gnathostomiasis is a food - borne parasitic zoonosis caused by the third stage larvae of the genus gnathostoma .
human infection is mainly resulted from eating raw or undercooked intermediate hosts ( e.g. fish , eels , and loaches ) or paratenic hosts ( e.g. crustaceans , freshwater fish , and mammals ) containing the third - stage ( l3 ) larvae .
the larvae can not mature in humans and keep migrating in the skin , subcutaneous tissues , or other organs .
gnathostomiasis is characterized by intermittent creeping eruptions and/or migrating swellings and eosinophilia ; larval migration to other tissues ( visceral larva migrans ) can result in a serious consequence .
if untreated , gnathostomiasis may remit and recur several times until death of the larvae up to 12 years after infection .
the endemic foci of gnathostomiasis have been predominantly distributed in japan and southeast asia , particularly thailand , but the disease is also endemic in cambodia , laos , myanmar , indonesia , the philippines , and malaysia .
human cases have also been reported in india , australia , brazil , and parts of south africa , and it has been regarded as an emerging disease . imported human cases of gnathostomiasis were also reported in the republic of korea .
recently , it has been known that this disease is endemic in the pacific region of mexico . in china
, gnathostomiasis occurred sporadically in 23 provinces , autonomous regions , or municipalities . until the year 2012
, 57 cases of gnathostomiasis have been reported in the chinese literatures ; however , only 1 case was reported in english . also , to our knowledge , no human cases of gnathostomiasis have been reported in henan province , china .
accordingly , the present study reports for the first time a human case of cutaneous gnathostomiasis in henan province , china .
a 52-year - old lady from zhengzhou city of henan province , central china , presented to the parasitology department of zhengzhou university on 22 august 2011 .
she had a 3-month history of recurrent appearance of migratory reddish swelling in the upper arm and on the back .
the initial lesions appeared on the left side of the back and subsequent lesions were observed in the left upper arm .
these swellings were characterized by a migrating edema with a cord - like shape and pruritic nodules .
the swellings reappeared in a different area close to the previous one after about 10 - 15 days of subsidence of the initial lesion .
she was an officer , denied a history of travel abroad , and never had any pets , nor had a history of intimate exposure to stray cats , dogs , or other domestic animals . on physical examination ,
initial laboratory testing revealed a normal white blood cell count of 4,900 , but with high eosinophilia ( 21.2% , 1,040 eosinophils / ml ) .
the serum specific antibodies against tissue - dwelling parasites ( paragonimus skrjabini , schistosoma japonicum , metacestode of taenia solium , and trichinella spiralis ) were assayed by elisa or immunofluorescence test ( ift ) , and shown to be negative . however , anti - sparganum antibodies were positive by elisa using excretory - secretory ( es ) antigens of spirometra erinacei spargana .
the optical density ( od ) of the serum samples from this patient was 0.46 , whereas the positive ( patients with sparganosis ) and negative ( normal persons ) controls were 0.55 and 0.21 , respectively .
serum samples were sent to the third affiliated hospital of sun yat - sen university and anti - sparganum antibodies were also positive .
skin biopsy was performed at 1 cm of the anterior end of the nodule near the axilla on the left side of the back on 28 august 2011 .
histopathologic examination of the biopsy samples revealed a dense superficial and deep dermal infiltrate of eosinophils and neutrophils but did not show any parasites .
one day after the skin biopsy , multiple migrating subcutaneous nodules reappeared on the patient 's back ( fig .
subcutaneous sparganosis was diagnosed on the basis of clinical manifestations and results of serologic tests , and the patient was treated with praziquantel ( 75 mg / kg / day in 3 doses for 3 days ) .
however , 1 day after the treatment , new migratory swellings occurred in the left upper arm ( fig .
1b ) ; anti - sparganum antibodies were re - assayed and remained positive . on further inquiring ,
she recalled that she had eaten undercooked eels . thus , gnathostomiasis was highly suspected on this history , together with symptoms such as recurrent migratory subcutaneous nodule and eosinophilia .
the serum sample was sent to the institute of parasitic diseases of zhejiang academy of medical sciences , dot immunogold filtration assay ( digfa ) using soluble antigens of the third stage larvae ( l3 ) of g. spinigerum presented by mahidol university in thailand showed that anti - gnathostoma antibodies were strongly positive , and anti - sparganum antibodies were only weakly positive .
the patient was treated with albendazole ( 1,000 mg / day , twice daily for 15 days ) .
one day after the beginning of the treatment , the migrating swellings in the left upper arm tended to be confined and a papule developed ( fig .
however , parasites were not found by examination of the puncture samples of the blister .
two days after the treatment , the papule disappeared but anti - gnathostoma antibodies were still positive ; laboratory testing revealed a white blood cell count of 5,800 , with 5.5% eosinophils .
after 1 month , laboratory findings showed an almost normal eosinophil count ( 3.3% ) . at her final follow - up at 18 months ,
although 13 species of the genus gnathostoma have been reported to date , 5 of them such as gnathostoma spinigerum , g. nipponicum , g. hispidum , g. doloresi , and g. binucleatum infect humans . out of these species ,
g. binucleatum is a major etiologic agent of gnathostomiasis in endemic areas of america , especially in mexico and venezuela .
g. spinigerum is the most common and important agent of gnathostomiasis in china . out of 57 cases with gnathostomiasis
reported in china during 1918 - 2012 , 54 cases were caused by g. spinigerum , 2 by g. hispidum and 1 by g. doloresi .
a previous survey showed that 23 species of animals ( 6 cyclops , 13 fish , 2 frogs , and 1 each of snake and bird ) served as the first or second intermediate host , or a paratenic host of g. spinigerum in 3 provinces ( jiangsu , anhui , and jiangxi ) of china .
the triad of eosinophilia , migratory lesions , and obvious exposure risk are highly suggestive of the diagnosis of gnathostomiasis .
the exposure risk usually include consumption of raw or undercooked fish ( in particular , swamp eels and loaches ) , or meat of intermediate or paratenic hosts .
the definite diagnosis was established by isolation of larvae from the lesions , but this is often difficult in migratory skin lesions .
the detection rate of larvae in skin biopsy specimens was only 24 - 34% of the cases .
treatment with albendazole may promote outward migration of the larvae to the dermis , and stimulate development of a papule or pseudo - furuncle containing the larva .
biopsy of a papule or pseudo - furuncle subsequent to treatment increases the likelihood of demonstrating the larva on skin biopsy specimens .
regrettably , our patient disagreed with a second skin biopsy . with introduction of antigens from l3 larvae of g. spinigerum ,
the serodiagnosis of gnathostomiasis became more convenient and efficient , although cross - reactivity with other parasitic infections remained a problem .
our patient was first misdiagnosed as sparganosis because of a cross - reactivity with in s. erinacei sparganun antigens .
.   found that a specific l3 antigen with a molecular mass of 24 kda had the greatest specificity and reacted only with sera from the patients with gnathostomiasis sera and not with those from other parasitic infections .
hence , immunoblot is now regarded as the most valuable serologic test and can be used as a confirmatory test of gnathostomiasis when specific antibodies to 24 kda component of g. spinigerum l3 larvae were detected .
although recommended dose of albendazole for gnathostomiasis is 400 mg / day for 21 days , our patient was cured with a shorter course of albendazole ( 1,000 mg / day for 15 days ) treatment .
although gnathostoma larvae were not found in the skin biopsy of our patient , the patient was diagnosed as cutaneous gnathostomiasis according to the following evidences : the history of eating undercooked eels , typical clinical manifestations ( recurrent migratory subcutaneous nodule ) , persistent eosinophilia , specific anti - gnathostoma antibodies , and a cure by albendazole . the excellent therapeutic response to albendazole
this case is most likely be caused by g. spinigerum which is the predominant agent of gnathostomiasis in china .
because clinicians outside of high endemic areas are unfamiliar with the disease , and therefore diagnosis is often missed or prolonged .
the classic triad of intermittent migratory swellings , persistent eosinophilia , and a history of eating raw freshwater fish should alert physicians to the possible diagnosis of gnathostomiasis .
recently , some chinese people have the habit of eating raw fish ; sashimi was often served in restaurants and hotels . in addition , some inhabitants like to eat quick - fried eels or scalded eel fillets .
if the fillet was too large and the time of scalding was insufficient , the temperature in the fillet center would not be sufficient to kill the larvae .
recently , l3 of gnathostoma spp . have also been detected from wild swamp eels sold at the market in henan and zhejiang provinces ( http://zjnews.zjol.com.cn/05zjnews/system/2011/10/28/017949925.shtml ) . in thailand ,
the infection rate of farmed and wild eels with g. spinigerum was 10.2% and 20.4% , respectively .
moreover , swallowing live loaches have become a folk remedy in some areas of china since some inhabitants believe the live loaches to have a medicinal role for treating diseases .
gnathostomiasis cases resulted from ingestion of native loaches or loaches imported from korea or mainland china were also reported in japan .
gnathostoma larvae were found in imported chinese loaches in korea . to prevent human gnathostoma infection
, the government , public health officials , and medical practitioners should be aware of misdiagnosis of zoonotic gnathostomiasis .
the best strategies for preventing gnathostomiasis are to educate people to only consume fully cooked meat , especially avoiding raw and undercooked freshwater fish and loaches in endemic areas . in conclusion , we report here a case of cutaneous gnathostomiasis in henan province , china based on the history of eating undercooked eels , recurrent migratory subcutaneous nodule , persistent eosinophilia , specific anti - gnathostoma antibodies , and cure by albendazole .
our study presents a risk of gnathostoma infection by consumption of undercooked freshwater fish ; therefore , fish inspection for gnathostoma larvae should be carried out for ensuring food safety and public health .
 the present study reports a human case of cutaneous gnathostomiasis with recurrent migratory nodule and persistent eosinophilia in china . a 52-year - old woman from henan province , central china , presented with recurrent migratory reddish swelling and subcutaneous nodule in the left upper arm and on the back for 3 months . 
 blood examination showed eosinophila ( 21.2% ) , and anti - sparganum antibodies were positive . 
 skin biopsy of the lesion and histopathological examinations revealed dermal infiltrates of eosinophils but did not show any parasites . 
 thus , the patient was first diagnosed as sparganosis ; however , new migratory swellings occurred after treatment with praziquantel for 3 days . on further inquiring 
 , she recalled having eaten undercooked eels and specific antibodies to the larvae of gnathostoma spinigerum were detected . 
 the patient was definitely diagnosed as cutaneous gnathostomiasis caused by gnathostoma sp . and treated with albendazole ( 1,000 mg / day ) for 15 days , and the subsequent papule and blister developed after the treatment . 
 after 1 month , laboratory findings indicated a reduced eosinophil count ( 3.3% ) . at her final follow - up 18 months later , the patient had no further symptoms and anti - gnathostoma antibodies became negative . 
 conclusively , the present study is the first report on a human case of cutaneous gnathostomiasis in henan province , china , based on the past history ( eating undercooked eels ) , clinical manifestations ( migratory subcutaneous nodule and persistent eosinophilia ) , and a serological finding ( positive for specific anti - gnathostoma antibodies ) . 
INTRODUCTION
CASE RECORD
DISCUSSION