Pediatric Trichinosis

In 1835, James Paget, a first-year medical student at Bartholomew's Hospital in London, observed the postmortem examination of a middle-aged man. The autopsy revealed extensive pulmonary tuberculosis. Paget also saw numerous miniscule chalky-colored spots in the corpse's muscles. He further verified the bony texture of these lesions and upon microscopic dissection, concluded that each lesion consisted of a coiled threadlike worm surrounded by a tiny calcified cyst. Paget’s professor, Richard Owen, confirmed his findings. Owen named it the genus Trichina, from the Greek term for hair, and the species spiralis.[1]

A parasitic zoonosis, trichinosis (or trichinellosis), is caused by human ingestion of raw or undercooked meat infected with viable larvae of parasitic roundworms in the genus, Trichinella. Genus Trichinella is a member of the phylum Nematoda within the kingdom Animalia. Within the Trichinella genus, 8 species are known. The species are further differentiated based on whether or not the worms encapsulate in the host’s muscle tissue.

Species that characteristically encapsulate are T.spiralis, T. nelsoni, T. nativa, T. murrelli and T. britovi. Three species, T. papuae, T.pseudospiralis, and T. zimbabwensis, do not encapsulate . Non-encapsulated species infect saurians and crocodilians. T. pseudospiralis infects birds . T.spiralis, T. nelsoni, T. nativa, T. murrelli and T. britovi infect mammalian hosts and encapsulate within the host’s tissues. These five species of parasitic roundworms are found in approximately 150 different carnivorous/omnivorous mammals. Throughout the world, pigs (swine) are the most common meat reservoir consumed by man. Humans are incidental hosts.[2]

For T.spiralis, larvae enter the human host when raw or undercooked meat is eaten with viable encysted larvae. In the stomach, larvae ex-cyst through acid-pepsin digestion. Peristalsis moves the larvae to the upper two-thirds of the intestine. There, they penetrate the columnar epithelium of the intestinal mucosa and occupy the cytoplasm of enterocytes. The intracellular larvae develop into mature worms through 4 molts, reaching adulthood in about 30 hours.[1, 3]

Adult T. spiralis male worms are less than 2 mm in length (approximately 1-1.5 mm long); adult female worms are longer, measuring closer to 5 mm. Maturation of the male and female worms occurs and mating follows. Five days post-copulation, each female worm can birth a huge number of live larvae (about 1000 larvae). The newborn larvae penetrate the gut lamina propria; move through the thoracic duct and into the venous circulation. They continue to move through the right side of the heart, the lungs, and then onto the left side of the heart and subsequently enter the systemic circulation. The larvae travel throughout the human body capable of entering any tissue cell. Presence of larvae in the circulation causes increased capillary permeability and vasculitis. Fine intravascular thrombi can occur. When the larval load is significant, these microvasculature changes cause cardiovascular, lung, and central nervous system (CNS) pathology. Host cells invaded by larvae will die with the exception of skeletalmyofibrils.[3]

Larvae favor striated skeletal muscle cells and prefer active muscle groups such as the diaphragm, the tongue, and the masticatory, intercostal, and pectoral muscles. Larvae burrow into individual muscle fibers, which are transformed and serve as nurturing nurse cells. These nurse cell–larva complexes further larval development until encystment occurs; a process taking about 3 weeks. After this period, the larvae, now about 1 mm long, are infective to another host, if eaten as improperly cooked meat. In humans, the larvae at this stage have reached a dead end. Larvae may remain viable for years in the human host, but usually die and calcify within the first year after cyst formation.

A fertile T. spiralis female produces approximately 500-1500 larvae over a 2-4 week period; the female is then, expelled in the feces due to the response of the host’s immune system. The host’s T-cell immune response is especially important in eradication of the adult female worms as studies of athymic mice (lacking T-cell function) show a longer intestinal phase in these mammals.[1]

In nature, the parasite's life cycle is maintained by carnivorous and omnivorous mammals that eat infected meat and by non-carnivorous animals that ingest food containing larvae-contaminated tissue from carcasses of infected animals.

Frequency

United States

Trichinosis (also known as trichinellosis ) is a reportable disease to the Centers for Disease Control and Prevention (CDC) Parasitic Diseases Hotline (parasites@cdc.gov). The clinical case definition for trichinosis is " Trichinella –positive muscle biopsy or a positive serologic test for trichinosis in a patient with one or more clinical symptoms compatible with trichinosis such as eosinophilia, fever, myalgia, or periorbital edema."

In the 1940s, an average of 400 cases and 10-15 deaths were reported each year. The incidence of trichinosis has significantly decreased since this time. From 1991-1996, 230 cases and 3 deaths were reported.[4] From 2002-2007, 66 cases were reported.[5] In approximately 60% of these cases, information on the suspected ingested food product was available. The frequency of implicated meat was 60% pork, 23% bear meat, 10% walrus meat, and 7% cougar meat. Sausage was the most commonly cited pork product. Sampling uncooked spiced pork used to make sausage is a common way to acquire infection.

Federal regulations and changes in management standards of the pork industry have played major roles in the decreased frequency of trichinosis. Today the vast majority of domestic swine in the United States are grain-fed and uninfected. Swine fed meat from uncooked garbage containing remnants of small mammals such as skunks, raccoons and rats, are at-risk to be infected if the feed contains Trichinella larvae-contaminated sources. Infections do occur sporadically in people who ingest undercooked bear meat.[6, 7]

International

Trichinosis usually occurs as point-source outbreaks in all areas of the world, except Australia and some South Pacific islands.[8, 9] Incidence is low in Europe due to mandatory inspection of pork for Trichinella species, although outbreaks have been reported.[10, 11] In Arctic regions, T. nativa is found in meat from walrus, seal, and polar bear.[12, 1] In Africa and southern Europe, most infections stem from T. nelsoni found in meat from wild canids and felids.[1]

Mortality/Morbidity

Potential clinical course and illness severity depend on the initial tissue load of viable larvae ingested and the number of newborn larvae produced per mature female.

• Most infections are asymptomatic or subclinical.

• One week post-ingestion, abdominal discomfort, nausea, vomiting and/or diarrhea may occur

  • When these symptoms occur, the illness is usually self-limited.

• Two to 8 weeks post-ingestion, symptoms can include fever, myalgias, and periorbital edema, urticarial rash, conjunctival hemorrhages and subungual hemorrhages.

  • During this time, the larvae are migrating into the host’s tissues.

• In patients with severe acute infection, there may be long-lasting sequelae (eg, muscle aches and pain, headaches, eye disturbances, cardiac symptoms).

• Although rare, the illness can cause death. Death is usually due to cardiac or CNS involvement and occurs 3-5 weeks post-ingestion. The mortality rate has decreased to about 0.3% due to improved patient care and pharmaceutical treatment.[6]

Race

This infection has no racial predilection.

Sex

Both sexes are equally susceptible. Differential rates of infection between sexes may reflect differences in behavior as related to food preparation and food choices.

Age

People of all age groups are susceptible.

Most cases of trichinosis with T.spiralis are subclinical. Symptoms appear only in heavily infected individuals. Predominant symptoms (ie, GI or systemic) vary and depend on the Trichinella species ingested. The incubation period can range from a few days to 2 months. Shorter incubation periods occur when the host’s larvae load is greater.

Patients with T. nativa infection experience symptoms related only to the enteral phase; onset is delayed when compared to infection with T. spiralis, although T. nativa infections may be fatal.[13] T. nelsoni and T. britovi both have low pathogenicity in their enteral and parenteral phases.

Early (enteral/intestinal) phase for T.spiralis

Within the first week post-ingestion, gastrointestinal (GI) symptoms such as diarrhea (most common), nausea, emesis and abdominal discomfort develop. These symptoms are non-specific and mimic clinical signs of many other illnesses such as food poisoning or a viral gastroenteritis illness. These symptoms are absent in patients with mild infections, who ingest only a few viable larvae.

Acute (parenteral) phase for T. spiralis

The parenteral phase occurs when the larvae are moving their way throughout the host organism, migrating to tissues with indiscriminate invasion of different cells. This stage starts 10-14 days post-ingestion and can last about 2 months.

Hallmarks of this phase are fever (in 90% of patients), myalgias (in 90% of patients), and periorbital edema (in 80% of patients). Myalgias are common in the masseters, diaphragm, and intercostal muscles. Pain usually occurs during physical exertion. Pain at rest typically occurs in those patients with severe disease. Less common symptoms during the parenteral phase of tissue invasion include headache (in 50% of patients) and urticarial skin rash (in 20% of patients), and conjunctival and subungual hemorrhages.

Concerning symptoms will occur during this phase, as the larvae are invading the cardiac and central nervous systems. Myocarditis can occur and is typically mild and transient in nature as the larvae leave the myocardium shortly after penetrating this tissue. Involvement of the central nervous system (CNS) is more problematic as larvae migration can cause CNS granulomas and petechial hemorrhages, leading to encephalopathy.[3]

Late phase for T. spiralis

The late stage begins 5-7 weeks after the initial infection and is characterized by the disappearance of most early signs and symptoms. However, myalgias and fatigue frequently persist. In one prospective study, these symptoms persisted in 98% of patients at 2 years and in 25% of patients after 10 years.[14]

Temperature curves illustrating a fever history exhibit variable intensity and duration; lasting for a few days in mild infection and up to 3-6 weeks in severe infections. General malaise and myalgias are also characteristic.

If periorbital or facial edema is present, it is symmetrical and produces a characteristic appearance, making patients unrecognizable. For this reason, trichinosis is often called the “disease of big heads”. Involvement of extraocular muscles can cause diplopia and blurred vision.[3]

Symptoms due to vasculitis or thromboembolic disease include subconjunctival and subungual (splinter) hemorrhages. If the cardiac, pulmonary, or nervous systems are involved, findings can indicate pericarditis, myocarditis, pneumonitis, or encephalopathy.

Most human infections are due to T. spiralis, the Trichinella species that commonly infects pigs, wild boars and rats.[15] T. murrelli is found in black bears, raccoons, red foxes, cougars and bobcats and is the predominant species infecting wild mammals of temperate North America[7] T. britovi is found in carnivores of Europe and western Asia (eg, wild boars, horses, foxes). T. nativa infects arctic and subarctic mammals such as bears, wolves, seals and walrus; T. nelsoni is common in African predators and scavengers (eg, hyenas, lions, panthers). All of these species encyst.

T. pseudospiralis, T. papuae and T. zimbabwensis are species that do not encyst. T.pseudospiralis infects birds and marsupials. T. papuae and T. zimbabwensis infect saurians, crocodilians andnonavian archosaurs . T. papuae has been linked to consumption of raw soft-shelled turtles[16] and in trichinosis epidemics in Thailand.[17, 18]

The following studies are indicated in trichinosis:

CBC (complete blood count) with indices

Peripheral eosinophilia is almost universal and is an early laboratory finding. Eosinophilia begins approximately 10 days after ingestion and may reach a peak of 5000/µL by 3-4 weeks after ingestion (range of about 50-70% of the white cell indices).

• Eosinophil counts remain elevated during the acute parenteral stage of infection, regress slowly, and may remain elevated (although at lower levels) for 3 months post-infection.

• Of grave concern is the absence of eosinophilia, eosinopenia or gradual disappearance of eosinophils during the parenteral phase of the illness. This serologic finding indicates an overwhelming infection, a sign of immunosuppression and carries a very poor prognosis.[3]

Leukocytosis (elevated white cell count) is typical and appears in the early phase of infection. The elevated white cell count subsides before eosinophil counts return to the normal reference range.

Muscle enzymes

Creatine kinase (CK), and lactate dehydrogenase (LDH) levels are elevated in 75-90% of cases. CK levels may increase as much as 10-fold, whereas the rise in LDH levels is less. Neither serum levels correlate with clinical disease severity.

Serum albumin

Hypoalbuminemia is a marker of severe clinical disease.

Serologic studies[19, 20]

In the US, immunodiagnostic tests currently available are enzyme immunoassays (EIAs). EIAs detect Trichinella -specific antibodies and use antigen preparations that may be either crude extracts prepared from homogenates of T. spiralis muscle larvae or excretory-secretory (ES) products produced by cultured larvae. The key antigenic product is secreted from stichocytes located on the anterior side of the larva. The T. spiralis larva-1 group, also named as TSL-1 group of larval secretory antigens, are conserved in all species/isolates of Trichinella and thus can be used to detect infection in animals or people infected with any of Trichinella species currently recognized.[21, 22]

Trichinella -specific antibody levels are usually not detected until 3 to 5 weeks post-infection, well after the onset of acute-stage illness. Antibody development is also affected by the infecting dose of larvae. The higher infecting dose induces a faster patient's antibody response. Repeat serum specimens should be drawn several weeks apart to demonstrate sero-conversion in patients whose initial EIA specimen was negative.[21]

EIAs with ES antigens detect antibodies earlier than bentonite flocculation (BF) test in 25% of serum specimens from patients with acute infection. The BF test typically becomes positive 3 weeks post-infection. EIAs also remain positive for longer period of time after infection than the BF, and are reactive in a larger proportion of persons with no clinical evidence of trichinosis.[21, 3]

EIA is used for routine screening. Present recommendations are to test all EIA-positive specimens using the BF test, for confirmation. Positive results by both tests indicate Trichinella infection within the last several years.

IgG, IgM, and IgE antibodies are detectable in many patients; however, tests based on IgG antibodies are most sensitive.[23] Typically these antibody levels peak in 2 or 3 months post-infection and then decline slowly over several years.

• Tests based on immunoglobulin G (IgG)–ELISA specific antibodies are most sensitive (100% positive on the 50th day of infection). However, IgG antibodies can persist for years after infection, even if the disease process itself was benign or asymptomatic. Morakote et al. reported that 31 months after T. spiralis infection, the diagnostic sensitivity of IgG-ELISA was 88%.[24]

• Morakote et al. further reported that IgM-ELISA’s peak sensitivity was 93% at 57th day post-infection. IgE-ELISA was 100% positive on the 85th day of infection. At 31 months post-infection, IgE-ELISA was positive 47%, while IgM-ELISA was sensitive only to 12%. Data from the IgM-ELISA appears to be a helpful indicator of infection within a 3-year (36 month) time frame.

• Of the three antibodies, immunoglobulin E (IgE)–class antibodies appear first and are typical positive at the parenteral phase of trichinosis; however IgE antibodies are seldom detected during this time because their serum half-life is relatively short. An IgG antibody is detectable early in patients with high-titers, cited at 23 days post infection.[24]

See the list below:

• Plain radiography may show calcified densities in soft tissues, indicating old infection, but is not useful in diagnosing acute infection.

• In patients with CNS involvement, brain CT scanning using ring enhancement following intravenous contrast reveals multiple small hypodense lesions in the hemispheric white matter.

See the list below:

• Stool examination: Charcot-Leyden crystals from eosinophils may be found in stools. Ova are not found in stools; larvae are rarely found in stools.

• Antigen detection: Circulating antigens can be detected by EIA or immunoradiometric assay and by monoclonal antibodies specific for antigens obtained from T spiralis muscle larvae, although these tests are not typically used for diagnosis.

• Polymerase chain reaction (PCR): In cases in which the diagnosis is questioned (eg, atypical presentations or patients who are immunosuppressed) or in early stages of infection when other test results are negative (eg, serologic studies), PCR testing used to detect Trichinella- specific DNA in muscle biopsy and blood specimens can be helpful.

See the list below:

• Definitive diagnosis can be made via biopsy of a tender skeletal muscle. The muscle tissue (0.2 to 0.5 grams) is best examined unfixed under low microscope power to detect whole larvae. In cases in which the diagnosis is unclear, this biopsy sample may confirm the suspected diagnosis using parasitologic or histologic studies.

• Electromyography (EMG) reveals changes of the myopathic type during the acute stage, but these changes are not pathognomonic for trichinosis. In most patients, bioelectric disturbances correspond in severity to the clinical course.

See the list below:

• Basophilic transformation of muscle fibers occurs within 4-5 days after larvae penetration (about 2 weeks post-ingestion) and is a valuable diagnostic criterion, even in cases, in which no larvae can be demonstrated. Only a portion of the affected muscle fiber undergoes basophilic transformation; the area that becomes the so-called larval nurse-cell.

  • Myofibrils disappear, the sarcoplasm becomes basophilic, and the cell nucleus is displaced to the center of the cell.

  • The larva can be observed within the affected nurse cell-larva complex.

  • Infiltration by eosinophils and mononuclear cells also occurs.

• Attempting diagnosis before larvae begin to coil (ie, < 2 wk after larvae enter the muscle cell) creates a risk of confusing the worm appearance with fragments of muscle tissue.

• Absence of a capsule and presence of a straight larva in the nurse-cell complex indicate an ongoing infection.

Attention to basic and advanced life support is mandatory in patients who present with severe cardiopulmonary or neurologic compromise.

Surgery is unnecessary unless a biopsy of a tender skeletal muscle is required.

Consultation with an infectious diseases specialist is often helpful. Consultation with a neurologist or cardiologist may be appropriate for patients who present with corresponding organ involvement.

Avoidance of under-cooked meat is preventative. Cooking thoroughly pork or bear meat until an adequate internal temperature is reached. Storing pork at – 15 ° C for almost 3 weeks is also effective in killing Trichinella larvae. See Deterrence/Prevention section.

Patient tolerance determines activity restrictions; myalgias are most common in association with activity during the acute parenteral stage.

Useful drugs in the management of trichinosis include anthelminthics to eradicate adult worms, corticosteroids for anti-inflammatory care, and nonsteroidal anti-inflammatory drugs or salicylates for analgesia. Salicylates are best avoided in children and teenaged patients with febrile illness due to risk of Reye syndrome.

Class Summary

Mebendazole and albendazole effectively eliminate adult worms from the GI tract. Thiabendazole is not recommended because of higher incidence of adverse effects. Evidence of these drugs' efficacy against tissue larvae is not well established. Because most patients continue to harbor adult worms in the gut during the acute phase of infection, treat all patients with confirmed or suspected trichinosis to prevent continued production of newborn larvae. A double-blind placebo-controlled treatment trial of Trichinella myositis in adults showed that mebendazole and thiabendazole improve muscle tenderness compared with placebo.[25]

Albendazole (Albenza)

Not approved by the FDA to treat trichinosis. Inhibits microtubule polymerization by binding to cytoplasmic beta-tubulin. Prevents use of nutrients by the parasite by affecting intestinal cells of the parasite, essentially starving it to death. Selectively toxic to parasites at indicated dose because binding to parasite beta-tubulin occurs at a much lower concentration than binding to mammalian protein.

Mebendazole (Vermox)

Inhibits microtubule polymerization by binding to cytoplasmic beta-tubulin. Prevents use of nutrients by the parasite by affecting intestinal cells of the parasite, essentially starving it to death. Selectively toxic to parasites at indicated dose because binding to parasite beta-tubulin occurs at a much lower concentration than binding to mammalian protein. The tab may be chewed, swallowed, or crushed and mixed with food. No fasting or purging is required.

Class Summary

Many clinical features and most complications in the acute stage of trichinosis are due to the host's immune response to larval antigens in the circulation or tissues. Corticosteroids, because of their potent anti-inflammatory actions, help control systemic inflammation. They should be used in all patients with severe or moderately severe disease. Systemic symptoms (eg, fever) dramatically respond to corticosteroid therapy within a few days.

Prednisone (Deltasone)

May decrease inflammation by reversing increased capillary permeability and by suppressing polymorphonuclear cell activity.

Class Summary

These agents have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is not known, but they may inhibit cyclooxygenase activity and prostaglandin synthesis. Other mechanisms may also be present, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell membrane functions.

Ibuprofen (Advil, Motrin)

DOC for patients with mild to moderate pain. Inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.

See the list below:

• Symptoms such as myalgias and headaches may persist long after the acute stage of disease has ended. Treatment with anthelminthic therapy during the acute stage has affected these late-stage symptoms.

• Treatment is entirely symptomatic.

See the list below:

• Hospitalize all patients with trichinosis who have severe and moderately severe disease. All pregnant women, regardless of disease severity, should be hospitalized for monitoring and treatment of complications. There is an increased risk of fetal loss with maternal infection.

• Hospitalization is also indicated for fluid and electrolyte management and for pain control.

Controlling infection in swine

Many countries have regulations that prohibit feeding raw abattoir scraps to domesticated pigs and that require inspection of commercial meat for Trichinella species.

Infection in pigs also results from scavenging on infected rodent populations. Controlling rodent populations decreases the prevalence of infection in pigs.

Meat preparation

The best way to prevent trichinosis is to adequately cook meat to a safe temperature before consuming. Meat should not be sampled until it is cooked. A food thermometer should be used to measure the internal temperature of cooked meat.

The United States Department of Agriculture (USDA) recommends the following guidelines for proper meat preparation.

• For Whole Cuts of Meat (excluding poultry and wild game). Cook to at least 145° F (63°C), as measured by a food thermometer placed into the thickest part of the meat; then allow the meat to rest for 3 minutes before carving or consuming.

• For Ground Meat (including wild game, excluding poultry): Cook to at least 160° F (71°C).

• For All Wild Game (whole cuts and ground): Cook to at least 160° F (71°C).

• Curing (salting), drying, or smoking meat alone does not consistently kill infective worms. Based on reports to the CDC, consuming homemade jerky and sausage have caused many cases of trichinosis.

• Cooking meats in microwave ovens does not effectively prevent infection because microwave cooking does not sufficiently heat all parts of the meat.[26]

Alternatively, freezing pork less than 6 inches thick for 7 days at -22°F (-30°C) or at 20 days at 5°F (-15°C) will kill any larvae/worms. Freezing wild game meats, unlike freezing pork products, may not effectively kill all larvae because some Trichinella species that infect wild game animals (eg, bear, seal, walrus) are freeze-resistant. These species possess an antifreeze molecule that protects the larvae from the harming and killing effects of extreme cold temperatures.

Additional points:

• Thoroughly wash hands with warm water and soap after handling raw meat.

• Properly clean meat grinders after each use.

• To help prevent Trichinella infection in animal populations, do not allow pigs or wild animals to eat uncooked meat, scraps, or carcasses of any animals, including rats, which may be infected with Trichinella.[26]

Clinical disease due to Trichinella species is classified based on the severity and likelihood of complications. The following classification also helps in patient management and prognosis:

• Asymptomatic infection - A history of exposure associated with eosinophilia but without signs and symptoms

• Abortive disease - Signs and symptoms that appear individually and not as a syndrome

• Benign disease - Full syndrome of low-intensity signs and symptoms and no complications

• Moderately severe disease - Full syndrome of significant intensity, rarely with complications

• Severe disease - Full syndrome of highly pronounced systemic signs and symptoms with metabolic disturbances (eg, hypoalbuminemia) and circulatory or neurologic complications

Complications occur in the early or acute stages of severe or, occasionally, in moderately severe trichinosis and can usually be prevented if patients receive adequate medical and pharmaceutical treatment during early stages of the disease.

• Cardiac: Although T. spiralis larvae do not become encapsulated in heart muscle tissue, focal cellular infiltrates consisting mainly of eosinophils and mononuclear cells are observed due to their transitory stay in the heart. Cardiac muscle changes are more extensive 4-8 weeks after ingestion. Arrhythmias and heart failure may occur in exceptionally heavy infection. A prospective study showed cardiac involvement in 13% of patients, almost all of which consisted of nonspecific ST-T changes and minimal pericardial effusions without impairment of systolic function.

• Pulmonary: Patients with lung involvement can present with pneumonitis or bronchitis.

• Central neurologic: In cases of very severe infection, migrating larvae may penetrate cerebral tissues from blood vessels. Patients may present with obtundation or excessive excitement. Some present with signs of meningitis.[27]

See the list below:

• Trichinosis is usually a self-limited illness, but death sometimes occurs if the number of infective larvae ingested is large.

• Early treatment helps prevent complications during the acute stage.

• Despite adequate treatment in the acute stage, infection may have long-lasting sequelae (eg, muscle aches, headaches, eye disturbances), especially in severe cases.

The key to preventing trichinosis is public education about the potential danger of eating any raw meat product, especially the meat of wild game animals.