History of discovery

Werner described a parasitic nematode in dogs in 1782 which he named Ascaris canis. Johnston determined that what Werner had described was actually a member of the genus Toxocara established by Stiles in 1905. Fữlleborn speculated that T canis larvae might cause granulomatous nodules in humans. In 1947 Perlingiero and Gyorgy described the first case of what was probably toxocariasis. Their patient was a 2-year old boy from Florida who had classical symptoms and esoinophilic necrotizing granulomas. In 1950, Campbell-Wilder was the first to describe toxocariasis in humans; she published a paper describing ocular granulomas in patients with endophthalmitis, Coasts disease, or pseudoglioma. Two years later, Beaver et al. published the presence of Toxocara larvae in granulomas removed from patients with symptoms similar to those in Wilder’s patients.

Clinical presentation

Physiological reactions to Toxocara infection depend on the host’s immune response and the parasitic load. Most cases of Toxocara infection are asymptomatic, especially in adults. When symptoms do occur, they are the result of migration of second stage Toxocara larvae through the body.

Covert toxocariasis is the least serious of the three syndromes and is believed to be due to chronic exposure. Signs and symptoms of covert toxocariasis are coughing, fever, abdominal pain, headaches, and changes in behavior and ability to sleep. Upon medical examination, wheezing, hepatomegaly

Hepatomegaly

Hepatomegaly is the condition of having an enlarged liver. It is a nonspecific medical sign having many causes, which can broadly be broken down into infection, direct toxicity, hepatic tumours, or metabolic disorder. Often, hepatomegaly will present as an abdominal mass...

, and lymphadenitis are often noted.

High parasitic loads or repeated infection can lead to visceral larva migrans (VLM). VLM is primarily diagnosed in young children, because they are more prone to exposure and ingestion of infective eggs. Toxocara infection commonly resolves itself within weeks, but chronic eosinophilia

Eosinophilia

Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds 0.45×109/L . A marked increase in non-blood tissue eosinophil count noticed upon histopathologic examination is diagnostic for tissue eosinophilia. Several causes are known, with the most common being...

 may result. In VLM, larvae migration incites inflammation of internal organs and sometimes the central nervous system. Symptoms depend on the organ(s) affected. Patients can present with pallor, fatigue, weight loss, anorexia, fever, headache, rash, cough, asthma, chest tightness, increased irritability, abdominal pain, nausea, and vomiting. Sometimes the subcutaneous migration tracks of the larvae can be seen. Patients are commonly diagnosed with pneumonia, bronchospasms, chronic pulmonary inflammation, hypereosinophilia, hepatomegaly, hypergammaglobulinaemia (IgM, IgG, and IgE classes), leucocytosis, and elevated anti-A and –B isohaemagglutinins. Severe cases have occurred in people who are hypersensitive to allergens; in rare cases, epilepsy, inflammation of the heart, pleural effusion, respiratory failure, and death have resulted from VLM.
Ocular larva migrans (OLM) is rare compared with VLM. A light Toxocara burden is thought to induce a low immune response, allowing a larva to enter the host’s eye. Although there have been cases of concurrent OLM and VLM, these are extremely exceptional. OLM often occurs in just one eye and from a single larva migrating into and encysting within the orbit. Loss of vision occurs over days or weeks. Other signs and symptoms are red eye, white pupil, fixed pupil, retinal fibrosis, retinal detachment, inflammation of the eye tissues, retinal granulomas, and strabismus

Strabismus

Strabismus is a condition in which the eyes are not properly aligned with each other. It typically involves a lack of coordination between the extraocular muscles, which prevents bringing the gaze of each eye to the same point in space and preventing proper binocular vision, which may adversely...

. Ocular granulomas resulting from OLM are frequently misdiagnosed as retinoblastoma

Retinoblastoma

Retinoblastoma is a rapidly developing cancer that develops in the cells of retina, the light-detecting tissue of the eye. In the developed world, Rb has one of the best cure rates of all childhood cancers , with more than nine out of every ten sufferers surviving into...

s. Toxocara damage in the eye is permanent and can result in blindness.

A case study published in 2008 supported the hypothesis that eosinophilic cellulitis may also be caused by infection with Toxocara. In this study, the adult patient presented with eosinophilic cellulitis, hepatosplenomegaly, anemia, and a positive ELISA

ELISA

Enzyme-linked immunosorbent assay , is a popular format of a "wet-lab" type analytic biochemistry assay that uses one sub-type of heterogeneous, solid-phase enzyme immunoassay to detect the presence of a substance in a liquid sample."Wet lab" analytic biochemistry assays involves detection of an...

 for T. canis.

Transmission

Transmission of Toxocara to humans is usually through ingestion of infective eggs. These eggs are passed in cat or dog feces, but the defecation habits of dogs cause T. canis transmission to be more common than that of T. cati. Both Toxocara canis and Toxocara cati eggs require a several week incubation period outside of a host before becoming infective, so fresh eggs cannot cause toxocariasis.

Many objects and surfaces can become contaminated with infectious Toxocara eggs. Flies that feed on feces can spread Toxocara eggs to surfaces or foods. Young children who put contaminated objects in their mouths or eat dirt (pica

Pica (disorder)

Pica is characterized by an appetite for substances largely non-nutritive . For these actions to be considered pica, they must persist for more than one month at an age where eating such objects is considered developmentally inappropriate...

) are at risk of developing symptoms. Humans can also contaminate foods by not washing their hands before eating.

Humans are not the only accidental hosts of Toxocara. Eating undercooked rabbit, chicken, or sheep can lead to infection; encysted larvae in the meat can become reactivated and migrate through a human host, causing toxocariasis. Special attention should be paid to thoroughly cooking giblets and liver to avoid transmission.

Reservoir

Dogs are the reservoir for Toxocara canis, but puppies pose the greatest risk of spreading the infection to humans. Infection in most adult dogs is characterized by encysted second stage larvae. However, these larvae can become reactivated in pregnant females and cross the placental barrier to infect the pups. Vertical transmission can also occur through breastmilk. Infectious mothers, and puppies under five weeks old, pass eggs in their feces. Approximately 50% of puppies and 20% of adult dogs are infected with T. canis.

Cats are the reservoir for Toxocara cati. As with T. canis, encysted second stage larvae in pregnant or lactating cats become reactivated. However, vertical transmission can only occur through breastfeeding. Although kittens are more of a risk for human infection than adult cats, the defecation habits of cats reduce the chances of human infection with T. cati.

Vector

Flies can act as mechanical vectors for Toxocara, but most infections occur without a vector.

Incubation period

The incubation period for Toxocara canis and cati eggs depends on temperature and humidity. Under ideal summer conditions, eggs can mature to the infective stage after two weeks outside of a host. Toxocara eggs can remain infectious for years, as they are very resistant to the effects of chemicals, as well as changes in temperature.

Morphology

Both species produce eggs that are brown and pitted. T. canis eggs measure 75-90 µm and are spherical in shape, whereas the eggs of T. cati are 65-70 µm in diameter and oblong. Second stage larvae hatch from these eggs and are approximately 0.5mm long and 0.02mm wide. Adults of both species have complete digestive systems and three lips, each composed of a dentigerous ridge.

Adult T. canis are found only within dogs and the males are 4–6 cm in length, with a curved posterior end. The males each have spicules and one “tubular tesis.” Females can be as long as 15 cm, with the vulva stretching one third of their bodylength. The females do not curve at the posterior end.

T. cati adult females are approximately 10 cm long, while males are typically 6 cm or less. The T. cati adults only occur within cats, and male T. cati are curved at the posterior end.

Life cycle

Both cats and dogs can become infected with Toxocara through the ingestion of eggs or by transmission of the larvae from a mother to her offspring. Transmission to cats and dogs can also occur by ingestion of infected accidental hosts, such as earthworms, cockroaches, rodents, rabbits, chickens, or sheep.

Eggs hatch as second stage larvae in the intestines of the cat or dog host (for consistency, this article will assume that second stage larvae emerge from Toxocara eggs, although there is debate as to whether larvae are truly in their second or third stage of development). Larvae enter the bloodstream and migrate to the lungs, where they are coughed up and swallowed. The larvae mature into adults within the small intestine of a cat or dog, where mating and egg laying occurs. Eggs are passed in the feces and only become infective after several weeks outside of a host. During this incubation period, molting from first to second (and possibly third) stage larva takes place within the egg. In most adult dogs and cats, the full lifecycle does not occur, but instead second stage larvae encyst after a period of migration through the body. Reactivation of the larvae is common only in pregnant or lactating cats and dogs. The full lifecycle usually only occurs in these females and their offspring.

Second stage larvae will also hatch in the small intestine of an accidental host, such as a human, after ingestion of infective eggs. The larvae will then migrate through the organs and tissues of the accidental host, most commonly the lungs, liver, eyes, and brain. Since L2 larvae cannot mature in accidental hosts, after this period of migration, Toxocara larvae will encyst as second stage larvae.

Diagnostics

Finding Toxocara larvae within a patient is the only definitive diagnosis for toxocariasis, however biopsies to look for second stage larvae in humans are generally not very effective. PCR, ELISA, and serological testing are more commonly used to diagnose Toxocara infection. Serological tests are dependant on the number of larvae within the patient, and are unfortunately not very specific. ELISAs are much more reliable and currently have a 78% sensitivity and a 90% specificity. A 2007 study announced an ELISA specific to Toxocara canis, which will minimize false positives from cross reactions with similar roundworms and will help distinguish if a patient is infected with T. canis or T. cati. OLM

Ocular larva migrans

Ocular larva migrans is the ocular form of the larva migrans syndrome that occurs when toxocara canis larvae invade the eye. They may be associated with visceral larva migrans...

 is often diagnosed after a clinical examination. Granulomas can be found throughout the body and can be visualized using ultrasound, MRI, and CT technologies.

Treatment

Toxocariasis will often resolve itself, because the Toxocara larvae cannot mature within human hosts. Corticosteroids are prescribed in severe cases of VLM or if the patient is diagnosed with OLM. Either albendazole (preferred) or mebendazole (“second line therapy”) may be prescribed. Granulomas can be surgically removed, or laser photocoagulation and cryoretinopexy can be used to destroy ocular granulomas.

Epidemiology

Humans are accidental hosts of Toxocara, yet toxocariasis is seen throughout the world. Most cases of toxocariasis are seen in people under the age of twenty. Seroprevalence is higher in developing countries, but can be considerable in first world countries, as well. In Bali, St. Lucia, Nepal and other countries, seroprevalence is over fifty percent. Previous to 2007, the U.S. seroprevalence was thought to be around 5% in children. However, Won et al. discovered that U.S. seroprevalence is actually 14% for the population at large.In many countries, toxocariasis is considered very rare. Approximately 10,000 clinical cases are seen a year in the U.S., with ten percent being OLM. Permanent vision loss occurs in 700 of these cases.

Young children are at the greatest risk of infection because they play outside and tend to place contaminated objects and dirt in their mouths. Dog ownership is another known risk factor for transmission. There is also a significant correlation between high Toxocara antibody titers and epilepsy in children.

Parasitic loads as high as 300 larvae in a single gram of liver have been noted in humans. The “excretory-secretory antigens of larvae… released from their outer epicuticle coat [and]… readily sloughed off when bound by specific antibodies” incite the host’s immune response. The tipping point between development of VLM and OLM is believed to be between 100 and 200 larvae. The lighter infection in OLM is believed to stimulate a lower immune response and allow for migration of a larva into the eye. Larvae are thought to enter the eye through the optic nerve, central retinal artery, short posterior ciliary arteries, soft tissues, or cerebrospinal fluid. Ocular granulomas that form around a larva typically are peripheral in the retina or optic disc.

Public health and preventions

Actively involving veterinarians and pet owners is important for controlling the transmission of Toxocara from pets to humans. A group very actively involved in promoting a reduction of infections in dogs in the United States is the Companion Animal Parasite Council -- CAPC

Companion Animal Parasite Council

The Companion Animal Parasite Council The Companion Animal Parasite Council The Companion Animal Parasite Council (also commonly referred to as CAPC, pronounced "Cap-C", is a non-profit organization (501c3) composed of practicing veterinarians, academic veterinary parasitologists, veterinary...

. Since pregnant or lactating dogs and cats and their offspring have the highest, active parasitic load, these animals should be placed on a deworming program. Pet feces should be picked up and disposed of or buried, as they may contain Toxocara eggs. Practicing this measure in public areas, such as parks and beaches, is especially essential for decreasing transmission. Also, sandboxes should be covered when not in use to prevent cats from using them as litter boxes. Hand washing before eating and after playing with pets, as well as after handling dirt will reduce the chances of ingesting Toxocara eggs. Washing all fruits and vegetables, keeping pets out of gardens and thoroughly cooking meats can also prevent transmission. Finally, teaching children not to place nonfood items, especially dirt, in their mouths will drastically reduce the chances of infection.

Toxocariasis has been named one of the neglected diseases of U.S. poverty, because of its prevalence in Appalachia, the southern U.S., inner city settings, and minority populations. Unfortunately, there is currently no vaccine available or under development. However, the mitochondrial genomes of both T. cati and T. canis have recently been sequenced, which could lead to breakthroughs in treatment and prevention.

External links

• CDC information page on toxocariasis.
• Roundworms: Cats and Kittens from The Pet Health Library
• Roundworms: Dogs and Puppies from The Pet Health Library
• Despommier, D. Toxocariasis: Clinical Aspects, Epidemiology, Medical Ecology, and Molecular Aspects. Clin Microbiol Rev. 2003;16:265–272.
• http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=153144
• CAPC Recommendations Ascarids