Sushi Worms Diagnostic Challenges

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Department Medicine Diagnostic Centre Swiss TPH Winter Symposium 2017 Helminth Infection from Transmission to Control Sushi Worms Diagnostic Challenges Beatrice Nickel

Fish-borne helminth infections Consumption of raw or undercooked fish - Anisakis spp. infections - Gnathostoma spp. infections

Case 1 32 year old man Admitted to hospital with severe gastric pain Abdominal pain below ribs since a week, vomiting Low-grade fever Physical examination: moderate abdominal tenderness Laboratory results: mild leucocytosis Patient revealed to have eaten sushi recently Upper gastrointestinal endoscopy was performed Carmo J, et al. BMJ Case Rep 2017. doi:10.1136/bcr-2016-218857

Case 1 Endoscopy revealed 2-3 cm long helminth Nematode firmly attached to / penetrating gastric mucosa Endoscopic removal of larva with a Roth net Carmo J, et al. BMJ Case Rep 2017. doi:10.1136/bcr-2016-218857

Anisakiasis Human parasitic infection of gastrointestinal tract by herring worm, Anisakis spp. (A.simplex, A.physeteris) cod worm, Pseudoterranova spp. (P. decipiens) Consumption of raw or undercooked seafood containing infectious larvae Highest incidence in countries where consumption of raw or marinated fish dishes are common: Japan (sashimi, sushi) Scandinavia (cod liver) Netherlands (maatjes herrings) Spain (anchovies) South America (ceviche) Source: http://parasitewonders.blogspot.ch

Life Cycle of Anisakis simplex (L1-L2 larvae) L3 larvae L2 larvae L3 larvae Source: Adapted to Audicana et al, TRENDS in Parasitology Vol.18 No. 1 January 2002

Symptoms Within few hours of ingestion, the larvae try to penetrate the gastric/intestinal wall acute gastric pain or abdominal pain low-grade fever nausea, vomiting allergic reaction possible, urticaria local inflammation Invasion of the third-stage larvae into gut wall can lead to eosinophilic granuloma, ulcer or even perforation.

Diagnosis and Therapy Leucocytosis Eosinophilia Dietary history (raw fish) Endoscopy: gastroscopic examination Serological tests Immunoblot ELISA length of Anisakis larvae 20-30 mm Removal of larvae during endoscopy with biopsy forceps If larvae can not be reached (intestinal Anisakiasis), Albendazole can be effective Source of image: David Hwang, Chonnam Med J 2012.

Case 2 31 year old woman Recurrent pruritic edema on her back and ribs Edema resolve spontaneously within 24-48 h Symptoms since 2 years, at least once a month Multiple consultations and allergological investigations did not bring any results Laboratory results: Mild eosinophilia (470 µl -1 ), no inflammatory signs Serological tests for parasites were negative (Trichinella, Toxocara, Filaria, Strongyloides, ) Stool analysis for parasites was negative Leroy, J., Travel Medicine and Infectious Disease (2017)

Case 2 Clinical examination Erythematous edema, subcutaneous cords with snake-like appearance Leroy, J., Travel Medicine and Infectious Disease (2017)

Case 2 The patient was from Thailand, living in France since 2 years, and frequently consumed raw fish dishes in Thailand Due to symptoms and the background of the patient, cutaneous gnathostomiasis was suspected Serological test (immunoblot) for Gnathostoma spinigerum was positive Patient received Ivermectin with complete remission

Gnathostomiasis Parasitic infection by nematodes of Gnathostomatidae family 6 human pathogenic species known Most human infections caused by: Gnathostoma spinigerum (endemic in Asia) Gnathostoma binucleatum (endemic in Central and South America) Consumption of raw or undercooked freshwater fish or parathenic hosts containing infectious L3 larvae Larvae penetrate the intestinal wall and migrate around the body Highest incidence in Asia, Central and South America

Gnathostoma spinigerum larva 500 µm Images by Françoise Brand Swiss TPH Basel 100 µm

Life Cycle of Gnathostoma spinigerum Source: Clin. Microbiol. Rev. July 2009 vol. 22

Symptoms Incubation period: few weeks to months Shortly after ingestion nausea, fever, urticaria might appear Eosinophilia Episodic appearance of migrating edema and erythema (CLM) Symptoms may last for years The larvae can survive for many years in the human body Clinical picture: Cutaneous larva migrans syndrome (CLM) Visceral larva migrans syndrome (VLM), not very frequent Neural larva migrans syndrome (NLM), meningoencephalitis Occular larva migrans syndrome

Diagnosis and Therapy Dietary history (raw freshwater fish) Eosinophilia Clinical picture, larva migrans syndrome Skin lesions associated with gnathostomiasis can also be caused by other helminth infections (e.g. dog/cat hookworm, Toxocara, ) Definitive diagnosis is only possibel by identification of the larva in biopsies, but not feasible in all cases Serology is method of choice Immunoblot (24 kda band) usually antigen of G.spinigerum Travel history is important (Asia or America) Treatment: Ivermectin or Albendazole

Gnathostoma serology G.spinigerum antigen (larvae from Laos) Patient with suspected gnathostomiasis Cutaneous larva migrans syndrome Consumption of ceviche in Belize and Guatemala 6 months before admission Serodiagnostic immunoblot with antigen of G.spinigerum was negative 1 = Positive control Laos: positive 2 = Negative control: negative 3 = patient serum: negative 4 = Positive control Peru: negative

Gnathostoma serology G.spinigerum antigen (larvae from Laos) G.binucleatum antigen (larvae from Ecuador) 1 = Positive control Laos: positive 2 = Negative control: negative 3 = Patient serum: negative 4 = Positive control Peru: negative 1 = Positive control Peru: positive 2 = Negative control: negative 3 = Patient serum: positive 4 = Positive control Laos: positive Neumayr, Am. J. Trop. Med. Hyg., 95(2), 2016, pp. 413 416

Serologic tests for «Sushi Worms» at Swiss TPH Anisakis spp. Gnathostoma spp. Angiostrongylus spp. Paragonimus spp.

Prevention of transmission Adequate cooking of marine seafood and freshwater fish at temperatures >60 C Freezing of fish and shellfish at 35 C for 15 hours or -20 C for 7 days destroys infective larvae Salting or marinating will not necessarily kill the parasites!

Acknowledgments Swiss Tropical and Public Health Institute Team of the Diagnostic Centre Hanspeter Marti Andreas Neumayr Karin Stoll University of Health Sciences, Vientiane, Lao PDR Youth Vonghachack