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Valai Bussaratid

and Pravan Suntharasamai



Diagnosis—two new serodiagnostic immunoblot tests have been developed.

Further reading—new references added.

Updated on 31 May 2012. The previous version of this content can be found here.
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Gnathostomiasis is an extraintestinal infection with larval or immature nematodes of the genus Gnathostoma (order Spirurida), the most common mode of human infection being consumption of undercooked freshwater fish. Clinical manifestations include recurrent cutaneous migratory swellings (common), creeping eruption (rare), and neurological deficits (occasional). Definitive diagnosis is by identification of the worm in surgical specimens; serological testing for antibody against gnathostoma antigen can confirm a presumptive diagnosis. Treatment of choice is albendazole or if possible, surgical removal of the worm in accessible areas and when the parasite can be located. Prevention is by avoiding all dishes that contain raw or poorly cooked flesh of animals or fish in or imported from endemic areas.

Aetiology, genetics, pathogenesis, and pathology

Five species of Gnathostoma are known to infect humans. Adult parasites live in the upper gastrointestinal tract of the definitive hosts: dogs, cats, and other mammals for Gnathostoma spinigerum, the most common infection in Thailand; pigs for G. hispidum and G. doloresi; weasels for G. nipponicum; and canines for G. binucleatum. Larvae from ova shed with the host’s faeces hatch in water and are ingested by Cyclops spp. copepods. These are eaten by freshwater fish, amphibians, reptiles, crustaceans, birds, or mammals; third-stage larvae are found in the walls of the viscera and in the muscles of these second intermediate hosts. Unless the second intermediate hosts are eaten by definitive hosts, the parasites cannot develop into reproductive adults, but they remain infectious to humans and other paratenic hosts.

Consumption of the raw or undercooked flesh of second intermediate and paratenic hosts is the most common mode of transmission. Skin penetration after contact with infected material is less important. Prenatal transmission can occur, as larvae have been recovered in neonates as young as 3 days old.


The nucleotide sequence analysis of the gnathostoma genome is incomplete. The 5.8S ribosomal DNAs are almost identical among species, whereas the internal transcribed spacer 2 region is a potential candidate as a genetic marker for the identification of gnathostoma species, because it varies considerably among species. The gene for a 24-kDa diagnostic glycoprotein of G. spinigerum has been identified.


The ingested larva penetrates the gut wall and migrates to the liver before wandering through almost any tissue except bone. Symptoms and signs vary according to the site and size of the inflammatory or haemorrhagic lesions induced intermittently along the migratory route.


Histopathological findings include mixed eosinophils and other inflammatory cell infiltration, areas of necrosis or haemorrhage, and occasionally parasite tracts. Occasionally, eosinophilic vasculitis or flame figures may be seen in skin biopsy. These findings are not characteristic for gnathostomiasis. The only diagnostic finding is the identification of a parasite. If the biopsy cuts through the bulb or cervical part of the worm, diagnostic features of G. spinigerum may be visible: a head bulb bearing eight transverse rows of spines or a cuticle bearing three-toothed spines.


Isolated G. spinigerum infections are reported frequently in Thailand, and sporadically in Japan, China, Bangladesh, India, Sri Lanka, South-East Asia, Cameroon, Zambia, Ecuador, Peru, and Australia. Infections with G. doloresi, G. nipponicum, and G. hispidum have been reported from Japan. In Mexico and Ecuador, G. binucleatum is the most common infection.

Gnathostomiasis can present in places far away from these endemic areas as a result of migration of the latently infected human host, or importation of the infective flesh of paratenic hosts. Consumption of a raw fish dish at a party can result in an outbreak.


All dishes that contain the raw or poorly cooked flesh of animals in or imported from endemic areas must be avoided. Those who prepare potentially infected flesh should use gloves if prolonged exposure is likely.

Clinical features

Nausea, vomiting, and epigastric pain may develop within 1 or 2 days of consumption of the infective food. Fever, pain in the right upper quadrant of the abdomen, chest pain, dry cough, and hypereosinophilia may develop within 1 to 2 weeks.

The primary invasive illness usually passes unnoticed, and so the incubation period is not known in most cases. General health is scarcely impaired, and fever is uncommon. The illnesses can be categorized according to the affected organs as below.

Cutaneous forms

Gnathostomal creeping eruption

This is rare in G. spinigerum infection, but more frequent with the other three species that are prevalent in Japan. The serpiginous track is similar to that caused by dog or cat hookworm larvae, but bigger and more variable in depth. A trail of subcutaneous haemorrhage is sometimes observed.

Cutaneous migratory swelling

The most common manifestation of human gnathostomiasis is intermittent swelling (Fig. The first swelling may develop 3 to 4 weeks after infection, and can occur anywhere; it may recur close to or distant from the original site. The swelling develops rapidly, and usually lasts for about 1 to 2 weeks. Frequently it is extensive, e.g. involving the whole wrist or hand. Swelling of the digits or plantar surfaces can be very painful and incapacitating. Itching is the main associated symptom. Regional lymphadenitis is usually absent. When swelling involves the eyelid, chemosis and conjunctival haemorrhage may be observed.

Fig. Migratory swelling in a 23-year-old man. (a) In the left orbital region for 5 days when seen on 5 June 1986. (b) At the right side of the upper lip on 9 June 1986, when the larva was picked out by needle puncture and squeezing.

Migratory swelling in a 23-year-old man. (a) In the left orbital region for 5 days when seen on 5 June 1986. (b) At the right side of the upper lip on 9 June 1986, when the larva was picked out by needle puncture and squeezing.

The worms can escape spontaneously through the skin or the conjunctiva. The interval between episodes of swelling varies from a few days to a few months, and rarely 1 to 2 years. Intermittent cutaneous migratory swelling can persist for more than 5 years.

Visceral forms

Visceral invasion, as described below for G. spinigerum infection, has not been reported in infections with other Gnathostoma species.

Spinocerebral gnathostomiasis

Involvement of the spinal cord commonly starts with intermittent agonizing shooting pains in a limb or a segment of the trunk, followed by paraplegia with urinary retention, and rarely, quadriplegia. Sensation is correspondingly impaired, and Brown–Séquard syndrome is sometimes seen. A few patients with haematoma and inflammation caused by brain invasion present with severe headache and vomiting, followed very quickly by coma, cranial nerve palsies, and/or hemiplegia. A rapidly advancing or changing pattern of neurological deficits is characteristic. Subarachnoid haemorrhage or eosinophilic meningitis without focal neurological deficit occasionally occurs.

The cerebrospinal fluid can be bloody, xanthochromic, or slightly turbid, with a minor increase in protein content. The proportion of eosinophils is higher than expected from haemorrhage per se.

Ocular gnathostomiasis

The parasite can be found in the anterior chamber (Fig. and the vitreous, having migrated through the sclera or the cornea. It can induce uveitis, iritis, intraocular haemorrhage, retinal detachment and scarring, and blindness.

Fig. Gnathostoma larva in the anterior chamber of the eye.

Gnathostoma larva in the anterior chamber of the eye.

(Courtesy of Professor Tiam Lawtiamtong.)

Auditory, pulmonary, intra-abdominal, and genitourinary gnathostomiasis

These uncommon forms can present with hearing loss, productive cough, pleurisy, intestinal obstruction, a painful intra-abdominal mass, and abnormal genital discharge.

Differential diagnosis

The diagnosis of cutaneous forms is based on clinical characteristics, geographical and dietary history, and by excluding other causes. Differential diagnoses include contact dermatitis, angio-oedema and urticaria, Calabar swellings (caused by Loa loa), fascioliasis, paragonimiasis, sparganosis, dirofilariasis, and noninfectious causes.

Gnathostoma infection is highly likely if rapidly advancing myelitis follows root pain, or if features of cerebral or subarachnoid haemorrhage occur in a person who is healthy apart from a history of cutaneous migratory swelling. Eosinophil pleocytosis is essential for the diagnosis, as is the exclusion of eosinophilic meningoencephalitis caused by Angiostrongylus cantonensis, Baylisascaris procyonis, or nonhelminthic encephalomyelitis.

In intraocular infections, the larvae of A. cantonensis can be distinguished from Gnathostoma species, as they are thinner, longer, and folding. They usually appear in the eyeball 2 to 3 weeks after the manifestation of eosinophilic meningoencephalitis.

Visceral gnathostomiasis usually depends on identifying the worm in surgical specimens (at autopsy the worms may have migrated away from the site of the main pathological lesion), or in secretions such as sputum, urine, or vaginal discharge.

Clinical investigation

The diagnosis is definitive if the worm can be identified in sections of surgical specimens, as described previously. The whole worm may be available if it emerges through the skin, in excretions and discharges, or from eye operations. Their sizes range from 0.34 × 2.2 mm to 1.0 × 16.25 mm. Their stage of development does not correlate with the duration of clinical illness. Infections with more than one worm are uncommon.

At present, there is no common serodiagnostic test available for all Gnathostoma species. An immunoblot test targeting a 24 kDa antigen for G. spinigerum infection has been used in Thailand and an immunoblot test targeting a 40kDa antigen for G. binucleatum has been developed in Mexico. A test using a recombinant 24 kDa antigen of advanced third-stage larvae of G. spinigerum is under development. Blood eosinophilia count (7–76%) occurs irregularly in about 60% of cases, and therefore is not necessary for presumptive diagnosis.

MRI can show tortuous tracks and haemorrhage in cerebral gnathostomiasis.

Criteria for diagnosis

Since the identification of the worm is not always possible, and clinical manifestations overlap with other illnesses, the diagnosis of gnathostomiasis requires the following criteria: (1), clinical presentation described above, and evidence of exposure to gnathostoma larvae, or (2), serological test positive for antibody against gnathostoma antigen, confirming the presumptive diagnosis.


Surgical removal is curative, but advisable only in accessible areas such as the eye or skin. Blind exploration of subcutaneous tissues in areas of diffuse swelling is not productive.

Oral therapy with albendazole at an adult dosage of 400 mg twice daily for 2 to 3 weeks induces migration of the parasite to the skin. The worms are frequently recovered between days 2 and 14 of treatment, picked out with a needle, excisional biopsy, or even scratched out by the patient’s fingernails. However, the success rate is only 6 to 7%. Recurrence of swelling in patients whose worms do not migrate to the skin is less frequent after albendazole treatment. Aminotransferases should be measured before this treatment, even though hepatotoxicity at this dosage is usually mild and reversible. Oral therapy with a single dose of ivermectin at 200 µg/kg is not superior to placebo or albendazole, but may be considered in patients in whom albendazole treatment fails.


Cerebral gnathostomiasis can be fatal, and blindness is frequent after intraocular infection. Patients can be reassured that central nervous system or intraocular involvement occurs in less than 1% of cases with cutaneous migratory swelling.

Further reading

Bussaratid V, et al. (2006). Efficacy of ivermectin treatment of cutaneous gnathostomiasis evaluated by placebo-controlled trial. Southeast Asian J Trop Med Public Health, 37, 433–40.Find this resource:

Bhaibulya M, Charoenlarp P (1983). Creeping eruption caused by Gnathostoma spinigerum. Southeast Asian J Trop Med Public Health, 14, 226–8.Find this resource:

    Caballero-Garcia M d L, et al. (2007). Protein profile analysis from advanced third-stage larvae (AdvL3) and adult worms of Gnathostoma binucleatum (Nematoda: Spirurida). Parasitol Res, 100, 555–60.Find this resource:

    Inkatanuvat S, et al. (1998). Changes of liver functions after albendazole treatment in human gnathostomiasis. J Med Assoc Thai, 81, 735–40.Find this resource:

    Kraivichian K, et al. (2004). Treatment of cutaneous gnathostomiasis with ivermectin. Am J Trop Med Hyg, 7, 623–8.Find this resource:

      Laummaunwai P, et al. (2004). Gnathostoma spinigerum: molecular cloning, expression and characterization of the cyclophilin protein. Exp Parasitol, 126, 611–6.Find this resource:

      Miyazaki I (1991). An illustrated book of helminthic zoonoses, pp. 368–409. International Medical Foundation of Japan, Tokyo.Find this resource:

        Nopparatana C, et al. (1991). Purification of Gnathostoma spinigerum specific antigen and immunodiagnosis of human gnathostomiasis. Int J Parasitol, 21, 677–87.Find this resource:

        Rusnak JM, Lucey DR (1993). Clinical gnathostomiasis: case report and review of the English language literature. Clin Infect Dis, 16, 33–50.Find this resource:

        Sirikulchayanonta V, Viriyavejakul P (2001). Various morphologic features of Gnathostoma spinigerum in histologic sections: Report of 3 cases with reference to topographic study of the reference worm. Southeast Asian J Trop Med Public Health, 32, 302–7.Find this resource:

        Suntharasamai P, et al. (1992). Albendazole stimulates outward migration of Gnathostoma spinigerum to the dermis in man. Southeast Asian J Trop Med Public Health, 23, 716–22.Find this resource:

        Swanson VL (1971). Gnathostomiasis. In: Marcial-Rojas RA (ed). Pathology of protozoal and helminthic diseases with clinical correlation, pp. 871–9. Williams and Wilkins, Baltimore.Find this resource:

          Uparanukraw P, et al. (2001). Cloning and expression of Gnathostoma spinigerum recombinant protein: matrix metalloproteinase. Parasitol Res, 87, 273–6.Find this resource: