Nematodes

Essentials of Diagnosis

• Intestinal nematodes: identification of characteristic eggs or parasites in stool.
• Bloodstream nematodes (filariasis): a clinical diagnosis can be made; a fresh blood smear may be confirmatory.
• Tissue nematodes: a clinical diagnosis can be made; a skin snip or other tissue examination may demonstrate the organism.

Accurate diagnosis usually requires correlation of clinical findings with appropriate specimens. For intestinal infections, repeated stool examinations increase sensitivity, whereas for tissue and blood nematodes, the timing of specimen collection and careful microscopic review are critical.

General Considerations

Nematodes (roundworms) are non-segmented, tapered, bilaterally symmetrical, cylindrical organisms with complete digestive tracts that reproduce sexually. Although > 500,000 species of nematodes have been described, only a small number are commonly encountered as human parasites. Most nematodes have complex life cycles, sometimes involving several larval forms and intermediate hosts or free-living stages. Pathogenic nematodes may be categorised as primarily intestinal parasites or extraintestinal tissue parasites (Table 1).

OTHER TISSUE NEMATODE INFECTIONS

TRICHINOSIS

Trichinella species are unique among tissue-dwelling nematodes because there is no intermediate arthropod vector stage. Trichinella nematodes parasitise carnivores. Adult worms parasitise the small intestine; infective larvae are released and migrate from the intestine to muscle tissues in the host, where they encyst and remain viable and infectious for several years. When the host tissues are eaten, the cyst walls are digested and the larvae mature again within several days in the intestine of the new host, perpetuating the life cycle. Normal hosts of Trichinella spp. include swine, rats, bears, foxes, walrus, and other carnivorous mammals. Humans are incidental hosts. Cooking meat to core temperatures of about 55°C (131°F) or freezing to -15°C (5°F) for 3 weeks kills Trichinella spp. larvae.

Clinical & Laboratory Findings

Mild infection is usually asymptomatic. Early (1 week) after infection, gastrointestinal symptoms predominate, including diarrhoea, nausea, or vomiting. After the second week, systemic symptoms predominate during the muscle invasion stage, including fever, myalgias, and malaise in most patients. Periorbital oedema with conjunctival chemosis and eyelid oedema is characteristic and common. Symptoms last between 4 and 8 weeks. Rarely, myocarditis or encephalitis may complicate the clinical course. In laboratory findings, eosinophilia after the 10th day, which is sometimes marked, is characteristic, as is elevated immunoglobulin E. Serum creatine phosphokinase and lactic dehydrogenase concentrations reflect myositis. Trichinella serology becomes positive at about 3 weeks after infection.

Treatment

Treatment for trichinosis remains controversial and is primarily supportive. If ingestion is known to have occurred within 24 hours, albendazole (400 mg twice daily for 60 days), mebendazole (200-400 mg 3 times daily for 3 days, then 400-500 mg 3 times daily for 10 days), or thiabendazole (25 mg/kg/day for 1 week) has been proposed to prevent infection. These drugs are not beneficial for established infection or muscle larvae. No specific therapy has been unequivocally demonstrated to be of benefit during the muscle invasion stage.

Prognosis

Spontaneous recovery is the rule, although full recovery may require weeks to months. Death is rare and typically results from myocarditis, encephalitis, or pneumonitis.

Prevention

The incidence of human trichinosis has declined in developed countries with measures designed to reduce the prevalence of trichinosis in hogs. Trichinella in wild game (or pork) can be killed by thorough cooking to an internal temperature above about 62°C (145°F) throughout all parts of the meat or to about 56°C (133°F) for more than 15 minutes, freezing to -15°C (5°F) for 20 days, or gamma radiation.

TOXOCARIASIS (VISCERAL LARVA MIGRANS)

Toxocariasis, or visceral larva migrans, is a syndrome caused by invasion of human extraintestinal tissues by larvae of Ascaris spp., for which humans are not the usual host of the adult worms. Toxocara canis, commonly found in dogs, is the most commonly implicated species; Toxocara catis (cats) and Baylisascaris procyonis (raccoons) have also been implicated. Puppies can be infected transplacentally or transmammarily. Pregnancy in dogs reactivates latent infections in the bitch. Animals harbouring adult ascarids in the intestine shed copious numbers of eggs into the environment. The eggs become infectious after 3-4 weeks and are highly resistant to harsh environmental conditions. Toxocara eggs may remain infectious for months to years. Human infection results from ingestion of eggs from faecally contaminated soil, as may occur, for example, in children with pica. Direct transmission from pets to humans does not occur because the eggs require maturation in soil before they become infective.

In young animals, ingested eggs hatch in the intestine and the larvae migrate through extraintestinal tissues, including the liver and lungs. The larvae induce coughing, are swallowed, and then mature into adults in the small intestine to complete the life cycle, which resembles that of A lumbricoides in humans. In older animals, humans, and other hosts such as mice or rats, larvae also hatch from ingested eggs and invade extraintestinal tissues, but they are unable to fully mature and may persist and migrate in tissues as "second-stage" larvae for about 6 months. If these second-stage larvae are ingested by a dog or cat, the larvae may complete their life cycle and develop into adult intestinal worms. Eosinophilic granulomas caused by toxocariasis most often involve the liver or lungs; involvement of the brain, eye, muscle, and skin has also been reported.

Clinical & Laboratory Findings

Visceral larva migrans is predominantly seen in children < 7 years old, and it may be associated with pica. Most cases appear to be asymptomatic. When symptoms occur, they are variable and depend on the organ systems involved but may include fever, cough or wheezing, and urticarial rash or skin nodules. Hepatomegaly is relatively common. Splenomegaly, lymphadenopathy, and evidence of myocarditis are less common.

Marked leukocytosis, sometimes exceeding 100,000 leukocytes/µL, and hypereosinophilia are common in visceral larva migrans. Polyclonal hypergammaglobulinaemia and anti-A or anti-B antibodies to isohaemagglutinin antigens (cross-reacting to T canis larval antigens) may occur. Eosinophilic spinal fluid pleocytosis may occur with central nervous system involvement. Chest x-ray abnormalities may be seen in one-third of patients. Toxocara serology may be helpful in confirming the diagnosis, but it should be remembered that, in some populations, the background prevalence of seropositivity in patients without clinically apparent visceral larva migrans may be high. Identification of larvae in tissue biopsy samples is diagnostic but not sensitive. Stool examination is not usually helpful.

Ocular visceral larva migrans warrants special consideration. Infection of the eye with Toxocara larvae usually presents as an isolated finding in patients with no known history of visceral larva migrans and without concurrent multifocal, systemic symptoms or signs. The ocular findings are typically a unilateral posterior or peripheral eosinophilic inflammatory mass. Serology may be negative. The ocular lesion may be mistaken for a retinoblastoma.

Treatment

No specific therapy has been proven effective. In many cases, symptoms are self-limited and supportive, symptomatic treatment is all that is required. Treatment with a variety of anthelmintic agents has been tried with limited success. These agents include albendazole, thiabendazole, mebendazole, diethylcarbamazine, or ivermectin. Corticosteroids may be of benefit in some patients, especially subconjunctival applications in ocular visceral larva migrans.

Prevention & Prognosis

Puppies, kittens, and household dogs and cats, especially when pregnant or nursing, should be screened and treated as necessary to prevent transmission to humans. Pica should be prevented. Most cases are self-limited, although symptoms may persist for months to several years.

DRACUNCULIASIS

Dracunculiasis, or guinea worm infection, is caused by infection with the tissue nematode Dracunculus medinensis. The parasite has been widely distributed in the Indian subcontinent, the Arabian Peninsula, and certain areas of West and Central Africa north of the equator. Human infection is acquired by drinking water that contains tiny copepods (Cyclops spp.; "water fleas") carrying infectious third-stage larvae. The larvae migrate to subcutaneous connective tissue, usually in the lower extremities, where they develop into adult worms over an extended incubation period that can last up to a year. The adult female may reach 60-80 cm in length. When the extremities are exposed to water, the head of the gravid female protrudes through an ulceration in the host's extremity, a loop of uterus prolapses, and it discharges large numbers of first-stage larvae into the water. The larvae are ingested by copepods to complete the life cycle.

An active eradication program by the World Health Organization (WHO) has led to a dramatic reduction in the incidence of dracunculiasis worldwide. Because no nonhuman reservoir is recognised, the disease may be eradicable in the near future.

Clinical Findings

A chronic peripheral cutaneous ulceration, from which the worm may protrude, is the hallmark of dracunculiasis. A local painful, stinging, or burning papule may be the first indication of impending ulceration. Generalised symptoms may occur with development of ulceration and include fever, nausea, vomiting, dyspnoea, urticaria or pruritus, or periorbital oedema. Ulcers on the foot frequently prevent ambulation and may result in long-lasting deformity and secondary infection (including ankle or knee joint infection). Tetanus may also complicate dracunculiasis. Dead or dying worms may trigger intense inflammatory reactions. In endemic areas, diagnosis is based on the typical clinical findings.

Treatment

No specific anthelmintic therapy is available to kill adult worms. Mechanical removal of worms has been practised for centuries. General treatment focuses on controlling complications, including bed rest, elevation of the affected extremity, wound care, and antibacterial therapy for secondary bacterial wound infections. Metronidazole, 250 mg orally 3 times daily, mebendazole, 400-800 mg orally daily, or thiabendazole 25 mg/kg twice daily may be helpful in promoting expulsion of the worm, as may immersion of the affected limb in water several times daily.

Prevention

Non-contaminated drinking water is the key to preventing dracunculiasis. The World Health Organization (WHO) prevention program has focused on providing clean drinking water using tube wells, hand pumps, or cisterns; treating drinking water supplies with temephos (to eliminate the copepods); or boiling water. Water can also be filtered to remove particles > 100 µm.

¹ The presence of a particular nematode depends heavily on geographic location. For example, tissue-dwelling nematodes are uncommon or non-existent in the United States.