, or in the environment (for example, drinking water); b) tissue cysts (and possibly tachyzoites) in animal tissues, including unboiled milk from goats; and c) congenital infection. Based on the levels of seroprevalence reported for people and for animals and birds, Toxoplasma can utilize a variety of sometimes complex parasite webs for transmission and is very successful at maintaining itself in a range of ecosystems around the world.

Dietary preferences influence the epidemiology of Toxoplasma.  For example, herbivores are most likely acquire the infection following the ingestion of oocysts from the environment, whereas carnivores could also become infected by ingesting tissue cysts in meat, and for carnivores the species of animals consumed can affect the likelihood of infection.  In a recent study in the United States significant risk factors for human exposure to T. gondii were identified as eating raw or undercooked foods (raw ground beef, rare lamb, locally produced cured, dried or smoked meat, unpasteurized goat milk, or raw oysters, clams or mussels - which can concentrate oocysts during filter feeding), and having three or more kittens (< 1 year old).  Recent outbreaks of water-borne toxoplasmosis in people suggest that the Toxoplasma status of domestic and free-ranging felids with access to reservoirs and other potable water sources might be important in some instances.   The oocysts of T. gondii can survive for long periods (up to years) in supportive environmental conditions, including in sea water.

Cats

In Canada a national serological survey in 2002 detected exposure to Toxoplasma in 19% of 287 cats taken to veterinary clinics.  Many people, animals and birds infected with T. gondii show few or no detectable clinical signs.  The clinical effects of T. gondii reflect the location of the lesions.  Clinical toxoplasmosis is more severe in congenitally (pre-natally) infected kittens than in older cats.  In cats of all ages the lungs are the most often affected, leading to pneumonia, but damage to other organs and tissues can also result in clinical disease, and sometimes the infection is generalized. 

Dogs

Although Toxoplasma occurs in dogs in Canada, other than a few case reports of eye involvement it is rarely associated with disease.  Evidence from other parts of the world indicate a similar pattern, with the lungs, liver and central nervous system most often affected.

Cattle

Clinical disease unequivocally associated with Toxoplasma has not been reported in cattle, and sub-clinical infections seem to be rare around the world, including in Canada.  In general it is believed that meat from cattle is an unlikely source of the parasite for people, at least in more developed regions of the world, but uncertainty remains.

Sheep and Goats

In Canada and around the world Toxoplasma is a major problem in sheep, and to a lesser extent goats, as a cause of abortion and neo-natal disease.  Ewes and nannies that are infected for the first time during pregnancy can pass the parasite pre-natally to their offspring which, depending on the stage of pregnancy when infection occurs, could abort, be stillborn or develop disease in the neonatal period,  Because of the development of an immunity, a ewe that aborts is unlikely to do the same problem in subsequent pregnancies..  Clinical toxoplasmosis is thought not to occur in sheep, but there are reports of multi-systemic disease in goats.

Horses

Toxoplasma gondii does not establish well in horses so sub-clinical and clinical infections are likely very rare.

Pigs

Serological surveys in many parts of the world have demonstrated that Toxoplasma infection is not uncommon in pigs.  In Canada, however, it appears to be very rare and viable parasites have not been found in sero-positive animals. This situation is likely the result of the widespread use of intensive management systems for pigs in this country.  Where T. gondii does occur in pigs these can be an important source of human infections.  Clinical toxoplasmosis appears to be very rare in pigs.

Poultry

Serological data indicate that T. gondii is not uncommon in poultry in many parts of the world, particularly in birds in extensive management systems, but the situation in Canada is not known in detail.  Reports of clinical toxoplasmosis in poultry are very rare, and indicate that the nervous system is the most likely target.  The transmission of T. gondii to people via eggs is very unlikely.

Other Animal and Bird Hosts

Around the world infection with Toxoplasma, and less commonly clinical disease asociated with the parasite, have been detected in a wide variety of mammals and birds, including pocket pets, caged and free-ranging birds, game animals, marsupials, New World primates and marine mammals.  Some of these records are from Canada.

People

Toxoplasma gondii infection in people can be acquired pre-natally from the mother (congenital infection) , or post-natally by ingestion of sporulated oocysts in felid faeces, water or the environment, of tissue cysts containing bradyzoites or, less commonly, of tachyzoites in animal tissues.  Infection with the parasite is not uncommon in people around the world, including Canada, but clinical disease is rare among  those with competent immune systems.  Congenital infections can result in abortion, stillbirth or lesions in the central nervous system, especially the eyes, and in other tissues.  Congenital infections in people can sometimes result in severe clinical disease, and clinical signs might not appear until weeks or months after birth. Congenital toxoplasmosis can also result in learning difficulties for children.  With acquired infections in immuno-competent people, Toxoplasma usually causes only a transient flu-like illness with fever, malaise and enlarged lymph nodes.   In people with compromised immunity, Toxoplasma is a more serious problem which most often affects the central nervous system.  Toxoplasma encephalitis was a major cause of  disease and death in people with HIV/AIDS, but its role  has lessened following the introduction of anti-retroviral drugs.

In felids with enteric infections, detection of T. gondii oocysts in faeces is the best method to diagnose patent infections, remembering that most cats will pass oocysts in their feces for a two to three week period once in their lives. The oocysts are unsporulated, sub-spherical, measure approximately 12µm by 10µm, and cannot be easily distinguished microscopically from those of non-pathogenic Hammondia hammondi or of the Isospora species infecting cats.

 

In both animals and people serological tests for antibody, using a variety of approaches, may be helpful, although for animals there are few validation data for the tests in animals, particularly wildlife.  In recent years a modified agglutination test (MAT) has been widely used for animals although there are validation data for this test only for pigs and sea otters.  In some instances an IgM titre can be used to identify a recent infection.

 

At post-mortem, detection of tissue cysts with bradyzoites, or tachyzoites, or of “typical” pathological changes, can help to establish the diagnosis. Immunohistochemistry is often helpful, as is bioassay using cats or mice as the test animals.

There are no products approved in Canada for the treatment of Toxoplasma gondii infection in animals.  Several products have been tried, however, especially in dogs and cats, among them trimethoprim and sulfamethoxazole, given in combination.  Care is required when treating animals with drugs that may be immunosuppressive, because previously latent T. gondii infection may be re-activated, with very serious consequences.

A vaccine that prevents abortion in sheep (Toxovax®) is commercially available in New Zealand and in some European countries. It is based on live attenuated organisms. A vaccine has also been developed and validated to reduce oocyst shedding in cats, but the logistics of producing the live, attenuated bradyzoites make the product commercially unrewarding. Vaccines to prevent the establishment of T. gondii infection in people and in meat animals have the potential to be helpful in minimizing the prevalence and severity of human infection, but are not yet available.

T. gondii depends on disrupting the parasite web that allows transmission. This may be possible in people and domestic animals, but in wildlife it is essentially impossible. For people or animals particularly at risk, reasonable caution regarding contacts with cats, and with handling and preparation of meats, and avoidance of obvious sources such as foetuses and placentae from ovine abortions, should all be beneficial. An intriguing study on T. gondii infection in children in Panama demonstrated that contact with dogs, not cats, was a significant risk factor for infection, perhaps because the dogs ate feces of infected cats and fecal material containing viable oocysts persisted in their haircoats.

The control of T. gondii in its various hosts depends on interrupting the transmission cycle primarily by preventing access to sporulated oocysts and tissue cysts.

The three major routes of transmission of T. gondii to people are: a) tissue cysts (and possibly tachyzoites) in animal tissues, including unboiled milk from goats; b) oocysts in the feces of cats, or in the environment; and c) congenital infection. People can also acquire T. gondii from blood transfusion or organ transplant. A 1999 publication estimated 225,000 cases of human toxoplasmosis diagnosed annually in the US, of which 50% were thought to be food-borne, with 400 to 4,000 congenitally infected babies born each year.  Another estimate indicates that in the United States approximately 1.25 million people have ocular toxoplasmsosis and that in most of these people the infection was acquired post-natally.  The data for these parameters in Canada would probably show lower prevalences for clinical disease, including ocular involvement.  Toxoplasma gondii infection in animals, birds and people has been described as the commonest of infections, but the rarest of diseases.

In 1994-95 there was a major outbreak of human toxoplasmosis in the Victoria (BC) area associated with a municipal water supply from one particular reservoir contaminated with faeces from cougars and domestic and feral cats with evidence of T. gondii infection.  Estimates suggest that several thousand people may have been infected.  Eye lesions were particularly common, and several pregnant women were at sufficient risk for abortion to be recommended.  It is possible that this outbreak was caused by a particularly virulent genotype of the parasite. Another waterborne outbreak, identified on the basis of risk factor analysis for seroprevalence, was reported in Brazil in 1997-99.

Meats in Canada with a relatively high risk of T. gondii infection include wildlife, probably especially black bears (of which approximately 80% are infected in the US), as well as lamb and mutton. In the US, pigs are the major domestic animal meat source for human T. gondii infection but the parasite appears to be very rare in pigs in Canada, probably because of the intensive management systems used in this country.

Elmore SA et al., (2011) Toxoplasma gondii in circumpolar people and wildlife. Vector-Borne and Zoonotic Diseases, In Press (available on journal website).

Scallan E et al. (2011) Foodborne illness acquired in the United States - major pathogens. Emerging Infectious Diseases 17: 7-15.

Dubey JP et al. (2009) Toxoplasmosis and other intestinal coccidial infections in dogs and cats. Veterinary Clinics of North America Small Animal Practice 39: 1009-1034.

Sibley LD et al. (2009) Genetic diversity of Toxoplasma gondii in animals and humans. Proceedings of the Royal Society of London Series B Biological Sciences 364: 2749-2761.

Dubey JP et al. (2008) Toxoplasma gondii infection in people and animals in the United States. International Journal for Parasitology 38: 1257-1278.

Hill DE et al. (2005) Biology and epidemiology of Toxoplasma gondii in man and animals. Animal Health Research Reviews 6: 41-61