Trichinella

Background

Trichinosis is the result of infection by the nematode Trichinella spiralis. Humans are infected incidentally when they eat inadequately cooked meat that contains larvae of Trichinella species. Most infestations do not cause symptoms, although heavy exposure can cause various clinical manifestations, including diarrhea, fever, myalgias, and prostration.

Pathophysiology

Although 8 species of Trichinella currently exist and are described taxonomically based on genetic, biochemical, and biological data, an additional 3 genotypes are acknowledged in the genus, but their taxonomic level is uncertain. The table below describes the taxonomically described species, including distribution, major host reservoir, infectivity of humans, resistance to freezing, and pathogenicity to humans.

Important Characteristics of Trichinella Species

Species


Distribution


Major Host Reservoir


Infectivity


Resistance to Freezing

Trichinella spiralis (T1)


Cosmopolitan


Swine, wild boar, bear, horse, fox


High


None

Trichinella nativa (T2)


Arctic


Bear, horse


High


High

Trichinella britovi (T3)


Temperate


Wild boar, horse


Moderate


None

Trichinella pseudospiralis (T4)


Cosmopolitan


Birds, omnivorous mammals


Moderate


None

Trichinella murrelli (T5)


Temperate, near arctic


Bear


Low


Low

Trichinella nelsoni (T7)


Tropical


Warthog


High


None

Trichinella papuae (T10)


Papua New Guinea


Warthog


Moderate


None

Trichinella zimbabwensis (T11)


Central Africa


Crocodiles


Unknown


None

Trichinella species require 2 hosts to maintain their life cycle. After development in a single host, they spread to the next through ingestion of infected flesh, as opposed to the traditional arthropod intermediate host. Trichinella species have 3 major life cycles in nature: pig-to-pig, rat-to-rat, and by carnivorous or omnivorous animals in the wild. Rats and pigs are the animals most commonly associated with trichinosis (see Image 1); however, depending on the region, walruses, seals, bears, polar bears, cats, raccoons, wolves, and foxes may also be infected.



The life cycle begins when raw or inadequately cooked meat is eaten that contains viable larvae housed inside a cyst wall, known as a nurse cell. The acidic environment in the host's stomach releases the larvae from the cyst wall. The free larvae migrate into the small intestine and attach to and penetrate the mucosa at the base of the villi. After 4 molts and over a period of 30-36 hours, they develop into adult worms and become obligate intracellular organisms. The adult male measures 1.5 X 0.05 mm, and the adult female measures 3.5 X 0.06 mm. Approximately 5 days after infection, the female begins shedding live newborn larvae (L1 stage). The female remains in the intestine for 4 weeks, releasing up to 1500 larvae. After an adequate inflammatory response develops in the intestine, the female is eventually expelled in the feces.

The newborn larvae enter the lymphatics and blood circulatory system and migrate to well-vascularized striated skeletal muscle. The parasite has a predilection for the most metabolically active muscle groups; therefore, the most frequently parasitized muscles include the tongue; the diaphragmatic, masseteric, intercostal, laryngeal, extraocular, nuchal, intercostal, and pectoral muscles; the deltoid; the gluteus; the biceps; and the gastrocnemius. In tissues other than skeletal muscle, such as the myocardium and brain, the parasites soon disintegrate, causing intense inflammation, and are then reabsorbed.

The larvae continue to grow over the next 2-3 weeks until they reach the fully developed L1 infective stage, when they increase in size up to 10-fold. The adult worms are viviparous. The larvae coil and develop a surrounding cyst wall, or nurse cell (except for T pseudospiralis, which does not encyst). The complete cycle takes 17-21 days. The larvae within the cyst wall reach an average size of 400 X 260 µm; however, lengths of 800-1000 µm have been described. The nurse cell–L1 complex may persist for 6 months to several years before calcification and death occur. The life cycle is complete when a compatible host ingests the infected muscle.

The intensity and frequency of exposure to infected meat determine the severity of the disease. The degree of infection is categorized as light (0-10 larvae ingested), moderate (50-500 larvae ingested), and severe (>1000 larvae ingested).

Frequency

United States

From 1997-2001, 72 cases were reported to the Centers for Disease Control and Prevention (CDC). Most cases were associated with eating wild game (43%), although 17% were associated with commercial pork products and another 13% from noncommercial pork products. Infections may also occur during foreign travel, especially to Mexico and Asia. The percentage of infected domestic swine in the United States is 0.001%; however, one autopsy study documented a 4% incidence of old infection.

International

In Europe, where pork inspection is mandatory, most cases are associated with horse or wild boar meat. In Latin America and Asia, domestic pork is the chief source of infection. The rate of Trichinella infection in swine in China is as high as 20%.

Mortality/Morbidity

· Although infections are most likely underreported in the United States, fewer than 25 cases are documented per year, with a very low mortality rate.

· Patients with light infection are usually asymptomatic. Those with mild symptoms improve in 2-3 weeks. Symptoms associated with heavy infections may persist for 2-3 months.

· Factors that may affect morbidity include the quantity of larvae ingested, the species of Trichinella (most notably T spiralis), and the immune status of the host. Patients succumb to exhaustion, pneumonia, pulmonary embolism, encephalitis, or cardiac failure and/or arrhythmia. Death from trichinellosis usually occurs in 4-8 weeks but may occur as early as in 2-3 weeks.

Race

Infections are related to cultural differences in food cooking and storing methods, specifically the inadequate cooking or freezing of meat.

Sex

· No differences in the rates of trichinosis between males and females are reported.

· Pregnant patients milder trichinosis symptoms than patients who are not pregnant; however, abortions and stillbirths have been reported.

· Symptoms are typically worse in females who are lactating than in females who are not.

Age

Children appear to be more resistant to infection; however, their symptoms may be more intense. Children also have fewer complications and recover more rapidly.

History

Knowledge of the incubation period can help pinpoint the source of the infection, both in individual cases and in outbreaks.

· The disease may progress from an enteric (ie, intestinal) phase to a parenteral (ie, invasive) phase to a period of convalescence.

· The intestinal phase usually causes symptoms in the first week of illness.

o Diarrhea is the most common symptom.

o Constipation, anorexia, and diffuse weakness may occur.

o Occasionally, severe enteritis due to a massive inoculum of Trichinella species occurs.

o Symptoms typically last 2-7 days but may persist for weeks.

o With certain Trichinella species and in certain population groups and geographic regions, the disease may not progress beyond the intestinal stage.

o Nausea is reported in 15% of patients, vomiting in 3%, and diarrhea in 16%.

o Dyspnea may occur with exertion.

o Abdominal discomfort and cramps may occur.

· The invasive phase corresponds to the migration of the larvae from the intestine to the circulatory system and eventually to the striated muscles. This phase is associated with a higher rate of symptoms than the intestinal stage.

o The duration varies from weeks to months.

o Severe myalgia develops in 89% of patients.

o The central nervous system (CNS) is involved in 10-24% of patients, with a mortality rate of 50%. Approximately 52% of patients present with headaches. Other symptoms include deafness, ocular disturbances, weakness, and monoparesis.

o Cardiac system involvement occurs during the third week of infection, with a mortality rate of 0.1%, often during the fourth to eighth week of infection. Death may result from congestive heart failure and/or arrhythmias.

o Pulmonary system involvement occurs in 33% of patients, with symptoms lasting up to 5 days. Patients present with dyspnea, a cough, and hoarseness.

· The convalescent phase, which corresponds to encystment and repair, may be present for months to years after infection.

o The encystment of larvae can lead to cachexia, edema, and extreme dehydration.

o Symptoms usually decrease around the second month, except in the case of T pseudospiralis infection, which may cause symptoms for several months.

Physical

· Intestinal phase

o Abdominal distention may be present.

o Macular or petechial rashes affect 20% of patients.

o Diarrhea may occur.

· Invasive phase

o After 2 weeks, 91% of patients have a fever that peaks around the fourth week. This degree of fever is unique among helminthic infections. Temperatures can reach 104°F (40°C).

o Weakness and/or myositis occur in 82% of patients. Muscles become stiff, hard, and edematous. Muscles with increased blood flow (eg, extraocular muscles, masseters, larynx, tongue, neck muscles, diaphragm, intercostals, limb flexors, lumbar muscles) are most frequently involved. Involvement of the diaphragm may result in dyspnea.

o Periorbital edema is reported in 77% of patients.

o Rash (macular or petechial) is reported in 15-65% of patients.

o Ocular findings include subconjunctival hemorrhages in 9% of patients, conjunctivitis in 55%, and incidences of chemosis and retinal hemorrhage.

o The CNS is involved in 10-24% of patients. Of these, 53-96% exhibit meningoencephalitis, 40-73% exhibit focal paralysis and/or paresis, 39-71% exhibit delirium, 20% exhibit decreased or absent deep-tendon reflexes, 17% exhibit meningitis, and 2% exhibit evidence of psychosis.

o Signs of cardiac system involvement include hypertension, increased venous pressure, and, in 18% of patients, peripheral edema.

o Subungual splinter hemorrhages occur in 8% of patients.

· Convalescent phase

o Edema is present in 18% of patients.

o Patients are easily fatigued.

o Weakness may occur.

o Weight loss may occur.

o Myalgia may occur.

o Ocular signs with chronic headaches may be present.

Causes

· Trichinella species develop in a single host and are spread from that host to the next without an arthropod intermediate. The intensity and frequency of exposure to infected meat determine the severity of the disease.

· Infections are related to cultural differences in food cooking and storing methods, specifically the inadequate cooking or freezing of meat.

Lab Studies

· Obtain a CBC count.

o Leukocytosis occurs in 65% of patients, with cell counts of up to 24,000/µL.

o Eosinophilia typically rises 10 days after infection, with total eosinophil counts of up to 8700/µL (40-80% of total WBC). The counts peak in 3-4 weeks and resolve over the next few months.

o Nearly all patients with trichinosis, either symptomatic or asymptomatic, exhibit eosinophilia. The only exception is in severe cases, when the eosinophil count may be severely depressed. A low eosinophil count indicates an increased mortality rate.

· Erythrocyte sedimentation rates are usually within the reference range.

· Obtain creatine kinase (CK) levels.

o CK levels are elevated to 17,000 U/L.

o CK (isoenzyme myocardial band [MB]) elevations may indicate myocardial involvement; however, as many as 35% of patients without cardiac involvement may have elevated CK-MB levels.

· Levels of lactate dehydrogenase isoenzymatic forms (ie, lactate dehydrogenase fraction 4 [LD4] and lactate dehydrogenase fraction 5 [LD5]) are elevated in 50% of patients.

· Immunoglobulin E levels are typically elevated.

· Serology results are not positive until 2-3 weeks after infection. They peak around the third month and may persist for years.

· Serology ratios do not correlate with the severity of disease or the clinical course. However, a strong positive test result usually indicates an early infection.

o Perform indirect hemagglutination.

o Bentonite flocculation results are usually not positive for more than 1 year after infection.

o Perform indirect immunofluorescence.

o Latex agglutination results are usually not positive for more than 1 year after infection.

o Enzyme-linked immunosorbent assay (ELISA) is 100% sensitive on day 50, with 88% of results remaining positive 2 years after infection.

· The immediate hypersensitivity skin test is no longer commercially available. Reactions results are positive (5 mm) at approximately day 17 and remain positive for life.

· Molecular techniques are being developed but have not been validated.

Imaging Studies

· In patients with CNS involvement, CT scanning and MRI with contrast enhancement may reveal 3- to 8-mm nodular or ringlike lesions.

Other Tests

· Electrocardiography

o Premature contractions

o Prolongation of the PR intervals

o Small QRS complexes with intraventricular block

o Flattening or inversion of the T waves, especially lead II and precordial leads

· Polymerase chain reaction

o Useful for isolating the parasite and subsequent genetic typing

o Primarily a research tool

Procedures

· Electromyelography

o Electromyelography may be helpful in diagnosing moderate-to-severe infection, but no pathognomonic findings exist. The test result may reveal acute myositis or diffuse myopathic dysfunction.

o Changes usually resolve 2-3 months after infection but may persist for 1-8 years.

· Lumbar puncture (to evaluate for suspected neurologic disease)

o Results are normal in 50-75% of patients.

o Larvae are found in 8-24% in patients.

o Eosinophilic meningitis may be present.

· Muscle biopsy provides a definitive diagnosis; however, it is rarely recommended except in difficult cases when serology tests are unhelpful.

o Obtain a 0.5- to 1-gram muscle biopsy specimen from the deltoid or gastrocnemius muscle because these are most easily accessible. The yield increases if the biopsy site is swollen or tender. Stain the specimen with hematoxylin and eosin (H&E) and examine multiple sections. Occasionally, larvae can be found after the muscle has been digested enzymatically.

o If a biopsy is performed prior to larvae coiling (beyond day 17 of infection), worm tissue can be confused with muscle tissue.

o A negative result does not necessarily exclude infection.

Histologic Findings

A histologic examination may reveal destruction of skeletal muscles, including a basophilic degeneration of the fibers observed on H&E-stained sections. Dead, nonencapsulated parasites can be observed. Muscle cells contain small hemorrhages and an accumulation of inflammatory cells (eg, eosinophils, lymphocytes, macrophages).

The results of a histologic examination in myocardial muscle are consistent with an immune-mediated reaction. Parasites migrate through the myocardium but do not encyst; however, a strong inflammatory reaction occurs, with numerous eosinophils, erythrocytes, fibrin deposits, and foci of necrotic myocardium. A mild-to-moderate pericardial effusion may also be present. Perivascular collections of eosinophils, lymphocytes, macrophages, and polymorphonuclear leukocytes develop in the CNS and are associated with areas of ischemia. Larvae may be surrounded by astrocytes and microglial cells.

Medical Care

In moderate-to-heavy infections, the goal is to stop the larval invasion into the host muscle.

· Within 1 week of ingestion of contaminated meat, administer albendazole (5 mg/kg/d for 1 wk), mebendazole (5 mg/kg/d for 1 wk), or thiabendazole (25 mg/kg/d for 1 wk).

o This drug is effective against worms limited to the intestinal lumen.

o The goal is to prevent systemic invasion.

o Thiabendazole does not affect tissue larvae.

· If tissue invasion occurs, the aim of therapy is to decrease subsequent muscle damage.

o The most effective treatment modalities include bed rest, analgesics, and antipyretics.

o Anthelmintic therapy has no proven role at this stage. Albendazole appears to be marginally effective and mebendazole less so. A trial of albendazole is justified in severe or prolonged infections. Avoid thiabendazole at this stage because of its adverse-effect profile.

o Prednisone at 50 mg/d can be used in severe infections, especially if hemodynamic instability or involvement of the central nervous, cardiac, or pulmonary systems is present.

o Steroids may decrease inflammation but may also hinder the eradication of the adult worm, resulting in a prolonged production of larvae.

Surgical Care

A muscle biopsy is necessary only if the diagnosis is unclear after equivocal clinical, laboratory, or serologic testing.

Consultations

· Infectious disease specialist

· Cardiologist, if evidence of cardiac involvement

· Neurologist, if evidence of neurologic involvement

Diet

No diet limitations are indicated; however, this is an excellent opportunity to educate patients regarding the avoidance of potentially infected meats and how to properly cook and store foods.

Activity

For severe infections, bed rest is recommended. This is especially important upon evidence of myocardial involvement because patients may deteriorate clinically during ambulation.

The mainstays of therapy include bed rest, antipyretics, and analgesics. Anthelmintic medications and steroids have a limited role in therapy. If anthelmintic medications are used, the drug of choice is albendazole, because it appears to have the best adverse-effect profile and efficacy.

Drug Category: Anthelmintics

The benzimidazole drugs albendazole, mebendazole, and thiabendazole are the available medications. These drugs bind helminthic beta-tubulin, which prevents microtubule assembly and inhibits glucose uptake, resulting in parasite immobilization and death.

Drug Name


Albendazole (Albenza)

Description


Decreases ATP production in worms, causing energy depletion, immobilization, and death. To avoid inflammatory response in CNS, administer with anticonvulsants and high-dose glucocorticoids. Available as 200-mg tabs. Practically insoluble in water; absorption enhanced if taken with fatty meal. Good penetration into CNS and better tolerated than thiabendazole.

Adult Dose


400 mg/d PO for 7 d

Pediatric Dose


<2 years: 200 mg/d for 3 d; repeat in 3 wk prn
>2 years: Administer as in adults

Contraindications


Documented hypersensitivity

Interactions


Coadministration with carbamazepine may decrease efficacy; dexamethasone and praziquantel may increase toxicity; cimetidine increases concentration; no noted interaction with theophylline

Pregnancy


C - Safety for use during pregnancy has not been established.

Precautions


Occasional reactions include abdominal pain, reversible alopecia, and increased serum transaminase activity; rare reactions include leukopenia, rash, and renal toxicity; monitor liver function and CBC counts every 2 wk; discontinue use if LFTs increase significantly (resume when levels decrease to pretest values)



Drug Name


Mebendazole (Vermox)

Description


Causes worm death by selectively and irreversibly blocking uptake of glucose and other nutrients in susceptible intestine, where helminths dwell. Available as 100-mg chewable tabs.

Adult Dose


200-400 mg PO tid for 7 d

Pediatric Dose


<2 years: Not established
>2 years: 5 mg/kg/d PO

Contraindications


Documented hypersensitivity

Interactions


Carbamazepine and phenytoin may decrease effects; cimetidine may increase levels

Pregnancy


C - Safety for use during pregnancy has not been established.

Precautions


Adverse effects include transient abdominal pain and diarrhea during initial therapy for massive infections (improves over first few days of therapy); rare reactions include leukopenia, agranulocytosis, and hypospermia; adjust dose in hepatic impairment



Drug Name


Thiabendazole (Mintezol)

Description


For mixed helminthic infections; inhibits helminth-specific mitochondrial fumarate reductase; alleviates symptoms of trichinosis during invasive phase. Little value in disease that spreads beyond lumen of intestines; absorption from GI tract is poor. Use limited because of adverse-effect profile. Available in 500-mg tab and 500-mg/5-mL susp. Administer with meals.

Adult Dose


50 mg/kg/d PO for 7 d

Pediatric Dose


<30 lb: Not established
>30 lb: 50 mg/kg/d PO divided q12h; not to exceed 3 g/d

Contraindications


Documented hypersensitivity

Interactions


May elevate theophylline serum levels, increasing toxicity (monitor serum levels and reduce dose prn)

Pregnancy


C - Safety for use during pregnancy has not been established.

Precautions


Approximately 50% of patients experience one or more adverse effects, including nausea, anorexia, vomiting, headache, pruritus, and dizziness; occasional reactions include leukopenia, crystalluria, rash, hallucination and other psychiatric reactions, visual and olfactory disturbances, and erythema multiforme; rare reactions include shock, tinnitus, intrahepatic cholestasis, convulsions, angioneurotic edema, and Stevens-Johnson syndrome; do not administer immediately before activities that require alertness; closely monitor in hepatic or renal dysfunction; before initiating therapy, supportive therapy is necessary for anemia, dehydration, or malnourishment; use in confirmed worm infestation (not prophylactically)

Drug Category: Analgesics

Pain control is essential to quality patient care. Analgesics ensure patient comfort and have sedating properties, which are beneficial for patients with pain.

Drug Name


Acetaminophen (Aspirin-Free Anacin, Tylenol, Feverall)

Description


DOC for pain in patients with documented hypersensitivity to aspirin or NSAIDs, upper GI disease, or current therapy with oral anticoagulants. Reduces fever by acting directly on hypothalamic heat-regulating centers, which increases dissipation of body-heat via vasodilation and sweating.

Adult Dose


325-650 mg PO/PR q4-6h prn

Pediatric Dose


10-15 mg/kg/dose PO/PR q4-6h prn

Contraindications


Documented hypersensitivity; G-6-PD deficiency

Interactions


Rifampin can reduce effects; coadministration with barbiturates, carbamazepine, hydantoins, and isoniazid may increase hepatotoxicity

Pregnancy


B - Usually safe but benefits must outweigh the risks.

Precautions


Hepatotoxicity possible in chronic alcoholism following various dose levels; severe or recurrent pain or high or continued fever may indicate a serious illness; contained in many OTC products (combined use with these products may result in cumulative acetaminophen doses that exceed recommended maximum dose)

Drug Category: Corticosteroids

Steroids decrease inflammatory response in the host.

Drug Name


Prednisone (Deltasone, Orasone, Sterapred)

Description


Use in severe infections with signs of shock or significant pulmonary, CNS, or cardiac involvement. Steroids reduce number of worms expelled from GI tract, which may increase number of larvae produced.

Adult Dose


40-60 mg/d PO for 3 d; then taper over 10 d

Pediatric Dose


Administer as in adults

Contraindications


Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections

Interactions


Coadministration with estrogens may decrease clearance; when used with digoxin, digitalis toxicity secondary to hypokalemia may increase; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics

Pregnancy


C - Safety for use during pregnancy has not been established.

Precautions


Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use

Further Inpatient Care

· Inpatient care is rarely needed.

· Consider trichinosis in cases of heavy infection with evidence of shock, encephalitis, myocarditis, or pneumonitis.

Further Outpatient Care

· Patients need continued monitoring because clinical improvement is slow.

In/Out Patient Meds

· Analgesics

· Antipyretics

· Anthelmintic medication for severe infections

Transfer

· Transfer to another level of care is rarely needed unless the diagnosis is in question or severe sequelae are present.

Complications

· Long-term sequelae of the CNS include decreased mental power, numbness of hands and feet, decreased stress tolerance, loss of initiative, and depression.

· Usually, full recovery occurs after cardiac or pulmonary involvement.

· Prolonged weakness and myalgias may occur.

· Adrenal gland insufficiency may occur.

· Obstruction of blood vessels may occur.

Prognosis

· Severe disease develops in only 5-20% of patients during epidemics.

Patient Education

· Adequate cooking and freezing methods prevent infections.

· The most effective measure to eradicate Trichinella species is by adequate cooking to kill the parasite.

o The current recommendation for heating is 160°F (71°C) for all food-borne disease. Trichinella species can typically be killed by adequate cooking to 140°F (60°C) for 2 minutes or 131°F (55°C) for 6 minutes

o If no trace of pink in fluid or flesh is found, these temperatures have been reached.

· Freezing is also an effective method for killing most species of Trichinella. For a 6-inch piece of meat, the recommended temperatures to kill larvae are as follows:

o 5°F (-15°C) for 20 days

o -10°F (-23°C) for 10 days

o -20°F (-29°C) for 6 days

· Salting, smoking, or drying the meat does not kill cysts.

· Excellent patient education resources regarding the esophagus, stomach, and intestine are available at eMedicine's Esophagus, Stomach, and Intestine Center. Patient education material specific to diarrhea is found in the article Diarrhea. Patient education material specific to vomiting and nausea is found in the article Vomiting and Nausea.

Medical/Legal Pitfalls

· Diagnosis is based on patient history and physical examination findings.

· Few laboratory tests and no significantly invasive or expensive procedures are required