Gnathostomiasis 

Updated: Apr 26, 2018
Author: Germaine L Defendi, MD, MS, FAAP; Chief Editor: Russell W Steele, MD 

Overview

Background

Gnathostomiasis is a food-borne parasitic infection that results from the human ingestion of the third-stage larvae of nematodes within the genus Gnathostoma. The most common species that infects humans is G spinigerum. Human infections are also caused by G hispidum, G nipponicum, G procyonis, G binucleatum and G doloresi. Gnathostomiasis is called by other terms in different countries worldwide such as Choko-Fushu Tua chid or chokofishi (Japan), consular disease (Nanjing), Shanghai rheumatism, Tau-cheed (Thailand), Woodbury bug (Australia), and Yangtze River edema. The larvae may be found in raw or undercooked protein food sources (eg, freshwater fish, chicken, snails, snakes, frogs, pigs) or in contaminated water. In rare instances, larvae can directly penetrate the skin of individuals who are exposed to contaminated food sources or freshwater.

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. In addition, Gnathostoma species commonly cause a parasitic eosinophilic meningitis, due to larval migration into the CNS.[1] Systemic infection is typically associated with peripheral eosinophilia, in which the percentage of eosinophils may exceed 50% of the circulating WBCs.

A classic triad that indicates infection is patient complaint of intermittent migratory swelling, predominance of eosinophilia in laboratory tests, and report of travel or residence in gnathostomiasis endemic areas (mainly Southeast Asia).[2]

Pathophysiology

Definitive hosts for Gnathostoma species include dogs, cats, pigs, wild boars, tigers, leopards, lions, minks, weasels, opossums, raccoons, and otters, in which adult worms live in a tumor-like mass within the host’s gastric wall. The definitive host is defined as the animal species in which the Gnathostoma species reproduce.  Adult worms range 13 to 55 mm in length. Adult females release eggs which are evacuated in the feces of the definitive host and later hatch as larvae in a freshwater environment (about 7 days later). Larvae in freshwater are eaten by tiny crustaceans (also known as copepods, tiny crustaceans of the genus Cyclops), which are in turn eaten by other animals, such as freshwater fish, eels, frogs, birds, and reptiles. 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 then ingested by second-intermediate hosts (fish, frogs, snakes, eels, chicken, pigs), in which the larvae again penetrate the gastric wall, migrate into muscle tissue, and mature into advanced third-stage larvae before encysting there.

Definitive hosts that eat an infected animal, can become infected and the larvae can mature into the adult form and complete the nematode’s life cycle. When flesh from the second-intermediate hosts is eaten, the larvae excyst in the stomach, penetrate the gastric wall, migrate to the liver, and travel to connective tissues and muscles. After 4 weeks, they return to the gastric wall to form the tumor-like mass in the upper digestive system, where they mature into adults in 6-8 months. 8-12 months after initial ingestion, the worms mate, and eggs pass into the host’s feces.

Humans become infected when they ingest third-stage larvae in raw or undercooked flesh of freshwater fish or other definitive hosts or when they drink, work in, or bathe in freshwater contaminated with larvae or infected copepods. Humans are non-required hosts. Gnathostoma species survive in humans but cannot mature into adult worms capable of reproduction. In humans, the larvae do not return to the stomach wall, but rather, they can migrate throughout the body for as long as 10-12 years. For this reason, eggs are rarely, if ever, found in human feces.

Two alternate routes of human infection have been suggested: ingestion of freshwater containing infected copepods (thus taking the place of a second intermediate host) or penetration of food handlers’ skin by third-stage larvae from infected flesh. Symptoms in humans occur as the late third-stage larvae migrate through tissues, causing intermittent symptoms of cutaneous or visceral larva migrans. The larvae have been observed to move at 1 cm/hour.

Within 24-48 hours post-ingestion, larvae invade the gastric and/or intestinal wall, causing eosinophilia and local symptoms. Larvae migrate to and through the liver. Their migration throughout the body begins 3-4 weeks to several years post-ingestion. Typically, episodes last 1-2 weeks. Over time, episodes are often less frequent, less intense, and shorter.

The exact pathogenicity of gnathostomiasis is not known, but it is believed that the symptoms are due to several mechanisms: the combined effects of mechanical damage secondary to larval migration, larval excretions and secretions, and the host's immunological response. Studies in Japan in the 1950s, defined the substances released contain various compounds, including one that resembles acetylcholine, a hyaluronidase, a proteolytic enzyme, and a hemolytic substance (hemolysin), Actions of these substances, in addition to the mechanical damage, cause the characteristic hemorrhagic tracks seen in the subcutaneous tissues in patients or in viscera or CNS postmortem studies.[3]

Epidemiology

Frequency

United States

A single, unconfirmed, human case of gnathostomiasis acquired in the United States has been reported[4] and it remains rare in individuals who are exposed abroad.

International

Gnathostomiasis is an uncommon disease, even in endemic areas of Japan, Korea,[5] Taiwan, Southeast Asia (Laos,[6] Malaysia, Thailand) and Latin America (mainly Mexico and Ecuador), although its incidence appears to be increasing, possibly due to changing diet.[7] It is most common in Thailand and Japan. In Thailand, it is the most common parasitic infection of the central nervous system (CNS) also called neurognathostomiasis. Neurognathostomiasis has only been reported in patients infected with G spinigerum.[8, 9] 6% of subarachnoid hemorrhages in adults and 18% of those in infants and children are due to gnathostomiasis in Thailand.

Pathogenicity in the CNS is from direct mechanical injury due to tearing, with or without destruction of the nerve tissue and its vascular structures. Additionally, inflammation and destruction of tissue due to toxin production occurs. Hallmark signs of neurognathostomiasis are hemorrhagic tracts, which have been documented postmortem throughout the spinal cord and cerebral tissue. Death occurs if vital structures in the brain stem are invaded, which may occur within 4 to 31 days following the onset of CNS symptoms, or if the larva burrows through a cerebral arteriole causing subarachnoid hemorrhage.[3]

Mortality/Morbidity

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

Race

No racial predilection has been reported.

Sex

No predilection has been reported, except in cases in which occupation, diet and social habits are gender specific. Overall, females are more commonly affected than males, except in Vietnam where the opposite is true.

Age

Adults are infected more often than children, most likely related by factors such as occupation, diet and/or social behavior. However, all ages are affected. Infection in a newborn has been reported suggesting either prenatal or perinatal transmission.

 

Presentation

History

Patients with gnathostomiasis may complain of mild malaise, fever, urticaria, anorexia, nausea, vomiting, diarrhea, and epigastric pain 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 larval migration to different parts of the body.

  • Skin and soft tissue - One or more areas involved with tenderness or swelling; creeping eruptions; pain, pruritus, and erythema; nodules or boils

  • Ophthalmologic - Decreased visual acuity, blindness, pain, and/or photophobia[10] due to migration of larvae along optic nerves

  • Otologic - Decreased hearing and/or tinnitus

  • Pulmonary - Cough, chest pain, dyspnea, and/or hemoptysis; coughing up of worm segments

  • GI - May mimic appendicitis, cholecystitis, or an intestinal mass lesion

  • Genitourinary - Hematuria

CNS involvement includes the following:[11, 3]

  • Radiculomyelitis (most common), radiculomyeloencephalitis, encephalitis

  • Low-grade fevers, headache, CNS depression and nonfocal neurologic symptoms

  • Eosinophilic meningitis

  • Subarachnoid hemorrhage

  • Excruciating radicular pain and or headache followed by paralysis, cranial nerve palsies or decreased sensorium over a few days

  • Migration of focal neurologic symptoms (eg, cranial nerve palsies, paralysis of an extremity, urinary retention)

Physical

Physical examination findings depend on the area of the body into which the larvae migrate. Single or multiple regions of the body may be involved. The main areas affected are cutaneous, ocular,[12] visceral and neurological.

Cutaneous

Skin and soft tissue:

  • Nodular migratory panniculitis (inflammation of the subcutaneous fat), especially of the trunk and upper extremities
  • Nonpitting edematous swelling
  • Creeping eruptions
  • Subcutaneous nodules or abscesses

Ocular

Eyes:

  • Uveitis (usually anterior)
  • Iritis
  • Intraocular hemorrhage
  • Increased intraocular pressure, glaucoma
  • Retinal scarring/detachment

Visceral

Pulmonary:

  • Pleuritic chest pain accompanied by cough
  • Lobar consolidation or collapse
  • Pleural effusions
  • Pneumothorax, hydropneumothorax

Gastrointestinal/genitourinary:

  • Tender right upper quadrant, mid-epigastrium, and/or right lower quadrant
  • Right lower quadrant mass
  • Hematuria

Neurological

CNS:

  • Fever, stiff neck, and/or photophobia (clinical indicators of meningitis)
  • Clinical signs of increased intracranial pressure
  • Migratory focal neurologic findings
  • Paralysis, cranial nerve involvement, and/or urinary retention

Causes

Travel to or from an endemic area

See the list below:

  • Southeast Asia, especially Thailand

  • Japan

  • China

  • Latin America, especially Mexico and Ecuador

  • Western Australia

  • South Central Africa

Dietary/occupational exposure or ingestion

See the list below:

  • Raw or undercooked freshwater fish (ceviche in Mexico and South America, sashimi in Japan, sum-fak in Thailand). Nematode larvae not present in saltwater fish.

  • Other raw or undercooked flesh

  • Contaminated freshwater

 

DDx

 

Workup

Laboratory Studies

The following diagnostic studies are indicated in gnathostomiasis:

CBC (complete blood count)

See the list below:

  • Eosinophilia may be present, particularly during the active phases of larval migration. Eosinophilic percentage may exceed 50% of the circulating WBCs.

  • Results may show leukocytosis.

Urinalysis

See the list below:

  • Rarely, microscopic hematuria is present.

  • The worm may be found.

Serology

See the list below:

  • Enzyme-linked immunosorbent assay (ELISA) to detect IgG antibodies and Western blot are diagnostic tests.[13]

  • Immunoblot testing for neurologic disease has been described.[14]

  • These tests are not widely available in the United States and many other countries.

Imaging Studies

Plain radiography

See the list below:

  • Pulmonary or GI findings

CT

See the list below:

  • CT rarely helps in localizing a soft tissue worm.

  • In CNS disease, CT may reveal evidence of intracranial hemorrhage, obstructive hydrocephalus, or meningeal inflammation.

Other Tests

Sputum examination may reveal a worm.

Procedures

Surgical extraction and/or resection can rarely help through identification of larvae in skin, subcutaneous tissue, gingivae, or wounds.

Lumbar puncture is helpful to evaluate cerebral spinal fluid for evidence of neurognathosomiasis. Results show the following:

  • 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. No CNS granulomas or parasite fragments are observed, a differentiating clinical finding from eosinophilic meningitis due to A cantonensis.

 

Treatment

Medical Care

The clinical presentation and course of gnathostomiasis 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

Medication Summary

Although surgical removal, when possible, is the treatment of choice in gnathostomiasis, albendazole appears to have an increasing role in complementing surgical intervention.[15] Ivermectin in a single dose is better tolerated than albendazole but may be less effective.[16] Mebendazole, which was formerly used, had variable results and due to significant toxicities should no longer be used. Adjunctive corticosteroid therapy, as an anti-inflammatory, may have a role in the treatment of CNS disease.

Anthelmintics

Class Summary

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

Albendazole (Albenza)

DOC for treating gnathostomiasis. A synthetic nitroimidazole that binds to tubulin, inhibits microtubule assembly, decreases glucose absorption, and inhibits fumarate reductase in the parasite. Poorly soluble in water, it is well absorbed when taken with a fatty meal. Concentration in the cerebrospinal fluid reaches 40% of that in the serum. Two treatment courses may be required.

Thiabendazole (Mintezol)

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.

Ivermectin (Mectizan, Stromectol)

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.

Corticosteroids

Class Summary

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

Dexamethasone (Decadron, Dexone)

Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reducing capillary permeability.

 

Follow-up

Further Outpatient Care

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

Further Inpatient Care

The need for inpatient care of patients with gnathostomiasis depends on the clinical presentation of the infection.

Transfer

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

Deterrence/Prevention

The USFDA recommends the following for fish preparation or storage to kill parasites:

  • Cooking: Cook fish adequately (to an internal temperature of at least 145° F [~63° C]).
  • Freezing: At -4°F (-20°C) or below for 7 days (total time), or -31°F (-35°C) or below until solid, and storing at -31°F (-35°C) or below for 15 hours, or -31°F (-35°C) or below until solid and storing at -4°F (-20°C) or below for 24 hours.

In addition:

  • Emphasize the need to avoid exposure.

  • Ingestion of raw and undercooked food should be avoided in endemic areas.

  • Marinating fish/meat in vinegar for 6 hours or in soy sauce for 12 hours kills the larvae.

  • Marinating in lime juice does not kill the larvae, even with prolonged exposure.

  • Contaminated water should be boiled for 5 minutes before use.

  • Proper food handling practices: Gloves should be worn or the hands should be washed frequently if exposure to possibly contaminated water or flesh is likely.

Complications

See the list below:

  • 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

See the list below:

  • Gnathostomiasis is seldom fatal, except in cases of 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.