Trichinellosis

INTRODUCTION — Trichinellosis (trichinosis) is a parasitic infection caused by nematodes (roundworms) of the genus Trichinella. Pigs and wild game are important sources of human infection [1]; a number of other animals are also epidemiologically important hosts [2]. Consumption of raw or undercooked meat is the principal mode of transmission.

EPIDEMIOLOGY — Trichinellosis occurs worldwide (figure 1). The prevalence of Trichinella infection is unknown, and there is significant underreporting of cases. A thorough literature review from 1986 to 2009 revealed 65,818 cases of trichinellosis and 42 deaths reported from 41 countries [3]. Most cases were reported in Europe, especially Romania, the former Soviet Union, and other parts of Central Europe [4,5]. Other countries with high prevalences of human infection are China, Thailand, Mexico, Argentina, and Bolivia.

There are 9 species and at least 13 genotypes of Trichinella [6]. Trichinellae are divided into those that encapsulate in host muscle tissue of mammals only and those that do not encapsulate and infect mammals, birds (one species), or reptiles (two species). All recognized species and genotypes can infect humans, but there are seven species of Trichinella that have been implicated in human disease [7,8]:

●T. spiralis is found worldwide in a great variety of carnivorous and omnivorous animals.

●T. nativa is found in arctic regions and infects bears, foxes, and walruses.

●T. nelsoni is present in Africa, south of the Sahara, where it is common in felid predators and scavenger animals, such as hyenas and bush pigs.

●T. britovi is found in temperate areas of Europe, western Asia, and western/southern Africa in carnivores but not domestic swine [9].

●T. pseudospiralis is found in mammals and birds worldwide [10-12].

●T. murelli is found in wild mammals in the United States and Japan [13].

●T. papuae is found in Papua New Guinea in domestic and feral pigs and in saltwater crocodiles and turtles [14]. It has also been reported from Thailand [15,16], Taiwan [17], and Cambodia [18].

An additional species, T. zimbabwensis, has been described in crocodiles in Tanzania [19]. Another species, Trichinella patagoniensis, is found mainly in cougars in South America [20]. The clinical importance of the additional known genotypes of Trichinella is not known [8].

Cattle are herbivores so they are not naturally infected, although beef can become contaminated with Trichinella larvae from pork during processing. Horse meat has also been associated with outbreaks of trichinellosis [21]. Since Trichinella infection in humans is strongly associated with the consumption of raw or undercooked meat, cultural factors and food preferences play an important role in the epidemiology of the disease [22].

In the United States, 90 cases of trichinellosis were reported between 2008 and 2012 [23], and pork (both domestic pigs and wild boar) accounts for only about 30 percent of cases [1]. As a result of improvements in swine production, trichinellosis has declined steadily in the United States. However, meat from noncommercial sources poses a particular risk; home-raised and home-slaughtered swine are not subject to the same safety and inspection standards as commercially produced products [24]. In addition, undercooked wild game, including bear, has emerged as an important source for infection with Trichinella [1,25-27]. Outbreaks of trichinellosis have been associated with wild boar, bear, deer, moose, walrus, and pork; clusters of cases tend to occur among groups that have consumed meat from a common infected animal [28].

Life cycle — The life cycle consists of two components: a domestic cycle and a sylvatic cycle (figure 2) [22]. The domestic cycle usually involves pigs and rodents; other domestic animals, such as horses, can be involved. The sylvatic cycle can involve a broad range of infected animals [29]. Animals most often implicated as sources of human infection include bear, moose, and wild boar [24,30].

Trichinellosis is caused by the ingestion of undercooked meat containing encysted larvae of Trichinella species from a domestic or sylvatic animal (except for T. pseudospiralis, T. papuae, and T. zimbabwensis, which do not encyst). The most frequent cause of infection is T. spiralis acquired by consumption of inadequately cooked pork from domestic pigs [31].

The larvae are released from the cysts following exposure to gastric acid and pepsin. Subsequently, they invade the small bowel mucosa where they develop into adult worms (females 2.2 mm in length; males 1.2 mm). The life span in the small bowel is about four weeks. After one week, the females release larvae that migrate to striated muscles, where they encyst.

Notably, in the Trichinella life cycle, adult worms and encysted larvae develop within a single vertebrate host. Infected animals serve as definitive hosts as well as a potential intermediate hosts. A second host is required to perpetuate the life cycle of Trichinella.

CLINICAL MANIFESTATIONS

Clinical course — In general, the severity of infection in humans correlates with the number of ingested larvae. Humans appear to be highly susceptible; exposure to few larvae can be associated with considerable risk of infection [32]. Mild infection (less than 10 larvae/g of muscle) can be subclinical. The incubation period is generally 7 to 30 days; it varies with the number of ingested larvae (which correlates with how well meat has been cooked), host immune status, and species of Trichinella [33,34]. Shorter incubation periods are generally associated with a more severe disease course.

For heavy infections, two clinical stages may be observed [35]:

●The intestinal stage occurs between the second and seventh day following ingestion, when encysted larvae are liberated from the meat by gastric juices. Larvae mature into adult worms that burrow into the intestinal mucosa. Fertilized female worms release new larvae about one week after ingestion and this continues for up to five weeks, depending upon the severity of the infection. This stage may be asymptomatic or may be accompanied by symptoms including abdominal pain, nausea, vomiting, and diarrhea. Prolonged diarrhea lasting for weeks has been attributed to repeated reinfection in previously infected and sensitized patients [36].

●The muscle stage develops after the first week of ingestion and represents the period when adult-derived larvae in the intestines disseminate hematogenously and enter skeletal muscle. For species other than T. pseudospiralis and T. papuae, each larva becomes encysted within a host muscle cell (picture 1); T. pseudospiralis and T. papuae larvae remain in the muscle without forming cysts. Both encysted and free Trichinella larvae remain viable for years.

The cardinal clinical manifestations of trichinellosis occur during the muscle phase of infection. As larvae enter skeletal muscles, muscle pain, tenderness, swelling, and weakness develop. The pain can be so extreme as to limit all movement, including breathing or moving the tongue. High fever lasting a number of weeks may be observed. Physical findings include subungual splinter hemorrhages (picture 2), conjunctival and retinal hemorrhages, periorbital edema and chemosis, visual disturbance, and ocular pain. Less common manifestations include macular or urticarial rash, headache, cough, dyspnea, and dysphagia. Hepatomegaly is occasionally observed [37].

In one outbreak of Trichinella involving 98 individuals in Turkey, the most frequent musculoskeletal symptoms reported were muscle pain (87 percent), joint pain (84 percent), subjective muscle weakness (76 percent), and diminished joint mobility (64 percent). The most frequently affected muscle groups included calves, upper arm, neck and shoulder girdle, and forearms. Muscle pain was reported more frequently in the upper than in the lower extremities. Joint pain was reported more frequently at rest than with activity. However, no objective evidence of arthritis or muscle weakness was noted on physical examination in any patient [38]. Another outbreak in Vietnam including 30 cases noted myalgia (88 percent), facial edema (63 percent), diarrhea (53 percent) and pain of the masseter muscles (43 percent) [34].

Progressive muscle encystment is associated with resolution of clinical manifestations even though the encysted larvae remain viable. Encapsulated parasites can persist for several years before they calcify and die [39]. For T. pseudospiralis larvae that do not encyst, clinical manifestations may include fatigue, postexercise weakness, and myositis that persist for several months to years [11,40].

Laboratory findings — During the early intestinal stage, there are no specific laboratory abnormalities. Leukocytosis and eosinophilia appear during the second week of the muscle stage. Nonspecific findings include elevated serum muscle enzymes (creatine kinase and lactate dehydrogenase) and hypergammaglobulinemia. (See "Muscle enzymes in the evaluation of neuromuscular diseases".)

Eosinophilia is a hallmark of clinical trichinellosis and is generally observed in most cases [34]. The proportion of eosinophils rises to a maximum of 20 to 90 percent in the third or fourth week. There is no correlation between the clinical course of disease and the degree of eosinophilia [33]. Eosinophilia may disappear in some heavily infected patients; this is considered to be a poor prognostic sign. In this setting, eosinopenia may be due to inflammation and/or superimposed bacterial infection. The erythrocyte sedimentation rate is often elevated; however, in severe trichinosis it may be low, especially in the setting of low serum protein levels [41,42].

Serious infection — Serious infections may include cardiac [43], central nervous system [44], renal, and/or pulmonary involvement. Fatal outcomes in acute trichinellosis usually result from myocarditis, encephalitis, or pneumonia. Thrombotic complications have also been described [45].

Cardiac disease — Cardiac involvement is not common, but it represents the most frequent cause of death in severe trichinellosis [35,46-48]. Larvae do not encyst in cardiac muscle but do invade the cardiac muscle and elicit an eosinophil-enriched inflammatory response and myocarditis [35,49]. In one retrospective study of 154 patients with trichinellosis, 56 percent had electrocardiogram abnormalities, mainly nonspecific ST-T wave changes [50]. However, life-threatening arrhythmias can occur and are the likely cause of death in many patients with Trichinella myocarditis. Another retrospective review including 10 patients noted one case of ST-elevation myocardial infarction [45].

Neurologic manifestations — Meningitis or encephalitis develop in 10 to 24 percent of patients with severe trichinellosis [35,49,51]. Neurologic manifestations may develop early or late and can be diffuse or focal in nature. Headache is common and is often exacerbated by movement. One report including 10 patients noted one case of sinus venous tract thrombosis [45]. Computed tomography and magnetic resonance imaging may show multifocal small lesions located in the cerebral cortex and white matter [52]. Pathologic findings can include edema, hemorrhage, emboli, infarctions, and perivascular infiltrates in fatal cases.

In one review of 77 Romanian patients with neurotrichinellosis, 60 percent made a complete recovery, 23 percent had sequelae, and 17 percent died. Lower eosinophil counts were observed among patients who died than patients who survived [53].

Pulmonary disease — Serious pulmonary involvement in trichinellosis is rare; in one series of 856 patients with acute trichinellosis, serious pulmonary involvement was observed in 6 percent of cases [54]. Pulmonary involvement may result from direct larval invasion of pulmonary tissues, myositis involving respiratory muscles, or secondary pyogenic pneumonia. Respiratory symptoms can also develop as a result of congestive heart failure due to myocarditis.

●Larval invasion of pulmonary tissues – Early during the stage of muscle invasion when intravascular larvae are passing through the lungs, a dry, nonproductive cough is common. Chest radiograph may demonstrate patchy basilar infiltrates, small micronodular lesions, or pleural effusions. These radiographic findings generally resolve over one to two weeks. Bronchitis is common between the third and fifth weeks of infection [35]. Patients frequently produce mucoid sputum, which may contain many eosinophils.

●Respiratory myositis – Myositis develops in response to encysted Trichinella larvae. The diaphragm may have a relatively high density of encysted larvae compared with other skeletal muscles. Diaphragmatic involvement can result in lower thoracic or epigastric pain and can cause sufficient weakness of the diaphragm to compromise respiratory function [47]. Painful intercostal myositis may further impair respiration [41]. These symptoms occur most frequently in the second and third weeks of infection.

Symptomatic involvement of the upper airway muscles can also occur. Affected patients may present with hoarseness or dysphagia due to involvement of the laryngeal muscles or the muscles of deglutition.

●Secondary bacterial pneumonia – Prolonged bed rest and impaired pulmonary toilet may predispose to secondary bacterial pneumonia in the late stages of severe infection. In one large series of patients hospitalized with trichinellosis, bronchopneumonia occurred in about 1 percent of cases [54].

Renal disease — Renal manifestations of trichinellosis are not common and generally occurs only in severe disease. Findings can include proteinuria, hematuria, casts, focal lesions, and renal failure [55].

DIAGNOSIS — The diagnosis of trichinellosis should be considered in patients with periorbital edema, myositis, and eosinophilia. Trichinellosis should be particularly suspected in individuals with these symptoms and a history of ingesting either inadequately cooked meat or a meat source also ingested by other symptomatic individuals.

Diagnosis is usually made based on clinical symptoms and is confirmed by serology. Less commonly, muscle biopsy may be used to identify encysted or non-encysted larvae.

Serologic tests — Many different serologic assays are available, including enzyme-linked immunosorbent assays (ELISAs), dot-ELISAs, indirect immunofluorescence, and latex agglutination. Serology is generally reliable; results can be confirmed with a Western blot [56].

Antibody levels are not detectable until after three or more weeks of infection so are not useful for early diagnosis. In addition, antibody levels do not correlate with the severity of the clinical course. Antibody tests may remain positive for years after cessation of clinical symptoms. Infection with other helminths and autoimmune diseases can cause false-positive serologic test results.

Antigen tests have been developed but have relatively poor sensitivity; in one series including 62 patients with confirmed infection, the assay was positive in 47 of patients [57].

Muscle biopsy — A definitive diagnosis may be established by identifying larvae on muscle biopsy (picture 1); this is not generally required but may be useful in the setting of diagnostic uncertainty [58]. The yield of muscle biopsy is highest in symptomatic muscles and near a tendinous insertion. In addition to routine histopathologic examination, the muscle should be examined after enzymatic digestion to free larvae. The specimen should also be examined undigested in a preparation of unfixed muscle compressed between microscope slides (picture 3).

It is difficult to differentiate Trichinella species larvae within muscle tissues by morphology. Molecular genetic assays, including multiplex polymerase chain reaction, have been developed for differentiation of Trichinella species and genotypes [59].

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of trichinellosis includes:

●Visceral larva migrans – Both visceral larva migrans and trichinellosis are associated with eosinophilia and may cause systemic involvement including pulmonary disease. However, trichinellosis consists primarily of muscle disease, which can occur in the setting of visceral larva migrans but is relatively uncommon. The diagnosis may be distinguished by serology. (See "Toxocariasis: Visceral and ocular larva migrans".)

●Strongyloidiasis – Both strongyloidiasis and trichinellosis are associated with gastrointestinal symptoms (abdominal pain, nausea, vomiting, and diarrhea) and eosinophilia. However, trichinellosis consists primarily of muscle disease, which does not generally occur in the setting of strongyloidiasis. The diagnosis may be distinguished by serology. (See "Strongyloidiasis".)

●Cysticercosis – Cysticercosis usually involves the central nervous system and is occasionally associated with muscle disease; trichinellosis is usually associated with muscle disease and is rarely associated with central nervous system involvement. The diagnosis may be distinguished by serology. (See "Cysticercosis: Clinical manifestations and diagnosis".)

●Dermatomyositis – Both dermatomyositis and trichinellosis are associated with muscle disease. Dermatomyositis is also associated with cutaneous involvement and autoantibodies, while trichinellosis is associated with eosinophilia and gastrointestinal symptoms. (See "Clinical manifestations of dermatomyositis and polymyositis in adults".)

●Sarcocystosis – Sarcocystosis and trichinellosis are both associated with consumption of undercooked meat, myositis, and eosinophilia. The diagnosis of sarcocystosis is established via biopsy. (See "Sarcocystosis".)

TREATMENT

General approach — The clinical course for most Trichinella infections is uncomplicated and self-limited. For mild infection, antiparasitic therapy is not required; symptomatic treatment with analgesia and antipyretics is appropriate.

Management of Trichinella infection with systemic symptoms (including central nervous system manifestations, cardiac inflammation, or pulmonary involvement) consists of antiparasitic therapy together with corticosteroids [60]. Antiparasitic therapy is useful for treatment of larvae burrowing into the gastrointestinal tract; a randomized trial including 46 patients with trichinellosis demonstrated that patients treated with mebendazole had less myositis and muscle pain than those treated with placebo [61]. However, the benefits of antiparasitic therapy in the setting of bloodborne larval invasion or encysting of muscle are uncertain; treatment after muscle invasion has occurred may fail to eliminate infective larvae from muscle [62].

Antiparasitics for treatment of trichinellosis include albendazole (400 mg orally with fatty meal twice daily for 10 to 14 days) or mebendazole (200 to 400 mg three times daily for three days, then 400 to 500 mg three times daily for 10 days) [63]. Data from treatment of patients with Echinococcus suggests albendazole levels are more predictable than mebendazole levels [22]. Prednisone may be administered concurrently in severe cases at a dose of 30 to 60 mg/day for 10 to 15 days.

Children and pregnant women — Transplacental transmission of larvae has not been correlated with symptomatic congenital infection nor have serious intranatal or postnatal newborn infections been described [64-66].

In general, administration of albendazole or mebendazole is generally not advisable during pregnancy or in children ≤2 years [33,67]. In the setting of intestinal and muscle stages of infection among these patients, anthelminthic treatment is usually not required. However, albendazole or mebendazole has been used in pregnant women with severe infection without adverse fetal effects [68]. In such cases, corticosteroid therapy should also be administered.

Postexposure prophylaxis — Postexposure prophylaxis may be effective for prevention of trichinellosis when given within six days; this was illustrated in a report of wild boar meat contamination with T. spiralis in Germany [69]. Among 37 exposed individuals who received mebendazole (5 mg/kg twice daily for five days) as postexposure prophylaxis, six developed trichinellosis; these cases occurred exclusively among individuals treated ≥6 days following exposure.

PREVENTION — Education regarding consumption of raw domestic and sylvatic animals that can be carriers of Trichinella parasites (if not properly tested for larvae as part of inspection) is an important component of prevention [22]. In addition, careful control of farming techniques for pigs (the most important source of Trichinella for humans) with veterinary oversight and use of certified feedstuff are needed.

Trichinella larvae in meat may be rendered noninfectious by heating to an internal temperature between 63°C to 77°C. Freezing at -15°C for three weeks, as in a home freezer, will also generally kill larvae, although arctic species are more resistant to freezing and may remain viable. Irradiation of sealed packed meat also inactivates larvae [70].

SUMMARY AND RECOMMENDATIONS

●Trichinellosis (trichinosis) is a parasitic infection caused by nematodes (roundworms) of the genus Trichinella. Pigs are the most important source of human infection, although a number of other animals are also epidemiologically important hosts. Consumption of raw or undercooked meat is the principal mode of transmission. (See 'Introduction' above.)

●The life cycle consists of two components: a domestic cycle and a sylvatic cycle (figure 2). The domestic cycle usually involves pigs and rodents; other domestic animals, such as horses, can be involved. The sylvatic cycle can involve a broad range of infected animals; animals most frequently implicated as sources of human infection include bear, moose, and wild boar. (See 'Epidemiology' above.)

●The severity of infection correlates with the number of ingested larvae; mild infection can be subclinical. Heavy infection may have two stages, the intestinal stage (in which larvae mature into adult worms that burrow into the intestinal mucosa) and the muscle stage (in which larvae disseminate hematogenously from the intestines and enter skeletal muscle). Symptoms during the muscle phase include muscle pain, tenderness, weakness, and periorbital edema. (See 'Clinical manifestations' above.)

●Eosinophilia is a hallmark of trichinellosis; it typically develops during the second week of the muscle stage. Nonspecific findings include elevated serum muscle enzymes (creatine kinase and lactate dehydrogenase) and hypergammaglobulinemia. (See 'Laboratory findings' above.)

●Serious infections may include cardiac, central nervous system, and/or pulmonary involvement. Fatal outcomes in acute trichinellosis usually result from myocarditis, encephalitis, or pneumonia. (See 'Serious infection' above.)

●Diagnosis is usually based on clinical symptoms and confirmed by serology. Antibody levels are not detectable until after three or more weeks of infection so are not useful for early diagnosis. A definitive diagnosis may be established by identifying larvae on muscle biopsy (picture 1); this is not generally required but may be useful in the setting of diagnostic uncertainty. (See 'Diagnosis' above.)

●The clinical course for most Trichinella infections is uncomplicated and self-limited. For mild infection, antiparasitic therapy is not required; symptomatic treatment with analgesia and antipyretics is appropriate. Management of Trichinella infection with systemic symptoms (including cardiac inflammation, central nervous system manifestations, or pulmonary involvement) consists of antiparasitic therapy together with corticosteroids. We suggest treatment with albendazole (Grade 2C); mebendazole is an acceptable alternative. Dosing is outlined above. (See 'Treatment' above.)

●Preventive measures include community education, prudent farming techniques, and attention to freezing and cooking techniques to inactivate Trichinella larvae in meat. (See 'Prevention' above.)