eMedicine Specialties > Pediatrics: General Medicine > Parasitology

Ancylostoma Infection

Vinod K Dhawan, MD, FACP, FRCP(C), Professor, Department of Clinical Medicine, University of California at Los Angeles; Professor of Medicine, Charles R Drew University of Medicine and Science; Chief, Division of Infectious Diseases, MLK-Harbor Hospital
Swati Garekar, MBBS, Staff Physician, Department of Pediatrics, Children's Hospital of Michigan; Basim Asmar, MD, Director, Department of Pediatrics, Division of Infectious Diseases, Children's Hospital of Michigan; Professor, Department of Pediatrics, Wayne State University School of Medicine

Updated: May 1, 2008

Introduction

Background

Hookworm is the common name for blood-sucking nematodes of the Ancylostomatidae family. The 2 species that most commonly infect humans are Ancylostoma duodenale and Necator americanus.

Members of the Ancylostoma genus cause the following 3 clinical entities in humans:

• Classic hookworm disease is a GI infection with chronic blood loss that leads to iron deficiency anemia and protein malnutrition. The disease is caused by A duodenale, the major anthropophilic hookworm, and, less commonly, by the zoonotic species Ancylostoma ceylanicum.
• Cutaneous larva migrans is an infection caused most commonly by larvae of Ancylostoma braziliense, whose definitive hosts include dogs and cats. The manifestations of cutaneous larva migrans are limited to the skin.
• Eosinophilic enteritis is a GI infection caused by the dog hookworm Ancylostoma caninum.¹ The disease is characterized by abdominal pain but no blood loss.

N americanus causes only classic hookworm disease, as defined above.

In 1880, an epidemic called miners' anemia occurred among Italian laborers building the Saint Gotthard railway tunnel in the Swiss Alps. A duodenale was responsible for the epidemic.

Pathophysiology

Eggs deposited on warm, moist soil develop into infective larvae over 5-7 days. Infective larvae are developmentally arrested and nonfeeding. If unable to infect a new host, the larvae die when their metabolic reserves are exhausted, usually in about 6 weeks. Humans are the major reservoir, and infection is maintained by continual contamination of soil by human feces.

Classic hookworm infection

The life cycle of hookworms is depicted in Media file 1. Humans acquire infection either by exposing skin to soil contaminated with A duodenale larvae or N americanus larvae or by ingesting soil contaminated with A duodenale larvae.

Eggs are passed in the stool undefined, and the larvae hatch in 1-2 days under favorable conditions (see Media file 2). The released rhabditiform larvae grow in the feces and/or soil undefined (see Media file 3). After 5-10 days, they become filariform larvae that are infective (see Media file 4). These infective larvae can survive for 3-4 weeks in favorable environmental conditions. 

Upon contact with the human host, the larvae penetrate the skin. The larvae elaborate a protease that helps the organisms bore through the skin. The larvae are carried through the veins to the heart and then to the lungs. They penetrate the pulmonary alveoli, ascend the bronchial tree to the pharynx, and are swallowed. During the migratory phase, larvae evoke an eosinophilic inflammatory response.

After passively reaching the proximal small intestine, larvae develop into adult, sexually mature male and female worms. The adult worm attaches with its mouth to the mucosa of the small intestine and begins to feed. The hookworm digests the tissue within its buccal capsule, using its teeth or cutting plates, powerful esophageal muscles, and hydrolytic enzymes. At the same time, the worm releases a potent anticoagulant, which causes profound bleeding from eroded capillaries in the lamina propria.

Larvae require about 6-8 weeks from the time of skin penetration to develop into adults. Worms mate in the small intestine, and the females deposit fertilized eggs into the lumen. Eggs begin to appear in feces about 8-12 weeks after infection. Worms change location every 4-8 hours, producing minute, bleeding, mucosal ulcerations. Adult worms are eliminated in 1-2 years, but longevity records can reach several years.

Following penetration of the host skin, some A duodenale larvae can become dormant (in the intestine or muscle). In addition, infection by A duodenale may also occur by the oral and transmammary route. However, N americanus requires a transpulmonary migration phase.

Larva migrans

The infective larvae of zoonotic species such as A braziliense do not elaborate sufficient concentrations of hydrolytic enzymes to penetrate the junction of the dermis and epidermis. These larvae remain trapped superficial to this layer, where they migrate laterally at a rate of 1-2 cm/d and create the pathognomonic serpiginous tunnels of cutaneous larva migrans. Larvae can survive in the skin for about 10 days before dying (even in untreated persons).

Eosinophilic enteritis

Larvae of A caninum typically enter a human host by skin penetration, although infection by oral ingestion is possible. These larvae probably remain dormant in skeletal muscles and create no symptoms.

In some individuals, larvae may reach the gut and mature into adult worms. Why some individuals sustain A caninum development and then respond with a severe localized allergic reaction is unknown.

Adult worms secrete various potential allergens into the intestinal mucosa. Some patients have been reported to have increasingly severe recurrent abdominal pain, which may be analogous to a response to repeated insect stings.

Frequency

United States

Classic hookworm infection is most common among travelers, immigrants, and adoptees from developing countries. A low prevalence of the infection, mainly due to N americanus, is still found in pockets of the southeastern United States.

Cutaneous larva migrans is endemic in the southeastern states and Puerto Rico. The dog hookworm, A caninum, has reportedly caused eosinophilic enteritis in Australia and the United States; increased human infections are anticipated because of the global distribution of dogs.

International

Human infection with A duodenale and N americanus is estimated to affect approximately one fourth of the world's population. These parasites drain the equivalent of all the blood from approximately 1.5 million people every day. Infection is most prevalent in tropical and subtropical zones, roughly between the latitudes of 45°N and 30°S. Hookworm infection occurs only in isolated temperate areas.

Infection is endemic in most developing countries. However, even in endemic regions, infection is usually confined to rural areas, especially where human feces are used as fertilizer or where sanitation is inadequate. In developed countries, infection is most commonly encountered in travelers, immigrants, and adoptees from developing countries.

A duodenale is the predominant species in the Mediterranean region, in northern regions of India and China, and in North Africa. A ceylanicum is found in focally endemic areas in southern Asia. N americanus is the predominant species in southern China, Southeast Asia, the Americas, most of Africa, and parts of Australia. This differential distribution is not absolute, and mixed infections with both species are common in individual patients.

Mortality/Morbidity

• As is true with most helminthic infections in endemic areas, relatively few persons carry heavy parasite burdens, although hookworm disease may be fatal, especially in infants.
• A single adult A duodenale causes about 0.2 mL of blood loss per day, and each adult N americanus causes about 0.02 mL blood loss per day.
• The extent of infection may be categorized as light (ie, <100 worms), moderate (ie, 100-500 worms), or heavy (ie, 500-1000 worms). People who develop an initial heavy infection seem to reacquire heavy infection, and individuals who are lightly infected reacquire light infections, which suggests an underlying genetic susceptibility.
  • Individuals with light infection have minimal blood loss and may have infection but not disease, especially if iron intake or reserves are adequate to compensate for the blood loss.
  • Moderate-to-heavy infections cause iron deficiency anemia.
• Hookworm anemia may be noted.
  • Hookworms are the leading cause of iron deficiency anemia in developing countries.
  • In one study involving 492 children, in children with N americanus, the prevalence of anemia and the prevalence of ferritin levels of less than 12 μ g/L were 60.5% and 33.1%, respectively; in children with A duodenale, the respective prevalences were 80.6% and 58.9%.²
  • The timing of anemia onset depends on the patient's preexisting iron stores.
  • Because iron is also required for the biosynthesis of neurotransmitters, anemia may affect cognitive development.
  • Significant anemia can cause growth and developmental delay.
• Malabsorption may occur.
  • Heavy infections can cause significant protein loss as the host loses RBCs and plasma.
  • Adult hookworms also secrete a potent inhibitor of digestive enzymes, which may contribute to malabsorption.
  • Malabsorption leads to hypoproteinemia, which aggravates malnutrition.
  • Malabsorption is more common in children than in adults.
• Anemia and protein malnutrition occur together in as many as 25% of infected individuals.

Sex

• Both sexes are equally susceptible.

Age

• In endemic areas, the highest prevalence is among school-aged children and adolescents, which may be because of age-related changes in exposure and the acquisition of immunity.
• Once infected, children are more vulnerable to developing morbidity because dietary intake often fails to compensate for intestinal losses of iron and protein, especially in developing countries.
• A fulminant form of acute GI hemorrhage associated with acute ancylostoma infection has been described in newborns.

Clinical

History

• Acute stage of classic hookworm disease
  • Pruritus at the site of larval penetration (also called ground itch or dew itch) is proportionate to the number of infecting larvae. Infection with zoonotic hookworms, especially A braziliense, can progress with a lateral migration of larvae that results in cutaneous tracts of larva migrans.
  • Cough and wheezing can occur about one week after exposure and is due to larval migration through the lungs. Unlike that in ascariasis, pulmonary symptoms are uncommon and usually mild, except in severe infections.
  • An acute intestinal phase occurs in heavy infections and is characterized by abdominal pain, nausea, anorexia, and diarrhea that usually develops around one month after infection.
  • Wakana disease is characterized by nausea, vomiting, dyspnea, and eosinophilia and occurs after the oral ingestion of a large number of infective A duodenale larvae. This may represent a severe immediate hypersensitivitylike reaction to A duodenale antigens.
• Chronic stage of classic hookworm disease
  • Moderate-to-heavy infections cause significant blood loss, which may manifest as melena. Once iron reserves are exhausted, anemia develops and causes symptoms such as fatigue and dyspnea upon exertion.
  • Deficits in physical and intellectual growth can occur, which may be irreversible when they occur during infancy.
• Eosinophilic enteritis: This is characterized by repeated episodes of abdominal pain in approximately 97% of affected individuals. These episodes typically occur with increasing severity and are associated with peripheral eosinophilia in almost 100% of patients and with leukocytosis in approximately 75% of patients. Extreme cases may mimic appendicitis or intestinal perforation.

Physical

• Acute stage of classic hookworm disease
  • Erythema with small papules or vesicles develops at the site of larval entry, typically on the feet, and usually persists for 1-2 weeks.
  • Intense scratching may lead to a secondary bacterial infection, which is quite common.
  • Scattered wheezing may be heard during larval migration through the pulmonary system.
• Chronic stage of classic hookworm disease
  • Pallor, chlorosis (greenish yellow skin discoloration), tachycardia, and other signs of high-output cardiac failure are caused by anemia.
  • Edema is caused by hypoproteinemia.
  • Signs of malnutrition are evident.
• Cutaneous larva migrans: This manifests as pathognomonic, raised serpiginous tracts ("creeping eruptions") with surrounding erythema that may last one month if untreated. Lesions are most commonly seen on lower extremities but may be limited to the trunk or upper extremities based on the site of entry of infective larvae.

Causes

• Several Ancylostoma species cause disease in humans, such as the following:
  • A duodenale primarily infects humans and is responsible for classic hookworm disease.
  • A ceylanicum primarily infects animals but can cause milder classic hookworm disease in humans.
  • A braziliense and A caninum also primarily infect animals (eg, cats, dogs); humans are accidental hosts. Both species can cause cutaneous larva migrans, although most cases are caused by A braziliense. A caninum causes eosinophilic enteritis.
• Hookworm microbiology includes the following:
  • Each adult A duodenale is about 1 cm in length. The buccal capsule of an adult worm has teeth to facilitate attachment to mucosa. A muscular esophagus creates suction in the buccal capsule.
  • Adult worms release hyaluronidase, which degrades intestinal mucosa and erodes blood vessels, resulting in blood extravasation. Worms also ingest some blood. An anticoagulant facilitates blood flow by blocking the activity of blood coagulation factors Xa and VIIa.
  • Adult worms also elaborate factors (eg, neutrophil inhibitory factor), which protect them from host defenses.
  • Each mature A duodenale female produces about 10,000-30,000 eggs daily; a female N americanus produces 5000-10,000 eggs daily. Under appropriate conditions, eggs develop into infective larvae.
  • Infective larvae are barely visible to the naked eye (ie, about 500-700 µm in length).
  • The natural life span is about one year for an adult A duodenale and 3-5 years for an adult N americanus.
  • The larvae's ability to enter a dormant state in the human host may be an adaptive response to increase the chances of propagation. If all larvae were to mature promptly during dry seasons of the year, females would release eggs onto inhospitable soil. Eggs produced and released during the wet season have a much greater chance of encountering optimal soil conditions for further development.
• Environmental conditions include the following:
  • The optimal conditions for egg development in soil are ambient temperatures of 20-30°C and warm, moist, well-aerated soil that is shielded from sunlight. These conditions occur during cultivation of numerous agricultural products (eg, tea in India, mulberry leaves in China, coffee in Central and South America, rubber in Africa). Hence, hookworm infections occur primarily in rural areas.
  • Larvae fail to develop in temperatures below 13°C and are destroyed by temperatures below 0°C and above 45°C. Drying and direct sunlight also kill larvae.

Differential Diagnoses

Anemia, Acute
Anemia, Chronic
Pneumonia
Scabies

Other Problems to Be Considered

Once iron deficiency anemia from blood loss is diagnosed, keep in mind that rare causes of intestinal blood loss (eg, polyps, Meckel diverticulum) are far less common in developing countries.

Respiratory symptoms with peripheral eosinophilia suggest a parasitic etiology.

Differentiation between scabies and cutaneous larva migrans is not always easy, especially if the latter occurs with atypical rash. Important distinguishing criteria for scabies are history of exposure, crusty lesions on the hands or feet, and generalized pruritus.

Workup

Laboratory Studies

• Stool examination
  • Stool concentration techniques are unnecessary because most individuals with clinically significant infection excrete a large number of eggs. Eggs are easily detectable in unconcentrated stool specimen at rates of about 1200 eggs/mL or more.
  • Each ovoid, thin-shelled egg measures approximately 60 X 40 µm (see Media file 2). Various methods (eg, Kato-Katz technique) can be used for quantitative assessments.
  • Eggs of A duodenale and N americanus cannot be differentiated using light microscopy. Larvae and adult worms can be distinguished by rearing filariform larvae in a fecal smear on a moist filter paper strip for 5-7 days (ie, Harada-Mori filter paper strip culture).
  • Distinguishing between the 2 species is not critically important for choosing the type of anthelminthic drug, except that arrested larvae of A duodenale can enter breast milk and cause vertical transmission; these arrested larvae can also reactivate after initial treatment and again cause intestinal disease without reinfection.
  • No eggs are found in cases of eosinophilic enteritis because adult A caninum worms do not produce eggs in human hosts.
  • Stool examination is not indicated in cases of cutaneous larva migrans because the diagnosis can be made clinically, and the larvae in almost all cases remain confined to the skin.
  • Progress is being made in polymerase chain reaction (PCR)-based methods for the specific diagnosis of hookworm infection.³
• CBC count
  • Peripheral blood eosinophilia is often initially noticed during an asymptomatic infection with human hookworms, possibly as early as during the larval migration through the lungs.
  • Eosinophilia (and raised serum immunoglobulin E [IgE] levels) is uncommon in cases of cutaneous larva migrans but is almost universally present in cases of eosinophilic enteritis.⁴
  • Cases of classic hookworm disease exhibit characteristic blood indices of iron deficiency anemia (eg, hypochromic microcytic).

Other Tests

• Serologic tests (eg, tests for A caninum) are usually available only in research laboratories.

Procedures

• In cases of eosinophilic enteritis, colonoscopy may reveal ileal and colonic ulceration and, occasionally, adult hookworms.

Treatment

Medical Care

• Classic hookworm disease
  • Most cases of classic hookworm disease can be managed on an outpatient basis with anthelminthic and iron therapy, complemented by appropriate diet.
  • Some patients with severe anemia and congestive heart failure may require hospitalization.
  • Blood transfusion is indicated in rare cases of acute severe GI hemorrhage. In patients with chronic anemia, blood transfusions (ie, packed RBCs) should be administered slowly and are usually followed by a diuretic to prevent rapid fluid overload.
• Cutaneous larva migrans: Specific anthelminthic treatment may be unnecessary for patients with cutaneous larva migrans who have minimal symptoms.

Surgical Care

Eosinophilic enteritis may mimic acute appendicitis or intestinal perforation, and, in some cases, diagnosis has been made during laparotomy. However, treatment for eosinophilic enteritis is medical (ie, mebendazole administration) rather than surgical.

Consultations

Consultations are usually unnecessary unless the anemia is severe or blood indices are equivocal.

Diet

The diet for patents with ancylostoma infection should be rich in iron and protein.

Medication

The treatment of classic hookworm infection has 2 components: (1) correcting the anemia, which is usually achieved by means of iron therapy and proper diet, and (2) expelling the intestinal parasites. In rare cases (eg, acute severe GI hemorrhage), blood transfusion may be needed to correct anemia.

Anthelminthic drugs effective against hookworms include pyrantel pamoate, benzimidazoles (eg, albendazole, mebendazole, thiabendazole), and ivermectin.^5,6 A single 400-mg dose of albendazole is the treatment of choice.⁷  Mebendazole 100 mg twice daily for 3 days is more effective than a single 500-mg dose. Several 11 mg/kg doses of pyrantel pamoate may be require for cure.

Anthelminthics

Most helminths, including hookworms, cannot replicate within a human host. Chemotherapy reduces the number of adult worms unless reinfection occurs.

Parasite biochemical pathways are different from those in human hosts; thus, toxicity is directed to the parasite, egg, or larvae. Mechanism of action varies within the drug class. Antiparasitic actions may include the following:

1. Inhibition of microtubules causes irreversible block of glucose uptake
2. Tubulin polymerization inhibition
3. Depolarizing neuromuscular blockade
4. Cholinesterase inhibition
5. Increased cell membrane permeability, resulting in intracellular calcium loss
6. Vacuolization of the schistosome tegument
7. Increased cell membrane permeability to chloride ions via chloride channels alteration

Because of the relative toxicity of thiabendazole, systemic administration is not recommended for GI nematode infections; safer alternatives are available. In children younger than 2 years, in whom experience with antihelminthics is limited, the World Health Organization (WHO) recommends administering half the adult dose of albendazole or mebendazole for patients with heavy hookworm infections. Pyrantel dosages are determined by patient weight. For pregnant women with heavy hookworm infections, the WHO recommends deworming treatment during the second or third trimester using albendazole, mebendazole, or pyrantel.

Albendazole (Albenza)

FDA-approved but considered investigational to treat hookworms; inhibits microtubule polymerization by binding to cytoplasmic b -tubulin; by affecting intestinal cells of parasite, prevents use of nutrients by parasite, essentially starving it to death.
Dosage shown is selectively toxic to parasites because binding to parasite b -tubulin occurs at a much lower concentration than binding to mammalian protein.
Because drug acts locally on worms within GI tract, action is not dictated by systemic drug concentration.
In children, albendazole appears superior to mebendazole for curing hookworm infestations (cure rates of approximately 90% for Ancylostoma and 75% for Necator using albendazole).

Dosing

Adult

For classic hookworm disease and eosinophilic enteritis: 400 mg PO once
For cutaneous larva migrans: 400 mg PO qd for 3 d

Pediatric

<6 years: Not established
>6 years: Administer as in adults

Interactions

Coadministration with carbamazepine may decrease efficacy; dexamethasone, cimetidine, and praziquantel may increase toxicity

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Information based on use to treat patients with hydatid disease and neurocysticercosis, for which the drug is used for prolonged periods (8-30 d for neurocysticercosis and 3 mo for hydatid disease); embryotoxic and teratogenic in pregnant rats and rabbits; no adequate studies in pregnant women, but no deleterious effects were recorded among 10 cases of women who were exposed accidentally to high doses of albendazole for systemic infection during first trimester and followed to term; excreted in animal milk; whether excreted in human milk unknown
Patients with abnormal liver function test (LFT) findings should be carefully evaluated before commencing therapy because drug metabolized in liver and associated with hepatotoxicity; most common adverse effect is reversible increase in serum aminotransferases (16%); abdominal pain, diarrhea, nausea, dizziness, and headache occasionally occur (just above 1%); causes reversible reductions in total WBC count in <1% of patients

Mebendazole (Vermox)

Recommended for treatment of eosinophilic enteritis; inhibits microtubule polymerization by binding to cytoplasmic b -tubulin; by affecting parasite's intestinal cells, prevents use of nutrients and essentially starves parasite to death; dosage shown is selectively toxic to parasites because binding to parasite b -tubulin occurs at much lower concentration than binding to mammalian protein; because drug acts locally on worms within GI tract, action not dictated by systemic drug concentration.
A repeat stool examination using a concentration technique is recommended after 2 wk, and retreatment is indicated if results are positive. No fasting or purging is required. Tab may be chewed, swallowed, or crushed and mixed with food.

Dosing

Adult

100 mg PO bid for 3 d or 500 mg PO once (some studies show better cure rates using multidose regimen)

Pediatric

<2 years: Not established
>2 years: Administer as in adults

Interactions

Carbamazepine and phenytoin may decrease effects; cimetidine may increase levels

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Found to be embryotoxic and teratogenic in pregnant rats at single PO doses as low as 10 mg/kg (approximately equal to the human dose, based on mg/m²); on the basis of these findings, not recommended in pregnant women, especially in first trimester; no adequate studies of administration in pregnant women, although postmarketing studies in 170 pregnant women who had inadvertently taken the drug did not reveal higher than usual incidence of spontaneous abortions or malformations; not known whether mebendazole is excreted in human milk; therapy may not eradicate dormant larvae residing in extraintestinal tissues because drug is poorly absorbed into systemic circulation
Abdominal pain and diarrhea may occur in massive infections and expulsion of GI worms; rare reports of neutropenia and agranulocytosis when used for prolonged periods and at higher than recommended doses; elevated liver enzymes and, rarely, hepatitis occur when mebendazole used for prolonged periods and administered in dosages substantially above those recommended

Pyrantel pamoate (Antiminth)

FDA-approved but considered investigational for this condition; depolarizing neuromuscular blocking agent that inhibits cholinesterases, resulting in spastic paralysis of the worm.

Dosing

Adult

11 mg/kg (5 mg/lb) PO for 3 d, not to exceed 1 g, without regard to ingestion of food or time of day

Pediatric

<2 years: Not established
>2 years: Administer as in adults

Interactions

In ascariasis, pyrantel and piperazine are mutually antagonistic and should not be used concomitantly; theophylline serum levels may increase in pediatric patients, following pyrantel pamoate administration

Contraindications

Documented hypersensitivity; hepatic disease

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in liver impairment, anemia, and malnutrition; transient GI symptoms, headache, and dizziness occasionally observed

Thiabendazole (Mintezol)

FDA-approved but considered investigational for this condition; indicated only for cutaneous larva migrans; inhibits microtubule polymerization by binding to cytoplasmic β -tubulin; by affecting intestinal cells of parasite, prevents use of nutrients, essentially starving parasite to death.
Dosage shown is selectively toxic to parasites because binding to parasite β -tubulin occurs at a much lower concentration than binding to mammalian protein.
Administer PO dose pc; tabs should be chewed before swallowing.

Dosing

Adult

Topical administration (for cutaneous larva migrans): Apply 10-15% susp to lesions 4-6 times daily for 2-5 d
PO: 25 mg/kg/dose bid for 2-5 d; not to exceed 1.5 g/dose

Pediatric

<30 lb: Not established
>30 lb: Administer as in adults

Interactions

May elevate serum levels of theophylline, increasing toxicity (monitor serum levels and reduce dose prn)

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Closely monitor in hepatic or renal dysfunction; before initiating therapy, supportive therapy necessary for anemic, dehydrated, or malnourished patients; use in confirmed worm infestation, not prophylactically; may cause nausea, vomiting, and mild CNS depression; associated with erythema multiforme, including Stevens-Johnson syndrome; animal studies reveal no teratogenic effects; no adequate studies in pregnant women; whether excreted in human milk unknown; potentially serious adverse reactions in infants requires decision whether to discontinue breastfeeding or thiabendazole

Ivermectin (Stromectol, Mectizan)

FDA-approved but considered investigational for this condition; recommended for treatment of cutaneous larva migrans; binds selectively with glutamate-gated chloride ion channels in invertebrate nerve and muscle cells, causing cell death.

Dosing

Adult

200 mcg/kg/d PO for 1-2 d

Pediatric

<5 years: Not established
>5 years: Administer as in adults

Interactions

May interact with other ligand-gated chloride channels (eg, those gated by GABA)

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Treat mothers who intend to breastfeed only when risk of delayed treatment outweighs possible risks to newborn caused by ivermectin excretion in milk; repeat courses of therapy may be required in patients who are immunocompromised; may cause drowsiness, nausea, vomiting, and mild CNS depression

Follow-up

Further Outpatient Care

• The recommended procedure is to repeat the stool examination using a concentration technique after 2-3 weeks; positive results indicate the need for retreatment.
• Complete the entire course of iron therapy to replenish iron stores, even after hemoglobin values return to normal.
• Be aware that reinfection is common in endemic areas.
• Dormant extraintestinal larvae of A duodenale may be resistant to currently available anthelminthic agents (which may have poor systemic absorption) and may be responsible for relapse.

Deterrence/Prevention

• Patients with classic hookworm infection are not directly contagious because the eggs excreted in their feces require a brief period in the soil to develop into infective larvae.
• Sanitary excreta disposal is the most effective deterrent but is not feasible in many developing countries.
• Wearing footwear cannot entirely prevent infection because larvae can penetrate any skin surface that comes in contact with contaminated soil. In addition, A duodenale larvae can be ingested.
• Mass or targeted chemotherapy programs may not control hookworm infection because reinfection is common in endemic areas, and dormant extraintestinal larvae of A duodenale may be resistant to currently available anthelminthic agents.
• A recent study assessed the health impact of a national control program that targeted schistosomiasis and intestinal nematodes in Uganda, which has provided population-based anthelmintic chemotherapy since 2003.⁸ Antihelmintic treatment delivered as part of a national helminth control program decreased infection and morbidity among schoolchildren and improved hemoglobin concentration. Deworming with use of anthelmintics (over and above iron supplementation) within antenatal care programs in hookworm-endemic areas may help prevent very low birthweight babies; this benefit may be higher in countries that do not have an antenatal iron supplementation program or in countries where the intensity of hookworm infections is higher.⁹
• Immunization with recombinant hookworm Ancylostoma -secreted proteins (ASPs) has been demonstrated to prevent migration of infective larvae through tissues in a murine model of ancylostomiasis. Efforts are underway for eventual development of a vaccine that combines at least 2 hookworm antigens: one that targets the larval stage of the life cycle, and another that targets the adult worm living in the GI tract.¹⁰

Complications

• Heavy parasitism in childhood occasionally leads to acute fulminating anemia with congestive heart failure. This occurs most often in epidemics associated with breakdowns in sanitation as a result of war or famine.
• In one study, children with helminthiasis (including hookworms and other helminths) and anemia were 8.7 times more likely to have stunted growth and 4.3 times more likely to be underweight than children without anemia and infection.¹¹

Prognosis

• Classic hookworm disease
  • With appropriate anthelminthic treatment and with iron and diet therapy, recovery from anemia and malnutrition is complete; however, some deficits in intellectual function may persist.
  • Reinfection is very likely in endemic areas and causes the cycle to repeat.
• Cutaneous larva migrans: Even in untreated persons, larvae die, and symptoms resolve within a few weeks to several months.
• Eosinophilic enteritis: This promptly responds to mebendazole therapy.

Patient Education

• Attempt to prevent reinfection by instructing patients to not walk barefoot in endemic areas and to wash hands thoroughly before meals.

Miscellaneous

Medicolegal Pitfalls

• Reactivated dormant larvae of A duodenale can migrate from tissue to repopulate the intestine or enter breast milk and infect infants.
• Because of high reinfection rates in endemic areas, drug therapy alone does not effectively decrease incidence of infection.

Special Concerns

• Children younger than 2 years
  • The infantile form of hookworm infection has significant mortality rates. A fulminant form of acute hookworm infection causing acute GI tract hemorrhage has been described in infants. These infants (often >2 mo) present with melena, abdominal distention, and hypotension, and they may have hematocrit values as low as 0.2-0.3%.
  • No practical method has been found to interrupt vertical transmission of infection.
  • Experience with anthelminthic drugs is limited for children in this age group. The WHO recommends administering half the adult dosage of albendazole or mebendazole in patients with heavy hookworm infections. Determine the dosage of pyrantel on the basis of the child's weight.
• Pregnancy and lactation: The WHO recommends deworming treatment (eg, albendazole, mebendazole, pyrantel) during the second or third trimester for pregnant women with heavy hookworm infections.
• Resistance: Recent reports have documented the emergence of resistance to mebendazole and pyrantel pamoate among human hookworm isolates.^12,13

Multimedia

Media file 1: Life cycle of Hookworm. Courtesy of CDC Atlanta.

Media file 2: Hookworm eggs examined on wet mount. The eggs of Ancylostoma duodenale and Necator americanus cannot be distinguished morphologically. Courtesy of CDC Atlanta.

Media file 3: Hookworm rhabditiform larva (wet preparation). Courtesy of CDC Atlanta.

Media file 4: Hookworm filariform larva (wet preparation). Courtesy of CDC Atlanta.

References

1. Prociv P, Croese J. Human eosinophilic enteritis caused by dog hookworm Ancylostoma caninum. Lancet. Jun 2 1990;335(8701):1299-302. [Medline].

2. Albonico M, Stoltzfus RJ, Savioli L, et al. Epidemiological evidence for a differential effect of hookworm species, Ancylostoma duodenale or Necator americanus, on iron status of children. Int J Epidemiol. Jun 1998;27(3):530-7. [Medline].

3. Gasser RB, Cantacessi C, Loukas A. DNA technological progress toward advanced diagnostic tools to support human hookworm control. Biotechnol Adv. Jan-Feb 2008;26(1):35-45. [Medline].

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Keywords

hookworm infection, hookworm, hookworm disease, Ancylostomatidae, Ancylostoma duodenale, Necator americanus, Ancylostoma caninum, Ancylostoma ceylanicum, Ancylostoma braziliense, cutaneous larva migrans, eosinophilic enteritis, iron deficiency anemia, protein malnutrition, iron deficiency anemia, protein malnutrition, helminthic infections, hookworm anemia, malabsorption, hypoproteinemia, malnutrition, GI hemorrhage, ancylostoma infection, ground itch, dew itch, Wakana disease, melena, leukocytosis, erythema

Contributor Information and Disclosures

Author

Vinod K Dhawan, MD, FACP, FRCP(C), Professor, Department of Clinical Medicine, University of California at Los Angeles; Professor of Medicine, Charles R Drew University of Medicine and Science; Chief, Division of Infectious Diseases, MLK-Harbor Hospital
Vinod K Dhawan, MD, FACP, FRCP(C) is a member of the following medical societies: American College of Physicians, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, and Royal College of Physicians and Surgeons of Canada
Disclosure: Pfizer Inc None None

Coauthor(s)

Swati Garekar, MBBS, Staff Physician, Department of Pediatrics, Children's Hospital of Michigan
Swati Garekar, MBBS is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Basim Asmar, MD, Director, Department of Pediatrics, Division of Infectious Diseases, Children's Hospital of Michigan; Professor, Department of Pediatrics, Wayne State University School of Medicine
Basim Asmar, MD is a member of the following medical societies: American Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society
Disclosure: Nothing to disclose.

Medical Editor

Michael D Nissen, MBBS, BMedSc, FRACP, FRCPA, Associate Professor in Biomolecular, Biomedical Science & Health, Griffith University; Director of Infectious Diseases and Unit Head of Queensland Paediatric Infectious Laboratory, Sir Albert Sakzewski Viral Research Centre, Royal Children's Hospital
Michael D Nissen, MBBS, BMedSc, FRACP, FRCPA is a member of the following medical societies: American Academy of Pediatrics, American Society for Microbiology, Pediatric Infectious Diseases Society, Royal Australasian College of Physicians, and Royal College of Pathologists of Australasia
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Martin Weisse, MD, Program Director, Associate Professor, Department of Pediatrics, West Virginia University
Martin Weisse, MD is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Pediatric Infectious Diseases Society
Disclosure: Nothing to disclose.

CME Editor

Robert W Tolan Jr, MD, Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine
Robert W Tolan Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa, and Physicians for Social Responsibility
Disclosure: GlaxoSmithKline Honoraria Speaking and teaching; MedImmune Honoraria Consulting; MedImmune Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching; Novartis Honoraria Speaking and teaching; sanofi pasteur Grant/research funds Unrestricted research grant; sanofi pasteur  Consulting; sanofi pasteur Honoraria Speaking and teaching; Tap Honoraria Speaking and teaching

Chief Editor

Russell W Steele, MD, Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine
Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association
Disclosure: None None None

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