Trichinosis

　　1. Etiology

　　Trichinella spiralis (commonly referred to as Trichinella) belongs to the Phylum Nematoda, Class Nematoda, and Genus Trichinella. The adult worm is small, with a slender anterior end and distinct sexual dimorphism. The male worm measures (1.4～1.6) mm×(0.04～0.05) mm, while the female worm is (3～4) mm×0.06 mm, with a body length more than twice that of the male. The adult's digestive tract includes the mouth, esophagus, intestine, and anus. The reproductive organs are all of the single-tube type, with the male having testes, vas deferens, seminal vesicle, and seminal duct. The seminal duct and rectum open into the cloaca. The posterior end of the worm has two clock-shaped copulatory spines, and sperms are released between the copulatory spines without a copulatory spicule.

　　The female reproductive organs include the ovary, oviduct, spermatheca, and uterus. The uterus is longer than the ovary and contains undivided egg cells that have developed into mature larvae near the opening of the vagina. The vagina is divided into a thin-walled part and a thicker, shorter part. The vulva is located at one-fifth of the anterior part of the worm body.

　　Scanning electron microscopy observations of the adult and larval stages of the Trichinella worms show that the central vertex of the anterior part of the male and female adults has a cleft-like opening, from which a spine extends out. The mouth is surrounded by bilaterally symmetrical broad swellings, resembling wings or butterflies, with an elliptical prominence surrounding the mouth. There are 12 to 14 symmetrically arranged small depressions on the outer epidermis of the wing-like swellings, which may be the openings of the sensory organs of the head. The anterior part of the larvae is not as developed as the adults, with only a spine extending out from a cleft-like mouth. Both adults and larvae have a smooth epidermis without microvilli or microholes, featuring annular transverse ridges at right angles to the body axis. The epidermis of the adults has openings of subcutaneous gland cells, known as skin pores, which start as a single row at the front third of the body and become double rows from one-third to the rear one-third. The skin pores are covered by special cap-like structures formed by the secretions of the subcutaneous glands. The larvae do not have skin pores. The reproductive aperture is not obvious during the larval stage but becomes more developed in the adult stage. The reproductive aperture of the females is the vulva, often in a cleft-like shape, sometimes semicircular. The male external genitalia display a pair of mating appendages, which are ear-like protrusions with a Y-shaped lateral side, with two pairs of papillae or small nodules inside, with one pair being digitate on the ventral side and the other being conical in shape on the dorsal side. Both the females and larvae have an anal pore at the end, but the males do not have an anal pore; the opening of the cloaca serves as the anal pore. The size of the larvae is approximately 100μm × 6μm.

　　The adult and larval stages of the Trichinella worms are both parasitic in the same host body, but they cannot develop from larvae to adults within the same host body. They must switch hosts in between. Humans and mammals such as pigs, cats, dogs, and rodents are susceptible to infection. The female Trichinella worms that reside in the pig intestines produce larvae, which circulate through the blood to the skeletal muscles where they form cysts. Humans can become infected by consuming pork that contains larvae in cysts. After entering the new host, the cysts are digested by gastric juices, the larvae are released in the duodenum, and they become parasitic in the duodenum, jejunum, and ileum, feeding on the intestinal mucosa. After 5 to 6 days and four molts, they become adults. After mating, the males die and are excreted out of the intestinal cavity. The females continue to grow and penetrate deeper into the intestinal mucosa, starting to produce larvae. The lifespan of the females can reach 1 to 2 months, with each female capable of producing 1,500 to 2,000 larvae. A few larvae that are produced on the surface of the intestinal mucosa are excreted outside the intestinal cavity, while the majority of larvae within the mucosa are transported to various organs and tissues throughout the body, primarily via the lymphatic vessels or small venules and the blood circulation. However, only those that reach the skeletal muscles can develop into cysts. The time spent by the larvae in the blood circulation is most frequent between 8 to 25 days after infection, with the earliest reaching the skeletal muscles within 9 days. Since the females continuously excrete larvae, the larvae entering the skeletal muscles can persist for 1 to 2 months as well.

　　After the larvae reach the skeletal muscle, they penetrate the microvessels and continue to grow to a size of 1mm over time, and undergo sexual differentiation. Due to the stimulation of their metabolites, the adjacent muscle fibers gradually encircle the larvae, forming a spindle-shaped cyst within about one month and maturing after 7 to 8 weeks. The size of the cyst is about (0.25～0.5) mm×(0.21～0.42) mm, and it begins to calcify from both poles after 6 months, and the larvae inside the cyst die with it, sometimes surviving for 3 to 5 years. The mature cysts can enter a new host and repeat their life cycle. The cysts of the nematode larvae are highly resistant in skeletal muscle, and can survive for 57 days at -12°C, and for 2 to 3 months in decayed meat. The larvae in the cyst can be killed at 70°C, but the larvae in the deep muscles can still maintain vitality, so if the cooking or steaming time is insufficient, it can also lead to infection after eating.

　　Two, Pathogenesis

　　The onset of this disease is related to the habit of eating raw pork, but it is not related to age, gender, occupation, and season. The incidence and severity of the disease are related to the degree of infection. If the number of larvae in the ingested pork is as high as 5 per kg of body weight, it can be fatal. However, there are also reports of clinical recovery without any special treatment when biopsies contain 75 larvae per gram of muscle. The lesions vary with the number of larvae entering the human body, their developmental stage, and the human body's response to the nematode. The reaction of those who have been infected before is usually mild; if a large number of larvae enter, there may be congestion, edema, hemorrhage, and superficial ulcers at the invasion site and the site of parasitism in the intestinal mucosa, leading to many gastrointestinal symptoms in the early stage. During the migration period of the larvae, there may be inflammatory reactions at the sites they pass through, such as acute endocarditis and pericarditis, systemic vasculitis, and edema. In the lungs, focal or extensive pulmonary hemorrhage, pulmonary edema, bronchopneumonia, and pleural effusion with blood may occur. Involvement of the central nervous system may result in non-suppurative meningitis changes and increased intracranial pressure, with larvae occasionally found in the cerebrospinal fluid. Larvae are only rarely found in the myocardium, and there may be pericardial effusion with larvae. The myocardium and endocardium may present with edema, congestion, focal rupture, and necrosis, with infiltration of lymphocytes, eosinophils, and neutrophils, which is clearly due to the toxic effects and allergic reactions caused by the larvae passing through. When a large number of larvae侵入 the skeletal muscle fibers, the effects on the human body caused by the nematode toxins and their metabolites, as well as the toxic substances produced by the destruction of muscle fibers, can lead to toxic myocarditis, fatty change of liver cells, and turbid swelling of renal cells.

　　骨骼肌中的幼虫和包囊以舌肌、咽肌、颈肌、胸大肌、腹肌、膈肌和肋间肌为最多。因这些肌肉活动频繁、血流丰富，进入的幼虫较多。肌糖原含量较低则有利于包囊形成。由于幼虫及其代谢产物的刺激，虫体周围有间质性肌炎、肌纤维变性，虫体逐渐蜷曲，最后形成包囊。包囊呈梭形，长轴与肌纤维平行。一个包囊内一般只一个幼虫，极少有2～3个或以上。包囊周围的肌细胞有炎症细胞浸润。时久则肌纤维萎缩，炎症反应减轻。随着包囊钙化，幼虫死亡，则留下若干异物反应。

　　幼虫极少在心肌中发现。有人认为心肌有较高的抵抗力，不适于幼虫生存而重新进入血液循环；或心肌肌膜较薄弱，未能将幼虫限制在肌纤维内；也有认为心肌不断收缩，使幼虫无法停留。

　　除上述主要脏器和组织的病变外，幼虫偶见于视网膜、胰、肝、肾、胎盘、乳腺、乳液、胆汁、骨髓、淋巴结、脑脊液中，造成相应的损害和症状。

　　重度感染者肺、心肌和中枢神经系统亦被累及，相应产生灶性（或广泛性）肺出血、肺水肿、支气管肺炎甚至胸腔积液；心肌、心内膜充血、水肿、间质性炎症甚至心肌坏死、心包积液；非化脓性脑膜脑炎和颅内压增高等。血嗜酸粒细胞常显著增多（除极重型病例外）。因虫体毒素和其代谢物以及肌纤维破坏所产生有毒物质对人体的影响，可出现中毒性心肌炎、肝细胞脂肪性变及肾细胞混浊肿胀。

　　潜伏期为2～46天，多数在14天以内，根据幼虫在体内的发育阶段，侵入部位和病变程度的不同，临床表现可分为小肠侵入期，幼虫移行期和包囊形成期，但各期之间不一定很有规律，也没有明显界限，症状轻重取决于幼虫侵入脏器与部位以及感染度，轻感染者可无症状或有轻微胃肠道症状和肌痛，重感染者临床表现复杂多样，甚至发病后3～7周内死亡。

　　1. Small intestine invasion stage:It belongs to the early stage, from the beginning of infection to the development of larvae into adults in the small intestine. Due to the larvae and adults burrowing into the intestinal mucosa, feeding on intestinal villi, causing congestion, edema, hemorrhage, and superficial ulcers, gastrointestinal symptoms appear early. About half of the patients have nausea, vomiting, diarrhea, abdominal pain, constipation, anorexia, etc., which usually subside after about a week, but most still feel fatigue, aversion to cold, and low fever.

　　2. Larval migration stage:It belongs to the acute phase, mainly the inflammatory response caused by the migration of larvae, such as acute endarteritis, systemic vasculitis, edema, myalgia, and fever. Fever usually occurs 1 week after infection,呈不规则或稽留热型, with a temperature of 38 to 40°C, sometimes up to 41°C, and can last for 2 to 3 months or more. It is often accompanied by headache, sweating, and various allergic skin rashes. The migration period of larvae may be accompanied by urticaria or maculopapular rash. The muscle cysts can form fibrosis or calcification into nodules, and myalgia often starts when the larvae reach the skeletal muscle and begin to form cysts. There is muscle swelling and a sense of hardness, with marked tenderness, often systemic, but the gastrocnemius is the most severe, with severe pain upon slight touch, almost in a paralytic state. Severe cases may also have difficulty with chewing, swallowing, and speaking, hoarseness, pain during breathing and eye movement, and myalgia can last for 3 to 4 weeks or more than 2 months.

　　Edema first appears in the eyelids, face, and temporal area, and in severe cases, it can affect the entire body, including the limbs and trunk, even leading to pleural effusion, ascites, and pericardial effusion. Edema usually appears around 1 week into the course, lasting for 2 to 4 weeks. Respiratory symptoms are more common 2 weeks after onset, with paroxysmal cough, more severe at night, mostly dry cough or white frothy sputum, occasionally with streaks of blood, and in severe cases, chest pain, rales at the base of the lung, and cardiomegaly with pulmonary hilum shadow expansion and variable pulmonary parenchymal infiltration. In severe cases, symptoms of the heart and nervous system may appear, including arrhythmias, systolic murmur at the apex, pericardial friction sound or pericardial effusion, heart failure, cardiogenic asthma, and coma, convulsions, etc. Cardiopulmonary failure is often an important cause of death.

　　Other symptoms include conjunctival and scleral edema, congestion, hemorrhage, blurred vision or diplopia, about 2/3 of the cases have subungual hemorrhage, and some cases have obvious lymph nodes, salivary gland swelling and pain, thrombosis in internal organs or limbs, complications such as pulmonary infarction, peritonitis, and a few cases have transient liver enlargement.

　　3. Cyst formation stage:This is the convalescent period. As the cysts form in the muscles, acute inflammation subsides, and systemic symptoms such as fever, edema, and myalgia gradually improve. The patient significantly loses weight and becomes weak, with myalgia and nodules that can last for several months. Symptoms completely disappear due to calcification of the cyst wall and death of the larvae. Severe cases present with cachexia and can die due to collapse, sepsis, or myocarditis.

　　The medical history and typical clinical manifestations show an increase in peripheral blood eosinophils during the acute phase, which can last for several months. Skin tests, immunofluorescence antibody tests, enzyme-linked immunosorbent assays, and American sticky flocculation tests show high positivity. A positive reaction appears 2 to 4 weeks after infection, and further diagnosis requires muscle biopsy to find nematode larvae.

　　1、流行病学资料：在流行区内病前有生食或食半生不熟的猪肉或其他动物肉及其肉制品史，或有集体发病者，为本病诊断提供重要线索。

　　1. Epidemiological data:In the epidemic area, those with a history of eating raw or undercooked pork or other animal meat and meat products before the onset of the disease, or those with mass onset, provide important clues for the diagnosis of the disease.

　　2. Clinical manifestations:Initially, gastrointestinal symptoms appear, followed by fever, edema, myalgia, and a significant increase in eosinophils. Those with these symptoms should be highly suspected of having the disease and further pathogenic examination is needed.

　　How to prevent trichinosis?

　　1. Strengthen health education, do not eat raw or undercooked pork.

　　2. Improve pig-raising methods, build pig pens reasonably, advocate pen-raising, isolate sick pigs, and do not feed pigs with animal fragments and offal containing Trichinella. The feed should be heated to at least 55℃ to prevent pig infection. Compost manure piles should be fermented and treated.

　　3. Rat control: Rats are the reservoir hosts of this disease. Efforts should be made to control the rat population and prevent them from contaminating food and pork.

　　1. Hemogram:During the active phase of the disease, there is moderate anemia and an increase in white blood cells, with a total count of (10-20) × 10^9/L. Eosinophils are significantly increased, reaching the highest level 3 to 4 weeks after onset; it can reach 80% to 90%, and it lasts for more than half a year; in severe infections, immune function is low, or there is concurrent bacterial infection, which may not increase.

　　2. Pathogenic examination:If there is leftover meat, take a sample to check for cysts, or digest the meat with pepsin, centrifuge, and take the sediment for methylene blue staining and microscopic examination to find larvae. Alternatively, feed the remaining meat to animals (rats), and check for larvae in the intestines 2 to 3 days later. If Trichinella larvae are found, the diagnosis can be confirmed. If the disease has been present for 10 days, a muscle biopsy can be performed, often taking a biopsy of the deltoid or gastrocnemius muscle, with a high positive rate.

　　In the early stage of diarrhea, larvae can be found in feces. During the migrating phase, larvae can occasionally be found in centrifuged blood, milk, pericardial fluid, and cerebrospinal fluid.

　　3. Immunological examination:

　　(1) Intradermal test: Use Trichinella larval extract antigen (1:2000 to 1:10000) to inject 0.1ml intradermally. After 15 to 20 minutes, the skin nodule is >1cm, and the red halo diameter is >2cm. In the control group, a negative reaction is considered positive when 0.1% thymol chloride 0.1ml is injected intradermally on the opposite forearm, and the intradermal test is positive. This method has high sensitivity and specificity, is simple, and results are obtained quickly.

　　(2) Serological examination: The detection of specific antibodies in the patient's serum using Trichinella solubilized antigen is helpful for diagnosis. Methods such as slide agglutination, latex agglutination test, complement fixation test, immunoelectrophoresis, indirect immunofluorescence antibody test, and enzyme-linked immunosorbent assay can be used to detect patient serum antibodies. The latter two methods have better sensitivity and specificity. For example, the antibody level in the convalescent phase may increase more than fourfold compared to the acute phase, which has greater diagnostic significance.

　　After treatment, the serum antibodies of trichinosis patients can exist for a relatively long time, so positive antibodies cannot distinguish current patients from those who have been infected and cured in the past. In recent years, China has adopted the single-antibody and polyclonal antibody sandwich method ELISA to detect serum circulating antigens in patients, with a positive rate of 67.7% (21/31) and 72.2% (26/36), while 50 healthy people and 142 patients with other nine kinds of parasitic diseases were all negative. In 20 patients with cysticercosis, only 1 (5%) was positive. Positive results of serum circulating antigens suggest the presence of active parasites in the body, so they can be used for diagnosis and to evaluate efficacy.

　　(3) Others: Muscle biopsy finds trichin larvae, routine urine examination may show proteinuria and granular or waxy casts and red blood cells. During the 3-4th week of the disease, globulin increases while albumin decreases, and even the proportion is reversed. Immunoglobulin IgE significantly increases.

　　Corresponding X-ray, B-ultrasound, ECG, and other examinations can be performed.

　　1. Do not eat raw or semi-raw pork and other animal meats and processed products (such as sausages), advocate separating raw and cooked food cutting boards, and prevent the contamination of tableware with raw meat屑.

　　2. Strengthen meat inspection:

　　Carefully implement the meat hygiene inspection system, strengthen food hygiene management, and do not allow pork without inspection to be marketed and sold. Pork infected with trichinosis must be destroyed resolutely, which is an important link in the prevention work.

　　3. Improve pork raising methods:

　　Pigs should not be raised freely, but should be confined, manage the feces, and maintain cleanliness and hygiene in the pigsty. The feed should be heat-treated to prevent pigs from eating meat屑 containing trichinosis. In addition, when washing meat water or washing pot water is mixed with forage to feed ruminants such as cattle, sheep, and horses, heat treatment should also be applied; otherwise, cattle, sheep, and horses can also be infected with trichinosis.

　　4. Eradicate the reservoir hosts in conjunction with health campaigns, eliminate the reservoir hosts of this disease such as rats, wild dogs, and other wild animals to reduce the source of infection.

　　First, treatment

　　3. General treatment: During the acute stage, bed rest, high-protein diet, fluid replacement, and attention to water and electrolyte balance should be ensured. Symptomatic treatment with antipyretics and analgesics can be administered when necessary. Magnesium sulfate enema can be given during the incubation period of the disease, 1-2 times a day, which helps expel adults and larvae from the intestinal cavity, reducing the opportunity for invasion.

　　2. Pathogen therapy:

　　(1) Albendazole: It is the first-line drug for the treatment of this disease, with good efficacy and killing action against nematodes in all stages, with mild toxic and side effects. The dose is 20mg/(kg·d), 500mg per dose for adults, 3 times a day, and the course of treatment is 5 days. When severe toxicosis occurs, Prednisone can be added 10mg per dose, 3 times a day. Side effects include slight drug reactions starting from the second day of taking the medicine, such as increased muscle pain, discomfort or hidden pain in the stomach, dizziness, and skin itching, all of which do not affect treatment.

　　(2) Fenbendazole: Effective against the intestinal and extraintestinal stages of Trichinella. In foreign countries, the dose is 22mg/(kg·d), 600mg/time for adults, once every 6 hours, for 2 weeks. A course of treatment is repeated every 2 months. Some individuals may experience a Yat-Sen-like reaction. For severe patients, the initial treatment is 200mg/d, taken in three divided doses orally, then 400-600mg/d, for 10 days or more.

　　(3) Thiabendazole: It has a broad-spectrum antihelminthic effect and has a good effect on the immature, adult, and migrating and cystic larvae of Trichinella. The dose is 25-50mg/(kg·d), taken in three divided doses, for 5-7 days, which is effective for early cases. However, for severe patients (estimated number of worms 1500-11500), treatment cannot prevent the occurrence of symptoms 4 days after infection, but can alleviate the symptoms and delay their onset. After multiple doses, dizziness, headache, nausea, vomiting, rash, and other side effects may occur. The incidence of side effects is high, and it is now rarely used.

　　(4) Flubendazole: 200mg, once/d, then 400-600mg/d, for at least 10 days.

　　3. Symptomatic treatment For severe patients, in addition to antipathogen drug treatment, adrenal cortical hormones can be used simultaneously, which have non-specific anti-inflammatory, antipyretic, and antiallergic effects, and can alleviate muscle pain and relieve toxic symptoms. Generally, hydrocortisone 100mg intravenous infusion or prednisone 10mg/time, 3 times/d orally, is used for 3-5 days. Recently, some people have applied plasma extraction therapy to treat 4 severe trichinosis patients, with significant improvement in clinical symptoms and no complications found.

　　II. Prognosis

　　The prognosis mainly depends on the degree of infection and individual response. Mild to moderate infected individuals have a good prognosis, while severe infected individuals often die of complications such as toxic shock, heart failure, meningitis, pneumonia, pulmonary embolism, etc. The mortality rate is 0-30%, generally 5%-6%. If the severe stage can be survived for 1-4 weeks, the prognosis is better. Patients with brain lesions can recover or leave sequelae such as hemiplegia or epilepsy.