Trichinosis (Trichinellosis)

Background

Trichinosis (trichinellosis) results from infection by a parasitic nematode belonging to the genus Trichinella. Trichinosis, although often unrecognized and underreported, has been an important disease in humans for thousands of years. An estimated 10,000 cases occur worldwide annually.^[46] Virtually all mammals are susceptible to infection; however, humans are especially prone to developing clinical disease via foodborne infection.^[1] Humans are infected when they ingest inadequately cooked meat that contains larvae of Trichinella species, usually Trichinella spiralis, which is present mainly in wild game meat or pork.^[46] Symptomatic infections characterized by diarrhea, myositis, fever, and periorbital edema develop when large numbers of larvae are ingested.^[2]

Species of Trichinella responsible for the infection are widely geographically distributed (see table), with habitats including the Arctic, temperate lands, and the tropics.^[3]

Table 1. Biologic and Zoogeographic Features of Trichinella Species

View Table

See Table

Reprinted from Adv Parasitol, Vol 63, Murrell KD, Pozio E, Systematics and epidemiology of Trichinella, pg 367, 2006, with permission from Elsevier.

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Pathophysiology

Trichinella species require 2 hosts to maintain their life cycles. After development in a first 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; however, depending on the region, walruses, seals, bears, polar bears, cats, raccoons, wolves, and foxes may also be infected. Life cycle of Trichinella species parasite is depicted in the image below.

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Life cycle of Trichinella in humans. Courtesy of Dickson Despommier, PhD, and Daniel Griffin, MD, PhD, Parasitic Diseases, 6th Ed, published by Parasi....

As a foodborne illness, the life cycle begins when raw or inadequately cooked meat that contains viable larvae inside a cyst wall (nurse cells) is consumed. 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 that measure 80 µm x 7 µm (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 will encyst; it will coil and develop a surrounding cyst wall or nurse cell to help it survive harsher conditions such as acidic environments (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 Trichinella life cycle is complete when a compatible host ingests the infected muscle (see images below).

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Trichinella nurse cell. Courtesy of Dickson Despommier, PhD, and Daniel Griffin, MD, PhD, Parasitic Diseases, 6th Ed, published by Parasites Without B....

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Encysted larvae of Trichinella species in muscle tissue, stained with hematoxylin and eosin (H&E). The image was captured at 400X magnification. Court....

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Trichinella larvae, in pressed bear meat, partially digested with pepsin. Courtesy of the US Centers for Disease Control and Prevention ((http://www.d....

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Larvae of Trichinella from bear meat. Courtesy of the US Centers for Disease Control and Prevention (http://www.dpd.cdc.gov/dpdx/HTML/Trichinellosis.h....

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).

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Epidemiology

Frequency

United States

National surveillance has documented a decline in the reported incidence of trichinosis in the United States since 1947, the first year nationwide data were collected systematically. Between 2011 and 2015, 80 reported cases occurred in 24 states and the District of Columbia. Of these cases, 57 (71%) had a confirmed or suspected source, 25 of which involved bear meat (44%), 13 involved wild boar meat (23%), and 9 involved unspecified pork (16%).^[49] One case was not linked to consumption of meat but to consumption of residual larvae on a preparation table.^[47] Often, infection resulted from ingestion of the meat sources, denoting that trichinosis could be considered a foodborne illness.

Trichinella is also tied to geopolitical factors, including movement of persons, livestock, and food (especially including 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. In 2008, an outbreak in Northern California affected 38 individuals who ate black bear infected with T murrelli.^[5] Data have also shown the presence of T murrelli in raccoons and coyotes.^[6]

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Epidemiology of trichinellosis in the US. Courtesy of Centers for Disease Control and Prevention (CDC) (https://www.cdc.gov/parasites/trichinellosis/r....

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Reported cases of trichinellosis 2011-2015. Courtesy of Centers for Disease Control and Prevention (CDC) (https://www.cdc.gov/parasites/trichinellosis....

International

In Europe, where pork inspection is mandatory, most cases of trichinosis 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%. Studies have also reported increase rates of trichinosis in former European countries such as Romania and Hungary due to political changes and regional food habits.^{[7, 8]} In addition, the European Centre for Disease Prevention and Control and the European Safety Authority reported 779 human cases of trichinosis in the European Union found in farm animals and wild animals, particularly in the latter.^[9]

The worldwide incidence of trichinosis has declined substantially during the past few decades, but outbreaks are still frequent, especially in developing countries.^{[10, 12]}

Mortality/Morbidity

Although Trichinella 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 trichinosis usually occurs in 4-8 weeks but may occur as early as in 2-3 weeks.

Race

Although Trichinella infections may be related to cultural differences in food cooking and storing methods (eg, the inadequate cooking or freezing of meat), outcomes do not vary based on race among infected individuals.

Culture

A 2017 outbreak involved the consumption of walrus meat in Alaska.^[47] The first point of healthcare contact included village healthcare centers, which are primarily used by Alaskan Native populations. Traditional cultural practices, including the hunting of polar bear and walrus, may lead to differential infection rates with Trichinella within Alaska Native communities.

Some studies have found that cultural practices, such as avoidance of pork consumption in Jewish and Muslim communities, may serve as a protective factor against Trichinella infection.^[48]

Sex

No differences in the rates of trichinosis between males and females are reported. Pregnant patients have milder trichinosis symptoms than patients who are not pregnant; however, abortions and stillbirths have been reported. Symptoms of trichinosis are typically worse in females who are lactating than in females who are not.

Age

Children appear to be more resistant to Trichinella infection; however, their symptoms may be more intense. Children also have fewer complications and recover more rapidly. The figure below shows the cumulative number of patients with trichinosis in the United States between 2011 and 2015, displayed by sex and age group. During this time period, a total of 80 cases were reported among persons whose age was known. Age was unknown for an additional patient, and sex was unknown for another patient. Of the 80 cases, 51 occurred in males and 29 in females. Among the 53 patients whose age was known, the median age was 37 years (range, 1-71 years).

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The number of cases of trichinellosis by age. Courtesy of Centers for Disease Control and Prevention (CDC) (https://www.cdc.gov/parasites/trichinellos....

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Prognosis

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

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Patient Education

Adequate cooking and freezing methods prevent trichinosis.

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

• 5°F (-15°C) for 20 days
• -10°F (-23°C) for 10 days
• -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 eMedicineHealth's Digestive Disorders 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.

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History

The European Center for Disease Control has proposed definitions and algorithms for diagnosis of acute trichinosis in humans.^[13] They focus on clinical, laboratory, and epidemiological criteria, along with a series of symptoms. The criteria can also be used to differentiate very unlikely, suspected, probable, highly probable, and confirmed cases (see Staging). Knowledge of the incubation period can help pinpoint the source of the infection, both in individual cases and in outbreaks.

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

Intestinal phase

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

Diarrhea is the most common symptom.

Constipation, anorexia, and diffuse weakness may occur.

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

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

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

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

Dyspnea may occur with exertion.

Abdominal discomfort and cramps may occur.

Invasive phase

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.

The duration varies from weeks to months.

Severe myalgia develops in 89% of patients.

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.

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.

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

Convalescent phase

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

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

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

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Physical

Intestinal phase

Abdominal distention may be present.

Macular or petechial rashes affect 20% of patients.

Diarrhea may occur.

Invasive phase

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).

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.

Periorbital edema is reported in 77% of patients.

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

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

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.

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

Subungual splinter hemorrhages occur in 8% of patients.

Convalescent phase

Edema is present in 18% of patients.

Patients are easily fatigued.

Weakness may occur.

Weight loss may occur.

Myalgia may occur.

Ocular signs with chronic headaches may be present.

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Causes

Trichinella species develop in a single host and are then 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.

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Complications

Apart from heavily infested cases of trichinosis, complications are rare. In severe cases, Trichinella larvae may migrate to the host organism's vital organs. Once the larvae reach the host's vital organs, they can cause dangerous, and even fatal, complications, including the following:

• Myocarditis^[14]
• Pneumonia^[14]
• Meningitis^[15]
• Encephalitis^[15]

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.

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Laboratory Studies

CBC count

Obtain a CBC count.

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

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.

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 rate

Erythrocyte sedimentation rates are usually within the reference range.

Creatine kinase

Obtain creatine kinase (CK) levels.^[16]

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

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.

Lactate dehydrogenase

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

Immunoglobulin E levels are typically elevated.

Serology

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.

Perform indirect hemagglutination.

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

Perform indirect immunofluorescence.

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

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

Hypersensitivity skin test

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

Molecular techniques are being developed but have not been validated.

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Imaging Studies

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

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Other Tests

Electrocardiography may show the following:

• Premature contractions
• Prolongation of the PR intervals
• Small QRS complexes with intraventricular block
• Flattening or inversion of the T waves, especially lead II and precordial leads

Polymerase chain reaction is useful for isolating the parasite and subsequent genetic typing. it is used primarily as a research tool.

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Procedures

Electromyelography

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.

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

Lumbar puncture

Lumbar puncture is used to evaluate for suspected neurologic disease.

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

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

Eosinophilic meningitis may be present.

Muscle biopsy

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

Obtain a 0.5- to 1-g 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.

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

A negative result does not necessarily exclude infection.

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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.

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Staging

Case definitions for human trichinosis include possible cases (not applicable), probable cases (patients who meet the clinical criteria and with an epidemiological link [below]), and confirmed cases (patients who meet the laboratory criteria and clinical criteria within the past 2 months).^[13]

Clinical criteria - At least 3 of the following: (1) fever, (2) muscle soreness and pain, (3) gastrointestinal symptoms, (4) facial edema, (5) eosinophilia, or (6) subconjunctival, subungual, and retinal hemorrhages

Laboratory criteria - At least 1 of the following: (1) demonstration of Trichinella larvae in tissue obtained by muscle biopsy or (2) demonstration of Trichinella -specific antibody response by indirect immunofluorescence, ELISA, or Western blot

Epidemiological criteria - At least one of the following: (1) consumption of laboratory-confirmed parasitized meat, (2) consumption of potentially parasitized products from a laboratory-confirmed infected animal, or (3) epidemiological link to a laboratory-confirmed human case by exposure to the same common source

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Medical Care

In moderate-to-heavy Trichinella 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) or mebendazole (5 mg/kg/d for 8-14 d). Note that mebendazole is no longer commercially available in the United States but can be obtained from Expert Compound Pharmacy (expertpharmacy.org).

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

The goal is to prevent systemic invasion.

Thiabendazole does not affect tissue larvae.

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Surgical Care

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

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Consultations

See the list below:

• Infectious disease specialist
• Cardiologist, if evidence of cardiac involvement
• Neurologist, if evidence of neurologic involvement

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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. For further details, see Prevention.

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Activity

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

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Prevention

The following suggestions for prevention and control of trichinosis in humans have been adapted from patient education materials by the Centers for Disease Control and Prevention:

• Cook meat to safe temperatures, using a food thermometer to measure the internal temperature of the cooked meat.
• Ensure appropriate temperatures are reached for different types of meat (listed on the CDC website).
• Wash hands and other food preparation and storage equipment with warm water and soap after handling raw meat.
• Ensure proper hygiene during preparation, serving, and storage of food.

Trichinella infection in animal populations can be prevented by not allowing domesticated and wild animals to eat uncooked meat of any animals that may be infected with Trichinella.

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Long-Term Monitoring

Patients need continued monitoring because clinical improvement is slow.

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Transfer

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

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Further Inpatient Care

Inpatient care is rarely needed.

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

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Medication Summary

It is difficult to differentiate the efficacy of drug therapy from natural recovery of infection in mild-to-moderate cases. Factors such as the Trichinella species involved, intensity and length of infection, and host response can aid in deciding on the treatment course.^[17] 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.

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Albendazole (Albenza)

• Dosing, Interactions, etc.

Clinical Context:  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.

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Mebendazole (Vermox)

• Dosing, Interactions, etc.

Clinical Context:  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.

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Thiabendazole (Mintezol)

• Dosing, Interactions, etc.

Clinical Context:  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.

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Class Summary

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.

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Acetaminophen (Aspirin-Free Anacin, Tylenol, Feverall)

• Dosing, Interactions, etc.

Clinical Context:  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.

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Class Summary

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

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Prednisone (Sterapred)

• Dosing, Interactions, etc.

Clinical Context:  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.

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Class Summary

Steroids decrease inflammatory response in the host.

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