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AUTHOR INFORMATION
| Section 1 of 10  |
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| Author: L Kristian Arnold, MD, Director, Clinical Training Center, Assistant Professor, Department of Emergency Medicine, Boston University School of Medicine |
| L Kristian Arnold, MD, is a member of the following medical societies:
American College of Occupational and Environmental Medicine, and
Society for Academic Emergency Medicine |
| Editor(s): Theodore Gaeta, DO, MPH, Residency Director, Clinical Associate Professor of Emergency Medicine in Medicine, Department of Emergency Medicine, New York Methodist Hospital; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine;
Mark L Plaster, MD, JD, Editor-in-Chief of Emergency Physicians' Monthly, Department of Emergency Medicine, Memorial Hermann Hospital System;
John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School;
and Scott H Plantz, MD, FAAEM, Research Director, Assistant Professor, Department of Emergency Medicine, Mount Sinai School of Medicine |
Disclosure
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INTRODUCTION
| Section 2 of 10  |
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Background: Trichinosis or trichinellosis is an infection due to Trichinella nematodes, most commonly Trichinella spiralis. James Paget, a first-year medical student in London, first described Trichinella infection of the diaphragm in a paper presented at the Abernethien Society February 6, 1835, 18 days prior to Richard Owen's presentation. Owen, who is generally attributed with the "discovery," presented Paget's observations to the Zoological Society. (An informative slide presentation, "Creationism, Dinosaurs, and Worms: The Discovery of Trichinella spiralis" can be found at The Trichinella Page. By the 1860s, trichiniasis/trichinosis was well-recognized as a disorder spread through infected pigs, leading to a cultural aversion to certain pork products, particularly German and Dutch sausage (Cook, 2001).
Pathophysiology: Infection is initiated by ingestion of viable larvae in raw or undercooked meat. Gastric action liberates the larvae, which are enclosed in intramuscular cysts. The liberated larvae develop into adults in the duodenum and jejunum, where they mate and bear offspring. The adult worms are expelled in the stool.
Newborn larvae penetrate the intestinal wall, enter the lymphatic system, and move via the bloodstream to areas of implantation. Although the exact mechanism has not been elicited, the newborn larvae have been implicated in a number of the clinical manifestations of severe infection. Newborn larvae have been found in cardiac and brain tissue in human and animal models, where they provoke an intense eosinophilic reaction. The life cycle is completed with the larvae encysting in striated muscle.
Larvae induce a number of changes in muscle fiber cells, turning them into nurse cells. The nuclei become hypertrophied. This is associated with inactivation of muscle gene transcription along with decreased expression of certain muscle-specific proteins. The infected muscle cell becomes developmentally arrested in the cell reproduction cycle at the gap2 or M phase.
A distinguishing feature between two general subclassifications of Trichinella species is whether the nurse cell forms a collagen capsule or not (Pozio and Bruschi, 2001).
Eosinophilia develops in response to the presence of the worm. Patients who develop neurologic and cardiac dysfunctions have marked hypereosinophilia associated with arteriolar microthrombi leading to areas of cerebral and myocardial infarction. Immunologic reactions also are deemed responsible for one of the hallmark clinical findings—palpebral edema.
The direct trauma of the larva encysting in muscle cells, coupled with the immunologic response, is responsible for other clinical features (eg, fever, myalgias). Ultimately, the intramuscular cysts typically calcify.Frequency:
- Internationally: Over the past 20 years, in spite of much awareness of both the presence of this infection and the efforts in many countries to control it, an increasing number of outbreaks have occurred throughout developed as well as developing countries (Murrell, 2000). Some authorities believe that trichinosis should be classified as an emerging/reemerging disease, particularly because of increasing reports of cases from some previously unaffected areas (Dupouy-Camet, 2000). Changes in ecosystem utilization, international trade of meats, and rising affluence in countries without well-established monitoring systems have all contributed to the increasing incidence (Pozio, 2001).
Although rare in countries with laws limiting the feeding of raw garbage/animal byproducts to commercially raised pigs and well-managed slaughterhouse surveillance systems, many countries have passed laws but fallen short on the implementation and quality assurance of the programs (Gajadhar, 2000). The cost of surveillance programs can be high and complex to install because of education and cultural issues (van Knapen, 2000). An international commission has developed a set of guidelines (Gamble, 2000).
Home raising of pigs, with feeding of raw garbage instead of grain, is still a common practice in a large part of the developing world. A study on medication effectiveness in Thailand reports 200-600 cases annually during celebrations of the Thai New Year, when communal feasting on pork is common.
Trichinosis must be considered a risk when eating the flesh of any animal that might have fed on uncooked animal flesh. Many animals generally not considered carnivorous eat meat products when presented in a form they can chew, ie, usually chopped, or ground and combined with vegetable matter. This most commonly occurs on small farms when animals are fed table scraps or the scraps from butchering another farm animal.
A 1998 report by the CDC of 2 case clusters from Germany demonstrates how marketing changes can alter disease demographics. As the report comments, cases in Europe historically were related to consumption of meat from a single pig by a group of people in a relatively small geographic area. This report is the first documentation of multiple persons infected from pork products that were made with meat transported from several geographic areas and combined at the processing plant.
In March 2001, the World Health Organization (WHO) reported a trichinosis outbreak in Italy, after immigrants from one of the newly independent states of eastern Europe and 2 members of an Italian family employing one of the immigrants consumed pork sausage sent from their home country. A similar cluster in Denmark in 2004 resulted from homemade sausage brought back following a vacation trip to their motherland by a group of Romanians (Samuelsson, 2004).
In these countries, the WHO report comments that some swine herds currently have a 50% prevalence of trichinosis, and thousands of human cases have been documented. The report correlates this increase in prevalence with a breakdown in social structure in these countries (state veterinary services, state farms), coupled with economic hardship and war. Travelers to these regions are strongly advised to avoid consumption of any pork sausage and to verify the adequate cooking of any pork prior to consumption. Pork products from this region should be considered suspect.
Although generally thought of as a disease of omnivorous or carnivorous animals, herbivores have demonstrated infection, most likely from prepared feed that contained remnants of infected animals. In France, horse meat, largely imported, has become the most common source with more than a dozen outbreaks involving more than 3000 human victims since 1976. Interestingly, the same meat exporting countries supply various other European Union countries that have no human trichinosis; unlike the French and Italians, those countries do not have the culinary habit of eating meat raw or minimally cooked (Boireau, 2000). Mutton and goat have become a recognized vector in countries where pig consumption is restricted for religious or economic reasons.
China has some of the highest recorded case numbers globally (Liu, 2002), Serologic population surveys have revealed prevalence rates of between 0.66-12%, varying somewhat from among regions depending on eating habits. Yunan province was found to be the most significantly affected province. Pigs are the primary vector with prevalence rates as high as 50% in slaughterhouse surveys in some provinces (Takahashi, 2000).
Marine mammals (polar bear, walrus, seal) have been identified as being vectors for Trichinella nativa, with human clusters of infection documented in Canada, although probably not limited to the western hemisphere. The Nunavik community of Northern Canada has developed a control program that owes much of its success to education and a high participation rate of hunters (Proulx, 2002).
Mortality/Morbidity: Specific death rate information is not established. Death is rare without development of neurologic and cardiac involvement.
- The primary morbidity is persistent myalgia and fatigue in cases that do not develop neurocardiac involvement.
- Following neurocardiac involvement, persistent variable dysfunction of either system may develop, depending upon the distribution of lesions.
Sex: Incidence is equal in males and females.
Age: All age groups reportedly have been affected; however, trichinosis most commonly occurs in persons aged 20-49 years.
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CLINICAL
| Section 3 of 10  |
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History: The usual incubation period of trichinosis is 8-15 days. Initial symptoms most commonly are intestinal due to the invasion of the intestinal wall by the juvenile larvae. Diagnosis depends heavily upon an epidemiologic history of ingesting potentially infected meat that was not cooked enough to kill the larvae. - Myalgia (75%) - Most commonly occurs in masseter, diaphragm, and intercostal muscles; may be severe to point of inability to ambulate or perform simple upper extremity or truncal tasks like feeding or sitting upright
- Fever (60-75%) - 38.5-40.5°C
- Diarrhea (40-60%) - Usually only in the acute intestinal proliferative and penetration phases of helminth infestation
- Facial edema (40-50%) - Usually considered one of the hallmark features, particularly when localized to the eyelids
- Cardioneurologic syndrome - Onset of these symptoms occurs in the first few days following general symptoms and prior to muscle invasion. The syndrome includes varying combinations of the following:
- Focal neurological deficits
- Acute myocardial injury (eg, myocarditis, sinus and atrial nodal dysfunction, congestive heart failure, infarction); also late myocarditis as isolated sequela possible
- Hypereosinophilia (>4000 granulocytes/mm3)
- Rash - This may occur in several forms.
- Palmar rash - Peripheral palmar and volar digital edema and erythema; desquamation occurs (10% in one study [Walsh, 2001])
Physical: - Palpebral edema (50-60%) - Usually considered one of the hallmark findings; may be associated with chemosis and proptosis (Astudillo, 2004)
- Muscle weakness and tenderness - Usually not true neurologic weakness but pain related
- Neurologic findings consistent with encephalopathy or focal deficits
- Cardiac findings of myocarditis, pericarditis, or ischemia
Causes: Trichinosis is a completely preventable infestation. The single most important causative factor is the consumption of inadequately cooked meat. Although most developed countries have surveillance programs to monitor meats entering the commercial market, these controls have been documented to fail. - Trichinella species of nematodes - Of the 10 recognized genotypes, the following are the most clinically significant, although others may not yet have been identified:
- T spiralis is the primary cause associated with domesticated animals.
- Trichinella britovi is seen frequently in wild boar, horses, and free-ranging swine. It has also been reported in bear in Japan where it has been given a separate classification, T9, because of minor genetic variations from the European T britova (Roy, 2003).
- Trichinella nelsoni is seen in various large carnivores of tropical Africa.
- T nativa has been documented in cougar, walrus, whale, and bear flesh, and it is associated with more prolonged diarrhea and fewer muscle symptoms. It is also more resistant to freezing than T spiralis.
- Trichinella pseudospiralis has been documented in birds and does not form a capsule in the muscle, thus leading to less muscle inflammation and pain. Conversely, the muscle phase seems to remain actively infective for a longer period, probably since, without cyst formation, ultimate calcification does not occur (Bruschi, 2002).
- Trichinella papuae in wild pigs has been identified in Papua-New Guinea as a source of infection among forest-dwelling hunters. It is a nonencapsulating form of Trichinella (Owen, 2001).
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DIFFERENTIALS
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Gastroenteritis Myopathies
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Patient Education
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WORKUP
| Section 5 of 10  |
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Lab Studies:
- CBC reveals eosinophilia in virtually all patients.
- UA may reveal myoglobinuria.
- Creatine kinase is elevated in 90% of patients.
- Parasite-specific indirect immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) titers (100%) and anti–newborn larvae antibodies (30%) are recommended. These may not be positive initially, and they also are subject to some cross-reactivity with other parasitic disorders making their specificity less when weakly positive (Yera, 2003). Western-blot analysis is used as a confirmatory evaluation (Robert, 1996).
Imaging Studies:
- Plain radiographs of the extremities
- Calcified densities in the muscles, indicating an old trichinization, may be the only positive radiographic findings.
- Radiographs do not help evaluate acute infestation.
- CT scan reveals focal deficits with small hypodensities in the cortex and white matter.
- CT scan may be helpful in patients demonstrating neurologic symptoms.
- Abnormal findings are unlikely in patients without neurologic symptoms.
- CT scanning of the orbits is warranted in patients with chemosis to rule out other causes of proptosis.
Other Tests:
- ECG may show signs of ischemia or pericarditis with nonspecific ST-segment changes. An ECG also may reveal a pericardial effusion.
Procedures:
- A muscle biopsy is the definitive diagnostic test but is not an ED procedure.
- Larvae are found free or encapsulated, depending upon the species of Trichinella causing the infection.
- At the time of biopsy, initial preparation may be made by crushing a portion of muscle tissue between 2 slides and viewing directly.
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TREATMENT
| Section 6 of 10  |
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Prehospital Care: Institute appropriate supportive therapy for patients presenting with symptoms of neurocardiac involvement. Emergency Department Care: - Patients with mild cases require no special care.
- Patients with more severe cases of muscle involvement may need basic supportive therapy (eg, oxygen, IV fluids).
- Cardiac monitoring is suggested for patients who present early. Cardiac findings are unlikely to develop late in the course (ie, after peripheral muscle invasion has started).
Consultations: - Infectious disease specialists
- Surgeons (for muscle biopsy)
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MEDICATION
| Section 7 of 10  |
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Anthelminthic therapy is generally considered only effective during the intestinal phase of infection. Because of the limited number of cases in any one outbreak, comparative trials at various stages of infection are lacking, leading to controversy regarding appropriate dosing (Watt, 2004). One trial during an outbreak in Italy assessed the effectiveness of mebendazole in patients several weeks following infection (Pozio, 2001). All patients became better in terms of decreased myalgias and other symptoms while under treatment, but between 3-45% had recurrence of various symptoms following a 10-day mebendazole course. In another study in Thailand, groups treated with mebendazole or thiabendazole had 100% resolution of myalgias reported at 4 months (Watt, 2000).
Corticosteroid treatment usually is instituted to reduce the immunologic response to the larvae. Jarisch-Herxheimer–like reactions have been described in patients with heavy larval loads following the administration of anthelmintic medications. This reaction is clinically manifested by a worsening of symptoms and is thought to be caused by a response to liberation of immunologically active components of the dying larvae. If the larval load is extremely high or in critical locations, this reaction may result in significant clinical deterioration resembling septic shock.
Drug Category: Glucocorticoids -- Frequently used to decrease myalgia and to limit eosinophilia when neurologic or myocardial involvement is present, although their efficacy has been questioned. Drug Name
| Prednisone (Deltasone, Orasone) -- Useful in treating inflammatory reactions. May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. | | Adult Dose | 0.05-2 mg/kg/d PO for 2 d, divided bid/qid; taper over 7 d |
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| Pediatric Dose | 4-5 mg/m2/d or 1-2 mg/kg PO qd; taper over 2 wk as symptoms resolve |
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| Contraindications | Documented hypersensitivity; viral or peptic ulcer disease; hepatic dysfunction; fungal, tubercular skin, or connective tissue infections |
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| Interactions | None of significance for short-term use; with long-term use (>1 wk), clearance may decrease when used concurrently with estrogens; when used with digoxin, may increase digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids; consider increasing maintenance dose |
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| Pregnancy |
B - Usually safe but benefits must outweigh the risks.
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| Precautions | Abrupt discontinuation of glucocorticoids may cause adrenal crisis; other possible complications include hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and severe infections |
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Drug Name
| Hydrocortisone (Solu-Cortef, Westcort) -- May be used in place of prednisone in patients too ill to take PO medications. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing the increased capillary permeability. |
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| Adult Dose | 15-240 mg IV/IM q12h |
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| Pediatric Dose | 1-5 mg/kg/d or 75-300 mg/m2/d IV/IM divided q12-24h |
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| Contraindications | Documented hypersensitivity; viral, fungal, or tubercular skin infections |
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| Interactions | None significant for short-term use; long-term use (>1 wk), may decrease corticosteroid clearance when used concurrently with estrogens; may increase digitalis toxicity secondary to hypokalemia when used concomitantly with digoxin |
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| Pregnancy |
C - Safety for use during pregnancy has not been established.
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| Precautions | Caution in patients with hyperthyroidism, osteoporosis, peptic ulcer, cirrhosis, nonspecific ulcerative colitis, diabetes, and myasthenia gravis |
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Drug Category: Anthelmintics -- Parasite biochemical pathways are sufficiently different from the human host to allow selective interference by chemotherapeutic agents in relatively small doses.Drug Name
| Mebendazole (Vermox) -- Causes worm death by selectively and irreversibly blocking glucose uptake and other nutrients in the susceptible adult intestine where the helminths dwell. |
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| Adult Dose | 100 mg PO bid for 3 d; administer second course if patient is not cured within 3-4 wk
More aggressive courses use up to 10 mg/kg/d for 10 d, particularly for muscle stage of the disease (Watt, 2004; Pozio, 2001)| Pediatric Dose | <2 years: Not established
>2 years: Administer as in adults| Contraindications | Documented hypersensitivity |
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| Interactions | Carbamazepine and phenytoin may increase mebendazole metabolism, decreasing its efficacy; conversely, cimetidine may increase mebendazole levels |
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| Pregnancy |
C - Safety for use during pregnancy has not been established.
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| Precautions | Adjust dose in patients with hepatic impairment |
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Drug Name
| Thiabendazole (Mintezol) -- Useful in mixed helminthic infections. Inhibits helminth-specific mitochondrial fumarate reductase and is indicated for alleviating symptoms of trichinosis during invasive phase. Little value in treatment of disease that has spread beyond the lumen of the intestines due to poor absorption from GI tract. Thiabendazole is not marketed in all parts of the world. |
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| Adult Dose | 50 mg/kg/d PO for 2 d divided q12h; not to exceed 3 g/d |
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| Pediatric Dose | <15 kg: Not established
>15 kg: 50 mg/kg/d PO divided q12h; not to exceed 3 g/d| Contraindications | Documented hypersensitivity |
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| Interactions | May elevate serum levels of theophylline, increasing its toxicity; monitor serum levels, and reduce dose if necessary |
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| Pregnancy |
C - Safety for use during pregnancy has not been established.
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| Precautions | Closely monitor in hepatic or renal dysfunction; prior to initiating therapy, supportive therapy is necessary for anemic, dehydrated, or malnourished patients; use in confirmed worm infestation (not prophylactically); may cause nausea, vomiting, and mild CNS depression |
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Drug Name
| Albendazole (Albenza) -- Decreases ATP production in the worm, causing worms' energy depletion, immobilization, and death. |
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| Adult Dose | 400 mg/d PO as a single dose; repeat in 2 wk if patient is not cured
Doses quoted in articles for muscular phase have been on the order of 10 mg/kg/d for 10 d (Pozio, 2001)| Pediatric Dose | <2 years: 200 mg/d PO in a single dose; repeat in 3 wk if infestation persists
>2 years: Administer as in adults| Contraindications | Documented hypersensitivity |
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| Interactions | Coadministration with carbamazepine may decrease efficacy; dexamethasone, cimetidine, and praziquantel may increase toxicity |
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| Pregnancy |
C - Safety for use during pregnancy has not been established.
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| Precautions | Discontinue use if LFTs increase significantly (resume when levels decrease to pretest values) |
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FOLLOW-UP
| Section 8 of 10  |
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Further Inpatient Care:
- Admit patients with neurologic or cardiac symptoms to the hospital for initiation of therapy.
- Consider patients with significant diffuse muscle involvement for hospitalization because they are at risk for Jarisch-Herxheimer–like reactions.
- Patients with suspected milder forms of the disease, who cannot be directly referred to a physician capable of performing a muscle biopsy, probably should be admitted as the quickest route to definitive diagnosis.
Further Outpatient Care:
- In suspected cases, arrange for surgical follow-up care in 1-2 days for muscle biopsy.
Deterrence/Prevention:
- Adequate cooking of all meat products is the primary deterrent to acquiring infection with the Trichinella species.
- Adequate cooking refers to the point at which no red meat remains.
- The US Code of Federal Regulations and the US Department of Agriculture have information regarding preparation of pork and appropriate times and temperatures needed to kill larvae. For cooking, pork must reach an internal temperature of 160°F (71°C); for freezing, it must remain at 5°F (-15°C) for 3 weeks.
Complications:
- Myocarditis with congestive heart failure
Prognosis:
- Recovery with resolution of signs and symptoms may occur in 5-6 weeks after infestation in many patients with disease limited to enteropathic and mild muscular involvement.
- Many patients with disease limited to muscle involvement may experience varying degrees of persistent fatigue and myalgia despite a full course of anthelminthic treatment. Patients infected with nonencapsulating species tend to have less muscle pain, although this pain is more persistent. Encapsulated species tend to eventually calcify, resulting in destruction of the larva and resolution of the painful inflammation.
- Patients with CNS, cardiac, or renal involvement may have protracted courses with persistent stiffness, neurological disorders, and heart or kidney dysfunction.
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MISCELLANEOUS
| Section 9 of 10  |
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Special Concerns:
- With increasing global travel to developing countries, warn travelers of trichinosis as a health risk (see Frequency). Ask patients about travel and eating habits.
- The global economic impact of trichinosis is high. In the European Union, for example, it costs more than $500 million per year for the domestic pig control program. In developing countries, including China, identification of clusters of infection have led to sacrificing large herds of pigs, a devastating event for small farmers who lack resources such as insurance (Pozio, 2000).
- Pregnancy: Transplacental migration of T britovi has been documented both in animal models and in humans (Cosoroaba, 1998; Dubinsky, 2001).
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BIBLIOGRAPHY
| Section 10 of 10 |
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Trichinosis excerpt |