AUTHOR AND EDITOR INFORMATION

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INTRODUCTION

Section 2 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
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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 μg/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

Section 3 of 11  

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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.

DIFFERENTIALS

Section 4 of 11  

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• Differentials
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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

Section 5 of 11  

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Lab 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

Section 6 of 11  

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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

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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.

Drug Category: 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.

FOLLOW-UP

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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

Section 9 of 11  

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Medical/Legal 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

Section 10 of 11  

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• Differentials
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• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Life cycle of Hookworm. Courtesy of CDC Atlanta.
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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.
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Media file 3:  Hookworm rhabditiform larva (wet preparation). Courtesy of CDC Atlanta.
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Media file 4:  Hookworm filariform larva (wet preparation). Courtesy of CDC Atlanta.
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REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• 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].
4. Jelinek T, Maiwald H, Nothdurft HD, Loscher T. Cutaneous larva migrans in travelers: synopsis of histories, symptoms, and treatment of 98 patients. Clin Infect Dis. Dec 1994;19(6):1062-6. [Medline].
5. Caumes E, Datry A, Paris L. Efficacy of ivermectin in the therapy of cutaneous larva migrans. Arch Dermatol. Jul 1992;128(7):994-5. [Medline].
6. de Silva N, Guyatt H, Bundy D. Anthelmintics. A comparative review of their clinical pharmacology. Drugs. May 1997;53(5):769-88. [Medline].
7. Horton J. Albendazole: a review of anthelmintic efficacy and safety in humans. Parasitology. 2000;121 Suppl:S113-32. [Medline].
8. Kabatereine NB, Brooker S, Koukounari A, Kazibwe F, Tukahebwa EM, Fleming FM. Impact of a national helminth control programme on infection and morbidity in Ugandan schoolchildren. Bull World Health Organ. Feb 2007;85(2):91-9. [Medline].
9. Larocque R, Casapia M, Gotuzzo E, MacLean JD, Soto JC, Rahme E. A double-blind randomized controlled trial of antenatal mebendazole to reduce low birthweight in a hookworm-endemic area of Peru. Trop Med Int Health. Oct 2006;11(10):1485-95. [Medline].
10. Diemert DJ, Bethony JM, Hotez PJ. Hookworm vaccines. Clin Infect Dis. Jan 15 2008;46(2):282-8. [Medline].
11. Hughes RG, Sharp DS, Hughes MC. Environmental influences on helminthiasis and nutritional status among Pacific schoolchildren. Int J Environ Health Res. 2004;14(3):163-77.
12. Bennett A, Guyatt H. Reducing intestinal nematode infection: efficacy of albendazole and mebendazole. Parasitol Today. Feb 2000;16(2):71-4. [Medline].
13. Flohr C, Tuyen LN, Lewis S, Minh TT, Campbell J, Britton J. Low efficacy of mebendazole against hookworm in Vietnam: two randomized controlled trials. Am J Trop Med Hyg. Apr 2007;76(4):732-6. [Medline].
14. American Academy of Pediatrics. Hookworm infection. In: 2000 Red Book: Report of the Committee on Infectious Diseases. 2000:321-2.
15. Hochedez P, Caumes E. Hookworm-related cutaneous larva migrans. J Travel Med. Sep-Oct 2007;14(5):326-33. [Medline].
16. Hotez PJ. Hookworm disease in children. Pediatr Infect Dis J. Aug 1989;8(8):516-20. [Medline].
17. Hotez PJ, Brooker S, Bethony JM, et al. Hookworm infection. N Engl J Med. Aug 19 2004;351(8):799-807. [Medline].
18. Hotez PJ, Pritchard DI. Hookworm infection. Sci Am. Jun 1995;272(6):68-74. [Medline].
19. Kucik CJ, Martin GL, Sortor BV. Common intestinal parasites. Am Fam Physician. Mar 1 2004;69(5):1161-8. [Medline].
20. Long SS, Pickering LK, Prober CG. Hookworm. In: Principles and Practice of Pediatric Infectious Diseases. 1997:1462-4.
21. Mandell GL, Bennett JE, Dolin R. Principles and Practice of Infectious Diseases. 2000:2941-2.

Article Last Updated: May 1, 2008