Trichinellosis/Trichinosis

Trichinellosis, formerly called trichinosis or trichiniasis (Trich from Greek thrix meaning hair), is an infection caused by nematodes of the genus Trichinella, most commonly T spiralis in humans. Through historical, paleopathologic, and, most recently, genomic studies, the complex intertwined history of humans, their food, and this worm has become better defined. Genomic evidence suggests the presence of Trichinella as a distinct species since some time in the mid to latter Miocene period (around 20 million years ago). ^[1] To date, 8 distinct species and 3 genotypes in 2 clads, encapsulated and nonencapsulated, have been found to infect mammals, birds, and reptiles around the globe. ^[2] Not all of these have been identified in humans.

The earliest human infection is reported to have been documented in an Egyptian mummy that dates to approximately 1300 BCE. ^[3] Religious injunctions on the consumption of pork may reflect early cultural awareness of this human-animal infection link. ^[4]

The first modern scientific observations of human Trichinella infection, from the autopsy of a man with "sandy diaphragm, were reported by medical student James Paget (of Paget disease) to a medical student society and published by his lecturer in clinical anatomy, Sir Richard Owen, then assistant curator at the Royal College of Surgeons. ^[3] The initial life cycle was worked out by Rudolf Virchow and associates over the years 1850-1870. ^[5]

By the 1860s, trichinellosis was well-recognized as a disorder spread through infected pigs, leading to a cultural aversion to certain pork products, particularly German and Dutch sausage. ^[6]

Geopolitical and cultural factors, such as increases in global movement of food products and persons, evolving into the 21^st century are leading to a resurgence of human infections in areas that have been free of infection for decades. ^[7] This resurgence has particular relevance to emergency medicine because people may present to EDs in areas with little or no presence of trichinellosis locally, as they may have contracted it while travelling and because early diagnosis is associated with improved treatment outcomes.

Early diagnosis depends on clinician awareness and uncovering relevant patient history since the initial clinical presentation may be nonspecific.

Infection is initiated by ingestion of viable larvae in raw or undercooked meat. Digestive action liberates the larvae. 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 elucidated, the newborn larvae have been implicated in cardiac and neurologic aspects of the disease. The life cycle is completed with the larvae invading a striated muscle cell.

Although the presence of larvae provokes an eosinophilia, they are generally resistant to any immunologic reaction from the host as they migrate out of the capillaries and penetrate muscle cells. Once in the cell, they alter cellular activity to turn the individual cells into "nurse cells." To nourish themselves in the nurse cell, the larvae stimulate angiogenesis leading to formation of a capillary rete around the invaded muscle cell. ^[8] Additionally, the normal cell life cycle of the invaded muscle cell enters a permanent arrest, with nuclear DNA remaining for the remainder of the life of the host at the G₂/M phase transition. ^[9] Nurse cell formation has also been demonstrated to have many features analogous to muscle cell repair. ^[10]

A distinguishing feature between two general subclassifications (clads) of Trichinella species is whether the nurse cell forms a collagen capsule. ^[11]

Patients who develop neurologic and cardiac dysfunctions have marked hypereosinophilia associated with arteriolar microthrombi, often simply from numbers of larvae, leading to areas of cerebral and myocardial infarction. ^[12] Immunologic reactions are also 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). Typically, the intramuscular cysts eventually calcify. See the image below.

Frequency

United States

Documented occurrence in the United States is now largely limited to sporadic cases or small clusters related to consumption of home-processed meats from noncommercial farm-raised pigs and wild game. ^[13] Trichinellosis has been a reportable disease since 1966. The Centers for Disease Control and Prevention (CDC) surveillance system has data as far back as 1947 demonstrating a significant decrease in cases from a peak of nearly 500 in 1948 to a total of 74 from 1997-2001, the most recent reporting cycle. ^[14] Human migratory patterns risk to upset this improvement as demonstrated by a report of a Laotian immigrant to the US developing trichinellosis after consuming lightly cooked commercially purchased pork. ^[15]

The US national surveillance system has been a passive system with links to state and local levels without active sampling of pork carcasses, an expensive practice used in some countries. ^{[16, 17]} The US Department of Agriculture has, however, used periodic surveillance of farm-raised pigs. In a 1999 study, the major risk factor for seropositivity in tested pigs was access to live wildlife or wildlife carcasses. ^[18] Rats, raccoons, skunks, and opossums have been shown to be wild sources of domestic pork contamination.

The decrease in infection of domestic pork in the United States has been associated with federal laws regarding commercial pork feeding practices directed at other pathogens, voluntary preharvest programs to control other risk factors such as exposure to rats in commercial herds, and attention to preparation guidelines. ^[19]

The USDA and the National Pork Board, an industry group, have developed the US Trichinae Certification Program. Based on principles proposed by the International Commission on Trichinellosis, this program relies on inspections of pork production sites with spot audits. ^[20]

Hunters and others who eat carnivorous game continue to be at risk. ^[20]

International

Reliable data on the incidence of trichinellosis varies around the world for several reasons. Initial clinical features of the disease overlap with other, more benign disorders, such as simple gastroenteritis. Characteristic signs of palpebral edema may not be recognized as representative of illness. Muscle pains from encysting of larvae may be delayed. In many parts of the world, for reasons ranging from difficult access to health care to poor public health reporting systems, presence of trichinosis may not be well documented unless occurring in clusters of cases. ^[21]

Since the 1980s, 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. ^[22] Some authorities believe that trichinellosis should be classified as an emerging/reemerging disease, particularly because of increasing reports of cases from some previously unaffected areas. ^[23] 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. ^[24]

Although rare in countries with laws limiting the feeding of raw garbage or 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. ^[25] The cost of surveillance programs can be high and complex to install because of education and cultural issues. ^[16] An international commission with representation from more than 40 countries has developed a set of guidelines and holds quadrennial scientific and policy meetings. ^[26]

Home raising of pigs, with feeding of raw garbage instead of grain, is still a common practice in a large part of the world at all levels of development. In many countries, pigs roam freely, leading to contact with sylvatic sources of infection. Celebration of the Thai New Year has been associated with 200-600 cases in a single year and is a known annual source of multiple cases. ^{[27, 28]} Group tourist travel has also been associated with cluster outbreaks. ^[29] In several Southeast Asian countries, raw pork sausage and other dishes are considered delicacies and are regularly associated with outbreaks.

Trichinellosis 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 will eat meat products when presented in a form they can chew, that is, 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. Rats also represent a reservoir in settings where raw animal scraps are left out for domestic animals to eat.

Market changes with international movement of processed food ingredients through either commercial channels or individual transport of products have presented a new source of difficulty in control. Two case clusters from Germany in 1998 were related to commercially produced sausage produced from meat transported from several different countries in Europe. ^[30] A 2007 outbreak in Poland with more than 180 confirmed cases was linked to one manufacturer of low price sausage. This outbreak even spread to Germany as cross-border shoppers returned with lower price sausage from the same Polish region. ^[31] Other clusters have occurred in relation to immigrant families bringing home-country delicacies back from vacation to their new countries of residence. ^{[32, 33, 34]}

The breakdown of state supported systems for farming, inspection and slaughter of meat products in the former Soviet Union countries of Eastern Europe, combined with culinary traditions, has been implicated in increasing presence of trichinellosis in these countries. ^[35]

The World Health Organization (WHO) reported that swine herds in some countries had a 50% prevalence of trichinellosis, and thousands of human cases had 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. ^[32]

In Eastern Europe, for example, following the break-up of the Soviet Union, large collective pig production facilities were replaced by smaller farms with free-ranging pigs, leading to increased contact with vectors such as rats. ^[36] Despite these socioeconomic-political forces, awareness and education have likely been the basis for decreasing caseloads over the ensuing years in some areas. ^[37] More recently, the economic strains on farmers in countries heavily impacted by a global recession in 2008 have increased the possibility of small farmers not adhering to safety practices involving extra cost. ^[38]

Travelers to regions with significant amounts of small-farm pig raising are strongly advised to consider any pork products to be suspect and to avoid consumption of any pork sausage. If eating pork or unidentified meat, adequate cooking should be personally verified. An outbreak in Turkey, a largely Muslim country, was attributed to an unscrupulous producer of meatballs adding pork from unverified farms to the beef and selling the meatballs as pure beef. ^[39]

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 trichinellosis; unlike the French and Italians, those countries do not have the culinary habit of eating meat raw or minimally cooked. ^[40] 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. ^[41] Serologic population surveys have revealed prevalence rates of between 0.66 and 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. ^[42] The Western Region Development strategy of the 1990s led to many people from the endemic regions of central and eastern China migrating with infected livestock to regions with previously very low incidence. An increased demand from tourist industry development has led to an increase in small producers using uncooked swill to feed pigs and not confining the pigs from wild vectors with a concomitant increase in pig prevalence to as high as 100% reported in one region. ^[43]

Arctic and subarctic mammals (polar bear, walrus, seal) have been identified as being vectors for Trichinella nativa. ^{[44, 45]} T nativa is resistant to freezing, even for months at -20^o C. Up to 60% of polar bears in Nunavik are infected. ^[46] Some Inuit have adjusted eating habits to avoid old male walruses as they are primarily scavengers, whereas the young feed primarily on shellfish. ^[47]

Consumption of wild boar prepared into sausage in Spain has led to human infection with T britovi in Spain and Sweden. ^[48] Wild boar have also been identified as a source of human infection in other areas in the Mediterranean basin, southeast Asia, and Pacific Islands. ^[49]

In recent years, the effect of consumer trends such as greater interest in "free ranging" and "antibiotic free" meats has been associated with an increase in trichinellosis among pigs destined to commercial markets in the United States. ^[50] and Europe. ^[51] The European Union has implemented a Trichinella monitoring program and the United States has developed a pilot program for Trichinell -free pig production. ^[52]

This rather extensive listing of international incidence of animal and human infection has been presented to offer some direct information regarding areas of particular concern as well as to further make the point of the importance of dietary and travel history in patients with diarrhea, particularly with associated myalgias and eosinophilia.

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.

Race

Trichinella infection does not vary among different races. Variations in disease presence are based more on cultural food preparation and consumption practices.

Sex

Incidence is equal in males and females unless particular culinary habits lead to higher exposure for one group. ^[53] Serological evaluation of a small case series of pregnant women suggests that transplacental migration of larvae is possible in humans. ^[54]

Age

All age groups reportedly have been affected; however, trichinellosis most commonly occurs in persons aged 20-49 years.

Although no good epidemiologic studies exist, there is evidence for potential transplacental infection of the fetus as it has been reported in different animals and in a fetus from a therapeutic abortion of an infected mother. ^{[55, 56]}