Toxocara canis, Toxocara cati and visceral and ocular larva migrans in people

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Phylum: Nematoda
Class: Rhabditea
Subclass: Rhabditia
Order: Ascaridida
Superfamily: Ascaridoidea
Family: Ascarididae

Toxocara canis is an ascarid nematode, related to the other ascarids in dogs and cats (Toxocara cati and Toxascaris leonina), and to the ascarids of horses (Parascaris equorum), pigs (Ascaris suum), and people (Ascaris lumbricoides). 

The adults of these various ascarids are large (up to 30 cm in length), they have relatively low host specificity, and their eggs are long-lived, thick-shelled and resistant to adverse environmental conditions. Additionally, their life cycles have many similarities, including larval development to the infective stage within the egg, and similar larval migration routes in the mammalian hosts.

Adult Toxocara canis are up to approximately 10 cm (males) and 18 cm (females) long and easily visible to the naked eye. Males and females have two long and narrow lateral cervical alae at the anterior end. Males have a short finger like projection at the posterior end. Eggs measure approximately 90 by 75 µm, and are sub-spherical with a thick, rough shell (“golf ball” appearance).

Toxocara canis occurs in dogs, other canids, and occasionally, usually as larvae in the tissues, in other mammals and birds, throughout the world, including Canada. In many regions Toxocara canis is probably the most common nematode of dogs. Most non-canid hosts are infected only with larval stages in their tissues, and not with adult parasites in the stomach and intestines.  At northern latitudes, T. canis tends to be replaced by Toxascaris leonina.  Recent data from Ontario, based on analysis of fecal examination results from laboratories in five clinics demonstrated T. canis prevalences of approximately 15% in animals less than six months of age (n=357), and 0.2% in older dogs (n=9059).  A sixth clinic reported a prevalence for T. canis of 11% in the latter age group, but only 20 animals were examined.  Prevalences of T. cati in the five clinics were 30% (n=359) and 0.4% (n=7801), respectively, in cats in the two age groups.

Human infection with larval T. canis is more common than is clinical disease.  In people, T. canis can cause visceral and ocular larva migrans, significant health problems in some areas of the world, especially in children in developing countries.  The prevalence of these conditions in people tends to be relatively high where there are many infected dogs and more or less uncontrolled contact between the dogs, especially pre-natally infected pups, and people, especially children.  In North America, T. canis infection in people is probably most common among the rural poor of the south eastern United States. A recent survey report in the US for September, 2009 to September, 2010 noted 68 newly diagnosed cases of ocular larva migrans in 23 states. Almost 60% of 44 cases lived in the South, and almost two thirds of 33 cases owned a pet.

Toxocara cati is believed, perhaps erroneously, to be a very rare cause of visceral or ocular larva migrans in people.  Toxascaris leonina has not been associated with either condition. 

Adult Toxocara canis are located in the stomach and small intestine of their domestic animal and wildlife hosts, and eggs leave the host in the feces. An infective second-stage larva develops in each egg after 3-4 weeks in ideal environmental conditions. This development is temperature-dependent. Following ingestion of infective eggs, in pups less than approximately 3 months old the larvae that have hatched from the eggs migrate via the vasculature through the liver to the lungs, where they break out from the branches of the pulmonary artery into the airways, are coughed up, swallowed and mature to adults in the GI system – this is a tracheal migration. In older dogs (> approximately 6 months), the larvae initially larvae follow a similar migration route, but once in the lungs do not enter the airways but leave the lungs in the pulmonary veins and are distributed in the bloodstream to a variety of tissues – this is a somatic migration. Between 3 and 6 months of age, there is a gradual transition from primarily tracheal to primarily somatic migration.

If a female dog becomes pregnant, larvae in the tissues are mobilized at the start of the third trimester, enter the vasculature, cross the placenta and enter the livers of the fetal pups. This is pre-natal infection. When the pups are born, the larvae complete their migration to the GI system and mature. Eggs can be present in the feces of pre-natally infected pups by 2-3 weeks after birth. Rarely, larvae may enter the mammary glands of the bitch and be transmitted to suckling pups in the milk during the first four or five weeks of lactation – this is trans-mammary infection. Nursing bitches may occasionally ingest pre-natally acquired larvae from the feces of the pups.These larvae, as well as any that were activated from the somatic tissues of the bitch during pregnancy and entered her intestine, can produce a usually transient patent infection in the bitch. For the development of T. canis in pups, the relative roles of infection acquired by the bitch prior to versus during pregnancy or lactation are not known. Larvated, infective eggs may also be ingested by a small mammal paratenic host, in which the larvae released follow a somatic migration. If the paratenic host is eaten by a dog, larvae are released and establish an adult infection in the dog’s GI system.

These life cycle patterns mean that T. canis is generally more prevalent, and infections are more intense, in young pups than in older pups or adult animals.

People become infected with T. canis by ingesting larvated infective eggs from the environment, and ocassionally by ingesting animal or avian tissues (for example, chicken livers) containg viable larvae.  Under Canadian conditions, a minimum of two to three weeks are required for eggs newly passed in the feces of dogs to become infective.  The eggs hatch in the stomach and the larvae released enter the gut wall and migrate via blood vessels and lymphatics to a variety of organs and tissues.  Larvae in the viscera, primarily the liver and lungs, are associated with visceral larva migrans, and those in the eyes with ocular larva migrans.  People are almost always a dead-end host for T. canis, but there are a few reports of adult parasites, and of adult T. cati, in the intestines of people.
 
Life Cycle: Toxocara canis

Toxocara canis is transmitted among dogs by two routes: vertically (prenatally) from pregnant bitch to the foetus: and horizonatlly through eggs in the environment, and occasionally through larvae in small mammal intermediate hosts that have ingested infective eggs. The former route can result in large patent infectons in pups up to a few months of age, particularly if they have not been treated. Because most of the larvae of T. canis hatched from eggs ingested by older pups and by adult dogs follow a somatic migration, resulting in larvae in the tissues rather than adult parasites in the intestinal lumen, patent infections are relatively rare in these age groups.

Infective larvated eggs are the origin of T. canis infection for people. A major source of these eggs in young pups following prenatal infection, and in the United States the presence in the home of a litter of pups less than three months old has been identified as a significant risk factor for the development of larva migrans associated with T. canis, as have pica (ingestion of unusual materials or objects) and geophagia (ingestion of soil) among children. Eggs of T. canis require at least two to three weeks to become infective, and they can survive in the environment for months, or even years. Studies in several countries have demonstrated that it is not difficult to find viable T. canis eggs in sandboxes, parks and other areas where dogs defecate.

Serosurveys of people with work-related contact with dogs (for example, veterinarians, veterinary assistants and kennel workers), including one in Toronto, have not demonstrated a higher prevalence of T. canis infection relative to matched controls. The exception was dog breeders and their employees in the United Kingdom, among whom seroprevalence was significantly higher than in controls and was positively correlated with years as a breeder, number of bitches whelping each year, and contact with the bitches and their pups.

Many people infected with Toxocara canis never show any clinical signs.  The clinical signs that do appear sometimes depend on the location(s) of the migrating larvae that are causing significant pathology.  The most commonly affected sites are the liver and lungs  (visceral larva migrans - VLM) and the eyes (ocular larva migrans - OLM) , but there are published reports of clinical disease associated with the parasite's larvae in other tissues.  In addition, exposure to T. canis - as assessed serologically - has been identified as a risk factor for a number of other clinical conditions in people, including chronic urticaria, asthma, epilepsy, and abnormal behaviour (for example, pathological hoarding).  Some of these associations are not supported by particularly robust evidence.

Visceral larva migrans is most common in children aged one to seven years (mean two years old) and those affected typically show malaise, fever, vague abdominal pain, coughing and wheezing, eosinophilia, leukocytosis and hypergammaglobulinaemia.  In massive infections there may be very severe pneumonia or central nervous system involvement.

Ocular larva migrans is most common in older children (more than eight years old) and adults and is usually associated with granulomatous retinal lesions.  These can result in a range of clinical signs, including loss of visual acuity, squinting and "seeing lights".  A single T. canis larva can cause clinically significant eye lesions, and in some cases blindness is the end result.  Ocular larva migrans is almost always unilateral and is rarely associated with visceral larva migrans.

Why some patients develop visceral larva migrans, and others the ocular form of the disease, is not known.  One suggestion is that the visceral larva migrans is usually associated with relatively large numbers of larvae, which generate a strong immunological response which halts larval migrations early - in the liver and lungs, whereas ocular larva migrans results from relatively few larvae which stimulate a weak response which allows the larvae to migrate further and into the eye.

A third form of clinical disease associated with T. canis larvae in people is covert larva migrans (CLM).  This was first reported in children in Ireland, and is characterised by a wide range of clinical signs, including hepatomegaly, cough, sleep disturbances, abdominal pain, headache and behavioural changes, all associated with elevated T. canis antibodies.  Among these clinical signs, the trio of abdominal pain, headache and cough were very strongly associated with high T. canis titres.  Subsequently, a series of similar (adult) patients were identified in France with weakness, pruritus, rash, dyspnoea, abdominal pain and eosinophilia, together with elevated T. canis titres.

While a patient's history, clinical signs and blood picture are helpful in reaching a diagnosis of  visceral occult and ocular larva migrans associated with Toxocara canis, a specific diagnosis depends on the detection of antibodies to the parasite in serum (for visceral, ocular and  covert) or in the vitreous humor of the eye (for ocular).  Currently, an ELISA is the immunological test of choice, but it has a poor sensitivity in ocular larva migrans. 

The treatment of human cases of visceral and ocular larva migrans associated with Toxocara canis is beyond the scope of these notes, other than to say that treatment of both conditions is possible, though not always straightforward.

Successful control of visceral and ocular larva migrans should have two major targets:

1) Removal of the adult parasites (the source of eggs) from dogs using the very effective and safe antiparasitic products that are approved in Canada.  For prenatally infected pups, and ideal protocol is treatments at  2, 4, 6, and 8 weeks of age and then monthly to 6 months, then every six months or annually.  A continuing issue related to the treatment of young pups is that most are not seen until 6 to 8 weeks of age, well after the recommended start of treatments.  It is important, therefore, that breeders are educated by veterinarians regarding the ideal protocols and are encouraged to follow them.  For older dogs, ideally treatment should be every six months or annually, and pregnant bitches should be treated along with the pups.  Local circumstances, particularly the prevalence of T. canis, may alter these protocols.

2) Responsible disposal of fecal material from dogs in the home, in the kennel and in public areas.  Essentially this means effective "pooper scoopers" and hand washing. 

Larva migrans in people caused by Toxocara canis has been reported from many areas of the world, and is most common where children have ready access to dogs, especially young pups, in an environment that is supportive of the development and survival of the eggs of the parasite and of ingestion by children of infective eggs.  Suitable areas include many developing countries with warm, moist climates, as well as the south eastern United States. 

It is probable that many cases of visceral larva migrans, and fewer cases of ocular larva migrans, are not diagnosed.  Published surveys of people in Canada revealed an overall seroprevalence of 8.8% in 113 veterinary personnel in Ontario in the early 1980s, 19.5% among 524 rural children and 14.0% among 449 urban children in Nova Scotia in the mid-1980s, and 2.0% among 50 Cree in a community in Quebec in the mid-2000s.  There are, however, only two published reports of larva migrans associated with this parasite in Canada.  The first was in 1958, in an eighteen month old boy in Saskatchewan with hepatomegaly, eosinophilia, a history of pica and a pup and a kitten in the home.  Subsequently, following a diagnosis of VLM in a seven year old child in Toronto, a review of case records from the Hospital for Sick Children for the period 1952 to 1978 revealed 18 possible or probable cases of visceral larva migrans, and three of ocular larva migrans.  There are no readily available data to indicate whether the situation in Toronto has changed since then, nor is there information for the rest of the country. 

In the United States, in 1991 it was estimated that approximately 160 cases of visceral larva migrans, and 600 cases of ocular larva migrans were being diagnosed annually.  More recent estimates suggest that between one and three million people in the United States are infected annually with T. canis, although not all are clinically affected.  Presumably many additional cases, particularly of the visceral form of the disease, were occurring but were not diagnosed.  Because of differences in climate and in social structure in Canada, particularly the relative absence of large numbers of rural poor, it would be unwise to use these data as a basis for calculating the incidence in this country.
 
Before T. canis was established as a cause of ocular disease, it seems that many eyes were removed from children because the parasitic lesions had been mis-identified clinically as retinoblastoma, a very serious tumour.

Lum FC et al., (2011) Ocular toxocariasis - United States, 2009-2010. MMWR 60 (22): 734-736.

Jenkins EJ et al., (2011) Old problems on a new playing field: helminth zoonoses transmitted among dogs, wildlife, and people in a changing northern climate. Veterinary Parasitology 182: 54-69.

Lee ACY et al., (2010) Epidemiologic and zoonotic aspects of ascarid infections in dogs and cats. Trends in Parasitology 26: 155-161.