AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

The phylum Nematoda, or roundworms, is the second largest phylum in the animal kingdom, encompassing up to 500,000 species. Members of this phylum are elongated, with bilaterally symmetric bodies containing an intestinal tract and a large body cavity.

Many roundworm species are free living, but a few are parasites of humans. Infection with intestinal roundworms constitutes the largest group of helminthic infections in humans. For example, an estimated 1 billion cases of ascariasis and 800 million cases of trichuriasis exist worldwide.

Pathophysiology

The life cycle of parasitic nematodes is clinically important. Some of these infections can be transmitted directly from infected to uninfected people; in others, eggs must undergo a process of maturation outside the human host. In a third category, the parasites may spend a part of their life cycle in the soil before becoming infective to humans.

As with other parasitic infections, definitive diagnosis depends on demonstration of the stage of the life cycle in the host. Nematodes, as with most other worms infectious to humans, almost never complete their entire life cycle in the human host.

The life cycles of nematodes are complex and highly varied. Some species, including Enterobius vermicularis, can be transmitted directly from person to person, while others, such as Ascaris lumbricoides, Necator americanus, and Ancylostoma duodenale, require a soil phase for development. Because most helminthic parasites do not self-replicate, the acquisition of a heavy burden of adult worms requires repeated exposure to the parasite in its infectious stage, whether larva or egg. Hence, clinical disease, as opposed to asymptomatic infection, generally develops only with prolonged residence in an endemic region.

Unlike the situation pertaining to protozoan infections, casual or a low degree of exposure to infective stages of parasitic nematodes usually does not result in patent infection or pathologic findings. Repeated or intense exposure to a multitude of infective stage larvae is required for infection to be established and disease to arise.

Eosinophilia and elevated serum immunoglobulin E (IgE) levels are features of many nematode infections; when unexplained, these symptoms should always prompt a search for occult roundworm infection. Humans do not appear to develop significant protective immunity to intestinal nematodes, although the mechanisms of parasite immune evasion and host immune responses to these infections have not been elucidated in detail.

Frequency

United States

• Trichuriasis: Recent estimates indicate that 2.2 million people are infected with T trichiura, mainly in the rural Southeast.
• Enterobiasis: This is the most common of all helminthic infections, with an estimated 42 million cases.
• Ascariasis: An estimated 4 million people, mainly in the Southeast, are infected with Ascaris species.
• Hookworm: This infection still has a low degree of prevalence in the Southeast.
• Strongyloidiasis: A prevalence rate of 0.4-4% has been estimated in southern states.
• Trichinosis: The prevalence rate is 4-20%.

International

• Trichuriasis: Infection with the nematode T trichiura is one of the most prevalent; approximately 800 million cases occur worldwide, most abundantly in warm, moist regions. Infection rates of up to 75% were found in young schoolchildren in Puerto Rico.
• Enterobiasis: Pinworm is also highly prevalent throughout the world, particularly in countries of the temperate zone. Children are infected most frequently.
• Ascariasis: Ascaris, or roundworm, infection is the common helminthic infection of humans, with an estimated worldwide prevalence of 1 billion. The causative organism, A lumbricoides, is cosmopolitan in distribution, being most abundant in tropical countries.
• Hookworm: Human infection with the 2 species of hookworm, A duodenale and N americanus, is estimated to affect approximately one fourth of the world's population.
• Strongyloidiasis: The infection is more common in tropical countries with poor sanitation, especially in countries of Southeast Asia and parts of Africa. Strongyloides stercoralis is also endemic in Jamaica and presumably elsewhere in the Caribbean.
• Trichinosis: Trichinella species are distributed throughout the world and are spread widely in nature among a large number of carnivorous animals, with humans acting as an incidental host.
• Dracunculiasis: Estimates of the number of people infected with Dracunculus medinensis in Africa, the Middle East, India, and other tropical areas range from 50-150 million. An aggressive eradication campaign has been underway to eliminate this parasite, which is called the Guinea worm.
• Filariasis: An estimated 120 million people are infected with Wuchereria bancrofti, Brugia malayi, and Brugia timori.
• Loiasis: Loa loa is irregularly distributed in West and Central Africa.
• Onchocerciasis: Onchocerca volvulus infects 20 million people in West, Central, and East Africa and another 1 million people in scattered foci in Central America and South America. The disease caused by this filarial worm is called river blindness.

Mortality/Morbidity

Nematode infections are usually asymptomatic or subclinical.

• Strongyloidosis may be fatal in immunocompromised patients and in newborns.
• Nematodes can cause some GI problems (eg, abdominal pain, diarrhea, anorexia, weight loss, malaise).
• Some of the more serious infections result in symptoms from inflammatory responses on vital organs and nutritional deficiencies.

Race

• No racial factors regarding nematode infections are known.

Sex

• No sex predilection is recognized.

Age

• E vermicularis infection is more common in children than adults.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

Several clinical signs and symptoms can occur in patients with nematode infections.

• Lung invasion - Löeffler or Löefflerlike syndrome (ascariasis, hookworm infections, strongyloidiasis)
• • Fever
  • Cough
  • Blood-tinged sputum
  • Wheezing
  • Rales
  • Dyspnea
  • Substernal pain
  • Pulmonary consolidations
  • Eosinophilia
  • Urticaria
  • Asthma
  • Angioneurotic edema
• Intestinal invasion
• • May be asymptomatic (small number)
  • Abdominal pain (usually vague)
  • Abdominal cramps/colic
  • Diarrhea
  • Vomiting (rarely)
  • Constipation (occasionally)
• Muscle and other tissue invasion - Trichinosis
• • Myalgias
  • Fever
  • Edema and spasm
  • Periorbital and facial edema
  • Photophobia
  • Sweating
  • Conjunctivitis
  • Weakness or prostration
  • Pain upon swallowing
  • Subconjunctival, retinal, and ungual hemorrhages
  • Rashes and formication
  • Encephalitis, myocarditis, nephritis
  • Pneumonia, meningitis, neuropathy
• Lymphatic filariasis - W bancrofti, B malayi, B timori
• • Inflammatory signs (pain, tenderness, swelling, erythema)
  • Lymphadenitis/lymphangitis
  • Orchitis
  • Fever
  • Abscesses
  • Obstructive signs (lymphatic varices, hydrocele)
  • Lymphedema and elephantiasis
  • Chyluria
  • Hypereosinophilia
• Loiasis - Loa loa
• • Calabar swellings (recurrent subcutaneous inflammation/swelling)
  • Eye worm (adults or larvae migrating under conjunctiva)
  • Eosinophilia (may exceed 70%)
  • Fever, irritability, urticaria, and pruritus
• Onchocerciasis - O volvulus
• • Dermatitis
  • Nodules
  • Lymphadenitis
  • Ocular changes
  • • Intraocular microfilariae
    • Punctate keratitis
    • Sclerosing keratitis
    • Anterior uveitis chorioretinitis
    • Optic neuritis
    • Optic atrophy
    • Glaucoma
    • Blindness (river blindness)
• Dracunculiasis - D medinensis, Guinea worm disease
• • Allergic manifestations
  • • Erythema
    • Urticaria
    • Pruritus
    • Nausea
    • Vomiting
    • Giddiness
    • Syncope
    • Fever (occasionally)
  • Local lesions
  • • Papule
    • Sterile blister
    • Ulceration
    • Abscesses
  • Worm protrusion from skin
• Toxocariasis - Toxocara canis/Toxocara cati, visceral or ocular larva migrans
• • Eosinophilia
  • Visceral larva migrans
  • Ocular larva migrans
• Cutaneous larva migrans - Ancylostoma braziliense, creeping eruption
• • Itching and red papules
  • Serpiginous track
  • Edema and acute inflammation
  • Scars
  • Secondary infection

Physical

• T trichiura infections: In heavily infected people, infection appears to manifest as mild anemia, bloody diarrhea (classic trichuris dysentery syndrome), growth retardation (chronic trichuris colitis with growth retardation), or rectal prolapse.
• E vermicularis (pinworm): The most common symptom in a pinworm infection is nocturnal perianal pruritus. Occasionally, the migration of the parasite may produce ectopic disease (eg, appendicitis, chronic salpingitis, ulcerative lesions in the small or large bowel). Enuresis has been blamed on the pinworm.
• A lumbricoides
• • A more serious complication of Ascaris infection is encountered when a mass of worms obstructs the lumen of the small bowel. This acute abdominal condition is commonly observed in children with heavy infections. The presentation is similar to that of acute intestinal obstruction, with vomiting, abdominal distention, and cramps.
  • Another obstructive syndrome is encountered when Ascaris worms invade the biliary duct and cause pancreatic-biliary ascariasis. The most common presenting feature is abdominal pain, observed in 98% of patients. Less common features include ascending cholangitis, acute pancreatitis, and, rarely, obstructive jaundice.
  • Ascariasis in pregnant women results in intrauterine growth retardation.
• Hookworms
• • The major manifestations of hookworm disease are iron deficiency anemia and chronic protein energy malnutrition. The development of these clinical features depends not only on the worm burden but also on the amount of absorbable dietary iron.
  • During the phase of worm attachment to small intestine mucosa, abdominal pain, diarrhea, and weight loss may be noted. In addition, malabsorption has been reported in children and, less commonly, in adults.
• S stercoralis
• • Burning or colicky abdominal pain, often epigastric, occurs and is associated with diarrhea and the passage of mucus.
  • Some patients may complain of nausea, vomiting, and weight loss, with evidence of malabsorption or of protein-losing enteropathy.
  • Massive larval invasion of the lungs and other tissues may occur with hyperinfection, usually in immunocompromised hosts. In this syndrome, the worm is able to complete its entire life cycle in the human, and the symptoms are related to the large burden of larvae migrating in the host.
  • Severe generalized abdominal pain, diffuse pulmonary infiltrates, ileus, shock, and meningitis or sepsis from gram-negative bacilli may occur.
• T spiralis: Myositis with pain, swelling, and weakness is common; it usually first develops in the extraocular muscles and then involves the masseters, neck muscles, limb flexors, and lumbar muscles.
• Some patients may complain of headache, cough, shortness of breath, hoarseness, and dysphagia.

Causes

• Ingestion of mature eggs in fecally contaminated food or drink
• Larval penetration of skin (hookworms and S stercoralis)
• Larvae introduced into human host by arthropod vector (mosquitoes for filariasis and flies for O volvulus)

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Other Problems to be Considered

Nonfilarial causes of lymphangitis include acute bacterial lymphangitis, phlebitis, and plague (unusual).

Nonfilarial causes of lymphedema, chyluria, and elephantiasis include the following:

• Infiltrative or granulomatous processes (eg, tumor, fungus)
• Chronic venostasis or phlebitis
• Cardiac insufficiency
• Nutritional deficiencies
• Heredity (eg, Milroy disease)
• Lateritious soil-obstructing lymphatics.

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• Stool examination for intestinal nematodes using native, zinc sulfate flotation, or formalin-ethyl acetate sedimentation techniques
• • Based on characteristics of eggs or larvae in stool or adult worm, if passed
  • Cellophane-tape impression for pinworms
• Examination of larvae or adult worms taken from the tissue, characteristic microfilariae on blood smear, eosinophilia
• Membrane filtration technique and thick blood smear (Giemsa stained) - For filariasis
• Distinction of species by larval examination - Challenging and may require expert examination
• Onchocerciasis - Identified by skin snip/biopsy showing larvae
• Enzyme-linked immunosorbent assay (ELISA) and, occasionally, biopsy for toxocariasis
• Muscle biopsy for trichinosis

Imaging Studies

• Larvae in sputum or adult worms observed on radiologic studies (uncommon)
• Lung radiography for Löeffler syndrome
• Ultrasound - Useful in the diagnosis of ascariasis as a cause of biliary tract disease

Other Tests

• Skin snip, nodulectomy, slit-lamp examination, and Mazzotti test - Helpful in onchocerciasis

Histologic Findings

Characteristic eggs/worms/larvae in tissue

TREATMENT

Section 6 of 11  

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

Medical Care

• Identify cause, and treat accordingly.
• In dracunculiasis, the best treatment is direct removal of worms from tissue, taking care not to break the worm.
• Treat secondary infections.

Surgical Care

• Acute intestinal obstruction and perforation in patients with ascariasis may require surgical treatment.
• Long-standing lymphatic filariasis due to W bancrofti and B malayi infection may require surgical intervention to increase lymphatic drainage. This is unusual and likely observed in long-term residents of endemic areas who have been subjected to extensive exposure to the parasite.

Consultations

• Gastroenterologists
• Parasitologists
• Radiologists
• Dermatologists
• Chest diseases specialists

Diet

No special diet is required.

Activity

No restrictions are necessary. In lymphatic filariasis, if edema is a problem, the patient may want to elevate legs while sitting.

MEDICATION

Section 7 of 11  

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The goals of pharmacotherapy are to eradicate the infestation, reduce morbidity, and prevent complications.

Drug Category: Anthelmintic agents

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

• Inhibition of microtubules causing irreversible block of glucose uptake
• Tubulin polymerization inhibition
• Depolarizing neuromuscular blockade
• Cholinesterase inhibition
• Increased cell membrane permeability resulting in intracellular calcium loss
• Vacuolization of the schistosome tegument
• Increased cell membrane permeability to chloride ions via chloride channels alteration

Drug Name	Mebendazole (Vermox)
Description	Indicated for treating E vermicularis (pinworm), T trichiura (whipworm), A lumbricoides (common roundworm), A duodenale (common hookworm), N americanus (American hookworm) in single or mixed infections. Efficacy varies as a function of such factors as preexisting diarrhea and GI transit time, degree of infection, and helminth strains. Causes worm death by selectively and irreversibly blocking uptake of glucose and other nutrients in susceptible adult intestine where helminths dwell.
Adult Dose	Ascariasis, hookworm, or trichuriasis: 100 mg PO qd for 3 d; alternatively, 500 mg PO once Enterobiasis: 100 mg PO once, repeat dose in 2 wk Trichinosis: 200-400 mg PO tid for 3 d initially; followed by 400-500 mg tid for 10 d
Pediatric Dose	<2 years: Not established >2 years: Administer as adults
Contraindications	Documented hypersensitivity
Interactions	Carbamazepine and phenytoin may decrease effects; cimetidine may increase levels
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Avoid use in pregnancy, especially first trimester; adjust dose in hepatic impairment

Drug Name	Ivermectin (Mectizan)
Description	Member of avermectin class (broad-spectrum antiparasitic agents). Unique mode of action. Binds selectively with high affinity to glutamate-gated chloride ion channels in invertebrate nerve and muscle cells. Increases permeability of cell membrane to chloride ions. Results in hyperpolarization of nerve or muscle cell, causing parasite paralysis and death. Also affects other ligand-gated chloride channels (eg, those gated by GABA). Active against various life-cycle stages of most nematodes. Active against O volvulus tissue microfilariae but not adult form. Activity against S stercoralis limited to intestinal stages.
Adult Dose	Strongyloidiasis: 200 mcg/kg PO qd for 1-2 d Cutaneous larva migrans (onchocerciasis): 150 mcg/kg PO as single dose; may repeat q6-12mo until asymptomatic
Pediatric Dose	<5 years: Not established >5 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in breastfeeding women; repeat courses of therapy may be required in immunocompromised patients; may cause nausea, vomiting, drowsiness, and mild CNS depression; patients with hyperreactive onchodermatitis may develop a severe immune reaction (ie, Mazzotti reaction) consisting of optic neuritis, chorioretinitis, proteinuria, pruritus, rash, and edema

Drug Name	Piperazine (Vermizine)
Description	Readily absorbed from GI tract, partially degraded in vivo, and excreted in urine. Paralyzes worm muscle; thus, worm expelled by normal intestinal peristalsis. Exhibits wide therapeutic index. Not available in the United States.
Adult Dose	Ascariasis: 3.5 g/d (hexahydrate equivalent) PO as single dose for 2 d Enterobiasis: 65 mg/d (hexahydrate equivalent) PO for 7 d; not to exceed 2.5 g/d
Pediatric Dose	Ascariasis: 75 mg/kg/d (hexahydrate equivalent) PO for 2 d; not to exceed 3.5 g/d Enterobiasis: Administer as in adults
Contraindications	Documented hypersensitivity; hepatic or renal dysfunction; seizure disorder
Interactions	Phenothiazines may increase risk of seizures; antagonizes pyrantel pamoate activity
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Most commonly reported reactions include GI and CNS effects, discontinue drug if adverse effects become significant; avoid prolonged, repeated, and excessive therapy due to potential neurotoxicity; caution in severe malnutrition and anemia

Drug Name	Pyrantel (Antiminth, Pin-Rid)
Description	Depolarizing neuromuscular blocking agent and cholinesterase inhibitor that results in spastic paralysis of worm. Active against E vermicularis (pinworm), A lumbricoides (roundworm), and A duodenale (hookworm).
Adult Dose	Hookworm: 11 mg/kg PO qd for 3 d; not to exceed 1 g/d Ascariasis: 11 mg/kg PO as single dose; not to exceed 1 g/d Enterobiasis: 11 mg/kg PO as single dose; not to exceed 1 g/d; repeat q2wk for 2 regimens
Pediatric Dose	<2 years: Not established >2 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Pyrantel and piperazine are mutually antagonistic in ascariasis; may increase theophylline serum levels
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in liver impairment, anemia, pregnancy, and malnutrition

Drug Name	Diethylcarbamazine citrate (Hetrazan)
Description	Effective in treating filariasis specific for W bancrofti, B malayi, and L loa. Does not contain any toxic metallic elements. Not recommended as DOC because of severe adverse effects. Recommended if therapy with mebendazole fails or unavailable.
Adult Dose	6 mg/kg/d PO divided tid for 14 d
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in renal dysfunction (reduce dose); gradual dose titration may be needed over first 3 d to reduce allergic reaction in patients with microfilariae in blood or skin; patients with hyperreactive onchodermatitis or L loa may develop a severe immune reaction (ie, Mazzotti reaction) consisting of optic neuritis, chorioretinitis, proteinuria, pruritus, rash, and edema

FOLLOW-UP

Section 8 of 11  

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

Further Outpatient Care

• Perform follow-up stool studies at 2 weeks, and re-treat if necessary.

Deterrence/Prevention

• Good hygiene and sanitation
• Avoidance of sources of infection (eg, arthropod bites, rivers/streams, contaminated soils)
• Public health activities such as vector control

Complications

• Vomiting worms - Ascariasis
• Worm migration
• • Cholangitis (migration to common bile duct)
  • Pancreatitis (migration to pancreatic duct)
  • Appendicitis (migration to appendix)
  • Diverticulitis (migration to diverticula)
• Liver abscess
• Intestinal obstruction, volvulus
• Intussusception
• Bowel penetration
• Anemia, hypoproteinemia - Hookworm
• CNS infection - Strongyloides
• Onchocerciasis - Blindness
• Filariasis - Lymphatic destruction leading to severe edema (elephantiasis)
• Neurohelminthiasis - CNS migrations and infection
• Visceral worms
• • Hepatitis
  • Splenomegaly
  • Pleuritis
  • Peritonitis
  • Eosinophilic granuloma
  • Other organ damage because larvae migrate for as long as 6 months

Prognosis

• Prognosis is good for patients with light-to-moderate infections. Prognosis depends on the organ infected and the extent of the infection.
• • Ascariasis should always be treated because of the risk of migrating adult worms.
  • Long-term diethylcarbamazine treatment and immunomonitoring of patients with filariae are essential in endemic areas to arrest and prevent pathology.

Patient Education

• Avoid fecally contaminated food, water, and soil.
• Avoid bites by arthropod vectors. Use insect repellants and other protective measures, eg, proper clothing.
• Avoid rivers, streams, and soils known to be infected.

MISCELLANEOUS

Section 9 of 11  

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• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Special Concerns

• In pregnancy, benzimidazoles (eg, mebendazole, albendazole) should not be used.
• Ivermectin has shown little teratogenic potential and has provided an effective therapy, although benefits should clearly outweigh risks.

MULTIMEDIA

Section 10 of 11  

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• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Strongyloides eggs in native examination from feces of a newborn.
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Media file 2:  Ascaris lumbricoides egg in feces (formalin-ethyl acetate sedimentation method).
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Media file 3:  A typical Trichuris trichiura egg in feces.
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Media type:  Photo

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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• Brooker S, Bethony J, Hotez PJ. Human hookworm infection in the 21st century. Adv Parasitol. 2004;58:197-288. [Medline]. [Full Text].
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• Mahmoud AAF. Intestinal Nematodes (Roundworms). Mandell: Principles and Practice of Infectious Diseases. 5th ed. London: Churchill Livingstone; 2000:2938-2949.
• Massara CL, Enk MJ. Treatment options in the management of Ascaris lumbricoides. Expert Opin Pharmacother. Mar 2004;5(3):529-39. [Medline]. [Full Text].
• Morrison DA, Hoglund J. Testing the hypothesis of recent population expansions in nematode parasites of human-associated hosts. Heredity. Apr 2005;94(4):426-34. [Medline].
• Negrao-Correa D, Teixeira MM. The mutual influence of nematode infection and allergy. Chem Immunol Allergy. 2006;90:14-28. [Medline]. [Full Text].
• Omura S, Crump A. The life and times of ivermectin - a success story. Nat Rev Microbiol. Dec 2004;2(12):984-9. [Medline]. [Full Text].
• Owen RL. Parasitic Diseases. Feldman: Sleisenger & Fordtran's Gastrointestinal and Liver Disease. 6th ed. Philadelphia, Pa: WB Saunders; 1998:1663-9.
• Pozio E, Gomez Morales MA, Dupouy-Camet J. Clinical aspects, diagnosis and treatment of trichinellosis. Expert Rev Anti Infect Ther. Oct 2003;1(3):471-82. [Medline]. [Full Text].
• Quinnell RJ, Bethony J, Pritchard DI. The immunoepidemiology of human hookworm infection. Parasite Immunol. Nov-Dec 2004;26(11-12):443-54. [Medline]. [Full Text].
• Walden J. Parasitic diseases. Other roundworms. Trichuris, hookworm, and Strongyloides. Prim Care. 1991;18:53-74. [Medline].
• Walker MD, Zunt JR. Neuroparasitic infections: nematodes. Semin Neurol. Sep 2005;25(3):252-61. [Medline]. [Full Text].

Article Last Updated: May 5, 2006