Onchocerciasis (Onchocerca Volvulus)

Infection with Onchocerca volvulus leads to onchocerciasis or river blindness. Onchocerciasis occurs primarily in West Africa but also Central and East Africa and is the world’s 2nd leading infectious cause of blindness. There are scattered foci in Central and South America. O. volvulus larvae are transmitted to humans by way of 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 subjects, clinical manifestations are due to localized host inflammatory reactions to dead or dying microfilariae. These reactions 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 PO) is the drug of choice and clears microfilariae from the skin for several months but has no effect on the adult worm. Treatment with ivermectin should be repeated at 3-6 mo intervals if there are continuing symptoms or evidence of eye infection. Adverse effects of ivermectin therapy include fever, urticaria, and pruritus and 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 loiasis may develop encephalopathy with ivermectin therapy. Doxycycline, which kills endosymbiont bacteria (Wolbachia) of O. volvulus, may contribute to amicrofilaremia. Personal protection includes avoiding areas where biting flies are numerous, wearing protective clothing, and using insect repellent. Vector control and mass ivermectin distribution programs have been implemented in Africa in a successful effort to reduce the prevalence of onchocerciasis.

Loiasis (LOA LOA)

Loiasis is caused by infection with the tissue nematode Loa loa. The parasite is transmitted to humans via 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, 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. 289-1), or eye pain. They resolve over several days to weeks and may recur at the same or different sites. Although lifelong residents of endemic regions may have microfilaremia and eosinophilia, these individuals 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 microfilarial levels, the dose of diethylcarbamazine should be increased gradually (children, 1 mg/kg PO on day 1, 1 mg/kg tid PO on day 2, 1-2 mg/kg tid PO on day 3, 6 mg/kg/day divided tid PO on days 4-21; adults, 50 mg PO on day 1, 50 mg tid PO on day 2, 100 mg tid PO on day 3, 6 mg/kg/day divided tid PO on days 4-21). Full doses can be instituted on day 1 in persons without microfilaremia. Individuals concurrently infected with O. volvulus are at increased risk for developing encephalopathy with ivermectin treatment. A single dose of ivermectin (150 µg/kg) decreases microfilarial densities in the blood in persons with high-density microfilaremia. A 3 wk course of albendazole can also be used to slowly reduce 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 PO once weekly) prevents infection in travelers who spend prolonged periods of time in endemic areas. L. loa do not harbor Wolbachia endosymbionts, and therefore doxycycline has no effect on infection.

Figure 289-1 Calabar swelling of the right hand.

(From Guerrant RL, Walker DH, Weller PF, et al: Tropical infectious diseases, Philadelphia, 1999, Churchill Livingstone, p 863.)

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 3rd stage larvae. The most common filarial zoonosis in the USA is Dirofilaria tenuis, a parasite of raccoons. In Europe, Africa, and Southeast Asia, infections are most commonly caused by the dog parasite Dirofilaria repens. The dog heartworm, Dirofilaria immitis, is the 2nd most commonly 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 x-ray 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 1-5 cm rubbery nodules in the skin of the trunk, 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. Diagnosis and 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 3rd 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 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 due to 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 and normal glucose levels, 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 for testing either 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.

Angiostrongylus Costaricensis

Angiostrongylus costaricensis is a nematode that infects several species of rodents and causes abdominal angiostrongyliasis, which has been described predominantly in Latin America and the Caribbean. The mode of transmission to humans, who are accidental hosts, is unknown. It is speculated that infectious larvae from a molluscan intermediate host, such as the slug Vaginulus plebeius, contaminate water or vegetation that are inadvertently consumed (chopped up in salads or on vegetation contaminated with their mucus secretions). Although this slug is not indigenous to the continental USA, it has been found on imported flowers and produce. The incubation period for abdominal angiostrongyliasis is unknown, but limited data suggest it ranges from 2 wk to several months after ingestion of larvae. Third stage larvae migrate from the gastrointestinal tract to the mesenteric arteries, where they mature into adults. These eggs degenerate and elicit an eosinophilic granulomatous reaction. The clinical findings of abdominal angiostrongyliasis mimic appendicitis, although the former are typically more indolent. Children can have fever, right lower quadrant pain, a tumor-like mass, abdominal rigidity, and painful rectal examination. Most patients have leukocytosis with eosinophilia. Radiologic examination may show bowel wall edema, spasticity, or filling defects in the ileocecal region and the ascending colon. Examination of stool for ova and parasites is not useful for A. costaricensis but is useful for evaluating the presence of other intestinal parasites. An ELISA is available for diagnosis on a limited basis from the Centers for Disease Control and Prevention, but the specificity of the test is low, and it is known to cross react with Toxocara, Strongyloides, and Paragonimus. Many patients undergo laparotomy for suspected appendicitis and are found to have a mass in the terminal ileum to the ascending colon. No specific treatment is known for abdominal angiostrongyliasis. Even though the use of anthelmintic therapy has not been studied systematically, thiabendazole or diethylcarbamazine has been suggested. The prognosis is generally good. Most cases are self-limited, although surgery may be required in some patients. Cornerstones of prevention include avoidance of slugs and not ingesting raw food and water that may be contaminated with imperceptible slugs or slime from slugs. Rat control is also important in preventing the spread of infection.

Dracunculiasis (Dracunculus Medinensis)

Dracunculiasis is caused by the guinea worm, Dracunculus medinensis. The World Health Organization has targeted dracunculiasis for eradication. As of 2008, the transmission of the infection was confined to 5 countries (Sudan, Ghana, Mali, Niger, and Nigeria), with Sudan reporting 61% and Ghana reporting 35% of global cases. Humans become infected by drinking contaminated stagnant water that contains immature forms of the parasite in the gut of tiny crustaceans (copepods or water fleas). Larvae are released in the stomach, penetrate the mucosa, mature, and mate. About 1 yr later, the adult female worm (1-2 mm in diameter and up to 1 m long) migrates and partially emerges through the human host skin, usually of the legs. Thousands of immature larvae are released when the affected body part is immersed in the water. The cycle is completed when larval forms are ingested by the crustaceans. Infected humans have no symptoms until the worm reaches the subcutaneous tissue, causing a stinging papule that may be accompanied by urticaria, nausea, vomiting, diarrhea, and dyspnea. The lesion vesiculates, ruptures, and forms a painful ulcer in which a portion of the worm is visible. Diagnosis is established clinically. Larvae can be identified by microscopic examination of the discharge fluid. Metronidazole (25 mg/kg/day tid PO for 10 days, maximum dose 750 mg) decreases local inflammation. Although the drug does not kill the worm, it facilitates its removal. The worm must be physically removed by rolling the slowly emerging 1 m long parasite onto a thin stick over a week. Topical corticosteroids shorten the time to complete healing while topical antibiotics decrease the risk of secondary bacterial infection. Dracunculiasis can be prevented by boiling or chlorinating drinking water or passing the water through a cloth sieve before consumption. Eradication is dependent on behavior modification and education.

Gnathostoma Spinigerum

Gnathostoma spinigerum is a dog and cat nematode endemic to Southeast Asia, Japan, China, Bangladesh, and India, but has been identified in Mexico and parts of South America. Infection is acquired by ingesting intermediate hosts containing larvae of the parasite such as raw or undercooked freshwater fish, chickens, pigs, snails, or frogs. Penetration of the skin by larval forms and prenatal transmission has also been described. Nonspecific signs and symptoms such as generalized malaise, fever, urticaria, anorexia, nausea, vomiting, diarrhea, and epigastric pain develop 24-48 hr after ingestion of G. spinigerum. Ingested larvae penetrate the gastric wall and migrate through soft tissue for up to 10 yr. Moderate to severe eosinophilia can develop. Cutaneous gnathostomiasis manifests as intermittent episodes of localized, migratory nonpitting edema associated with pain, pruritus, or erythema. Central nervous system involvement in gnathostomiasis is suggested by focal neurologic findings, initially neuralgia followed within a few days by paralysis or changes in mental status. Multiple cranial nerves may be involved, and the cerebrospinal fluid may be xanthochromic but typically shows an eosinophilic pleocytosis. Diagnosis of gnathostomiasis is based on clinical presentation and epidemiologic background. Brain and spinal cord lesions may be seen on CT or MRI. Serologic testing varies in sensitivity and specificity and is available through the Centers for Disease Control and Prevention. There is no well-documented effective chemotherapy, although albendazole (400 mg PO bid for 21 days) has been suggested to be useful. Multiple courses may be needed. Corticosteroids have been used to relieve focal neurologic deficits. Surgical resection of the Gnathostoma is the major mode of therapy and the treatment of choice. Blind surgical resection of subcutaneous areas of diffuse swelling is not recommended because the worm can rarely be located. Prevention through the avoidance of ingestion of poorly cooked or raw fish, poultry, or pork should be emphasized for individuals living in or visiting endemic areas.