Anisakiasis

　　1. Causes of Disease

　　Anisakiasis belongs to the Ascaridida, Ascarina, Anisakidae. It is currently known that there are more than 30 species of Anisakidae (Anisakidae), because the identification of larvae is relatively difficult, which is prone to homonymy. The most commonly recognized species that can cause human disease mainly include 4 genera: ① Anisakis, including Anisakis simplex, Anisakis typica, and Anisakis physeteris; ② Pseudoterranova, including Pseudoterranova decipiens, Phocanema, and Terranova; ③ Contraceacum; ④ Hysterothylacium, including Thynnascaris, etc. Fish in Chinese waters have been found to be parasitized by Anisakis simplex, Pseudoterranova, or Hysterothylacium, but there have been no reports of human infection. The adult Anisakiasis resembles Ascaris, with males measuring 31-90mm in length; females are 63-100mm. The adults parasitize the stomachs of marine mammals such as whales, dolphins, seals, and sea lions. The eggs are about 50.7μm×53μm in size, excreted into the seawater with the host's feces, and the fertilized ovum cells develop into embryos and become mature eggs containing the first-stage larvae. When the seawater temperature is suitable (about 10℃), the larvae inside the eggs hatch out, develop into the second-stage larvae, which are about 230μm long. They can swim freely in the seawater and can survive for 2-3 months. When the second-stage larvae are eaten by crustaceans in the seawater (the first intermediate host) such as krill, they penetrate the body cavity and develop into the third-stage larvae in the hemocoel. When marine fish and mollusks (the second intermediate host) eat crustaceans containing larvae, the larvae penetrate the digestive tract and its internal organs and muscle tissues to parasitize. Fish containing the third-stage larvae are eaten by marine mammals (the definitive host), and the larvae penetrate the gastric mucosa and grow in groups, developing into male and female adults, mating and laying eggs to complete their life cycle. Humans are not the appropriate host for Anisakiasis, and the third-stage larvae can parasitize various parts of the human digestive tract and can also cause visceral larva migrans. However, these larvae cannot develop into adults in the human body and generally die within 2-3 weeks.

　　The third-stage larvae of Anisakis species often migrate from the intestinal tract to various tissues within fish bodies, with the peritoneum being the most common. After the fish dies, the larvae migrate to the muscle within the body wall. The third-stage larvae within the fish body are slender and elongated, measuring about 30mm × 1mm, with lateral filaments, appearing Y-shaped in cross-section. There are three lips around the mouth (one on the dorsal side and two on the ventral side) and one boring tooth. The esophagus is a white cylindrical structure, which can be divided into the muscular part at the front end and the glandular stomach sac at the rear end, and it is connected to the intestine, with the anus at the end. The excretory pore opens at the level of the abdominal nerve ring, behind the boring tooth. The reproductive organs are distinct. The simple Anisakis larvae observed in the coastal waters of the East China Sea, the Yellow Sea, and the Beibu Gulf of northern China are about 18.73mm × 0.14mm in size, with an average esophageal length of 2.29mm and a tail length of 0.09mm. Japanese scholars have classified them into types I, II, and III based on their body length, width, and the morphological features of the stomach and tail. Experimental studies on the resistance of Anisakis larvae to physical and chemical factors show that a solution of 3% to 15% sodium chloride cannot quickly kill the larvae, which can survive for 96 to 233 hours; they can survive for 2.5 to 48 hours in 38-degree alcohol; 0.2 to 2.2 hours in 60-degree alcohol; 17.6 to 75.3 hours in 15% vinegar; 1 to 3 hours in 30% vinegar; 5.5 to 6 hours in garlic juice; 29.8 hours in soy sauce and 154.6 hours in chili sauce. The larvae in herring bodies can only be killed after being frozen at -18℃ for 48 hours, -20℃ for 2 hours, and can survive for 50 days at 2℃. Live larvae have been found in frozen fish imported from North Korea and the former Soviet Union in China. The larvae in the deep muscles of large fish may not necessarily be killed during freezing storage. This larva can be killed by heating to 60℃.

　　Second, Pathogenesis

　　The third-stage larvae of Anisakis simplex enter the human body through the mouth, and the larvae have strong piercing power, which can penetrate the mucosa of the pharynx, stomach, or intestines to cause lesions. The symptoms of the initial infection are mild and not easy to detect. After multiple repeated infections, the body becomes sensitized, causing more severe reactions. When the larvae penetrate the mucosa of the gastrointestinal tract, they absorb tissue components, causing an inflammatory reaction characterized by the infiltration of eosinophils. If the larvae continue to penetrate, they can reach the submucosal layer, causing mucosal edema, hemorrhage, proliferation and thickening of connective tissue, and accompanied by lymphatic dilation and lymphangitis. The larvae are often found in the central part of the lesion tissue. After several days, an eosinophilic abscess appears around the worm body, followed by the death and decomposition of the worm, gradually forming an eosinophilic granuloma, which can cause intestinal obstruction and intestinal necrosis. In severe cases, the larvae can even penetrate the intestinal wall, migrate to the mesentery, liver, pancreas, abdominal wall, inguinal canal, and oral mucosa after entering the abdominal cavity. Pathological tissue specimens removed from the surgery of the stomach or intestines show localized tumors, hemorrhage, erosion, and ulcers under the mucosa, thickening of the intestinal wall, up to two or three times the normal size, which is the cause of intestinal stenosis and obstruction.

　　The pathological sections show that there are one to several worm cross-sections in the submucosal layer, which are mostly curled due to the invasion of the worms into this layer. Sometimes, remnants of worm fragments or necrotic tissue can be seen at the center of the lesion, or only the cuticle or gaps of the worm remain due to the reasons of tissue preparation. There is a large number of eosinophils, plasma cells, and macrophages around the worm. According to the degree of pathological damage, Shujiu Chi (1966) divided the pathological tissue images into four types: Type I foreign body phlegmon type; Type II abscess type; Type III abscess granuloma type; Type IV granuloma type. From the onset of the disease, the lesions transition from Type I to IV. Type I and II are exudative inflammatory stages, showing severe edema of the gastric and intestinal walls; Type III and IV belong to proliferative inflammatory stages, with granulomas around the abscesses composed of epithelioid cells.

　　It can be complicated by intestinal obstruction, intestinal perforation, and peritonitis.

　　1. Intestinal obstruction:It refers to the obstruction of intestinal contents in the intestines. It is a common acute abdominal disease, which can be caused by various factors. In the early stage, the obstructed intestinal segment has anatomical and functional changes first, followed by fluid and electrolyte loss, intestinal wall circulation disorders, necrosis, and secondary infection, which can finally lead to sepsis, shock, and death.

　　2. Intestinal perforation:It refers to the process of intestinal contents leaking into the peritoneal cavity due to penetration of intestinal lesions through the intestinal wall, which is one of the serious complications of many intestinal diseases, causing severe diffuse peritonitis, mainly manifested as severe abdominal pain, abdominal distension, symptoms and signs of peritonitis, and can lead to shock and death in severe cases.

　　3. Peritonitis:It is the inflammation of the parietal peritoneum and visceral peritoneum of the abdominal cavity, which can be caused by bacterial, chemical, physical injury, etc., and can be divided into primary peritonitis and secondary peritonitis according to the pathogenesis. Acute purulent peritonitis involving the entire abdominal cavity is called acute diffuse peritonitis.

　　The severity of symptoms is closely related to the number of infecting worms, the site of寄生 and the duration of infection, Anisakis simplex larvae can be寄生 in the pharynx, gastric and intestinal mucosa, but the most common site is the stomach, about twice that of the intestine, Japan reported the most cases of gastric Anisakis simplex disease (97.3%).

　　The incubation period is generally 2-20 hours, according to a report from Japan, the shortest time from eating raw fish to onset is 30 minutes, the longest is 168 hours, 64% of cases onset within 3-8 hours, 88% within 12 hours, the incubation period of intestinal Anisakis simplex is longer, generally onset 1-5 days after eating fish slices, clinical symptoms and signs can be described as follows according to the site of larvae invasion:

　　1. Anisakis simplex disease of the stomach

　　It can be divided into acute and chronic types. The former is an Arthus-type allergic inflammation caused by reinfection; the latter is a localized allergic reaction caused by the first infection, with larvae寄生 in the gastric corpus and gastric angle accounting for more than 85%; clinical manifestations include upper abdominal pain or cramping, recurrent attacks, often accompanied by nausea and vomiting; a few have lower abdominal pain, occasionally diarrhea, 70% of patients have positive occult blood in feces, peripheral blood eosinophils are significantly increased, gastro-X-ray barium meal examination in 150 cases, including 68 cases with gastric angle widening, gastric antrum rigidity, narrowing or stiffness during gastric peristalsis; 16 cases with filling defect-like changes, gastric edema is judged based on the disappearance of softness when compressed and the swelling of gastric mucosal folds, 70 cases with visible filling defects and coarse folds, 34 cases with gastric edema and mucosal fold swelling involving the gastric corpus with marked deformation, 113 cases of X-ray film examination all showed the worm body, 150 cases of gastroscopy examination, except for the cardia, worm bodies were visible in all, more in the gastric angle and gastric corpus, locally there are indistinct mild swellings and swelling of folds; in 38 cases, there was slight bleeding and erosion in the gastric mucosa at the site of worm penetration, 151 worms were detected in 150 cases, all of which were third-stage larvae of Anisakis simplex, among which 1 case had 3 worms, 3 cases had 2 worms, and the rest had 1 worm each.

　　2. Intestinal Anisakiasis

　　The male-to-female ratio is approximately 1.8:1, with patients mainly aged 10 to 39 years. The affected sites include the duodenum, jejunum, ileum, cecum, appendix, and rectum. Sudden and severe abdominal pain, nausea, vomiting, bloating, low fever, followed by diarrhea, tarry mucus stools, tenderness in the lower right abdomen and umbilical area, and sometimes accompanied by urticaria, etc. Patients often undergo surgery due to intestinal perforation, peritonitis, or localized intestinal necrosis. The larvae of this type are found in the lesion tissue, and the diagnosis is confirmed.

　　3. Esophageal Anisakiasis

　　A 77-year-old female patient was reported in Japan. One day before the onset, she experienced pain in the epigastric region after dinner with sashimi. At midnight, she felt a piercing pain under the sternum, belching, and sought medical attention the next morning. An immediate fiberoptic endoscopy was performed, and a white worm body was found in the lower esophagus, removed with forceps, and identified as Anisakis larvae.

　　When consuming raw sea fish slices, the larvae of Anisakis directly penetrate into the mucosa of the pharynx, causing itching in the throat, nausea, or coughing. The larvae can often be coughed up or vomited out with phlegm. In recent years, there have been many reported cases in the eastern and western coasts of the United States. Sometimes, a laryngoscope examination can reveal the worm body, which is usually removed with forceps to relieve symptoms.

　　4. Extra-intestinal Anisakiasis

　　This larva can penetrate the intestinal wall into the peritoneal cavity, then migrate to the liver, pancreas, omentum, mesentery, ovary, subcutaneous tissue of the abdominal wall, inguinal or oral mucosa, etc., causing peritonitis, eosinophilic granuloma, and subcutaneous nodules, which are often misdiagnosed as malignant tumors.

　　The main source of infection for this disease is fish, so avoiding the consumption of raw or undercooked sea fish slices is the primary preventive measure. Fish should be cooked thoroughly before eating. After being frozen at -20℃ for 24 hours, Anisakis can be completely killed, so various types of sea fish should be frozen at -20℃ for 24 hours before being marketed to effectively reduce the risk of infection in the population. Strengthening the health inspection of imported fish, strict quarantine of seafood, and preventing contaminated products from entering the market.

　　1. Immunological examination

　　A positive reaction is observed in the intradermal test using purified antigens of Anisakis simplex, with an increase in specific IgE in the patient's serum. Positive reactions in latex agglutination tests, indirect fluorescent antibody tests, and others have certain reference value.

　　2. Pathological tissue examination

　　In the case of cellulitis, abscess, abscess granuloma, and granuloma types of lesions, the worm body, the section of the cuticle or muscle layer of the worm body can be seen during the pathological examination of the surgical resection specimen.

　　3. Examination of molecular biological techniques

　　Recent research has established a method based on polymerase chain reaction (PCR-RFLP) and single-strand conformation polymorphism (SSCP) using simple heterophyliasis, the different ribosomal DNA fragments of Blattodea and Ascaris lumbricoides, which can be used for the diagnosis of heterophyliasis in humans and animals.

　　4. Gastroscopy

　　Confirmation can be made by finding the larva and pathological histological examination finding the transverse section of the worm body. Gastroscopy shows that the gastric mucosa has an increased amount of mucus, rugae are swollen, and there are live larvae with white transparent heads piercing the gastric mucosa, which are spiraled or S-shaped coiled. The mucosa around the worm body is eroded, with clots, bleeding, or white fur-like changes.

　　5. Barium X-ray examination

　　Gastric X-ray manifestations: ① The gastric angle is widened, showing a reverse parabolic shape; ② The gastric margin is rigid, bilaterally defined, the gastric wall is irregular, and there are defects in the degree of filling; ③ The gastric rugae are swollen, and the intestinal barium examination shows that the barium presents in a segmented pattern, and the affected area can be seen with sawtooth or club-shaped shadows, with dilated intestines above.

　　Nutritional therapy for heterophyliasis:

　　1. Charcoal pot cake 60g, Amomum xanthioides, fennel, tangerine peel, Sichuan pepper, Atractylodes macrocephala, each 6g, finely ground, 6g each time, taken with warm water.

　　2. Silver ear lean meat soup

　　Ingredients: 20 grams of silver ear, 300 grams of pork trotters (left with moon), one papaya, one slice of ginger.

　　Preparation: Pork trotters (left with moon) scalded and passed through cold water; silver ear soaked through, scalded and passed through cold water; papaya peeled and cored, cut into pieces. Bring a sufficient amount of water to a boil, add silver ear, papaya, pork trotters (left with moon), and ginger, and bring to a boil. Simmer over low heat for two and a half hours, season with salt.

　　3. Eel congee: 1 eel, cut into small pieces, 250g of glutinous rice. Boil into thin porridge, season with salt, ginger, scallion, etc. and eat.

　　I. Treatment

　　There is currently no effective drug treatment, and it has been reported that albendazole treatment of the disease has some efficacy. Fiberoptic gastroscopy should be performed early for heterophyliasis of the stomach, esophagus, and esophagus, and the worm should be removed immediately upon finding the worm body. For heterophyliasis of the intestine, conservative therapy is adopted, and the condition should be strictly observed while antifungal and antiallergic treatments are given. If complications such as intestinal perforation, peritonitis, or intestinal obstruction are found, immediate surgical treatment should be performed.

　　II. Prognosis

　　The prognosis is generally good, but it is poor if there are serious complications.