Tissue Nematodes

Life Cycle

Human infection with T. canis , T. cati , and B. procyonis usually begins when embryonated eggs are ingested. Humans come into contact with these eggs accidentally when their environment is contaminated by fecal material from dogs, cats, or raccoons that harbor adult worms ( Fig. 277.2 ). ^, After ingestion, these eggs are triggered to hatch, releasing larvae that penetrate the wall of the small intestine and enter the circulation. In humans, the larva migrates through various tissues, unable to complete their life cycle, and end up dying in the tissues they invade ( Fig. 277.3 ).

When the embryonated eggs are ingested by their definitive host, they undergo the classic ascarid life cycle, including hatching, intestinal penetration, and entering the circulation. In the definitive zoonotic host, they migrate to the lungs and, within approximately 3–5 days after initial ingestion, are coughed up and swallowed. The larvae then return to the intestine, where they mature into adult worms after a period of 60–90 days from the time of egg ingestion. The adult worms produce eggs that are released into the environment and become infective after 2–4 weeks of maturation in the soil. Although adult worms only live for 4–6 months, embryonated eggs can survive for several years in warm, moist soils. Infection can occur through ingestion of eggs from the soil, transplacentally, or through breast milk.

Clinical Features

The clinical manifestations of toxocariasis are largely dependent on which tissues are invaded and vary based on host factors such as age and immunologic status, as well as pathogen aspects such as inoculum size, number of exposures, and tropism of particular strains. ^, The pathology is felt to be due to the host immune response to dead and dying larvae in the viscera ( Fig. 277.4 ). The spectrum of disease ranges from an undefined number of subclinical infections with minimal symptoms that do not prompt patients to seek medical attention to fully symptomatic VLM or OLM with inflammation and pathology in multiple organs. Covert toxocariasis is a less severe form of infection that likely results from chronic exposure and presents as wheezing and eosinophilia, which can be misdiagnosed as asthma.

VLM is the most commonly recognized clinical syndrome and presents with a febrile illness and eosinophilia, hepatosplenomegaly, bronchospasm, or a myriad of other localizing symptoms depending on the localization of the nematode larva. In the years before the liver biopsy was replaced by serologic testing for diagnosis, nematode larva were commonly isolated from eosinophilic granulomas in the liver. Pulmonary symptoms, potentially confused with asthma, may be accompanied by infiltrates apparent on chest imaging. Myocarditis and nephritis also can develop. If larvae invade the central nervous system, infected individuals may develop encephalopathy, seizures, or functional intestinal disorders. While Toxocara spp . can cause death in puppies; death is rare in human infection. When death occurs in humans, it is attributed to the involvement of the myocardium or central nervous system.

OLM is a devastating manifestation that tends to occur in older children and adolescents and presents as visual impairment isolated to one eye. Larvae that have invaded the retina trigger an immune response as the larvae start to die. This immune response leads to granuloma formation that can result in deformation of the retina and detachment of the macula. In some cases, these lesions have been visualized on ophthalmic examination, and due to their visual similarities with retinoblastoma, could lead to unnecessary enucleation of the infected eye.

B. procyonis is a common infection of raccoons. Humans are exposed through ingestion of embryonated eggs that are shed in sylvatic or peri-domestic settings when raccoons gain access to attics, decks, or gutters. Although it is rare, the clinical consequences of B. procyonis infection is generally more severe than that caused by T. canis . Neural larva migrans can result in neuro-devastation, even with anthelmintic chemotherapy and steroids. B. procyonis larvae are larger, up to 2 mm compared to 0.5 mm for T. canis and T. cati , and have the unique ability to continue to grow in size inside the infected human and should be included in the differential of eosinophilic meningitis. ^,

Diagnosis

Key to the diagnosis of T. canis, T. cati , and B. procyonis infection is including these pathogens in the differential diagnosis of a child, adolescent, or returning traveler presenting with an unexplained febrile illness with eosinophilia and a compatible history. A combination of clinical presentation, appropriate risk factors, and a positive serological test support the diagnosis. The recommended test for toxocariasis detects IgG against excretory-secretory antigens derived from Toxocara larvae. This Toxocara enzyme-linked immunosorbent assay (ELISA) is available through the US Center for Disease Control and Prevention (CDC) and is estimated to be 78% sensitive and 92% specific when using the appropriate cutoff. One of the challenges is that the test detects an immune response to the larval form of the nematode and does not necessarily confirm current active infection. Although a biopsy demonstrating larvae is definitive, this is rarely indicated. The diagnosis of OLM also incorporates a consistent ophthalmological examination ( Fig. 277.5 ). Stool examination of infected individuals is not helpful as these tissue nematodes are unable to complete their life cycle in humans, and thus adult egg-producing worms are never present in the human gastrointestinal tract. Although a serological test has been developed for B. procyonis that has high sensitivity and specificity, many human cases are not diagnosed until autopsy ( Fig 277.6 ).

Treatment

While there is limited evidence-based guidance, T. canis and T. cati can be treated with albendazole 400 mg orally twice a day for a total of 5 days (adult and pediatric dose). The other commonly used drug, mebendazole, is poorly absorbed outside the gastrointestinal tract, although some success has been reported in patients who ingest 1 g or more of this agent for a 21-day course. Symptomatic treatment, including administration of corticosteroids, has been helpful for suppressing intense manifestations of the infection. OLM is treated either by surgery (vitrectomy), antihelmintic chemotherapy, and/or corticosteroids. In the case of ocular involvement with active inflammation, the role of antihelmintic therapy is unclear, owing to the lack of knowledge regarding the intra-ophthalmic pharmacokinetics and pharmacodynamics and the impact of therapy on outcomes.

There are a limited number of cases diagnosed to date, so there is little overall experience with antihelmintic therapy for baylisascariasis, but good outcomes have been reported with high-dose albendazole 25–50 mg/kg/day in divided doses started promptly and continued for 10–20 days with concomitant steroids. ^{, ,}

Prevention and Medical Ecology

Limiting human exposure to infective embryonated eggs in the environment is a critical aspect of decreasing the disease burden due to these invasive tissue nematodes. Once introduced into the environment, the infective eggs can remain viable for months to years due to their resistant acellular outer shell. This acellular layer allows these eggs to withstand extreme temperature changes, various degrees of desiccation, and even harsh chemicals. ^, Any strategies to rid contaminated soil of these hardy eggs must overcome these barriers.

Once introduced into the soil by the indiscriminate deposition of fecal material by dogs, cats, and raccoons, eggs can be distributed through the environment. The common earthworm is efficient at re-distributing fecal material back up to the surface, even with eggs initially buried up to 2 feet below the surface. Various domestic animals distribute contaminated soil on their paws, while ground-feeding birds such as pigeons, starlings, and sparrows may carry eggs further afield on their feet and beaks. ^, Eggs also may also enter municipal drinking water supplies and end up in waters used for recreational purposes where inadvertent water ingestion can result in infection. In this public health challenge, veterinarians may have the most striking impact by encouraging pet owners to deworm their pets.

Life Cycle

Rats are the definitive host for Angiostrongylus spp. Angiostrongylus infect a number of species of wild rats, including the common wharf rat. These worms live and lay eggs in the pulmonary arteries of rats. The released eggs move through the capillaries in the lung and then penetrate into the alveolar spaces. From the alveolar spaces, the larvae migrate up the respiratory tree and are swallowed down into the gastrointestinal tract to ultimately pass out of the rat in feces. A. cantonensis larvae incubate in the soil before being consumed by a variety of mollusks and crustaceans . Humans are infected when they inadvertently consume the larval stages of A. cantonensis in uncooked snails, slugs, or raw vegetables contaminated with secretions from these invertebrates. A. costaricensis larvae are generally restricted to infecting only one invertebrate host, the slug, and in most cases, the specific slug known as Vaginulus plebeius. Humans are infected when they inadvertently consume these slugs, the larval stages present in uncooked snails or slugs, or raw vegetables contaminated with secretions from these invertebrates.

Clinical Features

In most cases, human infection with Angiostrongylus spp. results in the failure of the worm to complete its life cycle. Once in a human host, the larvae often migrate to the brain or rarely to the lungs, as has been observed in infants and small children. The larvae then die surrounded by eosinophilic inflammation. The pattern of clinical presentation varies with each species of this nematode. A. cantonensis third stage larvae usually migrate to the meningeal capillaries, where the dying larvae cause an eosinophilic meningoencephalitis. Part of the pathology can involve vascular thrombosis and aneurysms. A. cantonensis is the most common cause of eosinophilic meningitis outside of the developed world and should be considered in the differential of travelers returning from endemic areas.

Individuals infected with A. costaricensis present with fever, bitemporal or frontal headache, and meningismus. Vomiting is reported in the majority of cases, as are migrating painful paresthesias, which may persist for weeks to months. Although eosinophilic meningitis is characteristic on cerebral spinal fluid examination, focal lesions are usually not present on head CT or MRI, and this can be useful in distinguishing the disease from other etiologies, such as G. spinigerum and neurocysticercosis. The natural course of the disease without treatment sees the resolution of symptoms in 1–2 weeks, but for some individuals, the disease can be protracted. Disease duration and severity may be worse in children.

Diagnosis

Diagnosis of Angiostrongylus spp. is based on clinical presentation and polymerase chain reaction (PCR), which can be performed on cerebrospinal fluid but lacks high sensitivity. Serologic testing is not widely available but is performed by some research laboratories and has been used to confirm suspected cases post-treatment.