Gnathostomiasis : Report of a case and brief review

Nematodes of the genus Gnathostoma can cause a spectrum of disease in humans. This includes a distinctive syndrome of intermittent migratory subcutaneous swellings, central nervous system involvement with high morbidity and mortality and occasionally, involvement of other organs. Gnathostomiasis is endemic in southern and eastern Asia, particularly Thailand, but has recently been reported from Ecuador and Mexico. Diagnosis is usually based on clinical, epidemiological and serological findings. A recent study suggests that treatment with albendazole is effective. This report describes a patient diagnosed in Canada in whom evidence of pericarditis was associated with gnathostomiasis and in whom treatment with albendazole appears to have been effective.

G NATHOSTOMA SPINIGERUM WAS FIRST IDENTIFIED IN THE gastric tumour of a tiger in 1836 (1).Human gnathostomiasis was first reported from Thailand in 1890 in a woman presenting with a breast mass (2).The disease is being recogn ized with increasing frequency due to better appreciation of the clinical features and improved diagnostic techniques.It is sufficiently com-mon in endemic regions that occasional cases can be expected in North America, yet North American physicians are often not familiar with the disorder.Two recent developments make awareness of this infection mor e important: the recognition of endemic foci in the westem hemisphere and evidence that medical therapy is effective.

HOUSTON
This report describes a patient whose gnathostomiasis was diagnosed in a very nontropical Canadian city and who had clinical evidence of pericardial involvement which has been reported only once previously.

CASE PRESENTATION
A 31-year-old woman of Thai origin was referred because of eosinophilia and recurrent superficial swellings.
She first noticed the swelling about six years previously and described almost identical recurrences a pproximately once a year since then.Each episode was characterized by the rapid appearance of a mildly painful swelling over the right lower forearm lasting about two weeks.Episodes were not accompanied by fever or other systemic symptoms nor by swelling or pruritis at any other site.She specifically denied any history of serious neurological disease or chest pain.She was entirely well between episodes.She had presented with similar symptoms to a physician in Canada two years previously.A peripheral eosinophilia was present and Strongyloides larvae were found on stool examination at that time, but the eosinophilia resolved after treatment with thiabendazole.Her past history was otherwise negative.
The patient had spent most of her life in a small village in northern Thailand.Although now married to a Canadian, she continues to spend about six months each year in Thailand.She admitted e<j.ting a variety of local foods in Thailand including uncooked fish.
On examination she was afebrile and looked well.There was a subcutaneous swelling 4 to 5 em in diameter with poorly defined margins over the distal right forearm.It was mildly tender but neither warm nor red.The only other abnormality on physical examination was a loud pericardia] rub.This was documented by two physicians at the first visit and was noted at a subsequent visit two weeks later in spite of having been found to be absent on one examination in the interval.The cardiovascular system was otherwise completely normal with no evidence of tamponade.
The absolute eosinophil count was 5.9x10 9 /L.Ch est x-ray and electrocardiogram were normal; echocardiography revealed a trace of pericardial Duid.Western blot examination of serum using a somatic extract of the third stage larva of Gnathostoma spinigerum (3) supported the clinical diagnosis of gnathostom iasis.
The swelling resolved completely without specific treatment.Albendazole 400 mg twice daily was given by mouth for 14 days starting several weeks after resolution of the swelling.No adverse effects were associated with the treatment.Th e pericardia! rub was absent on each of several examina tions performed more than two weeks after initial presentation.No recurrent swelling had been noted when the patient was contacted 30 months after comp letion of therapy and the absolute eosinophil count at 21 months was 0.2x10 9 /L.and Gnathostoma doloresi (6) have been described.Life cycle (Figure 1): First-stage larvae in water are ingested by a tiny crustacean, cyclops.Second-stage larvae in infected cyclops are in turn ingested by a second intermediate host, frequently one of several species of fresh water fish.The parasite penetrates the gastric wall and the third-stage larva encysts in the muscle of the second intermediate host.'Secondary' infection with third-stage larvae, of another second intermediate host, can occur if it ingests the 'primary' second intermediate host.This has been demonstrated experimentally in at least 33 animals including crustaceans, fish, amphibians, reptiles, birds and mammals, and appears to occur commonly in nature (7).The infection is productive only in the definitive hosts-dogs, cats and some wild animals -where larvae mature in the wall of the stomach, mate there and release eggs into the feces.The eggs hatch in water producing firststage larvae.
The main source of human infection is thought to be ingestion of inadequately cooked Desh of either the 'primary' or 'secondary' second intermediate hosts harbouring third-stage larvae.Fresh water fish and domestic poultry may be the most important.sources (8).Based on animal models, it is thought that ingestion of water containing infected cyclops may be an occasional mechanism for human infection (9).Experimentally, the parasite can penetrate the intact.skin of cals, indicating lhal handling the flesh of infected fish cou ld also be a source of human infection (10).Three cases of apparent perinatal transmission h ave been reported ( 11, 12) .Human infection involves third-stage larvae of either sex and of varying degrees of malurily, ranging from 2.2 lo 16.25 mm in length (11).Geographic distribution: Most cases of human gnathostomiasis have been reported from Asia, particularly Thailand but including China, Japan and several countries of southeast.Asia from Bangladesh lo the Philippines.One case was reported in a woman who had lived only in Europe and Israel (13).RecenUy there has been a number of reports of human gnathostomiasis from Latin America ( 14-16) and infested fresh water fish have been documented there (17).Clinical features: It is thought that.symptoms and organ damage in gnathostomiasis are due to mechanical tissue injury produced by this macroscopic nematode in its migrations.
The incubation period between ingestion of gnalhosloma larvae and the first.development.of cutaneous symptoms is three lo four weeks (7).Abdominal pain and vomiting occurred within 24 to 48 h, followed by pulmonary, lhen cutaneous symptoms in a common source outbreak involving nine individuals who consumed raw fish at. a party (18).
The clinical features of reported cases of gnathostomiasis are documented in lwo comprehensive reviews (9, 19).The most.common presentation is that. of recurrent subcutaneous swellings which are usually painless but sometimes associated with pain sufficient to result in confusion with bacterial cellulitis .These swellings reflect the migration of lhe parasite.They may last.one to two weeks and recur at intervals of weeks lo months at the same or different sites.Systemic symptoms are not usually noted.A peripheral eosinophilia is usual but not.invariable.A superficial creeping eruption has also been described (20).There is a tendency for recurrences lo become less frequent and less severe over time but they may persist for over 10 years inclicating that the parasite may live that long in the human host.A syndrome of migratory subcutaneous nodules may also be seen in paragonimus infections (62).
The most.serious manifestation of gnathostomiasis is central nervous system (CNS) involvement., first proven only in 1967 (21) although it had been previously suspected (22.23).Recognized presentations include encephalitis.painful radiculitis, myelitis, cranial nerve palsies.subarachnoid hemorrhage (24) and eosinophilic meningitis or combinations of these.Gnathostoma.unlike angiostrongylus.does not seem lobe neurotropic but to involve the CNS only by chance.Brain involvement and subarachnoid hemorrhage have also been described in infections wilh Paragonimus Gnathostomiasis westermani var szechuanensis (62).CNS gnathostomiasis may occur in any age group.Only 7% of 162 patients in one report had a history of intermittent migratory cutaneous swellings while 4% had unilateral eyelid swelling (25).
Peripheral eosinophilia is usual in CNS gnathostomiasis-an eosinophilia of greater than 10% was found in 57% in one series (25).Cerebrospinal fluid (CSF) pleocytosis with at least 10% eosinophils is present at some point in lhe course of nearly all patients with CNS gnathostomiasis (25,26).The other important.cause of eosinophilic meningitis.Angiostrongylus cantonensis, is also endemic in parts of southeast Asia but the clinical syndrome is usually one of meningeal involvement.only and is self-limiting (27).Among 162 patients with CNS gnathostomiasis, bloody or xanthochromic CSF was found in 64%, CSF pressure was elevated in more than half.CSF protein exceeded 50 mg/ 100 mL in 72% but CSF glucose was depressed in only 10% (25).
Case fatality was at least 12% among 162 patients with probable CNS gnathostomiasis in the largest.series (25).The authors believed the true case fatality rate was considerably higher since 38 patients were taken home unimproved, many critically ill.Sixly-five per cent were considered 'improved', many with persisting neurological deficits.Autopsies of patients with CNS gnaU1ostomiasis have revealed grossly visible worm tracks with accompanying necrosis and hemorrhage in the brain or spinal cord (28).
There is one report.in the literature of a patient with a pericardia!effusion, documented by echocardiogram, associated with gnathostomiasis (56).The patient.. of Nepalese origin, also had a pleural effusion, peripheral eosinophi lia and intermittent migratory swellings over the chest wall from one of which a gnathostome was removed.Following removal of the worm (and treatment with diethylcarbamazine) the patient ex'Perienced prompt clinical and radiological improvement.without relapse.

Diagnosis:
The diagnosis of gnathostomiasis is usually made in the presence of a distinctive clinical syndrome.most often intermittent migratory swellings or compatible CNS disease, in a person from an endemic area.Retrieval and identification of the worm confirm the diagnosis with certainty when this is possible.Even when the worm is missed.histology of the panniculitis lesions is said by one author lo be characteristic ( 14).The presence of a marked peripheral blood eosinophilia is typical but not invariable (57).Skin testing for gnathostomiasis has been used.but.recent develop-ments in serological testing appear to be very prom ising (3 ,58).
Treatment: Until recently the only treatment known to be effective was removal of the worm.Corticosteroids may speed resolution of cutaneous swell ings (56) but have not been proven to have any benefit in the most serious form of the disease -in the CNS (25).Ivermectin and albendazole appear to have a therapeutic effect in anima l models (59,60) .One recent report describes the elimin a tion of episodes of intermittent migratory swelling at six months follow-up in 89 of 100 patients treated orally with either 400 mg daily or 400 mg bid of a lbendazole for 21 days (61), while recurren ces were noted in all 12 placebo recipients.Eosinophilia resolved in more than 90% of those treated but in only one of 12 placebo recipi e nts, and serological titres declined in th e treat-ACKNOWLEDGEMENTS: The author gratefully acknowledges the assistance of Dr Wan pen Chaicumpa.Mahiclol Un iversity.Thailand.who perfom1ecl the serological testing on this patient.and Sm ith Kline Beecham for providing albenclazole.ment but not the p lacebo group .Interestingly, treatment appeared to provoke m igration of the la rvae to the skin where 22 were removed from 21 patients.It is to be hoped that longer follow-up and fu rther experience will confirm these very encouraging results.There are no reports of a lbendazole treatment of CNS disease.

REFERENC ES
In tl1e presented patient the typical h istory and appeara nce of intermittent migratory swellings, the epidemiological history, and the positive serological test clearly indicate a diagnosis of gnathostomiasis.A pericardia !rub is an objective cl inical find ing which is rarely if ever 'incidental'.The striking temporal association of a pericardia!rub with an episode of interm ittent m igra tory swelling.and the a bsence of an alternative cause, strongly s uggest that it was related to gnathostomiasis.