Case Report: The First Direct Evidence of Gnathostoma spinigerum Migration through Human Lung.

Gnathostomiasis is a helminthic infection caused by the third-stage larvae of nematodes of the genus Gnathostoma. The life cycle in humans starts with an enteric phase, with the worm perforating the gastric or intestinal mucosa to reach the peritoneal cavity and migrating through the human body. Subsequent penetration through the diaphragm may produce pleuropulmonary symptoms. We herein present a previously healthy 56-year-old Thai man from Southern Thailand who was an ex-smoker presented with chronic dry cough progressing to hemoptysis after consuming grilled swamp eels and freshwater fish. Chest computed tomography showed consolidation at the lingular segment, and the differential diagnosis was primary lung cancer and pulmonary tuberculosis. The lung tissue biopsied during bronchoscopy displayed segments of organisms with the phenotypic characteristics of Gnathostoma spp., and abundant eosinophils were seen in the alveolar tissue. Gnathostoma spinigerum infection was confirmed by a Western blot assay for G. spinigerum-specific 24-kDa reactive band. The patient received albendazole, and a follow-up chest radiograph revealed improvement in the consolidation in the lung and reduction in hemoptysis. We report the first direct evidence including pathology and immunohistochemistry of Gnathostoma invasion via the human lung, with clinical and radiographic presentations mimicking either malignancy or chronic infection.

Molecular Identification of the Etiological Agent of Human Gnathostomiasis in an Endemic Area of Mexico.

Human gnathostomiasis, which is endemic in Mexico, is a worldwide health concern. It is mainly caused by the consumption of raw or insufficiently cooked fish containing the advanced third-stage larvae (AL3A) of Gnathostoma species. The diagnosis of gnathostomiasis is based on epidemiological surveys and immunological diagnostic tests. When a larva is recovered, the species can be identified by molecular techniques. Polymerase chain reaction (PCR) amplification of the second internal transcription spacer (ITS-2) is useful to identify nematode species, including Gnathostoma species. This study aims to develop a duplex-PCR amplification method of the ITS-2 region to differentiate between the Gnathostoma binucleatum and G. turgidum parasites that coexist in the same endemic area, as well as to identify the Gnathostoma larvae recovered from the biopsies of two gnathostomiasis patients from Sinaloa, Mexico. The duplex PCR established based on the ITS-2 sequence showed that the length of the amplicons was 321 bp for G. binucleatum and 226 bp for G. turgidum. The amplicons from the AL3A of both patients were 321 bp. Furthermore, the length and composition of these amplicons were identical to those deposited in GenBank as G. binucleatum (accession No. JF919679), corroborating our previous morphological finding that G. binucleatum is the etiological agent for human gnathostomiasis in the endemic area of Sinaloa, Mexico.

Emerging infections: mimickers of common patterns seen in dermatopathology.

The following discussion deals with three emerging infection diseases that any dermatopathologist working in the northern hemisphere can come across. The first subject to be dealt with is gnathostomiasis. This parasitic disease is produced by the third larvarial stage of the parasite that in most patients is associated with the ingestion of raw fish. Epidemiologically, it is most commonly seen in South East Asia, Japan, China, and the American continent, mainly in Mexico, Ecuador, and Peru. Nowadays, the disease is also seen in travelers living in the developed countries who recently came back from visiting endemic countries. The disease produces a pattern of migratory panniculitis or dermatitis with infiltration of eosinophils in tissue. The requirements for making the diagnosis are provided, including clinical forms, common histological findings on skin biopsy as well as the use of ancillary testing. Buruli ulcer, a prevalent mycobacterial infection in Africa, is described from the clinical and histopathological point of view. The disease has been described occasionally in Central and South America as well as in developed countries such as Australia and Japan; Buruli ulcer has also been described in travelers returning from endemic areas. Clinically, the disease is characterized by large, painless ulcerations with undermined borders. Systemic symptoms are usually absent. Classical histological findings include a particular type of fat necrosis and the presence of abundant acid fast bacilli in tissue. Such findings should raise the possibility of this disease, with the purpose of early therapeutically intervention. Lastly, the infection by free living ameba Balamuthia mandrillaris, an emerging condition seen in the US and Peru, is extensively discussed. Special attention is given to clinical and histological characteristics, as well as to the clues for early diagnosis and the tools available for confirmation.

Vulvitis migratoria causada por gnatostomiasis importada / Migratory vulvitis caused by imported gnathostomiasis

Resumen La gnatostomiasis es una parasitosis emergente en países no endémicos. Este nematodo zoonótico requiere de agua dulce para su ciclo de vida, donde sus larvas se enquistan principalmente en peces. La migración subcutánea de las larvas produce habitualmente una paniculitis eosinofílica de rápido avance. Se describe un caso clínico de un paciente con una lesión migratoria, sin mejoría clínica con terapia antibacteriana. La búsqueda de factores de riesgo, sumado a la evolución y a los hallazgos de laboratorio hizo sospechar el diagnóstico. La gnatostomiasis debe ser sospechado en pacientes con lesiones de piel migratorias, que han consumido pescado crudo durante viajes a países endémicos en Sudamérica o Asia.

Gnathostomiasis is an emerging disease in non-endemic countries. This zoonotic nematode requires aquatic freshwater environments to complete its life cycle where larvae get encrusted in fishes. Typically, the infection manifests as migratory subcutaneous lesion caused by the larvae trak, which produces an eosinophilic panniculitis. Here we describe a patient who presented a migratory lesion with no response to antimicrobial therapy, a careful travel and food history together with specific laboratory tests led to the correct diagnosis. Gnathostomiasis should be suspected in patients with migratory skin lesions who have consumed raw freshwater fish during travel to endemic countries in South America or Asia.

Cloning and expression of a 16-kDa recombinant protein from Angiostrongylus cantonensis for use in immunoblot diagnosis of human angiostrongyliasis.

Angistrongylus cantonensis is a zoonotic nematode parasite and causative agent of human angiostrongyliasis, which clinically presents as eosinophilic meningitis or meningoencephalitis. Diagnosis of the disease is problematic since parasitologic findings are infrequent, and infection determinations must be based on the clinical symptoms and serological tests with limited specificities and sensitivities. The aim of the present study was to identify and generate a novel recombinant protein from A. cantonensis and evaluate its efficacy in the diagnosis of human angiostrongyliasis when incorporated into a Western blot serodiagnostic system. A cDNA protein expression library from adult A. cantonensis was constructed, followed by immunoscreening with serum from confirmed infected patients to identify and isolate immunoreactive clones. One clone, designated fAC40, possessed a partial sequence encoding a LisH protein domain with a predicted molecular weight of 16 kDa and containing four predicted antigenic peptides. By incorporating recombinant fAC40 in Western immunoblot tests using a serum panel consisting of confirmed and clinically diagnosed cases of human angiostrongyliasis and other helminthic infections, fAC40 exhibited a sensitivity and specificity of 91.8 and 100 %, respectively, and a positive and negative predictive value of 100 and 97.19 %, respectively, in the diagnosis of angiostrongyliasis. Importantly, it was not reactive with antibodies from serum of patients infected with Gnathostoma spinigerum and Cysticercus cellulosae, infections that clinically present neurological symptoms similar to angiostrongyliasis. These data demonstrate that the 16-kDa recombinant protein from A. cantonensis possesses high potential as a candidate antigen for a more sensitive and specific serodiagnosis of human angiostrongyliasis.

Tropical dermatology: cutaneous larva migrans, gnathostomiasis, cutaneous amebiasis and trombiculiasis.

In today's world, many people can travel easily and quickly around the globe. Most travel travel-related illnesses include fever, diarrhea, and skin disease, which are relatively uncommon in returning travelers. We review four of the most common emerging infestations and skin infections in the Americas, which are important to the clinical dermatologist, focusing on the clinical presentation and treatment of cutaneous larva migrans, gnathostomiasis, cutaneous amebiasis, and trombiculiasis.

[Foodborne dermatosis after traveling: gnathostomiasis]. / Dermatosis de origen alimentario al regreso de un viaje: gnathostomiasis.

We describe a case of a 32-year-old man, resident in Buenos Aires, with dermatologic manifestations compatible with gnathostomiasis. The patient had traveled to Colombia in the month prior to the onset of symptoms. There, he repeatedly ate ceviche (raw fish marinated in lemon juice). He presented with an erythematous migratory panniculitis accompanied by eosinophilia. He underwent skin biopsy of a lesion and pathological diagnosis was "eosinophilic panniculitis". The triad of migratory panniculitis, eosinophilia and consume of raw fish during the trip to Colombia was suggestive of gnathostomiasis. Ivermectin treatment started out with good initial response but subsequent relapse. We performed a new treatment with the same drug with good results and no relapses during three years of follow up. The dermatological disease is common upon return from a trip, and is the third leading cause of morbidity in travelers. It is very important to recognize cutaneous manifestations of disease as many of them are potentially serious and may compromise the patient's life if not promptly diagnosed and treated.

Dermatosis de origen alimentario al regreso de un viaje: gnathostomiasis / Foodborne dermatosis after traveling: gnathostomiasis

Se describe el caso de un paciente de 32 años de edad, residente en Buenos Aires, con manifestaciones dermatológicas compatibles con gnathostomiasis. Había realizado un viaje a Colombia en el mes previo a la aparición de la sintomatología. Allí consumió cebiche (pescado crudo marinado en jugo de limón) en reiteradas oportunidades. El cuadro clínico se presentó como paniculitis eritematosa y migratoria acompañada de eosinofilia sanguínea. Se le realizó biopsia cutánea de una lesión y el diagnóstico anatomopatológico fue "paniculitis eosinofílica". La tríada de paniculitis migratoria, eosinofilia sanguínea y el consumo de pescado crudo durante el viaje a Colombia fue sugestiva de gnathostomiasis por lo que se indicó tratamiento con ivermectina con buena evolución inicial y recaída posterior. Se realizó un nuevo tratamiento con la misma droga con buena evolución y sin recaídas durante tres años de seguimiento. La afección dermatológica es un motivo frecuente de consulta al regreso de un viaje, y representa la tercera causa de morbilidad en viajeros. Es muy importante el reconocimiento de las enfermedades que pueden tener manifestación cutánea, ya que muchas de ellas son potencialmente graves y pueden poner en riesgo la vida del paciente si no son oportunamente diagnosticadas y tratadas.

We describe a case of a 32-year-old man, resident in Buenos Aires, with dermatologic manifestations compatible with gnathostomiasis. The patient had traveled to Colombia in the month prior to the onset of symptoms. There, he repeatedly ate ceviche (raw fish marinated in lemon juice). He presented with an erythematous migratory panniculitis accompanied by eosinophilia. He underwent skin biopsy of a lesion and pathological diagnosis was "eosinophilic panniculitis". The triad of migratory panniculitis, eosinophilia and consume of raw fish during the trip to Colombia was suggestive of gnathostomiasis. Ivermectin treatment started out with good initial response but subsequent relapse. We performed a new treatment with the same drug with good results and no relapses during three years of follow up. The dermatological disease is common upon return from a trip, and is the third leading cause of morbidity in travelers. It is very important to recognize cutaneous manifestations of disease as many of them are potentially serious and may compromise the patient's life if not promptly diagnosed and treated.

Cutaneous gnathostomiasis with recurrent migratory nodule and persistent eosinophilia: a case report from China.

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).

Gnathostoma spinigerum infection in the upper lip of a Korean woman: an autochthonous case in Korea.

Autochthonous human gnathostomiasis had never been reported in the Republic of Korea. We report here a case of Gnathostoma spinigerum infection in a 32-year-old Korean woman, presumed to have been infected via an indigenous route. The patient had experienced a painful migratory swelling near the left nasolabial fold area of the face for a year, with movement of the swelling to the mucosal area of the upper lip 2 weeks before surgical removal of the lesion. Histopathological examinations of the extracted tissue revealed inflammation with heavy eosinophilic infiltrations and sections of a nematode suggestive of a Gnathostoma sp. larva. The larva characteristically revealed about 25 intestinal cells with multiple (3-6) nuclei in each intestinal cell consistent with the 3rd-stage larva of G. spinigerum. The patient did not have any special history of travel abroad except a recent trip, 4 months before surgery, to China where she ate only cooked food. The patient is the first recorded autochthonous case of G. spinigerum infection in Korea.

Gnathostomiasis in a patient who frequently consumes sushi.

A 45-year-old woman presented for evaluation of a solitary pruritic nodule on the abdomen that suddenly appeared 3 weeks before. She was healthy without a significant medical history, travel history, exposures, medications, or pets. She reported that she consumed sushi at least weekly in the city of San Francisco. A punch biopsy revealed a superficial and deep perivascular and interstitial infiltrates consisting of lymphocytes, plasma cells, and many eosinophils. Most notably, there was a parasite centered in the reticular dermis with prominent lateral chords, a well-developed muscular esophagus, and an intestine that contained a brush border and multinucleate cells. Evaluation of these histological sections by the Centers for Disease Control and Prevention determined the parasite to be a nematode of the genus Gnathostoma. The patient underwent a systemic work-up for gnathostomiasis, including imaging, and no other abnormalities were found. She completed a 3-week course of albendazole and has remained asymptomatic since the biopsy of her abdominal lesion. Although gnathostomiasis is often a systemic illness, this patient did well with apparently only localized cutaneous disease. Gnathostomiasis should be considered in patients who present with nonspecific papules and nodules, especially when there is a history of frequent consumption of raw fish.