trichinosis

Trichinosis, also called trichinellosis, or trichiniasis, is a parasitic disease caused by eating raw or undercooked pork and wild game infected with the larvae of a species of roundworm Trichinella spiralis, commonly called the trichina worm. There are eight Trichinella species; five species are encapsulated and three are non-encapsulated. ^[1] Only three Trichinella species are known to cause Trichinosis: T. spiralis, T. nativa, and T. britovi. ^[1] The few cases in the United States are mostly the result of eating undercooked game, bear meat, or home reared pigs. It is most common in the developing world and where pigs are commonly fed raw garbage.

History of the discovery

• 1835:London: On February 2, 1835 Philip Vargas, a first year medical student, observes Trichinella spiralis while conducting a dissection on a cadaver.^[2] The significance of this event is that he is the first to observe Trichinella and to microscopically analyze it.^[2] Without informing Vargas, Thomas Wormald sends Richard Owen a sample of the parasite from the same cadaver in which Vargas had made the discovery. Owen then publishes a paper describing the parasite and calls it Trichina spiralis but does not give Vargas the deserved credit.^[2]

• 1846:Philadelphia: Joseph Leidy finds Trichinella cysts in his pork dinner and hypothesizes that trichinosis is caused by consuming undercooked pork.^[2] However, scientists disregard his hypothesis.^[2]

• 1857: Germany: Rudolph Leuckart gives infected meat to mice and discovers that the ingested worms “had not only come out of their cysts into the gut of the mice, but also had become much bigger than they had been when encysted in the muscle of their former host.”^[2]

• 1859: Germany: After dissecting a dog that had been fed Trichinella infected tissue Rudolph Virchow finds that the Trichinella larvae become adult nematodes that are not Trichuris. Virchow hastily sends these findings to the Paris Academy of Sciences, but his messy handwriting delays the translation and publication of his letter.^[2] Even though Virchow beats Leuckart to the experiment, Leuckart rushes to have the results from his own experiments with pigs published by the Paris Academy in September 1859.^[2] However, his messy handwriting leads to the inaccurate reporting of the actual number of worms found in the pig’s intestine. [4] Leuckart’s paper claimed that Trichinella became Trichuris.^[2] In September 1859 Virchow’s paper is finally published and his findings contradict Leuckart’s hypothesis; after further experimentation Leuckart recognizes that Virchow is correct.^[2]

• 1860:*Germany: Friedrich Zenker performs autopsy on female servant who died of Trichinosi and recognizes the parasite.^[2] Zenker’s contribution is “that he realized that the intestinal adults were the progenitors of the larvae in the muscle”.^[2] He also discovers how Trichinosis is transmitted and established the pathogenicity of Trichenella spiralis.^[2] Virchow, Zenker, and Leuckart made significant contributions to understanding the life cycle of T. spirela. Virchow discovered that the worms matured in the small intestine. ^[2] Zenker concluded that the worm was parasitic and proposed that the larvae reached the muscles through the lymphatic system.[4] Leuckart discovered larvae in the uterus of the adult female worm.^[2]

• 1862: Friedreich of Heidelberg is the first to perform a muscle biopsy to diagnose Trichinosis. ^[2]

• 1895-1896: Name changed from Trichina spiralis to Trichinella spiralis.^[2]

• 1896: T.R. Brown discovers that Eosinophilia is a clinical sign of Trichinosis.^[2]

• 1897: The three Swedish explorers heading towards the North Pole might have died of Trichinosis from eating infected polar bear meat.^[2]

• 1960’s:Kenya: Comparative infection studies reveal that there are different species of Trichinella and that they each can only infect certain species of animals.^[1]

Signs and symptoms

The great majority of trichinosis infections have either minor or no symptoms and no complications[1]. There are two main phases for the infection: enteral (affecting the intestines) and parenteral (outside the intestines).The symptoms vary depending on the phase, amount of encysted larvae ingested, age, gender, and host immunity. ^[3]Trichinosis initially involves the intestines. Within 1-2 days of contagion, symptoms such as nausea, heartburn, dyspepsia, and diarrhea may appear. Later on, as the worms encyst in different parts of the human body, other manifestations of the disease may appear, such as headache, fever, chills, cough, eye swelling, joint pain and muscle pain, petechiae, and itching. The most dangerous case is worms entering the central nervous system. They cannot survive there, but they may cause enough damage to produce serious neurological deficits (such as ataxia or respiratory paralysis), and even death. The central nervous system is compromised by Trichinosis in 10-24% of reported cases. ^[4] Trichinosis can be fatal depending on the severity of the infection; death can occur 4–6 weeks after the infection.^[5] Death is usually caused by myocarditis, encephalitis or pneumonia.^[6]

Life cycle

The domestic cycle involves humans, pigs, and rodents. Pigs become infected when they eat raw infected meat, especially infected rodents. Humans become infected when they eat raw or undercooked infected pork. After humans ingest the cysts from infected undercooked meat, pepsin and hydrochloric acid help free the larvae in the cysts into the small intestine.^[3] The larvae then migrate to the small intestine and invade the columnar epithelial cells; the process of how the columnar cells are invaded is still unknown. ^[2] In the small intestine, the larvae molt four times before becoming adults. ^[3] Thirty to 34 hours after the cysts were originally ingested, the adults mate and within five days produce larvae. ^[3] The worms can only reproduce for a limited period of time because the immune system will eventually expel them from the small intestine.^[3] Genetic studies with laboratory rats seem to indicate that the host’s genetic make-up can determine the duration of the intestinal phase and that “T-cell dependent antigen is necessary for protection against the intestinal phase of the infection”. ^[5] The larvae then use their piercing mouth part called the “sylet” to pass through the intestinal mucosa and enter the lymphatic vessels and then enter the bloodstream. ^[2] The larvae use the capillaries in striated muscle to arrive at their final destination: the muscle fiber cells.^[5] It is believed that the larvae enter the muscle cells through mechanical means. ^[2] The muscle cell that a larva takes over is referred to as the nurse cell. In just three weeks the larvae induce dramatic changes in the muscle cells. ^[7] For instance, the larvae increase the size of the cell’s nucleus and create a “placenta” like structure around the muscle cell called a circulatory rete. ^[7] How can the larvae induce angiogenesis (formation of new blood vessels) around the muscle cell? It is hypothesized that the larvae's genes activate certain genes of the host’s cell to induce these dramatic changes. ^[7] Because humans do not typically get eaten by other animals “humans are a parasitic dead end.” ^[7]

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Diagnosis

Serological (blood) tests and skeletal muscle biopsy (2-4 mm³) are the two main ways of diagnosing Trichinosis.^[6] Eosinophilia is usually the earliest indicator of trichinosis.^[3] Another indicator of being infected is a high level of muscle enzymes like creatinine phosphokinase. ^[3] Both means of testing were developed in the late 1800s. In 1898, Thomas R. Brown published an article in which he concluded the following: “[T]here is a marked increase in the percentage of eosinophilic cells in the blood in trichinosis. [T]his increase may be used as a diagnostic sign in this disease”.[10] A more modern but expensive means of diagnosis is the use of antibody detection technology such as enzyme-linked immunosorbent assays (ELISA).^[3]

Treatment

Symptoms can be treated with aspirin and corticosteroids. Thiabendazole can kill adult worms in the intestine; however, there is no treatment that kills the larvae. Mebendazole (200-400 mg three times a day for three days) or Albendazole (400 mg twice a day for 8-14 days) are given to treat trichinosis.^[8]These drugs should not be given to pregnant women. ^[3] Mebendazole interferes with the parasites microtubule assemblage. This drug does not have severe side effects but “mild nausea, vomiting, diarrhea, and abdominal pain have been reported infrequently.” ^[9] Rare side effects, usually with high-dose therapy, are hypersensitivity reactions (rash, urticaria), agranulocytosis, alopecia, and elevation of liver enzymes.^[9] Prednisolone (20-60 mg per day for the first few days) can be given to ease the side effects of inflammation.^[3] Albendazole also inhibits microtubule formation and has “larvicidal effects”. ^[9] Albendazole does not normally cause severe side effects, but on occasion the following side effects have been reported: “Mild and transient epigastric distress, diarrhea, headache, nausea, dizziness, lassitude, and insomnia.” ^[9]

Vaccination research

Currently there are no vaccines for Trichinella spiralis. However, several mice studies aiming to produce vaccine candidates have yielded promising results. For instance, Dea-Ayuela et al. (2006) used extracts and excretory-secretory products from first stage larvae to produce an oral vaccine.^[10] In order to prevent the gastric acids from dissolving the antigens before reaching the small intestine, scientists encapsulated the antigens in a microcapsule made of copolymers. This vaccine significantly increased CD4+ cells and increased antigen-specific serum IgGq and IgA, resulting in a statistically significant reduction in the average number of adult worms in the small intestine of mice. The significance of this approach is that if the white blood cells in the small intestine have been exposed to Trichinella antigens (through vaccination) then when an individual gets infected the immune system will respond to expel the worms from the small intestine fast enough to prevent the female worms from releasing their larvae. Yuan Gu et al. (2008) tested a DNA vaccine on mice which “induced a muscle larvae burden reduction in BALB/c mice by 29% in response to T. spiralis infection”.^[11] Researchers trying to develop a vaccine for Trichinella have tried to using either “larval extracts, excretory-secretory antigen, DNA vaccine, or recombinant antigen protein.” ^[11]

Epidemiology

Trichinosis was known as early as 1835 to have been caused by a parasite, but the mechanism of infection was unclear at the time. It was not until a decade later that American scientist Joseph Leidy pinpointed undercooked meat as the primary vector for the parasite, and not until two decades afterwards that this hypothesis was fully accepted by the scientific community [2].

Approximately 11 million individuals are infected with Trichinella; Trichinella spiralis is the species responsible for most of these infections. ^[12]Infection was once very common, but is now rare in the developed world. The incidence of Trichinosis in the U.S. has decreased dramatically in the past century. For instance, in 1930, 1 out of every 6 persons in the U.S. had trichinosis then by 1970 this incidence rate had decreased to 1 out every 25.^[5] From 1997 to 2001, an annual average of 12 cases per year were reported in the United States. The number of cases has decreased because of legislation prohibiting the feeding of raw meat garbage to hogs, increased commercial and home freezing of pork, and the public awareness of the danger of eating raw or undercooked pork products.^[13]

In the developing world, most infections are associated with undercooked pork. For example, in Thailand, between 200 and 600 cases are reported annually around the Thai New Year. This is mostly attributable to a particular delicacy, larb which calls for undercooked pork as part of the recipe. In parts of Eastern Europe, the WHO (World Health Organization) reports that some swine herds have trichinosis infection rates above 50%, and there are correspondingly large numbers of human infections [3].

It is also important to keep in mind that major socio-political changes can produce conditions that favor the resurgence of Trichinella infections in swine and consequently humans. For instance, “the overthrow of the social and political structures in the 1990s” in Romania led to an increase in the incidence rate of trichinosis.^[14] There is also a high incidence of trichinosis among refugees from Southeast Asia.^[5] China reports approximately 10,000 cases every year and is therefore the country with the highest numbers of cases. ^[5] In China, between 1964-1998 over 20,000 people were infected with Trichinosis and over 200 people died. ^[15]

It has been suggested that trichinosis may be one of several factors that led to religious prohibitions in Islam and Judaism against eating pork products, such as in the kashrut and dhabiĥa halal dietary laws. The medieval Jewish philosopher Maimonides advocated such a theory in The Guide for the Perplexed, as did medieval Islamic authorities.^[16] This topic is controversial.

International Commission on Trichinellosis

The International Commission on Trichinellosis (ICT) was created in 1958 in Budapest and is aiming to exchange information on the biology, the physiopathology, the epidemiology, the immunology, and the clinical aspects of trichinellosis in humans and animals. Prevention is a primary goal. Since the creation of the ICT, its members (more than 110 from 46 countries) have regularly gathered and worked together during meetings held every 4 years : the International Conference on Trichinellosis.

Prevention

• Cooking meat products to an internal temperature of 165 °F (74 °C) for a minimum of 15 seconds.
• Cooking pork to a uniform internal temperature of at least 144 °F (62.2 °C), per USDA Title 9 section 318.10. It is prudent to use a margin of error to allow for variation in internal temperature and error in the thermometer.
• Freezing pork less than 6 inches thick for 20 days at 5 °F (−15 °C) or three days at −4 °F (−20 °C) kills larval worms.
• Cooking wild game meat thoroughly. Freezing wild game meats, unlike freezing pork products, even for long periods of time, may not effectively kill all worms. This is because the species of trichinella that typically infects wild game is more resistant to freezing than the species that infects pigs.
• Cooking all meat fed to pigs or other wild animals.
• Keeping pigs in clean pens with floors that can be washed (such as concrete).
• Not allowing hogs to eat uncooked carcasses of other animals, including rats, which may be infected with trichinosis.
• Cleaning meat grinders thoroughly when preparing ground meats.
• Control and destruction of meat containing trichinae, e.g., removal and proper disposal of porcine diaphragms prior to public sale of meat.

The Centers for Disease Control and Prevention makes the following recommendation: "Curing (salting), drying, smoking, or microwaving meat does not consistently kill infective worms."^[17] However, under controlled commercial food processing conditions some of these methods are considered effective by the United States Department of Agriculture.^[18]

The United States Department of Agriculture (USDA) and Animal and Plant Health Inspection Service (APHIS) are responsible for the regulations concerning the importation of swine from foreign countries. The Foreign Origin Meat and Meat Products, Swine section covers swine meat (cooked, cured and dried, and fresh). The USDA and APHIS developed the National Trichinae Certification Program. This is a voluntary “pre-harvest” program for U.S. swine producers “that will provide documentation of swine management practices” to reduce the incidence of Trichinella in swine.^[19] The CDC reports that 0.013% of U.S. swine is infected with Trichinella. ^[19]

See also

• List of parasites (human)

References

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External links

• International Commission on trichinellosis web pages