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Disease

The manifestations of zoonotic hookworm infection are the result of inflammatory reaction to the migrating larvae in the skin or, less commonly, migration in deeper tissues such as lungs, intestinal tract, or possibly the eye. In definitive host infections, larvae can enter the tissues but in humans the larvae of most species of animal hookworm cannot penetrate beyond the dermis. The larvae of A. braziliense will migrate in the epidermis and cause CLM for several weeks before dying, after which lesions in the skin resolve spontaneously. A. caninum and A. ceylanicum larvae can penetrate more deeply and have been associated with other clinical syndromes including eosinophilic enteritis. Eosinophilic pneumonitis has been reported to occur in patients with CLM, possibly due to deeper larval penetration involving the lungs. Allergic reactions may occur in multiply-exposed individuals with extreme inflammatory response around the exposed area of the skin.

Cutaneous larva migrans (CLM) in a patient’s foot over the course of one week. Photos courtesy of Florida Department of Health, Duval County Epidemiology

The incubation period for CLM is typically short, with signs and symptoms developing several days after larval penetration of the skin. However, in some cases onset of disease may be delayed for weeks to months. The median time to symptom development in reported outbreaks of CLM ranged from 10 to 15 days. The most common symptom is intense pruritis, which usually develops first, followed by the appearance of an irregular raised track with erythema, presumably marking the progress of the larva from the site of penetration. The track may move in the skin over time, but it is important to note that the location of the track does not necessarily relate to the location of the larva which is randomly moving ahead of the track formation. Typically, the track moves several millimeters per day and is about 3 mm wide. Single tracks or multiple tracks may be present, depending on the severity of infection. CLM is usually found in parts of the body that have had unprotected contact with contaminated soil or sand, often bare feet or skin not covered by clothing. Complications may develop such as vesiculobullous lesions and edema or, rarely, folliculitis. Eosinophilia may or may be present and is more likely when deeper tissue penetration occurs. Less common disease manifestations include eosinophilic enteritis, ocular larva migrans and diffuse unilateral subacute retinitis (DUSN). Rarely, eosinophilic enteritis has been associated with Ancylostoma caninum infections, probably due to deeper migration of larvae or possibly inadvertent consumption of infective larvae. Cases of ocular larva migrans have been attributed to zoonotic hookworm larvae migration to the eye, based on the smaller size of these larvae relative to Toxocara or Baylisascaris larvae. Zoonotic hookworm larvae migration has been suggested as a cause of DUSN, largely based on epidemiological features.

Diagnosis

CLM is a clinical diagnosis based on the presence of the characteristic signs and symptoms and exposure history. For example, the diagnosis can be made based on presence of raised erythematous tracks with pruritis on the feet or lower extremities of a patient with recent travel history to tropical areas. There is no serological testing for zoonotic hookworm infection and skin biopsy is not sufficiently sensitive to diagnose CLM since the location of the migrating larva cannot be predicted by the track. Differential diagnoses include hookworm, gnathostomiasis, and strongyloidiasis. Other conditions such as cutaneous pili migrans, myiasis, and scabies should also be considered.

Treatment

Since the zoonotic hookworm larvae usually will die after 5 – 6 weeks in the human host, the course of CLM is considered self-limiting. Some reports have described delayed onset and persistent clinical diseases. Treatment may be indicated to help control symptoms and to resolve secondary bacterial infections. Various treatment modalities have been proposed, including cryotherapy and topical anthelminthic therapy. However, these treatments require localization of the larvae for effect, which is usually not possible. Repeated application of topical anthelminthics over large areas of skin has been shown to be effective in some cases but this may be impractical. Treatment with albendazole or ivermectin are curative. In severe or relapsing cases, especially with folliculitis, additional doses may be necessary. Children younger than 2 years of age or under 15 kg body weight may be treated with topical preparations.

Oral albendazole is available for human use in the United States. Oral ivermectin is available for human use in the United States.

Drug	Adult Dose	Pediatric Dose
Albendazole	400 mg per day by mouth for 3 to 7 days	Children aged > 2 years: 400 mg per day by mouth for 3 days This drug is contraindicated in children younger than 2 years age.
Ivermectin	200 mcg/kg by mouth as a single dose	Children over 15 kg weight: 200 mcg/kg by mouth as a single dose

Albendazole

Albendazole is pregnancy category C. Data on the use of albendazole in pregnant women are limited, though the available evidence suggests no difference in congenital abnormalities in the children of women who were accidentally treated with albendazole during mass prevention campaigns compared with those who were not. In mass prevention campaigns for which the World Health Organization (WHO) has determined that the benefit of treatment outweighs the risk, WHO allows use of albendazole in the 2nd and 3rd trimesters of pregnancy. However, the risk of treatment in pregnant women who are known to have an infection needs to be balanced with the risk of disease progression in the absence of treatment.

Pregnancy Category C: Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal, or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.

It is not known whether albendazole is excreted in human milk. Albendazole should be used with caution in breastfeeding women.

The safety of albendazole in children less than 6 years old is not certain. Studies of the use of albendazole in children as young as one year old suggest that its use is safe. According to WHO guidelines for mass prevention campaigns, albendazole can be used in children as young as 1 year old. Many children less than 6 years old have been treated in these campaigns with albendazole, albeit at a reduced dose.

Ivermectin

Ivermectin is pregnancy category C. Data on the use of ivermectin in pregnant women are limited, though the available evidence suggests no difference in congenital abnormalities in the children of women who were accidentally treated during mass prevention campaigns with ivermectin compared with those who were not. The World Health Organization (WHO) excludes pregnant women from mass prevention campaigns that use ivermectin. However, the risk of treatment in pregnant women who are known to have an infection needs to be balanced with the risk of disease progression in the absence of treatment.

Ivermectin is excreted in low concentrations in human milk. Ivermectin should be used in breast-feeding women only when the risk to the infant is outweighed by the risk of disease progress in the mother in the absence of treatment.

The safety of ivermectin in children who weigh less than 15kg has not been demonstrated. According to the WHO guidelines for mass prevention campaigns, children who are at least 90 cm tall can be treated safely with ivermectin. The WHO growth standard curves show that this height is reached by 50% of boys by the time they are 28 months old and by 50% of girls by the time they are 30 months old, many children less than 3 years old been safely treated with ivermectin in mass prevention campaigns, albeit at a reduced dose.

Page last reviewed: May 26, 2020

Content source: Global Health, Division of Parasitic Diseases and Malaria