shelly amieva trichinosis hard copy

1
Shelly Amieva
Parasites and Pestilence
February 27, 2009
Trichinosis
Introduction
Unlike AIDS or Malaria, Trichinosis and Trichinella spiralis, the etiological agent of
Trichinosis, no longer make the front cover of immunology or parasitology journals. However,
this lack of popularity does not mean that Trichinosis is a disease of the past or that Trichinella
spp. are parasites not worth researching. Approximately, 11 million individuals are infected with
Trichinella spp.1 Incredibly, once Trichinella spiralis larvae invade a muscle cell, they have the
ability to induce angiogenesis in the muscle cells they reside in.2 While most people shiver at the
mention of avian flu or hemorrhagic fever, Trichinosis once was a disease that also inspired great
fear. Trichinosis outbreaks sometimes had devastating effects on village populations. For
instance, in Germany between 1860 and 1880 there were 8,491 cases of Trichinosis and in1865
in the small village of Hedersleden an outbreak had a mortality rate of 30%.3
The history of the discovery of T. spiralis is just as fascinating as its biology. The history
of the discovery is plagued with controversy and it involves a renowned doctor taking undue
credit for its discovery and reveals the competitive nature of the scientific community.4 The
discovery of this disease intertwined science and politics and allowed politicians to use health
policy as a means to protect economic interests. For instance, by the early 1880’s the U.S. had
become the world’s main pork exporter but since it was one of the few developed countries that
did not inspect pork for Trichinella, most European countries used this as an excuse to set-up
embargoes against American pork.3 Then the biotechnological revolution of the 20th century led
to the discovery that there are 8 different species of Trichinella.4 Therefore, Trichinosis is an
interesting and important disease worthwhile studying from both a biological and historical lens.
Agent:
Trichinella spiralis is a parasitic worm and the etiological agent of Trichinosis.4 The only
way to distinguish between species is to perform a biochemical analysis. 4 Molecular studies
have found the greatest genetic variability for T. spiralis in East
Asia, meaning that this species probably originated in this
region. 4 Trichinella spp. belong to the phylum
Nemathelminthes. Nematodes are more commonly known as
roundworms because unlike the worms from the phylum
plathyhelminthes nematodes are cylindrical and have a digestive
tract.5 Female nematodes tend to be larger than the males.5 The
worms that cause Trichinosis reside in the cells of skeletal
muscle. 5
“Posterior end of male worm (T. spiralis) by scanning electron microscopy.”
Source: Campbell, W. C. (1983). Trichinella and Trichinosis. New York:
Plenum Press.
2
Taxonomy4
Kingom: Animalia
Phylum: Nemathelminthes
Class: Nematoda
Order: Trichocephalida
Family: Trichinellidae
Genus: Trichinella
Species:
-spiralis
- nativa
- britovi
-murrelli
- nelsoni
- pseudospiralis
- papuae
-zimbabwensis
Synonyms
Other names for Trichinosis include1:
-Trichinellose
-Trichinellosis
-Trichinose
-Trikinose
-Triquiniase
-Triqunosis
-ICD9: 124
-ICD10: B75
History of the Discovery
-1835:
*London: On February 2, 1835 James Paget, a first year medical student, observes
Trichinella spiralis while conducting a dissection on a cadaver.³ The significance of this
event is that he is the first to observe Trichinella and to microscopically analyze it. ³
*Without informing Paget, Thomas Wormald sends Richard Owen a sample of the
parasite from the same cadaver in which Paget had made the discovery. ³ Owen then
publishes a paper describing the parasite and calls it Trichina spiralis but does not give
Paget the deserved credit. ³
3
James Paget.
Source: Sir James Paget, 1st Baronet. (2009). In Encyclopædia Britannica. Retrieved February 26, 2009, from
Encyclopædia Britannica Online: http://www.britannica.com/EBchecked/topic/ 438256/Sir-James-Paget-1st-Baronet
Richard Owen.
Source: Campbell, W. C. (1983). Trichinella and Trichinosis. New York: Plenum Press.
-1846:
*Philadelphia: Joseph Leidy finds Trichinella cysts in his pork dinner and hypothesizes
that trichinosis is caused by consuming undercooked pork. ³ However, scientists
disregard his hypothesis. ³
-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.” ³
4
-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.³
Virchow hastily sends these findings to the Paris Academy of Sciences, but his messy
handwriting delays the translation and publication of his letter. ³ 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. ³ However,
his messy handwriting leads to the inaccurate reporting of the actual number of worms
found in the pig’s intestine. ³ Leuckart’s paper claimed that Trichinella became
Trichuris. ³ 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. ³
-1860:
*Germany: Friedrich Zenker performs autopsy on female servant who died of
Trichinosis and recognizes the parasite. ³ Zenker’s contribution is “that he realized that
the intestinal adults were the progenitors of the larvae in the muscle”. ³ He also discovers
how Trichinosis is transmitted and established the pathogenicity of Trichenella spiralis. ³
* 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. ³
Zenker concluded that the work was parasitic and proposed that the larvae reached the
muscles through the lymphatic system. ³ Leuckart discovered larvae in the uterus of the
adult female worm. ³
-1862:
*Friedreich of Heidelberg is the first to perform a muscle biopsy to diagnose Trichinosis.³
-1895-1896:
*Name changed from Trichina spiralis to Trichinella spiralis. ³
-1896:
*T.R. Brown discovers that Eosinophilia is a clinical sign of Trichinosis. ³
-1897:
*The three Swedish explorers heading towards the North Pole might have died of
Trichinosis from eating infected polar bear meat. ³
-1960’s:
*Kenya: Comparative infection studies reveal that there are different Trichinella species
and that they each can only infect certain species of animals. ³
5
History of Policy Concerning Meat Inspection and Trichinosis:
-1863: *Mandatory inspection of pigs in the Duchy of Brunswick. ³
Right:“An old Danish cartoon envisioning the arrest of a trichina
by the police.”
Source: Campbell, W. C. (1983). Trichinella and Trichinosis.
New York: Plenum Press.
Above:“Early trichonoscopy in germany. Butchers bring their pork to the inspector’s office. From a newspaper of
1881. Granger Collection, New York.”
Source: Campbell, W. C. (1983). Trichinella and Trichinosis. New York: Plenum Press.
-1867:
*Friedrich Küchenmeister’s Ueber die Nothwendigkeit und allgemeine Durchführung
einer mikroskopischen Fleischbeschau (About the Need for and General Implementation
of Microscopic Meat Inspection) is published. ³
-1879-1888:
*Many European countries ban the importation of pork from the U.S. because
trichinoscopy of slaughtered pig was not practice in the U.S. ³
-1890:
*President Harrison “approve[s] a bill for the introduction of trichinoscopy of export
pork. This bill did not protect U.S. citizens consuming pork.” ³
-1970:
*“The incidence of Trichinella in swine in the U.S. in 1970 was higher than in Germany
in 1870…” . ³
-2000:
* National Trichinae Certification Program (Pilot) is established in the U.S.
Clinical Presentation:
There are two main phases for the infection: enteral (affecting the intestines) and
parenteral (outside the intestines).6The symptoms vary depending on the phase, amount of
6
encysted larvae ingested, age, gender, and host immunity. 6 An individual’s experience with
symptoms can vary from having no symptoms to having symptoms that are “moderately
severe.”5 Symptoms also vary during the parenteral phase but eosinophilia (a high number of
eosinophils) and fever are the most common symptoms. 5 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. 1 Below is a table with the most common
symptoms and signs observed and the time period and phase in which they are usually observed.
Symptoms and Signs of Trichinosis
(Table based on Capo & Despommier 1996)
Weeks after
Ingestion
Phase
% of people who
develop
symptom/sign
Sign/Symptom
1 week
enteral
upper abdominal pain
--
1 week
enteral
diarrhea
--
1 week
enteral
vomiting
--
1 week
enteral
malaise
--
1 week
enteral
fever
30-90%
2 weeks
parenteral
myalgia (muscle pain)
30-100%
2 weeks
parenteral
paralysis state
10-35%
2 weeks
parenteral
perioribtal edema (accumulation of fluid around
the eye)
15-90%
2 weeks
parenteral
facial edema (accumulation of fluid around the
face)
15-90%
2 weeks
parenteral
headache
75%
2 weeks
parenteral
skin rash
15-65%
2 weeks
parenteral
difficulty swallowing
35%
2 weeks
parenteral
conjuctivitis
55%
2 weeks
parenteral
insomnia
--
2 weeks
parenteral
weight loss
--
2 weeks
parenteral
peripheral nerve sensation
--
2 weeks
parenteral
hot flashes
--
2 weeks
parenteral
hoarseness
5-20%
2 weeks
parenteral
bronchitis
5-40%
2 weeks
parenteral
splinter hemorrhages of the nail beds or retinae
--
2 weeks
parenteral
visual disturbances
--
7
2 weeks
parenteral
paralysis of ocular muscle
--
3 weeks (+)
parenteral
vertigo
--
3 weeks (+)
parenteral
deafness
--
3 weeks (+)
parenteral
aphasia
--
3 weeks (+)
parenteral
convulsions
--
Transmission
Wild carnivores and omnivores can become infected with Trichinella spp. when they eat
carrion.³ Humans become infected if they eat raw or undercooked meat from these infected
animals. ³ Vertical transmission from mother to fetus has been reported. 6 Trichinella spp. are
notorious for being able to infect a broad scope of animals including mammals, reptiles, and
birds. ³ Certain species of Trichinella can only infect a specific group of animals. For instance, T.
pseudospiralis is the only species that can infect birds. 4 Only three Trichinella species are
known to cause Trichinosis in humans: T. spiralis, T. nativa, and T. britovi. 4
Reservoir:
Trichinella spp. can infect mammals, birds, and reptiles; they affect carnivores,
omnivores, and even marine mammals. 1 Swine are the best known reservoir and the main
reservoir for T. spiralis. However, the main reservoirs vary across countries, for instance in
Europe the red fox (Vulpes vulpes) tends to be the main reservoir. 1 However, the raccoon dog
(Nyctereutes procyonoides) is the main reservoir in Finland and horsemeat tends to be a common
source of infection. 1 T. nativa can be found in walruses and polar bears while T. britovi can
infect foxes, dogs, cats, and raccoons . 4 The chart below indicates the animals that serve as a
source of infection for humans and the table below shows a more detailed list of the reservoirs
for Trichinella.
Source: Capo, Virginia & Despommier, Dickson D. (1996). Clinical Aspects of Infection with Trichinella spp. Clinical
Microbiology Reviews, 9, 47-54.
8
Distribution and Reservoirs of Trichinella spp. (Table based on Pozio & Murrell 2006)
Species
Common Reservoirs
Geographic Distribution
T. spiralis
domestic pigs, wild boars , horses, and
synathroopic rats
Europe, Egypt, China, Russia,
Southeast Asia, Argentina, Chile,
Mexico, New Zealand, U.S.
T.nativa
wildlife of arctic and subarctic
including bears and walruses
Holarctic Region (Canada,
Greenland, Alaska & New
Hampshire, Byelorussia, Estonia,
Finland, Latvia, Lithuania,
Norway, Russia, Sweden, Siberia,
China, Kazakhstan, Kyrgyzstan,
and Tajikistan)
T. britovi
mustelids, viverridae, red foxes, jackals,
wolves, brown bears
Palearctic region and Northern and
Western Africa
T. murrelli
bob cat, black bear, coyote, raccoon, red
fox, dog, cat, and horse
North America
T. nelsoni
hyena, jackal, bat-eared fox, domestic
dog, lion, cheetah, bush pig and
warthog
Eastern Africa (Kenya to South
Africa)
T. pseudospiralis
birds, fox, Indian mole rat, and
marsupials, wild boars
Palearctic, Nearctic, and Australia
T. papuae
sows, wild pigs, and crocodile
Papua New Guinea
T. zimbabwensis
crocodile and monitor lizard
Zimbabwe, Mozambique, Ethiopia
9
Vector:
There are no known vectors for Trichinella spp.
Incubation Period
The incubation period is usually10 -20 days but can range from 1week -10weeks. 1 The
duration period is a function of the number of larvae consumed. 6
Morphology³

adult males:
-colorless
-length: 1.0-1.5mm
-width: 0.03 mm
-smooth cuticle and exhibits pseudosegmentation
-pair of flattened copulatory appendages and accessory papillae
-copulatory bell
“Trichinella spirals male posterior.”
Source:Dept. of Zoology, University of Manitoba (2000). “Trichinella spiralis.” Retrieved January 25, from
http://www.umanitoba.ca/faculties/science/zoology/faculty/dick/z346/trichhome.html

adult females:
-colorless
-length: 2.5-3.5mm
-width: 0.05mm
- smooth cuticle and exhibits pseudosegmentation
-no copulatory appendages and vulva is visible
“Adult female of Trichinella spiralis.”
Source: Upton, S.J. “Adult female of
Trichinella spiralis.” Online image. Kansas
State University: Biology 625 Animal
Parasitology. Retrived February 15, 2009,
http://www.k-state.edu/parasitology/
625tutorials/ Trichinella01.html
“Trichinella spirals female posterior.”
Source: Dept. of Zoology, University of Manitoba (2000). “Trichinella spiralis.” Retrieved January 25, from
http://www.umanitoba.ca/faculties/science/zoology/faculty/dick/z346/trichhome.htm
10

infective first stage larva:
-salmon colored
-length: 1.0mm
-width: 0.03mm
-smooth cuticle and exhibits pseudosegmentation
-no hypodermal glands
-rounded ends, no appendages or projections
“Trichinella larvae, freed from their cysts in
the muscle tissue of an Alaskan bear.”
Centers for Disease Control and Prevention
(2008). “Image Library: Trichinellosis.”
Retrieved Retrieved February 22, 2009,
fromhttp://www.dpd.cdc.gov/DPDX/HTML
/ Frames/S-Z/Trichinellosis
/body_Trichinellosis_mic1.htm
Epidemiology:
Global Perspective: Trichinella spp. are found worldwide. Approximately 11 million
individuals are infected with Trichinella; Trichinella spiralis is the species responsible for most
of these infections. 1 In 1993, there were 1,975 cases of trichinosis reported in Europe. 1
China reports approximately 10,000 cases every year and is therefore the country with the
highest numbers of reported cases. 1 In China, between 1964-1998 over 20,000 people were
infected with Trichinosis and over 200 people died.7 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.8 There is also a high incidence of Trichinosis among refugees from Southeast Asia. 3
United States: 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 to1out every 25. 5 Between 1997-2001 there was an average of
12 cases per year.9
Source: Roy, S. L, lopez, a. S., Schantz, P.M., (2003).
Trichinellosis Surveillance-United States, 1997-2001.
Mortality and Morbidity Weekly Report. Center for
Diseases Control and Prevention. 52(SS06), 1-8.
11
Source: Gideon (1994). Gideon Informatics Inc. Retrieved January 31, 2009, from
http://web.gideononline.com/web/epidemiology/?gdn_form=dmlldz1HZW5lcmFsJmRpc2Vhc2U9MTI0MTA=
Life Cycle of Trichinella
Trichinella spp. is transmitted through two cycles: sylvatic and domestic. In the sylvatic
cycle Trichinella spp. is transmitted through predator-prey interactions or scavengers eating
carrion.³ Predators and scavengers include foxes, bears, rats, and walruses.³ Humans can become
a dead end host in this cycle by consuming infected game meat.³
“Sylvatic Cycle.”
Source: Campbell, W. C. (1983). Trichinella and Trichinosis.
New York: Plenum Press.
12
The domestic cycle involves humans, pigs, and rodents. Pigs become infected when they
eat raw infected meat from 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. 6 The larvae then
migrate to the small intestine and invade the columnar epithelial cells; the process of how the
columnar cells are invaded is unknown.³ In the small intestine, the larvae molt four times before
becoming adults. 6 Thirty to 34 hours after the cysts were originally ingested, the adults mate
and within five days to produce larvae. 6 The worms can only reproduce for a limited period of
time because the immune system will eventually expel them from the small intestine. 6 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 mouthpart
called “sylet” to pass through the intestinal mucosa and enter the lymphatic vessels and then
enter the bloodstream.³ 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. ³ 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. 2 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. 2 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. 2 Because humans typically do not get eaten
by other animals “humans are a parasitic dead end.” 2
Source: Centers for Disease Control and Prevention (2008). “Image Library: Trichinellosis.” Retrieved January 26,
2009, http://www.dpd.cdc.gov/dpdx/HTML/ImageLibrary/SZ/Trichinellosis/ body_Trichinellosis_il1.htm
13
“Trichinella sp. larvae encysted in muscle cell.”
Source: Centers for Disease Control and Prevention (2008). “Image Library: Trichinellosis.” Retrieved February 22,
2009, http://www.dpd.cdc.gov/dpdx/HTML/ImageLibrary/SZ/Trichinellosis/ body_Trichinellosis_il1.htm
Diagnostic Tests
Serological (blood) tests and skeletal muscle biopsy (2-4mm³) are the two main ways of
diagnosing Trichinosis. 1 Eosinophilia is usually the earliest indicator of trichinosis. 1 Another
indicator of being infected is a high level of muscle enzymes like creatinine phosphokinase. 1
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). 6
“Trichinella spiralis larvae in peripheral blood.”
Source: Centers for Disease Control and Prevention (2008). “Image Library: Trichinellosis.” Retrieved Retrieved
February 22, 2009, from http://www.dpd.cdc.gov/DPDX/HTML/Frames/SZ/Trichinellosis/body_Trichinellosis_mic1.htm
Management and Treatment
Corticosteroids can be administered but doctors have to keep in mind that corticosteroids
suppress the immune system and thus can worsen the intestinal phase. 5 Mebendazole (200-400
mg three times a day for three days) or Albendazole (400 mg twice a day for 8-14 days) are used
to treat trichinosis. 5 These drugs should not be given to pregnant women. 6 Mebendazole
interferes with the parasites microtubule assemblage. This drug does not have severe side effects
14
but “mild nausea, vomiting, diarrhea, and abdominal pain have been reported infrequently.”11
Rare side effects, usually with high-dose therapy, are hypersensitivity reactions (rash, urticaria),
agranulocytosis, alopecia, and elevation of liver enzymes. 11 Prednisolone (20-60 mg per day for
the first few days) can be given to ease the side effects of inflammation. 5 Albendazole also
inhibits microtubule formation and has “larvicidal effects.” 11Albendazole 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.”11
Source of pictures: Rosenthal, P. J. (10th Ed.) (2007), Basic & Clinical Pharmacology, “Chapter 54. Clinical
Pharmacology of the Anthelmintic Drugs.” The McGraw-Hill Companies, Inc, Retrieved February 19, 2009
http://www.accessmedicine.com/content.aspx?aID=2511514
Public Health and Prevention Strategies/Vaccines
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.12 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 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”.13 Researchers trying to develop a vaccine for
Trichinella have tried to using either “larval extracts, excretory-secretory antigen, DNA vaccine,
or recombinant antigen protein.” 13
The two most important ways of preventing Trichinosis are through legislative measures
concerning meat production and increasing public awareness of properly cooking pork and game
meat. 1 The Centers for Disease Control and Prevention (CDC) has several recommendations for
preventing infection including freezing pork at low temperatures, fully cooking pork and wild
game meat, and not feeding pigs raw meat.14 For more information please visit the following
website: http://www.cdc.gov/ncidod/dpd/parasites/trichinosis/factsht_trichinosis.htm
The United States Department of Agriculture (USDA) and Animal and Plant Health
Inspection Service (APHIS) are responsible for the regulations concerning the importation of
15
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.15 The CDC reports that 0.013% of U.S. swine is infected with
Trichinella. 15
Useful web links
*For basic information about Trichinosis visit:
http://www.cdc.gov/ncidod/dpd/parasites/trichinosis/factsht_trichinosis.htm
*For more information about the National Trichinae Certification Program visit:
http://www.aphis.usda.gov/vs/trichinae/
*For more detailed information about the biology of Trichinosis visit:
http://www.trichinella.org/index_synopsis.htm
16
References
1
Gideon (1994). Gideon Informatics Inc. Retrieved January 31, 2009, from
http://web.gideononline.com/web/epidemiology/?gdn_form=dmlldz1HZW5lcmFsJmRpc2Vhc2
U9MTI0MTA=
2
Comes, C. The art of being a parasite. (2005). Chicago, IL: The University of Chicago Press.
3
Campbell, W. C. (1983). Trichinella and Trichinosis. New York: Plenum Press.
4
Pozio, E., & Murrell, D. K. (2006). Systematics and Epidemiology of Trichinella. Advances in
Parasitology, 63, 368-439.
John, D. T., & Petri Jr., W. A. (9th Ed.) (2006). Markell and Voge’s Medical Parasitology. St.
Louis, MI: Elsevier Inc.
5
6
Capo, V. & Despommier, D. D. (1996). Clinical Aspects of Infection with Trichinella spp.
Clinical Microbiology Reviews, 9, 47-54.
7
Gu, Y., Li, J., Zhu, X., Yang, J., Li, Q., Liu, Z., Yu, S. & Li, Y. (2008). Trichinella spiralis:
Characterization of phage-displayed specific epitopes and their protective immunity in BALB/c
mice. Experimental Parasitology, 118, 66-74.
8
Blaga, R., Durand, B., Antoniu, S., Gherman, C., Cretu, C.M., Cozma, V., Boireau, P. (2007).
A dramatic increase in the incidence of Human trichinellosis in Romania over the past 25 years:
impact of political changes and regional food habits. American Journal of Tropical Medicine and
Hygiene, 983–986.
9
Roy, S. L, lopez, a. S., Schantz, P.M., (2003). Trichinellosis Surveillance-United States, 19972001. Mortality and Morbidity Weekly Report. Center for Diseases Control and Prevention.
52(SS06), 1-8.
10
Brown, T. R. (1898). Studies on trichinosis, with especial reference to the increase of the
eosinophilic cells in the blood and muscle, the origin of these cells and their diagnostic
importance. Clinical Laboratory of the Johns Hopkins University and Hospital.
17
Rosenthal, P. J. (10th Ed.) (2007), Basic & Clinical Pharmacology, “Chapter 54. Clinical
Pharmacology of the Anthelmintic Drugs.” The McGraw-Hill Companies, Inc, Retrieved
February 19, 2009 http://www.accessmedicine.com/content.aspx?aID=2511514
11
12
Dea-Ayuela, M. A., Iniguz, S.R., Fernandez, F.B. (2006). Vaccination of mice against
intestinal Trichinella spiralis infections by oral administration of antigens microencapsulated
in methacrilic acid copolymers. Vaccine, 24, 2772–2780.
13
Gu, Y., Li, J., Zhu, X., Yang, J., Li, Q., Liu, Z., Yu, S., Li, Y. (2008). Trichinella spiralis:
Characterization of phage-displayed specific epitopes and their protective immunity in BALB/c
mice. Experimental Parasitology, 118, 66–74.
14
Centers for Disease Control and Prevention (2008). Trichinellosis Factsheet. Retrieved
January 27, 2009, http://www.cdc.gov/ncidod/dpd/parasites/trichinosis/factsht_trichinosis.htm
15
APHIS. USDA Animal and Plant Health Inspection Service APHIS - Veterinary Services.
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