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Clinical gnathostomiasis: case report and review of the English-language literature.

Human gnathostomiasis is most frequently caused by the nematode Gnathostoma spinigerum. This disease is endemic to Southeast Asia, particularly Thailand and Japan. The clinical presentation is most commonly characterized by localized, intermittent, migratory swellings of the skin and subcutaneous tissues, often in association with localized pain, pruritus, and erythema. Since this worm can migrate to deeper tissues, any organ system may become involved. Characteristically, patients with gnathostomiasis have a moderate to severe elevation of the peripheral eosinophil count, with values not uncommonly exceeding 50% of the total white blood cell count. With modern-day travel and immigration, cases of gnathostomiasis are being diagnosed with increased frequency in the United States. Because of its rarity in this country, however, gnathostomiasis often is not included in an initial differential diagnosis despite the characteristic triad of intermittent migratory swelling, a history of travel to Southeast Asia, and eosinophilia. We report a case of cutaneous gnathostomiasis diagnosed in the United States, and we present a clinical review of the English-language literature on human gnathostomiasis.

Adult↗

Diagnostic values of IgG4 in human gnathostomiasis.

The diagnostic values of immunoglobulin G subclass antibodies from patients with gnathostomiasis were assessed by immunoblot technique. Antigen was prepared from crude extracts of Gnathostoma spinigerum advanced third-stage larvae obtained from naturally infected eels. The sera were obtained from 14 parasite-confirmed gnathostomiasis cases, 63 patients with other helminthic infections and 13 healthy controls. Nine prominent IgG4 reactive bands appeared with molecular weights of 94, 51, 47, 43, 38, 24, 21, 20 and 15 kDa. The diagnostic sensitivity of each of the nine reactive bands ranged from 100% to 64.3% in 14 parasite-confirmed gnathostomiasis cases. All (100%) confirmed cases recognized the 21 kDa antigenic band, but not other helminthic infections or parasite-free control. Recognition of 21 kDa antigen in G. spinigerum advanced third-stage larvae crude extracts is the most specific diagnostic marker for human gnathostomiasis, with 100% sensitivity and specificity. The 20 and 24 kDa protein bands were additional diagnostic bands for confirming diagnosis of infection where the 21 kDa band was faint. No specific binding of IgG1, IgG2, or IgG3 antibodies was observed in any sera from confirmed gnathostomiasis cases.

Adult↗

Current status of gnathostomiasis dorolesi in Miyazaki Prefecture, Japan.

Gnathostomiasis is an important food-borne parasitic zoonosis caused mainly by ingesting uncooked or undercooked flesh of freshwater fishes. Although four distinct species of the genus Gnathostoma were identified as the causative agents for human gnathostomiasis, human infections with G. doloresi have been found only in Japan, concentrated in Miyazaki Prefecture. So far we have found 25 cases in Miyazaki Prefecture. Although most of these patients were of cutaneous gnathostomiasis, two patients presented to the hospital with unusual clinical manifestations; one case was a pulmonary gnathostomiasis diagnosed by immunoserological methods, and the other was an ileus caused by migration of the late 3rd stage larva in the colonic tissue, which was found by post-operative histopathological examination. Although cutaneous lesions such as creeping eruption or mobile erythema are the common clinical features of gnathostomiasis, caution should be paid to the presence of such unusual cases.

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[Gnathostomiasis caused by Gnathostoma spinigerum etiologically diagnosed upon extraction of the worm from the skin].

We report a patient with gnathostomiasis in whom a specific diagnosis of Gnathostoma spinigerum infestation was made morphologically upon removal of the worm. A 47-Year-old Japanese male on a business trip to Vietnam ate fried frog with a Vietnamese friend in January 2002, the friend was diagnosed with gnathostomiasis in June 2002. The patient noted swelling of the right leg with migration to the right arm, prompting him to our hospital in February 2003. Hematologic examination showed eosinophilia, and specific anti-gnathostome antibody was detected by a dot enzyme-linked immunosorbent assay (Dot ELISA) in the serum. He was diagnosed as gnathostomiasis, and was given albendazole 400 mg b.i.d. On day 11 of therapy the patient removed a larval worm from the right palmar lesion by pinching with his nails. The worm was identified as G. spinigerum based on morphologic characteristics including number of hooklets on its head-bulb. When gnathostomiasis is suspected, albendazole should be administered before incision of the skin lesion.

Albendazole↗

Short report: gnathostomiasis in Mexico.

Gnathostomiasis is an important food-borne parasitic zoonosis that is endemic mainly in Asian countries where some people prefer to eat raw freshwater fish. In North America, the first recorded case of gnathostomiasis was in Mexico in 1970, and the numbers of gnathostomiasis patients in Mexico seems to be increasing dramatically with time. However, the epidemiology of this disease in Mexico has never been described in detail. Here we review the current status of gnathostomiasis in Mexico.

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MR imaging findings in cerebrospinal gnathostomiasis.

Human gnathostomiasis is an infection caused mainly by Gnathostoma spinigerum, a nematode. Infected humans can present with various clinical manifestations. Serology is the criterion standard for diagnosing gnathostomiasis, whereas MR imaging represents a complementary tool for assessing severity and extent of disease. We report two definite cases of gnathostomiasis that were confirmed by the immunoblotting technique. MR imaging of the cervical cords showed cord enlargement and diffuse high signal intensity, mainly of the gray-white matter regions. MR imaging of the brain showed hemorrhagic tract and scattered deep intracerebral hemorrhage with diffuse, fuzzy white matter lesions with nodular enhancement. Severe gnathostomiasis was unresponsive to treatment.

Adolescent↗

Tolerability of ivermectin in gnathostomiasis.

At present, no universally-accepted effective treatment for cutaneous gnathostomiasis is available. At the Hospital for Tropical Diseases, Mahidol University, albendazole 400 mg twice a day for 14 days is commonly prescribed for patients diagnosed with cutaneous gnathostomiasis. The efficacy of albendazole to induce outward migration of the parasite was less than or around 20% in 2 studies. Research for alternative, more efficacious treatment, is needed. In this prospective open-labeled study, we assessed the safety of ivermectin in 20 Thai patients diagnosed with cutaneous gnathostomiasis. Ivermectin, one time only, at dosages of 50, 100, 150, or 200 microg/kg bodyweight, was given orally to 4 groups of patients, 5 patients each group. Adverse events were recorded and laboratory tests were obtained before and after treatment. No serious adverse events occurred in this study. Forty adverse events were possibly related to ivermectin. The adverse events were malaise (35%), myalgia (30%), drowsiness (30%), pruritus (20%), nausea/vomiting (20%), dizziness (15%), diarrhea (15%), feeling of shortness of breath (10%), feeling of palpitations (10%), constipation (5%), anorexia (5%), and headache (5%). These adverse events were self-limited and not dose-related. Laboratory abnormalities were found in 3 patients (15%). Transient microscopic hematuria, pyuria, and mildly elevated liver enzymes were found in 1 patient each. Ivermectin single dose, of 50,100, 150, and 200 microg/kg bodyweight, is considered safe in Thai patients. Future trials of ivermectin on human gnathostomiasis may be performed using dosages up to 200 microg/kg bodyweight.

Adult↗

Efficacy of ivermectin treatment of cutaneous gnathostomiasis evaluated by placebo-controlled trial.

Previous studies have revealed that ivermectin treatment for gnathostomiasis can reduce parasitic loads in animals and make recurrent subcutaneous swelling subside in 76% of patients. Our study aimed to evaluate the efficacy of ivermectin for cutaneous gnathostomiasis treatment in a placebo-controlled trial. This study was a prospective randomized placebo-controlled study performed at The Bangkok Hospital for Tropical Diseases, Mahidol University, Thailand. Thirty patients with a serologically confirmed diagnosis of cutaneous gnathostomiasis were enrolled. Seventeen patients in the ivermectin treated group received a single dose of 12 mg ivermectin (200 microg/kg bodyweight), while 13 patients in the control group received a single dose of 40 mg of vitamin B1. The follow-up period was 1 year. Of the 17 patients, 7 (41.2%) responded to ivermectin, while no patient responded to placebo. The mean (95% Cl) time to the first recurrence of subcutaneous swelling with ivermectin and in the placebo groups were 257 (184-331) and 146 (42-250) days, respectively, (p=0.102). Although this study revealed no significant difference in the mean time to first recurrence of swelling between the ivermectin and placebo groups, there was a trend towards ivermectin efficacy against gnathostomiasis in previous animal and human studies. Further studies with different doses of ivermectin and larger sample sizes, and close monitoring for ivermectin tolerability and treatment response are necessary to confirm an efficacy of ivermectin.

Adult↗

Historical review and current status of gnathostomiasis in Asia.

The genus Gnathostoma contains at least twelve distinctive species. Among these, 6 species, namely G. spinigerum, G. hispidum, G. doloresi, G. vietnamicum, G. malaysiae and G. nipponicum, are found in wild animals in Asia. Related to human gnathostomiasis, G. spinigerum has long been believed as the only causative species. Until the early 1980s, all gnathostomiasis cases found in major endemic areas in Asia, such as Thailand, China and Japan, were caused by infection with G. spinigerum. In the early 1980s in Japan, new gnathostomiasis cases appeared in urban areas and these cases were shown to be caused by G. hispidum, of which larvae were found in loaches imported from Taiwan, Korea, or mainland China. Recently infections with G. nipponicum caused by eating locally obtained loaches raw, were found in 2 humans in Mie Prefecture, and 14 cases of infection with G. doloresi, probably caused by eating raw slices of freshwater fishes, were found in Miyazaki Prefecture. So far four Gnathostoma species are responsible for zoonotic infections in humans. Since G. hispidum and G. doloresi, like G. spinigerum, are widely distributed in Asia, care should be taken with the identification of species causing gnathostomiasis.

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Gnathostomiasis in Southeast Asia.

Five species of Gnathostoma are at present reported from Southeast Asia with specific diagnostic characteristic of each. Also important references relating to the specific characters of the species concerned were mentioned, and the known experimental life cycles of three species namely G. spinigerum, G. hispidum, and G. doloresi found in the region were compared. The incomplete experimental study on the life cycle of G. vietnamicum is presented but the investigation on the life cycle of G. malaysiae is not yet initiated. Methods of transmission, symptoms and signs, the diagnosis and treatment of animal and human gnathostomiasis were also summarized. Effective therapeutic value of many anthelmintic drugs has not been satisfactory, by screening test on white mice previously infected in the tissue with G. spinigerum larvae. However, successful result of treatment was reported on one Japanese gnathostomiasis patient with thiabendazole. In the treatment of animal gnathostomiasis, Ancylol disophenol seems to be he effective drug for eliminating adult and migrating stage in the experimentally infected cats. Brief preventive measures against human gnathostomiasis was mentioned.

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Two cases of imported gnathostomiasis in Spanish women.

Reported here are two new cases of imported cutaneous gnathostomiasis that occurred in two Spanish women. The first patient acquired the helminth infection while travelling in Southeast Asia and the second in Mexico. Although the highest prevalence of gnathostomiasis infection is in Southeast Asia, the disease is now an emerging public health problem in some countries of Latin America. The cases reported here demonstrate the increasing frequency with which human gnathostomiasis is being diagnosed in nonendemic countries as a result of more extensive international travel and migration.

Adult↗

Specific antigen of Gnathostoma spinigerum for immunodiagnosis of human gnathostomiasis.

Sera from four patients with parasitologically confirmed gnathostomiasis, 15 patients with presumptive gnathostomiasis, 64 patients with various parasitic infections and 19 healthy adults were studied by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis for their reactivities against somatic extract of Gnathostoma spinigerum third-stage larvae (L3). It was found that the L3 extract was highly complex consisting of more than 20 antigenic components, a few of which gave reactions with sera from the healthy controls. Extensive cross-reactions of the parasite's antigen with sera from patients with other parasitic infections occurred. A specific antigen of G. spinigerum with a mol. wt of 24,000 (24k) was found to react with all parasitologically proven patients, five of the presumptive patients, one of the patients with other parasitic infections and none of the healthy individuals. This 24k component of G. spinigerum is a potential diagnostic antigen for use in the immunodiagnosis of human gnathostomiasis.

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Imported cutaneous gnathostomiasis: report of five cases.

Gnathostomiasis has rarely been described outside endemic countries. We report on a series of 5 patients (4 females, 1 male, mean age 42.2 years) who returned to France from South-East Asia and presented with cutaneous gnathostomiasis. The cutaneous lesions appeared within a mean period of 62 d (range 10-150 d) after return. They consisted of creeping eruptions in 3 patients (in addition one also had papules, one had nodules and hepatitis, and one had hepatitis; all 3 had profound asthenia) and recurring migratory swellings in 2 patients. The mean eosinophil count was 1546/mm3 (range 398-3245/mm3). Diagnosis was based on positive serological tests in 3 patients and seroconversion in 2 patients, and was confirmed by identification of Gnathostoma hispidum in a biopsy specimen from one of the seropositive patients. Albandazole (1-4 courses) was given as treatment. Recurrences may occur up to 24 months after apparent cure without reinfection. Gnathostomiasis should be considered when patients return from tropical countries and present with migratory swellings or creeping eruption that does not respond to the usual treatment for cutaneous larva migrans. Serological tests may be negative initially and thus need to be repeated to check for seroconversion. Treatment may require multiple courses of albendazole and a prolonged period of follow-up is necessary before cure can be confirmed.

Adult↗

Migratory facial swelling due to gnathostomiasis.

Two cases of facial gnathostomiasis in female Thai patients are described. Gnathostomiasis is caused by a roundworm, Gnathostoma spinigerum. In both patients the disease was characterised by intermittent and migratory swelling of the face. At present no effective therapy is available. Surgical removal of the parasite would be a curative treatment; it is however, rarely successful due to the parasite moving relatively rapidly within the soft tissues. The disease can be prevented by avoiding undercooked meat including fish. In endemic areas such as Southeast Asia, gnathostomiasis must be considered in cases of oro-facial swelling of otherwise unknown cause.

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A case of gnathostomiasis in a European traveller returning from Mexico.

Hundreds of human cases of gnathostomiasis have recently been reported from Mexico, where the disease is becoming a public health problem. We report a case of gnathostomiasis in a French tourist returning from Mexico. Tourists travelling in endemic countries are at risk of gnathostomiasis and should be advised about the risks of eating raw fish as a suspected source of infection.

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Gnathostomiasis: a review of a previously localized zoonosis now crossing numerous geographical boundaries.

Expansion in international travel and increases in immigration have resulted in an increased number of persons in Europe and other Western countries who have returned from foreign travel with parasitic infections rarely seen previously in the United States. Among the diseases caused by helminthic parasites is gnathostomiasis, a disease caused by Gnathostoma spp. Once confined primarily to Southeast Asia, it now is a public health concern in Mexico and other countries. This article reviews the causes and epidemiology of gnathostomiasis, the life cycle of the helminth, the clinical picture and diagnosis of gnathostomiasis, and the treatments for and means of avoiding the disease.

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Gnathostomiasis: clinicopathologic study.

Gnathostomiasis is a systemic parasitic disease that is caused by the ingestion of contaminated raw fish, the intermediate host. Involvement of the skin is a common event, and when it does happen, it can produce a superficial or creeping eruption, pseudofurunculosis, and nodular migratory panniculitis. We carried out a retrospective study of 946 cases of gnathostomiasis; 66 of them had skin biopsies. The diagnosis was made based on clinical and epidemio-logic findings as well as the therapeutic response. The most common skin finding was nodular migratory panniculitis affecting the trunk. Most of the patients were males between 20 and 40 years of age. Histopathologically, we were able to see the larva and make a definitive diagnosis in 15 cases, and in 12 cases, the worm was retrieved during the surgical procedure. In remaining cases, despite of our inability to identify the larva, the histopathologic changes were quite characteristic and included: dermal and hypodermal edema with dense mixed infiltrates composed of eosinophils admixed with lymphocytes and neutrophils, eosinophilic vasculitis, flame figures, areas of necrosis, and hemorrhage. Thus, the presence of these histopathologic features in the context of a clinical picture suggestive of gnathostomiasis allows the pathologist to make the correct diagnosis.

Adolescent↗

Gnathostomiasis possibly caused by Gnathostoma malaysiae.

Gnathostomiasis is rarely reported in travelers, although the disease remains a major public health problem in Southeast Asia. A creeping eruption and Quincke's edema (slowly migrating erythema with pruritus) appeared in two Japanese men who had eaten raw freshwater shrimp in Myanmar. A Gnathostoma larva was found in subcutaneous tissue from one of the men. Four species causing human gnathostomiasis, G. hispidum, G. doloresi, G. nipponicum and G. spinigerum, can be distinguished based on the number of nuclei in intestinal epithelial cells of infected larvae, in cross-section. In G. hispidum, only a single large nucleus is found. Morphologically, our larva was initially identified as G. hispidum. However, since the number of epithelial cells was greater and the body width was larger than those of a "large-type" 3rd-stage larva of G. hispidum, the larva was then identified as a 3rd-stage larva of G. malaysiae, Miyazaki and Dun, 1965, as reported by Setasuban et al, (1991). Since no human cases caused by this species of Gnathostoma have previously been encountered, this appears to be the first report of gnathostomiasis due to G. malaysiae.

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