AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

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

INTRODUCTION

Section 2 of 11  

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

Background

Gnathostomiasis is a rare infection that most often results from ingestion of the third-stage larvae of the nematode Gnathostoma spinigerum, although several other species also cause human disease. The larvae may be found in raw or undercooked meat (eg, freshwater fish, chicken, snails, frogs, pigs) or in contaminated water. Rarely, larvae penetrate the skin of individuals who are exposed to contaminated meat or water.

Any organ system can be involved, but the most common manifestation of infection is localized, intermittent, migratory swelling in the skin and subcutaneous tissues. Such swelling may be painful, pruritic, and/or erythematous. Angiostrongylus cantonensis and Gnathostoma species are common causes of parasitic eosinophilic meningitis, which results from their random migration into the CNS.¹ Infection is typically associated with peripheral eosinophilia, in which the eosinophils may exceed 50% of the circulating WBCs. The classic triad of infection is intermittent migratory swelling, eosinophilia, and travel to endemic areas (mainly Southeast Asia).²

Pathophysiology

Definitive hosts for Gnathostoma species include dogs, cats, tigers, leopards, lions, mink, opossums, raccoons, and otters, in which the adult worms live in a tumor in the gastric wall. Eggs leave an aperture in the tumor that opens on the stomach lumen and pass into water in the feces. After approximately one week, the eggs develop into larvae, which hatch and are then ingested by the first intermediate host, minute crustaceans of the genus Cyclops. Larvae penetrate the gastric wall of the copepods, migrate through the body cavity, and mature into second-stage and early third-stage larval forms. The copepods are ingested by the second intermediate hosts or definitive hosts (eg, fish, frogs, snakes, chicken, pigs), in which they again penetrate the gastric wall, migrate into muscles, and mature into advanced third-stage larvae before encysting.

When flesh from these hosts is eaten, the larvae excyst in the stomach, penetrate the gastric wall, migrate through the liver, and travel to the connective tissue and muscles. After 4 weeks, they return to the gastric wall to form the tumor, where they mature into adults in 6-8 months. At 8-12 months after initial ingestion, the worms mate, and eggs begin to pass into the feces of the host.

Humans become infected when they ingest third-stage larvae in raw or undercooked meat of the definitive host or when they drink, work in, or bathe in water contaminated with larvae or infested copepods. Cases of probable prenatal transmission in humans have occurred as well. In humans, the larvae do not return to the stomach wall, but rather, they migrate randomly throughout the body for as long as 10-12 years. For this reason, eggs are rarely, if ever, found in human feces.

Within 24-48 hours of ingestion, larvae invade the gastric and/or intestinal wall, resulting in eosinophilia and local symptoms. They migrate to and through the liver. Their migration through the body begins 3-4 weeks to several years after ingestion. Typically, episodes last 1-2 weeks. Over time, episodes are often less frequent, less intense, and shorter. Disease is thought to result from mechanical damage to tissues caused by gnathostome migration; gnathostome production and/or the action of toxins that resemble those of acetylcholine, hyaluronidase, protease, and hemolysin; and the host's response to the infestation.

Frequency

United States

Human cases of gnathostomiasis acquired in the United States have not been reported and it remains rare in individuals who are exposed abroad.

International

Gnathostomiasis is an uncommon disease, even in endemic areas of Southeast Asia (including Japan, Korea, Laos, Malaysia, Taiwan, and Thailand) and Latin America (mainly Mexico and Ecuador), although its incidence appears to be increasing, possibly because of changing dietary habits. It is most common in Thailand and Japan. In Thailand, it is the most common parasitic infection of the CNS. In Thailand, 6% of subarachnoid hemorrhages in adults and 18% of those in infants and children are due to gnathostomiasis.

Mortality/Morbidity

Gnathostomiasis can persist 10-12 years and may cause significant morbidity because of its propensity to involve any part of the body. Random invasion of the CNS, which is the major cause of mortality, may lead to death in 8-25% of patients or long-term sequelae in 30% of patients with CNS involvement.

Race

No predilection has been reported.

Sex

No predilection has been reported, except in cases in which occupational or dietary exposure is related to gender roles.

Age

No predilection has been reported, except in cases affected by factors related to occupational or dietary exposure.

CLINICAL

Section 3 of 11  

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

History

Mild malaise, fever, urticaria, anorexia, nausea, vomiting, diarrhea, and epigastric pain may occur as the larvae migrate through the gastric and/or intestinal wall. Right upper quadrant pain may accompany the liver-migration phase of the illness. Further symptoms depend on the subsequent migration of the larvae.

• Skin and soft tissue - One or more areas involved with tenderness or swelling; creeping eruptions; pain, pruritus, and erythema; nodules or boils
• Pulmonary - Cough, chest pain, dyspnea, and/or hemoptysis; coughing up of worm
• GI - May mimic appendicitis, cholecystitis, or an intestinal mass lesion
• Genitourinary - Hematuria
• Ophthalmologic - Decreased visual acuity, blindness, pain, and/or photophobia
• Otologic - Decreased hearing and/or tinnitus
• CNS
• • Radiculomyelitis (most common), radiculomyeloencephalitis, encephalitis, and/or meningitis may result. Condition may mimic or cause subarachnoid hemorrhage.
  • Agonizing neuritic pain followed by paralysis or decreased sensorium over a few days is typical.
  • Migration of focal neurologic symptoms and signs (eg, cranial nerve palsies, paralysis of an extremity, urinary retention) is typical. With eosinophilic meningitis caused by A cantonensis, CNS depression, low-grade fevers, headache, and nonfocal neurologic symptoms and signs (except for occasional cranial nerve VII or VIII involvement) are more typical.

Physical

Physical examination findings depend on the area of the body into which the larvae migrate. Single or multiple regions may be involved.

• Skin and soft tissue
• • Panniculitis
  • Intense, nonpitting edema
  • Creeping eruptions
  • Subcutaneous nodules or abscesses
• Pulmonary
• • Lobar consolidation or collapse
  • Pleural effusions
  • Pneumothorax
  • Hydropneumothorax
• GI
• • Tender right upper quadrant, mid epigastrium, and/or right lower quadrant
  • Right lower quadrant mass
• Ophthalmologic
• • Uveitis
  • Iritis
  • Intraocular hemorrhage
  • Increased intraocular pressure
  • Retinal scarring/detachment
• CNS
• • Fever, stiff neck, and/or photophobia
  • Evidence of increased intracranial pressure
  • Migratory focal neurologic findings
  • Paralysis, cranial nerve involvement, and/or urinary retention

Causes

• Travel to or from an endemic area
• • Southeast Asia, especially Thailand and Japan
  • Latin America, especially Mexico and Ecuador
  • Australia
  • Asia and the Middle East
• Dietary/occupational exposure or ingestion
• • Raw or undercooked freshwater fish (ceviche in Mexico and South America, sashimi in Japan, sum-fak in Thailand)
  • Other raw or undercooked flesh
  • Contaminated water

DIFFERENTIALS

Section 4 of 11  

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

Other Problems to be Considered

Angiostrongylus cantonensis
Baylisascaris procyonis
Cysticercus cellulosae
Encephalitis
Eosinophilia-myalgia syndrome
Loa loa
Pentastomiasis
Sparganosis
Subarachnoid hemorrhage

WORKUP

Section 5 of 11  

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

Lab Studies

• CBC count
• • Eosinophilia may be present, particularly during the active phases of larval migration. Eosinophils may exceed 50% of the circulating WBCs.
  • Findings may reveal leukocytosis.
• Urinalysis
• • Rarely, microscopic hematuria is present.
  • The worm may be found.
• Serology
• • Enzyme-linked immunosorbent assay (ELISA) and the Western blot are promising diagnostic tests.
  • These tests are not widely available in the United States and many other countries.

Imaging Studies

• Plain radiography - Pulmonary or GI findings
• Xerography - Rarely helps in localizing a soft tissue worm
• CT
• • CT rarely helps in localizing a soft tissue worm.
  • In CNS disease, CT may reveal evidence of intracranial hemorrhage, obstructive hydrocephalus, or meningeal inflammation in one half of the cases.

Other Tests

• Sputum examination may reveal a worm.

Procedures

• Surgical excision and/or resection rarely help in making the diagnosis by revealing the larvae in the skin, subcutaneous tissue, gingivae, or wounds.
• Lumbar puncture may be helpful.
• • Pleocytosis (20-1430 WBCs, but typically <500, with a mean of 250)
  • Eosinophilia (5-94%, with a mean of 38%)
  • Xanthochromia, some RBCs

Histologic Findings

When found, larvae are 2.5-12.5 mm by 0.4-1.2 mm. In tissue, eosinophils predominate, with the presence of fibroblasts, histiocytes, and foreign-body giant cells; this finding may suggest an eosinophilic granuloma. In the CNS, migratory tracts may be present with perivascular infiltration of eosinophils, plasma cells, and lymphocytes. Unlike eosinophilic meningitis due to A cantonensis, no CNS granulomata or parasite fragments are observed.

TREATMENT

Section 6 of 11  

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

Medical Care

The clinical presentation and course dictate the appropriate measures.

Surgical Care

The only definitive treatment is surgical removal of the worm, which is possible only when it is accessible.

Consultations

Consultation with infectious diseases and other appropriate specialists, as dictated by the clinical circumstances, is reasonable.

MEDICATION

Section 7 of 11  

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

Although surgical removal, when possible, is the treatment of choice, albendazole appears to have an increasing role in complementing surgical intervention.³ Ivermectin in a single dose is better tolerated than albendazole but may be less effective.⁴ Mebendazole, which was formerly used, had variable results and significant toxicities and should no longer be used. Adjunctive corticosteroid therapy may have a role in the treatment of CNS disease.

Drug Category: Anthelmintics

These agents are the drugs of choice when surgical treatment is not possible or successful. Parasite biochemical pathways are different from the human host, thus toxicity is directed to the parasite, egg, or larvae. The mechanism of action varies within the drug class. Antiparasitic actions may include the following:

• Inhibition of microtubules that causes 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	Thiabendazole (Mintezol)
Description	A synthetic benzimidazole that should be used only when albendazole is not available because of its toxicities and questionable efficacy. Its mechanism of action is thought to be similar to that of albendazole.
Adult Dose	50 mg/kg/d PO divided q12h for 5 d; not to exceed 3 g/d
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	May elevate serum levels of theophylline, increasing toxicity (monitor serum levels and reduce dose prn)
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	Clinical experience in children <30 lb is limited; nausea, vomiting, and vertigo occur in as many as 50% of patients; may cause rash, hypersensitivity, erythema multiforme, leukopenia, and hallucinations; caution in renal or hepatic impairment

Drug Name	Ivermectin (Mectizan, Stromectol)
Description	Binds selectively with glutamate-gated chloride ion channels in invertebrate nerve and muscle cells, causing cell death. Half-life is 16 h; metabolized in liver.
Adult Dose	150-200 mcg/kg/d PO as single dose
Pediatric Dose	<5 years: Not established >5 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	May interact with other ligand-gated chloride channels, such as those gated by GABA
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 the newborn caused by ivermectin excretion in milk Repeat courses of therapy may be required in immunocompromised patients May cause nausea, vomiting, and mild CNS depression; may cause drowsiness

Drug Category: Corticosteroids

These agents may have an ancillary role in reducing inflammation associated with CNS gnathostomiasis.

FOLLOW-UP

Section 8 of 11  

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

Further Inpatient Care

• The need for inpatient care depends on the clinical presentation of the infection.

Further Outpatient Care

• Most patients are treated on an outpatient basis, as the clinical circumstances dictate, except in cases with complications or CNS involvement.

Transfer

• The need for transfer depends on the availability of necessary services and specialists.

Deterrence/Prevention

• Emphasize the need to avoid exposure.
• Ingestion of raw and undercooked food should be avoided in endemic areas.
• Freezing meat at -20°C for 3-5 days kills the larvae.
• Marinating meat in vinegar for 6 hours or in soy sauce for 12 hours kills the larvae.
• Lime juice does not kill the larvae, even with prolonged exposure.
• Contaminated water should be boiled for 5 minutes before use.
• Gloves should be worn or the hands should be washed frequently if exposure to possibly contaminated water or flesh is likely.

Complications

• In Thailand, 6% of subarachnoid hemorrhages in adults and 18% of those in infants and children are due to gnathostomiasis.
• Pneumonia, sepsis, paralysis, and/or long-term neurologic sequelae are possible.

Prognosis

• Gnathostomiasis is seldom fatal, except in CNS disease.
• Long-term morbidity is possible because of tissue injury during migration.
• With CNS disease, the mortality rate is 8-25%; one third of survivors have long-term sequelae.

MISCELLANEOUS

Section 9 of 11  

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

Medical/Legal Pitfalls

• Epidemiology is the key to diagnosis.
• • Obtain the patient's travel and dietary history.
  • Ask about significant exposures.
• Failure to consider the diagnosis in the appropriate clinical setting is a pitfall.

Special Concerns

• Pregnancy
• • Three documented cases of intrauterine transmission of gnathostomiasis have been reported.
  • The use of antiparasitic agents is contraindicated in pregnancy.

FURTHER READING

Section 10 of 11  

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

See Image 18 at the McGill Faculty of Medicine Web site.

REFERENCES

Section 11 of 11

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

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16. Kraivichian K, Nuchprayoon S, Sitichalernchai P, et al. Treatment of cutaneous gnathostomiasis with ivermectin. Am J Trop Med Hyg. Nov 2004;71(5):623-8. [Medline]. [Full Text].
17. Laummaunwai P, Sawanyawisuth K, Intapan PM, Chotmongkol V, Wongkham C, Maleewong W. Evaluation of human IgG class and subclass antibodies to a 24 kDa antigenic component of Gnathostoma spinigerum for the serodiagnosis of gnathostomiasis. Parasitol Res. Aug 2007;101(3):703-8. [Medline].
18. Ligon BL. Gnathostomiasis: A review of a previously localized zoonosis now crossing numerous geographical boundaries. Semin Pediatr Infect Dis. Apr 2005;16(2):137-43. [Medline].
19. Magana M, Messina M, Bustamante F, Cazarin J. Gnathostomiasis: clinicopathologic study. Am J Dermatopathol. Apr 2004;26(2):91-5. [Medline].
20. Michaels MG. Eosinophilic meningitis. In: Long SS, Pickering LK, Prober CG, eds. Principles and Practice of Pediatric Infectious Diseases. Churchill Livingstone; 2003:312-5.
21. Moore DA, McCroddan J, Dekumyoy P, Chiodini PL. Gnathostomiasis: an emerging imported disease. Emerg Infect Dis. Jun 2003;9(6):647-50. [Medline].
22. Nawa Y, Hatz C, Blum J. Sushi delights and parasites: the risk of fishborne and foodborne parasitic zoonoses in Asia. Clin Infect Dis. Nov 1 2005;41(9):1297-303. [Medline].
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25. Preechawat P, Wongwatthana P, Poonyathalang A, Chusattayanond A. Orbital apex syndrome from gnathostomiasis. J Neuroophthalmol. Sep 2006;26(3):184-6. [Medline].
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Article Last Updated: Feb 6, 2008