Clinical manifestations

Presentation and course

The clinical syndromes related to Trichinella infection vary widely, from asymptomatic to fatal, depending on the number and sites of parasitic infestation. The natural history of symptoms and signs closely parallels the biological evolution of the parasite and the responses of the host. The first stage of infection manifests as a nonspecific gastroenteritis, which usually occurs 2 to 7 days after ingestion of contaminated food. During this enteric phase, adult worms and larvae invade duodenal and jejunal mucosa and cause an inflammation. Signs and symptoms at this state depend on the number of larvae. When worms are present in small numbers, this phase may be hardly noticeable or entirely absent. A large number of worms, however, can produce signs and symptoms of acute enteritis such as diarrhea (sometimes bloody), nausea, vomiting, and abdominal pain, which may last up to several weeks.

Characteristic manifestations of Trichinella infection are caused by larvae migration and invasion of target tissues, primarily muscles. Tissue invasion by the larvae begins 6 to 10 days after exposure and is followed by encystment in muscle about two weeks later. The severity of symptoms of this phase is also related to the number of larvae produced. Most moderately severe infections are associated with approximately 50 to 100 larvae per gram of muscle, whereas infections in the range of 1 to 10 larvae per gram of muscle are usually asymptomatic. The presence of more than 1000 larvae per gram of muscle is considered critical or fatal.

Diffuse inflammatory response caused by larvae or their products leads to fever of varying degree and duration, headache, maculopapular rash, focal edema, local inflammation, leukocytosis, and eosinophilia. The extraocular muscles, masseters, diaphragm, intercostals, deltoids, and the muscles of the tongue, larynx, and neck are most heavily infested. Involvement of extraocular and facial muscle, which usually develops early in the stage of muscle invasion, results in periorbital and facial edema and chemosis of the bulbar conjunctiva. Subconjunctival and splinter hemorrhages under the fingernails can be observed during the early phase of larvae migration. Involvement of mastication muscle results in difficulties in chewing or even trismus. Edema of the tongue and pharyngeal muscles may cause dysphagia. Diffuse and intense muscle involvement in severe cases is associated with muscle pain, especially of the diaphragm. The calves and forearm muscles are usually painful, and pain is worse during movement.

Myalgia usually reaches maximum within three weeks. Besides muscle pain, change in muscle consistency to “stony hard” is a characteristic finding. Weakness of various degrees is usually observed in the involved muscles. The weakness may be extreme and can result in rapidly progressive tetraparesis. The tendon reflexes may be decreased.

The most serious complications are related to involvement of the heart, central nervous system, and lungs (ie, the organs with the greatest number of endarterioles) (26). Cardiac involvement generally manifests in the form of myocarditis, which usually occurs during the third week of infection. Myocarditis is by far the most common cause of death in fatal trichinosis. Trichinous myocarditis may initially manifest as tachycardia or chest pain and may mimic acute myocardial infarction. The severity of myocardial abnormalities may range from benign, reversible, nonspecific ECG abnormalities to fatal congestive heart failure. Although, in most cases, trichinous myocarditis can resolve completely, persistent myocarditis and sinus arrest requiring permanent pacemaker implantation has been reported (11). Changes in ECG patterns can be evident in 20% to 30% of patients. Such ECG abnormalities include T-wave changes, low voltages of the QRS complexes, intraventricular and atrioventricular conduction disturbances, ST-segment depression, premature ventricular contractions, and infarct patterns (57; 56). In severe infections, death often occurs between the fourth and eighth weeks. Besides myocarditis, involvement of pericardium and endocardium has been also reported. Moderate to large pericardial effusion can be detected in trichinous pericarditis (04). Endocardial damage with superimposed mural thrombosis has also been also reported (01). A prospective study showed that cardiac involvement appeared to be lower (13%) than previously reported and that the most common manifestation is pericardial effusion rather than myocarditis (36). Pulmonary involvement can occur in 6% of patients and may manifest as pneumonia, pleural effusion, or pulmonary hemorrhage (30). Cough and shortness of breath can occur. Severe pulmonary involvement requiring ventilatory support has been reported (10).

Involvement of the central nervous system occurs in 10% to 20% of patients and is usually associated with heavy Trichinella infection. The mortality rates may be as high as 50% (14; 26; 20). Clinical manifestations of CNS trichinosis consist of both diffuse encephalopathy and focal neurologic deficits. The first indication of the cerebral invasion occurs during the second week, the larval migratory stage. This produces varying degrees of encephalitis manifested by emotional instability, psychotic behavior, delirium, insomnia, inattentiveness, disorientation, lethargy, headache, or memory loss. These nonspecific mental symptoms are frequently mild and evanescent, although they can be severe and prolonged. Localized or focal nervous system involvement may occur during the third week, the encystment stage. The presence of meningoencephalitic symptoms, developed during the larval migratory stage, need not be the harbinger of the more severe and irreversible focal involvement. However, when focal involvement does occur, it is often superimposed on previous meningeal or encephalitic symptoms and is rarely the sole manifestation. Various focal neurologic signs can develop in this stage, including cranial nerve deficits, paresis, aphasia, convulsions, cerebellar syndromes, and coma (26). Occlusion of cerebral venous sinus causing extensive venous infarction and intracerebral hemorrhage may occur (25).

Renal involvement in trichinosis has been rarely reported (55). Proteinuria can be detected in 84.8% of cases and hematuria in 30.4%, and casts can be observed in urine specimens from 23.9% of patients (43). Renal failure occurs in 8.7% of patients. Changes in renal function may be secondary to systemic hypoperfusion in combination with severe myoglobinuria.

The clinical manifestations of trichinosis can be different depending on species of trichinae. Infection with T spiralis appears to cause a more severe symptomatology during the enteric phase, longer duration of parasite-specific IgG, and longer increased creatine phosphokinase level than those with T britovi (52). In children, T britovi infection causes less myalgia, facial or eyelid edema, eosinophilia, and increased serum creatine kinase than in adults who consumed the same amount of infected meat (45). A clinical syndrome of trichinosis with prolonged diarrhea without fever and with brief muscle symptoms has been reported from the Arctic area (38). A longer period of muscle invasion (up to more than four months) resulting in persistent myositis has been described in trichinosis caused by T pseudospiralis (32).

Prognosis and complications

The severity and prognosis of trichinosis in humans depends on the parasitic burden. In most cases, the symptoms are considered mild or even asymptomatic. On the other hand, the prognosis in patients with heavy larvae burden (more than 1000 larvae per gram of muscle) is poor and may be fatal.

Damage to internal organs can occur during the phase of larvae migration. Such larvae migration-induced tissue injuries are usually fully recoverable. However, damage causing permanent deficit can also occur. These deficits include hemorrhagic maculopathy with focal atrophy of retinal pigment epithelium, permanent cardiac conduction defect, and various forms of permanent focal neurologic deficits.

The existence of a clinical syndrome related to chronic Trichinella infection is still an issue of debate. Persistence of antibody, especially IgG, in human trichinosis has been confirmed by a number of studies. Harms and colleagues demonstrated that 38% of cases still had IgG antibody to T spiralis after 10 years (29). Such persistent antibody may result from progressive destruction of Trichinella larvae in muscle. Besides persistent seropositivity, clinical analysis in these patients documented complaints from a substantial number of patients in the form of generalized weakness, fatigability, chronic myalgia, etc. (21; 34). However, there are still insufficient data on which to conclude that chronic trichinosis exists as a distinct entity.

Clinical vignette

A 38-year-old male villager was referred to a university hospital with the chief complaint of painful muscle swelling involving the calves, arms, and face. Three months prior to admission, he ate a meal made from uncooked boar meat. A few days after ingestion, he had abdominal cramps, vomiting, and watery diarrhea. The intestinal symptoms persisted for a week and then improved gradually. Despite improvement, he developed low-grade fever and diffuse painful muscle swelling involving the calves, arms, and muscles of mastication. Chewing and swallowing became difficult and painful. Muscle pain progressively worsened during the first month of the symptoms. During the same period, other villagers who ate meat from the same source were also affected. The patient was initially treated by local health personnel. Mebendazole (400 mg per day) was given for the period of one month, but no substantial improvement was evident. Mebendazole was withdrawn and thiabendazole (2 g per day) was prescribed for the period of two weeks. However, the clinical response was still unsatisfactory. He was then referred to the university hospital for management. On admission, his body temperature was 37.3°C, while other vital signs were normal. The obvious physical findings were diffuse muscle swelling and tenderness, which was more severe in the muscles of the calves and forearms. Neither splinter hemorrhage nor facial edema was noted. Routine laboratory tests revealed a high percentage of eosinophil (1440 cells per mm3). The serum creatine phosphokinase level was 2395 IU/L. Muscle biopsy was performed, and the pathological result showed nonencapsulated and actively motile Trichinella larvae. The serological study revealed positive IgG antibody against Trichinella antigen (ELISA). DNA typing demonstrated the DNA profile, which was consistent with T pseudospiralis. Albendazole (800 mg per day) was prescribed. Two days after treatment, the patient developed dyspnea and fever. Prednisolone (30 mg per day) was started and continued for five days. The patient improved within a few days. The muscle swelling gradually decreased and disappeared within two weeks of treatment. Albendazole was continued for a total of four weeks. One month after treatment, the clinical examination showed no muscle swelling, and all laboratory tests were normal. However, the patient still felt early fatigue after exercise.

Biological basis

Etiology and pathogenesis

Trichinosis is caused by zoonotic infestation of nematode in the genus Trichinella. This genus comprises at least seven species (T spiralis, T nelsoni, T britovi, T nativa, T pseudospiralis, T murelli, and T papuae) and three additional genotypes (Trichinella T6, related to T nativa, and Trichinella T8 and T9, related to T britovi) (47). At least six species of Trichinella have been known to cause human infections (ie, T spiralis, T nelsoni, T britovi, T nativa, T pseudospiralis, and T murelli). Though the most common species reported to be responsible for human trichinosis is T spiralis, the prevalence of human infections with other species has not yet been verified (50; 03; 17; 32). An outbreak of trichinosis possibly caused by T papuae was reported in Taiwan in which eating raw soft-shelled turtles (Pelodiscus sinensis) was the suspected mode of infection (37). In Cambodia, an outbreak of T papuae occurred due to wild pigs; 33 people were infected, eight of whom died (09). An outbreak of trichinosis, caused by consumption of bear meat infested with T murelli, was reported (28).

A variety of sylvatic and domestic animals can serve as reservoir hosts of trichinae. In general, sylvatic trichinosis affects carnivores with cannibalistic and scavenger behaviors, whereas domestic pigs and synanthropic rats serve as the most important sources of the infection with T spiralis in domestic habitats (46). Raptorial birds, marsupials, wild canids, rodents, domestic pigs, and monkeys have been reported to be the source of T pseudospiralis infection (51).

The life cycle of T spiralis requires both enteral and parenteral phases. After ingestion of infected meat, the first stage larvae are released and pass into the duodenum and jejunum. At the intestinal wall, the 1 mm larvae enter common cytoplasm shared by approximately 45 enterocytes and located at the level of the platform of the crypts and above. Throughout its morphogenesis, four molts rapidly occur within 30 hours, generating juvenile males and females. The mature female is 3 mm long, whereas the male is half of the female size. The site where mating occurs is virtually unknown. The male can copulate with the female more than once (15). After copulation, the viviparous female produces hundreds to thousands of newborn larvae over a life span of 3 to 5 weeks. Generally, the adults derive their metabolic energy from aerobic pathway, whereas the larvae use mainly anaerobic energy generation (58).

During the migratory phase, the newborn larvae pass through the intestinal wall into the lymphatic vessels and circulatory system. Once in a capillary bed of a given tissue, the larvae penetrate the circulation in a random fashion. By this route, larvae can reach any organs, and then they seed and provoke an inflammatory reaction.

During the parenteral phase, the larvae resume their lives as an intracellular parasite only in skeletal muscle. The infected striated muscle is transformed to nurse cells. This process takes 20 days to complete. The infected muscle cells enter the cell cycle, repositioning in G2/M arrest and resulting in muscle gene expression, which is normally restricted to G0/G1 of the cell cycle. The host regulatory factors expressed as a consequence of cell cycle repositioning renders the expression of nondifferentiated muscle characteristics, such as increased acid phosphatase activity and collagen capsule formation. On the other hand, classic characteristics of differentiated muscle cells containing myofibrillar proteins such as myosin heavy chain, alpha-actin, and alpha- and beta-tropomyosin are undetected in chronically infected cells (31). The nuclei of the infected host cells appear enlarged and contain well-developed nucleoli. The cytoplasm becomes robust and shows no sign of degeneration except the loss of mitochondria. The maintenance of intracapsular metabolically active parasites requires nutrient acquisition and waste disposal through angiogenesis surrounding the capsule. Structurally, the nurse cell-infective first-stage larva complex is set apart from all other host cells by its thick collagen and circulatory rate, arising after the 12th day of intramuscular invasion (15).

Meanwhile, the larvae slowly mature, and after 16 days they reach the length of 800 to 1000 µm and a width of 30 µm. Three weeks after muscle penetration, they will have increased their length 10-fold, becoming coiled in the process and residing in an ellipsoid cyst measuring 500 µm long and 250 µm wide. It takes about three months for these cysts to fully develop.

No preference to any fiber types is observed. Muscles of the diaphragm; masseter; extraocular muscles; muscles of the tongue, larynx, and neck; intercostal muscles; and deltoid muscles are preferentially parasitized. Sites of attachment to tendon are particularly prone to be affected. Eventually, the inflammation subsides, leaving mature cysts in skeletal muscles, where they can remain dormant for years.

Mechanisms underlying vital organ involvement are still debated. Whether disseminated larvae alone or with an associated toxemia account for the damage to the internal organs has not yet been clearly demonstrated. A purely mechanical theory suggests that the larva cause the occlusion of small cerebral endarterioles, resulting in distal ischemia. This hypothesis was supported by neuropathological examination, which revealed multiple arteriolar fibrinocruoric thrombi not associated with inflammatory changes, similar to those observed in patients with disseminated intravascular coagulation (20). However, although direct invasion of myocardium and brain parenchyma by T spiralis has been evident, larva encystment in these organs has been reported only rarely. Actually, cardiac involvement, generally nonspecific inflammatory myocarditis, is often predominantly eosinophilic. The coexisting cardiac and CNS involvement in severe trichinosis resembles that observed in patients with hypereosinophilic syndrome. This observation raises the possibility that toxic substances released from eosinophil are responsible for cellular destruction in severe trichinosis, not the parasitic invasion per se. However, the role of eosinophilia in trichinellosis is still controversial. It should be noted that eosinophils could have a protective role due to their cytotoxic effect against newborn larvae in an antibody dependent cellular cytotoxicity system. The observation that eosinophil number decreases massively in severe infections supports the protective role of eosinophils (06).

Epidemiology

Human trichinellosis has been documented in 55 (27.8%) countries around the world. Trichinella sp infection has been documented in domestic animals (mainly pigs) and in wildlife of 43 (21.9%) and 66 (33.3%) countries, respectively (48). The calculation based on the results of a systematic review of the worldwide epidemiology and clinical impact of human trichinellosis between 1986 and 2009 revealed the estimated global incidence rate to be 469.2 to 985.3 cases per billion persons per year, and the global mortality rate to be 0.300 to 0.828 per billion persons per year (16). The global number of disability-adjusted life years due to trichinellosis was estimated to be 76 per billion persons per year (95% credible interval: 38-129). In the United States, from 2008 to 2012, the mean annual incidence of trichinellosis was 0.1 cases per one million population, with a median of 15 cases per year (61).

The reported incidence of human trichinosis depends on control of the meat industry, practices of eating and preparing meat, and the extent to which the disease is recognized. The prevalence and intensity of infection in man and in pigs has been markedly reduced. In the 1930s an overall prevalence at 16.1% was reported from examinations of 5313 human diaphragms obtained at autopsy in a study conducted throughout the United States by the National Institute of Health. Since the United States Public Health Service began recording statistics on trichinosis in 1947, the number of reported cases has decreased steadily from an average of 400 cases with 10 to 15 deaths reported each year in the late 1940s to 57 cases per year with three deaths from 1982 to 1986 (02). From 1991 to 1996, three deaths in 230 cases (an average of 38 cases per year) were reported to the Centers for Disease Control and Prevention (39). Data regarding the suspected food items revealed that pork products (especially sausage) were implicated in 60% of cases. Today, the proportion of trichinosis attributed to the consumption of commercial pork has declined, causing the proportion associated with wild game meat and noncommercial meat to increase. Global data from 2010 to 2015 show a major shift in the source of infection wherein game meat accounts more of the percentage (54%, compared with 46% of domestic pig) compared with the study from 1989 to 2009 (42%, compared with 53% of domestic pig) (41).

Species of trichinae that cause human trichinosis differ with geographic distribution (33). T spiralis, the major causative outbreak agent, causes domestic trichinosis and is the only species with good infectivity for swine and rats; T spiralis has worldwide distribution. T nelsoni is found in various large carnivores of tropical Africa and has caused intensive infection in man. T britovi causes sylvatic trichinosis in the temperate zone of the Palearctic region. The main reservoirs are foxes, wolves, and occasionally, boars. The primary hosts for T nativa are Arctic carnivores such as polar bears, arctic foxes, and walruses. T pseudospiralis is primarily a parasite of raptorial birds, marsupials, wild canids, and rodents. In Thailand and France, meat from wild pigs infected with T pseudospiralis was the source of human trichinosis (32; 53). The observation of the presence of T pseudospiralis in domestic pigs and brown rats suggested that in particular epidemiological situations, this parasite can be transmitted by a domestic cycle to human environment. T papuae, the second nonencapsulated species, was reported to cause human trichinosis in Papua New Guinea. The prevalence among the people living in this area was high (28%), and infection was due to eating raw or undercooked wild pig (44). The main reservoir of this Trichinella species remains unknown.

Prevention

The main control measures are through garbage and cooking of meat. Regular meat control has contributed greatly to the reduction of human trichinosis attributed to commercial pork. Ready-to-eat pork products, such as cold-smoked sausage, must be processed to eliminate Trichinella larvae. The regulations require that commercial heating of pork must reach an internal temperature of at least 58°C (23). Guidelines for preparation of pork in the home recommend cooking to reach an internal temperature of 160°F. In addition, pork less than six inches thick can be rendered safe if frozen to -5°F (-17°C) for 20 days, -10°F (-23°C) for 10 days, or -20°F (-29°C) for six days. It should be noted that muscle larvae of Trichinella nativa, its related genotype Trichinella T6, and Trichinella britovi can survive extended periods of freezing in the muscles of some of their natural hosts, including pigs (49). Therefore, pork from areas where T britovi is endemic, especially countries in Europe, should not be treated by freezing alone as a method to protect human health.

Noncommercial sources of meats, as from wild animals and small rural farms not using modern hog management practices, still represent a significant health problem. Public education concerning the potential dangers of eating any raw meat product or wild game is important in the prevention of Trichinella infection. Since the prevalence of travel-associated trichinosis was reported to be increased (0.5% of all cases reported between 1975 and 1982 compared to 5.5% between 1982 and 1989), physicians involved in pretravel counseling should provide more information about the dangers of improperly prepared meat products.

Vaccination has been of interest in the prevention of trichinosis. Live attenuated vaccines, natural antigen vaccines, recombinant protein vaccines, and DNA vaccines have been studied in rodent’s model. Although swine vaccines have been developed, no preventive efficacy has been reported. However, new DNA vaccines are under development. These vaccines are promising due to its cost-effectiveness and long-lasting immunity. More research on swine model is needed in the future (60).

Differential diagnosis

Confusing conditions

Differential diagnoses of trichinosis differ with the phase of disease as well as its clinical manifestation.

Enteric phase. The symptoms occurring in the enteric phase cannot be differentiated from other causes of gastroenteritis.

Acute muscle pain and weakness. Differential diagnosis should include causes of acute myopathy, anterior horn cell disease, or acute neuropathy (eg, infectious myositis, polymyositis, drug-induced myopathy, poliomyelitis, and Guillain-Barre syndrome). Severe pain and stiffness of involved muscles are important clinical clues for the diagnosis of trichinosis. The muscle involvement in cysticercosis, another parasitic myopathy, can also manifest by muscle weakness and tenderness; however, the clinical course is usually subacute or chronic, and most patients are asymptomatic. The important features of involved muscles in symptomatic patients are pseudohypertrophy and nodularity on deep palpation. Radiological examination, even in asymptomatic patients, usually reveals “rice-like” calcification.

Splinter hemorrhage. Splinter hemorrhage usually appears in early phase of trichinosis and may raise concern of infective endocarditis, vasculitis, antiphospholipid syndrome, and even chronic meningococcemia (27). Because splinter hemorrhage is not a specific sign, history taking and physical examinations are still encouraged to rule out these diseases.

Prominent bulbar symptoms. The differential diagnosis includes myasthenia gravis, polymyositis, and the bulbar form of poliomyelitis.

External ophthalmoplegia. The differential diagnosis includes myasthenia gravis, thyrotoxic ophthalmopathy, pseudotumor oculi, and other causes of extraocular infiltration.

Associated or underlying disorders

Eosinophilia-myalgia syndrome. Apart from Trichinosis itself, the differential diagnosis of eosinophilia-myalgia syndrome includes acute tropical myositis, sarcoidosis, granulomatous myositis, polymyositis, collagen vascular diseases, neoplastic myositis, eosinophilic myositis, myalgia associated with tryptophan ingestion, and toxoplasma myositis (12). Toxoplasma myositis is relatively rare but resembles those of trichinosis. Ingestion of raw meat has been found to be the cause of this disease. Confirmation of the disease is by detecting immunoglobulin to toxoplasmosis or muscle biopsy (13).

Systemic involvement. Cardiac involvement in trichinosis may be confused with other causes of heart failure, including ischemic heart disease. Clinical signs and symptoms of CNS trichinosis can resemble acute meningitis, encephalitis, CNS vasculitis, or even acute psychotic disorders. Although clinical syndromes of CNS trichinosis are myriad and none of the clinical signs are diagnostic, these syndromes usually coexist with acute diffuse myositis and myocardial injury. Such a combination is considerably helpful in the diagnosis of neurotrichinosis.

Diagnostic workup

Trichinosis should be considered in patients with fever, myalgia, periorbital edema, eosinophilia, and a history of recent consumption of poorly cooked meat, especially pork. In addition to the history of consumption of a pork product, the most valuable and informative evidence is eosinophilia. Eosinophilia (above 300/mm3) is seen in most cases and usually develops in the first 10 days after infection. However, in severe infections, eosinophilia may be delayed for weeks.

During the acute stage of infection, a massive decrease of eosinophils in people with severe trichinellosis is a predictor of a severe outcome, and a sudden decrease to 1% or less might predict patient death (06). Increased erythrocyte sedimentation rate can be found in 29% of patients. The serum creatine phosphokinase level is elevated in 46% of patients. Electromyogram usually demonstrates both myopathic features and fibrillation potentials, resembling those observed in polymyositis.

A definitive diagnosis is established by demonstration of larvae in muscle, blood, or cerebrospinal fluid. Muscle biopsy should not be performed sooner than two weeks after infection because younger larvae may be digested in the pepsin-hydrochloric acid mixture used in the diagnostic test. At least one gram of muscle should be taken, weighed, pressed, and digested after a small portion is removed for histologic examination. For a rapid diagnosis, compression of a gross specimen of muscle and examination under the microscope often reveal motile larvae. The obtained muscle tissue should be serially sectioned and carefully searched for larvae. Microscopic features at the acute infection stage show parasites coiled within pseudocyst formed by host connective tissues. After several years of encystment, calcification of the cyst can occur. Muscle biopsy usually reveals the inflammatory response due to the necrosis of muscle fibers as well as the invasion by parasites. In the early stage of muscle invasion, polymorphonuclear leukocytes and eosinophils are conspicuous. These inflammatory aggregations are replaced by mononuclear cells in the more chronic stage of the disease.

Several serologic tests assisting in diagnosis of trichinosis have been developed, eg, the indirect immunofluorescence assay (IFA), the enzyme-linked immunosorbent assay (ELISA), competitive inhibition assay (CIA), and the immunoelectrotransfer blot (IETB) assay using either crude somatic or excretory-secretory antigens. The sensitivity and specificity of these tests depends on the types of antigens and timing of the tests (59). The ELISA, with excretory-secretory (ES) product of the muscle larva or tyvelose antigen, can be used as the primary diagnostic of choice to detect infections in humans. However, according to the recommendation of the International Commission on Trichinellosis, positive results from at least two screening tests are required to confirm the diagnosis: for example, screening by ELISA to detect the response against soluble antigen and by indirect immunofluorescence assay to detect antibodies that react with antigens on the larva’s cuticle. When a single preliminary serological test is positive, another test, such as an immunoelectrotransfer blot or competitive inhibition assay, might be performed for confirmation (24).

Different species of Trichinella that infect humans exhibit unique biological characteristics, allozymes, and DNA profiles. Serological methods cannot be used to differentiate species. Practically, a molecular technique based on the polymerase chain reaction known as random amplified polymorphic DNA provides an effective tool for rapid and specific detection of Trichinella species (03). The technique of polymerase chain reaction-restriction fragment length polymorphism of various parasitic proteins, eg, mitochondrial cytochrome c-oxidase subunit I, 43 kDa excretory-secretory protein, are also useful for identification of Trichinella species (42; 62). A significant increase in gelatinolytic activity for pro-matrix metalloproteinases-9 (MMP-9) was observed in T britovi-infected patients compared to the control group. Therefore, MMP-9 might be considered a marker of inflammation in T britovi patients (05).

Besides occasionally elevated protein concentration, the CSF examination usually has a normal result (14; 20). Although peripheral eosinophilia is a prominent finding, significant hypereosinophilia in CSF has not been reported. Presence of trichinous larvae in CSF has been reported occasionally. Computed tomography scan of the brain usually shows multiple small hypodensity lesions in the cerebral cortex and white matter. A hyperdensity area, indicating intracranial hematoma, has also been reported (25). Multiple small cortical infarcts with Gd-DTPA enhancement can be observed by MRI (18).

The Centers for Disease Control case definition for trichinosis is as follows: (1) Trichinella-positive muscle biopsy or positive serologic test for trichinosis in a patient with a clinical syndrome compatible with trichinosis (including eosinophilia, fever, myalgia, and periorbital edema) or (2) in an outbreak, at least one person must meet criteria 1, with associated cases defined by either a positive serologic test for trichinosis or clinical symptoms compatible with trichinosis (including eosinophilia, fever, myalgia, and periorbital edema) in persons who have shared the epidemiologically implicated meal or have consumed the implicated meat product.

Management

Symptomatic and supportive treatments are the mainstay in management of trichinosis. In mild cases, limited bed rest, analgesics, and antipyretics are usually adequate to control muscular discomfort and fever. In severe cases, corticosteroids are strongly recommended in order to alleviate general symptoms of the disease (fever, myalgia, etc.) and to inhibit eosinophilic activation, degranulation, and cytotoxicity (40; 20). The suggested dose is 40 to 60 mg of prednisone daily. Because corticosteroids may prolong the enteric phase of infection, their use is recommended for only a limited time. Simultaneous initiation of antihelminthics is also suggested because corticosteroids may contribute to the spread of other parasites, eg, strongyloides. Supportive measures, such as intravenous fluids, antibiotics when indicated, and assisted or controlled respiration if necessary, are of importance in severe trichinosis. The beneficial effect of plasmapheresis for treating severe trichinosis has been reported; however, the data are still limited, and this treatment should be considered experimental (35).

Benzimidazoles (thiabendazole, mebendazole, and albendazole) are recommended in treatment of trichinosis. In order to be effective, they must be administered before the end of acute stage (52). Thiabendazole was the first drug proven to be effective in treatment of experimental trichinosis. The recommended dosage in humans is 25 to 50 mg/kg twice a day (maximum dose, 3 gm/day for an adult) for 5 to 7 days. Side effects of this drug, especially nausea and vomiting, develop in 50% of recipients and, thus, limit its clinical use. Mebendazole, 200 to 400 mg three times a day for three days followed by 400 to 500 mg three times a day for 10 days, may be also effective for the tissue phase of trichinosis and is better tolerated. However, this drug has poor intestinal absorption, which limits its use in extraintestinal trichinosis. Albendazole, 800 mg/kg in four divided doses, is the most recommended treatment regimen. Although its efficacy in treatment of acute trichinosis is not superior, as compared to thiabendazole, this agent is better tolerated (07). Despite their comparable initial response, albendazole is possibly more effective than thiabendazole in treatment of residual larvae (19). In severe infections, massive release of antigenic substances may cause Jarisch-Herxheimer-like reactions with these antihelminthics, and coadministration with corticosteroids is recommended.

Special considerations

Pregnancy

No definite clinical evidence is available regarding transplacental transmission of trichinosis. An immunological study showed the presence of specific immunoglobulins and isotypes against excretion-secretion products from muscle larvae and newborn larvae of T. spiralis in newborn whose mothers had trichinellosis during pregnancy. These data suggest that newborn larvae transplacental passage is possible (54).