Other Tissue Nematodes

Onchocerciasis (Onchocerca Volvulus)

Infection with Onchocerca volvulus leads to onchocerciasis or river blindness . Onchocerciasis occurs primarily in West Africa but also in Central and East Africa and is the world's 2nd leading infectious cause of blindness. There have been scattered foci in Central and South America, but the infection is now thought to be eliminated in the Americas. O. volvulus larvae are transmitted to humans by the bite of Simulium black flies that breed in fast-flowing streams. The larvae penetrate the skin and migrate through the connective tissue and eventually develop into adult worms that can be found tangled in fibrous tissue. Adult worms can live in the human body for up to 14 yr. Female worms produce large numbers of microfilariae that migrate through the skin, connective tissue, and eye. Most infected individuals are asymptomatic. In heavily infected individuals, clinical manifestations are a result of localized host inflammatory reactions to dead or dying microfilariae and subcutaneous adult worms surrounded by a palpable fibrous capsule. Cutaneous and ocular reactions to microfilariae produce pruritic dermatitis, punctate keratitis, corneal pannus formation, and chorioretinitis. Adult worms in subcutaneous nodules are not painful and tend to occur over bony prominences of the hip. The diagnosis can be established by obtaining snips of skin covering the scapulae, iliac crests, buttocks, or calves. The snips are immersed in saline for several hours and examined microscopically for microfilariae that have emerged into the fluid. The diagnosis can also be established by demonstrating microfilariae in the cornea or anterior chamber on slit-lamp examination or finding adult worms on a nodule biopsy specimen. Ophthalmology consultation should be obtained before treatment of eye lesions.

A single dose of ivermectin (150 µg/kg orally) is the drug of choice and clears O. volvulus microfilariae from the skin for several months but has no effect on the adult worm. Treatment with ivermectin should be repeated every 6-12 mo until the patient is asymptomatic or has no evidence of eye infection. Adverse effects of ivermectin therapy include fever, urticaria, and pruritus, which are more frequent in individuals not born in endemic areas who acquired the infection following periods of intense exposure, such as Peace Corps volunteers. Patients with concurrent high-density microfilaremia from loiasis may develop potentially fatal encephalopathy with ivermectin therapy. Treatment with ivermectin should be withheld until Loa loa microfilaremia can be reduced. Moxidectin is a promising new agent. Personal protection includes avoiding areas where biting flies are numerous, wearing protective clothing, and using insect repellent. Programs of mass treatment with ivermectin have been implemented in Africa in an effort to reduce the prevalence of onchocerciasis.

The World Health Organization (WHO) set goals for onchocerciasis elimination by 2020 using mass drug administration with ivermectin. Elimination can be declared only after 3 yr of posttreatment surveillance without microfilaria detection in skin biopsies.

Nodding syndrome , a form of epilepsy in African children living in focal areas of Uganda and South Sudan, was epidemiologically associated with onchocerciasis, but an etiologic link was not established. Recently, researchers identified neurotoxic autoantibodies that cross-react with O. volvulus proteins, which were found more frequently in people with nodding syndrome than in those in the same village without the syndrome. Nodding syndrome may be an autoimmune epileptic disorder triggered by O. volvulus infection.

Loiasis (Loa Loa)

Loiasis is caused by infection with the tissue nematode Loa loa. The parasite is transmitted to humans by diurnally biting flies (Chrysops) that live in the rain forests of West and Central Africa. Migration of adult worms through skin, subcutaneous tissue, and subconjunctival area can lead to transient episodes of pruritus, erythema, and localized edema known as Calabar swellings , which are nonerythematous areas of subcutaneous edema 10-20 cm in diameter typically found around joints such as the wrist or the knee ( Fig. 323.1 ). They resolve over several days to weeks and may recur at the same or different sites. Lifelong residents of L. loa –endemic regions may have microfilaremia and eosinophilia but are often asymptomatic. In contrast, travelers to endemic regions may have a hyperreactive response to L. loa infection characterized by frequent recurrences of swelling, high level eosinophilia, debilitation, and serious complications such as glomerulonephritis and encephalitis. Diagnosis is usually established on clinical grounds, often assisted by the infected individual reporting a worm being seen crossing the conjunctivae. Microfilariae may be detected in blood smears collected between 10 am and 2 pm . Adult worms should be surgically excised when possible.

Diethylcarbamazine is the agent of choice for eradication of microfilaremia, but the drug does not kill adult worms. Because treatment-associated complications such as pruritus, fever, generalized body pain, hypertension, and even death may occur, especially with high microfilaria levels, the dose of diethylcarbamazine should be increased gradually in such cases ( children : 1 mg/kg orally on day 1, 1 mg/kg 3 times daily on day 2, 1-2 mg/kg three times daily on day 3, 2 mg/kg three times daily on days 4-21; adults : 50 mg orally on day 1, 50 mg three times daily on day 2, 100 mg three times daily on day 3, 2 mg/kg three times daily on days 4-21). Full doses can be instituted on day 1 in persons without microfilaremia (3 mg/kg orally three times daily for 12 days). A 3 wk course of albendazole can also be used to slowly reduce L. loa microfilarial levels as a result of embryotoxic effects on the adult worms. Antihistamines or corticosteroids may be used to limit allergic reactions secondary to killing of microfilariae. Personal protective measures include avoiding areas where biting flies are present, wearing protective clothing, and using insect repellents. Diethylcarbamazine (300 mg orally once weekly) prevents infection in travelers who spend prolonged periods in endemic areas. L. loa do not harbor Wolbachia endosymbionts, and therefore doxycycline has no effect on infection.

Infection With Animal Filariae

The most commonly recognized zoonotic filarial infections are caused by members of the genus Dirofilaria. The worms are introduced into humans by the bites of mosquitoes containing third-stage larvae. The most common filarial zoonosis in the United States is Dirofilaria tenuis, a parasite of raccoons. In Europe, Africa, and Southeast Asia, infections are usually caused by the dog parasite Dirofilaria repens. The dog heartworm , Dirofilaria immitis, is the second most frequently encountered filarial zoonosis worldwide. Other genera, including Dipetalonema -like worms, Onchocerca, and Brugia, are rare causes of zoonotic filarial infections.

Animal filariae do not undergo normal development in the human host. The clinical manifestations and pathologic findings correspond to the anatomic site of infection and can be categorized into 4 major groups: subcutaneous, lung, eye, and lymphatic. Pathologic examination of affected tissue reveals a localized foreign body reaction around a dead or dying parasite. The lesion consists of granulomas with eosinophils, neutrophils, and tissue necrosis. D. tenuis does not leave the subcutaneous tissues, whereas Brugia beaveri eventually localizes to superficial lymph nodes. Infections may be present for up to several months. D. immitis larvae migrate for several months in subcutaneous tissues and most frequently result in a well-circumscribed, coinlike lesion in a single lobe of the lung. The chest radiograph typically reveals a solitary pulmonary nodule 1-3 cm in diameter. Definitive diagnosis and cure depend on surgical excision and identification of the nematode within the surrounding granulomatous response. D. tenuis and B. beaveri infections present as painful, rubbery, 1-5 cm nodules in the skin of the trunk, of the extremities, and around the orbit. Patients often report having been engaged in activities predisposing to exposure to infected mosquitoes, such as working or hunting in swampy areas. Management is by surgical excision .

Angiostrongylus Cantonensis

Angiostrongylus cantonensis, the rat lungworm, is the most common cause of eosinophilic meningitis worldwide. Rats are the definitive host. Human infection follows ingestion of third-stage larvae in raw or undercooked intermediate hosts such as snails and slugs, or transport hosts such as freshwater prawns, frogs, and fish. Most cases are sporadic, but clusters have been reported, including clusters related to consumption of lettuce contaminated with intermediate or transport hosts. Even though most infections have been described in Southeast Asia, the South Pacific, and Taiwan, shipboard travel of infected rats has spread the parasite to Madagascar, Africa, the Caribbean, and most recently Australia and North America. Larvae penetrate the vasculature of the intestinal tract and migrate to the meninges, where they usually die but induce eosinophilic aseptic meningitis. Patients present 2-35 days after ingestion of larvae with severe headache, neck pain or nuchal rigidity, hyperesthesias and paresthesias (often migrating), fatigue, fever, rash, pruritus, nausea, and vomiting. Neurologic involvement varies from asymptomatic to paresthesias, severe pain, weakness, and focal neurologic findings such as cranial nerve palsies. Symptoms can last for several weeks to months, especially headache. Coma and death from hydrocephalus occur rarely in heavy infections. Peripheral blood eosinophilia is not always present on initial examination but peaks about 5 wk after exposure, often when symptoms are improving. Cerebrospinal fluid (CSF) analysis reveals pleocytosis with >10% eosinophils in more than half of patients, with mildly elevated protein, a normal glucose level, and an elevated opening pressure. Head CT or MRI is usually unremarkable. The diagnosis is established clinically with supporting travel and diet history. A sensitive and specific enzyme-linked immunosorbent assay (ELISA) is available on a limited basis from the Centers for Disease Control and Prevention (CDC) for testing CSF or serum.

Treatment is primarily supportive because the majority of infections are mild, and most patients recover within 2 mo without neurologic sequelae. Analgesics should be given for headache. Careful, repeated lumbar punctures should be performed to relieve hydrocephalus. Anthelmintic drugs have not been shown to influence the outcome and may exacerbate neurologic symptoms. The use of corticosteroids may shorten the duration of persistent and severe headaches. There is a higher incidence of permanent neurologic sequelae and mortality among children than among adults. Infection can be avoided by not eating raw or undercooked crabs, prawns, or snails.