Cysticercosis
Introduction
Cysticercosis or
Cysticercosis is an infection caused by the pork tapeworm, Taenia solium.
Figure.
Tapeworm.
http://mtherald.com/images/tapeworm.jpg
Infection occurs when the tapeworm larvae enter human body
and form cysticerci (cysts)
. Figure.
Cysticercus
http://www.gate.net/~mcorriss/PV1a.JPG
The presence of
cysticercerci within the human central nervous system (CNS) is called neurocysticercosis.
(1)Neurocysticercosis, is the most common parasitic infection of the brain
worldwide. (2)(3)
Figure.
Neurocysticercosis in the parietal lobe.
http://www-lab.biomedicas.unam.mx/cistimex/Galeria/FIGURA%2021.jpg
Agent
(classification and taxonomy)
The main cause of human
cysticercosis is the larval form of Taenia solium (pork tapeworm).
T.solium is a platyhelminth of the
cestoidean class, the cyclophyllidea order and the taeniidae family. The common
larval stage of T.solium was also known as Cysticercus cellulosae.
Synonyms – NONE
History of Discovery
The earliest refernce to tapeworms were found in the works
of ancient Egyptians that date back to almost 2000 BC. (4) The description of
measled pork in the History of Animals written by Aristotle (384-322 BC) showed
that the infection of pork with tapeworm was known to ancient Greeks as that
time (4). Recent examination of evolutionary histories of hosts and paratistes
and DNA evidence show that over 10,000 years ago, ancestors of modern humans in
Figure.
ancestor of modern humans
http://occultopedia.com/images_/hominid.jpg
Cysticercosis was
described by Johannes Udalric Rumler in 1555; however, the connection between
tapeworms and cysticercosis had not been recognized at that time. (5) Around
1850, Kuchenmeister fed pig meat containing cysticerci of T.solium to humans awaiting execution in a prison, and after they
had been executed, he recovered the developing and adult tapeworms in their
intestines. (4)(5)(6) By the middle of the 19th century, it was
established that cysticercosis was caused by the ingestion of the eggs of T.solium. (6)
Clinical Presentation in
Humans
1. Cysticercosis in muscles
Cysticerci can develop in any voluntary muscle in humans.
(2) Invasion of muscle by cysticerci can cause myositis, with fever and eosinophilia,
and muscular pseudohypertrophy, which initiate with muscle swelling and later
progress to atrophy and fibrosis. (2) In most cases, it is asymptotic since the
cysticerci die and become calcified.
Figure.
Calcification in muscles due to cysticercosis.
http://www.rad.washington.edu/staticpix/mskbook/CysticercosisKnees.jpg
2. Neurocysticercosis
Neurocysticercosis present in many
forms, depending on the localization of the cysts and disease activity.
(2) 60% of the patients with cysticerci
are found to have them in the brain. (2) As the stage of cysticerci reflect the
sign, symptoms and treatment of neurocysticercosis, it is important to
understand the natural history of CNS cysts. (3) In the case of cysticerci in the brain
parenchyma, four major stages have been classified: (3)
In stage 1, immature cysts
appear within 1-4 weeks during which the oncosphere lodges to the brain and
finally expands into a cyst. It is mainly asymptomatic, although flu-like
illness, rare seizures, rare increased intracranial pressure from massive
infestation has been recorded. (3)
In stage 2, the cysticerci
become mature and viable about 2 months after egg ingestion. The cyst possess a
protoscolex with the cyst bladder and causes no or minimal surrounding
inflammation or edema. The cysticerci also down-regulates host cellular
immunity. Stage 2 cysts are also asymptomatic, and can persist for more than 10
years. (3)
Figure. CT scan of the brain shows:
multiple cysts in vesicular, some cyst in colloidal stage (stage 3) surrounded
by perilesional edema, and calcified lesions on both cerebral hemisphere.
http://biomed.uninet.edu/2004/n3/foyaca-n/fig4.gif
Stage 3 possess colloid or
degenerating cysts with thick cystic fluid, thickened capsule, and appear two
to 10+ years after the cyst becomes mature.
The cyst no longer prevents a host immune response and its antigens leak
from the bladder wall. The intense inflammation is provoked around the
degenerating cyst. Most patients bearing stage 3 develop clinical signs and
symptoms such as seizures, occasional focal neurological signs, headaches,
nausea, vomiting, lethargy from increased intracranial pressure and altered
mental status. (3)
Figure. Parenchymal cysticercosis:
the uneven development of cysticerci as vesicular stage (stage 2) (arrow) and
colloidal stage (stage 3) (arrow head) and other granular colloid phase (star).
http://www-lab.biomedicas.unam.mx/cistimex/Galeria/Cap2_Page_03_Image_0002.jpg
At stage 4, the cyst is calcified. The surrounding
inflammation drops since the dead cyst no longer produces foreign antigens.
Common clinical features includes persistent non-provoked seizures although
most of the patients are asymptomatic. (3)
In meningeal cysticercosi,
cysticerci often do not develop into typical cysts, and become racemose lacking
a scolex and becoming lobes in thin-walled bladders. (3) These cysts increase
and slowly leak their antigen
into the subarachnoid CSF producing meningitis and can further develops into arachnoiditis,
which may lead to obstructive hydrocephalus, cranial nerve involvement,
intracranial hypertension, arterial thrombosis and stroke. (2)(3)
In intraventricular
Cysticercosis, the cyst occurs in the lateral, third or fourth ventricles which
may be asymptomatic or if they block the flow of CSF, they may cause increased
intracranial pressure. (3)
Figure. MRI scan of Ventricular Cyst with Scolex http://www-lab.biomedicas.unam.mx/cistimex/Galeria/Cap2_Page_27_Image_0001.jpg)
3. Ophthalmic
Cysticercosis
In some cases, cysticerci may be found in the globe,
subconjunctiva, extraocular muscles, and subconjunctiva (2)(3). Depending on the location, they may cause
visual difficulties that fluctuate with eye position, retinal edema,
hemorrphage, a decreased vision or even a visual loss (2)(3).
Figure. Right eye showing smooth,
horizontally oval subconjunctival swelling. http://www.bhj.org/journal/2002_4404_oct/images/fig1_693.jpg
4.
Subcutaneous Cysticercosis
Subcutaneous
cysts are in the form of firm, mobile nodules, occurring mainly on the trunk
and extremities (8). Patients with subcutaneous nodules sometimes feel painful
(8).
Figure. Multiple subcutaneous
nodules on the chest wall and calcified lesions on chest X-ray.
http://biomed.uninet.edu/2004/n3/foyaca-n/fig1.gif
Transmission
Humans can
be transmitted by ingesting the eggs or larvae from eating undercooked pork
that contains viable cysticercosis larvae or from fecally contaminated food or
water. (1-3) The adult tapeworm develops in humans after the ingestion of
infected meat; however cysticercosis occurs after the ingestion of eggs, either
from external sources or from their own feces (2).
Figure. Pig heart with vesicular cysticerci.
http://www-lab.biomedicas.unam.mx/cistimex/Galeria/Cap4_Page_08_Image_0002.jpg
Pigs get infected with cysticerci when they ingest human
feces.
Figure. Pig eating feces.
http://www-lab.biomedicas.unam.mx/cistimex/Galeria/Cap4_Page_03_Image_0001.jpg
Reservoir
Humans and
Pigs are reservoirs.
Vector
None
Incubation Period
Months to years(10+ years)
Morphology
T.solium worms may reach a length of
several meters (2). The scolex has four suckers , and a double crown of
prominent hooks, which attach to the intestinal mucosa. (2)
Figure.
Tapeworms
http://biology.unm.edu/ccouncil/Biology_203/Images/SimpleAnimals/tapeworm.jpg
Figure.
Scolex found in the electron microscope.
http://www-lab.biomedicas.unam.mx/cistimex/Galeria/Cap1_Page_05_Image_0001-1.jpg
Taenia solium eggs are spherical and
30-40 nm in diameter. (3)
Figure. T.solium egg in the electron scanning microscope.
http://www-lab.biomedicas.unam.mx/cistimex/Galeria/Cap1_page09-2.jpg
The cysticercus larva completes development in about 2
months. (2)It is semitransparent, opalescent white, and elongate oval in shape
and may reach a length of 0.6 to 1.8 cm (2).
Figure.
Cysticercus
http://sunsite.ualberta.ca/Projects/Bio-DiTRL/images/med_jpeg/m18560101.jpeg
Life Cycle
Figure.
Life cycle of cysticercosis
http://www.dpd.cdc.gov/dpdx/images/ParasiteImages/A-F/Cysticercosis/Cysticercosis_LifeCycle.gif
As seen from the diagram, the life cycle involves humans as a definite host and pigs as an intermediate host. Pigs ingest contaminated food or water that contains eggs or proglottids from human’s feces. The ova develop into cysticercus in pig muscles. Human becomes infected when they ingest raw or undercooked “measly pork” that contains viable cysticercus. Upon reaching the small intestine, the scolex attaches to the intestinal wall and continue to grow a chain of proglottids. T.solium releases three to six proglottids/day, bearing 30,000-70,000 eggs per proglottids into the intestine. (3) Nearly 250,000 eggs are passed daily into the human feces and to the environment and the cycle continue (3).
Infection with cysticercus occur after humans consume the ova through self-infection via the fecal-oral route or the ova from exogenous sources. (2) Humans, in this case, are intermediate hosts (3). The ova are digested in the stomach and release oncosphere which penetrate intestinal wall and reach the bloodstream (1). These oncospheres develop into cysticerci in any organ but common in brain, subcutaneous tissue or eyes (2)(3).
Diagnostic Tests
The traditional method of demonstrating T.solium eggs in stool samples diagnose
only taeniasis (1). Though the presence
of T.solium eggs or proglottids in
the feces does not necessary mean the infection with cysticercus, those
patients should be evaluated serologically since autoinfection via fecal-oral
route, can potentially result in cysticercosis (1).
In CDC’s immunoblot assay,
cysticercosis-specific antibodies can react with structural glycoprotein
antigens from the larval cysts of T.solium
(1). Therefore, the serum samples from patients with other microbial infections
do not react with any of the T.solium
derived antigens. The positions of the seven diagnostic glycoproteins are
marked and selected based on how fast they can move in SDS-PAGE. The test is so far 100% specific and has
higher sensitivity than any other immunoassay systems.
Figure.
Typical antibody reactions in CDC’s immunoblot for cysticercosis.
http://www.dpd.cdc.gov/dpdx/IMAGES/ParasiteImages/A-F/Cysticercosis/CysticerWB.JPG
Neuroimaging
with CT or MRI is the most useful method to diagnose neurocysticercosis (3). CT
scan shows both calcified and uncalcified cysts, as well as distinguishing
active and inactive cysts (2). MRI can detect intraventricular cysts while CT
scan cannot (3).
Management and
Therapy
Treatment includes medical
drugs such as antihelminthic drugs and corticosteroids or surgical removal of the cyst. Surgical treatment includes
direct excision of ventricular cysts, shunting procedures, and removal of cysts
via endoscopy (2)(3). Albendazole is preferable
over praziquantel due to its lower cost and corticosteroids and anticonvulsants
do not reduce CSF and brain drug levels (3). Moreover, the results from
meta-analysis study have shown that
albendazole is more effective than praziquantel in terms of clinically
important outcomes in patients with neurocysticercosis (9)
In the case of brain
parenchymal cysticercosis, treatment depends on the stage of cyst development.
In immature cyst stage (stage 1), high-dose corticosteroids are administered to
reduce the edema but antihelminth drugs have been found to be harmful (3). Vesicular or viable cysts (stage 2) are often
asymptomatic, and usually are not treated with antihelminth drugs, while
surgical removal of the cyst, along with albendazole is indicated in the
colloid cyst stage (stage 3) (3). No antihelminthic treatment is administered
in dead calcified cysts stage (stage 4) (3).
In the case of cysts in
globe, surgical cyst removal is necessary, while antihelminth drug with
steroids alone might be sufficient to treat cysts outside globe (3). Treatment
recommendations for subcutaneous cysticercosis includes surgery, praziquantel
and albendazole (8).
Epidemiology
Cysticercosis
is highly endemic in Central and South America, and some parts of Africa and
Public Health
and Prevention Stategies
Cysticercosis is considered as “tools-ready disease” according to WHO (12).
International Task Force for Disease Eradication in 1992 reported that
cysticercosis is potentially eradicable (13). It is feasible because there are
no animal reservoirs besides humans and pigs and T.solium. The only source of
T.solium infection for pigs is from
humans, a definite host (11). Theoretically, breaking the life cycle seems easy
by doing Figure. Life cycle of cysticercosis (http://www.dpd.cdc.gov/dpdx/images/ParasiteImages/A-F/Cysticercosis/Cysticercosis_LifeCycle.gif)
intervention strategies from various stages in the life
cycle (11).
For example,
(a)
Massive
chemotherapy treatment of infected humans, improving sanitation and education
humans are major ways to discontinue the cycle at step 1, in which eggs from
human feces are transmitted to other humans and/or pigs.
(b)
Cooking
of pork or freezing them and inspecting meat are effective means to cease the
life cycle at step 3.
(c)
The
management of pigs by treating them or vaccinating them is another possibility
to intervene step 4 of the life cycle.
Intervention by concurrent treatment of humans and pigs
The
intervention strategies to eradicate cysticercosis includes surveillance of
pigs in foci of transmission and massive chemotherapy treatment of humans (13).
In reality, control of T.solium by a
single intervention, for instance, by treating only human population will not
work because the existing infected pigs can still carry on the cycle (14). The
proposed strategy for eradication is to do multilateral intervention by
treating both human and porcine populations (14). It is feasible because
treatment pigs with oxfendazole have been shown to be effective and once
treated, they are protected from further infections for at least 3 months (15).
Limitations
Even
with the concurrent treatment of humans and pigs, the complete eliminate is
hard to achieve. In one study conducted
in 12 villages in Peru, both humans and porcine are treated with praziquantel
and oxfendazole, with the coverage of more than 75% in humans and 90% in pigs
(16) The result shows a decreased in prevalence and incidence in the
intervention area; however the effect did not complete eliminate T.solium. The possible reason includes
the incomplete coverage and re-infection. (17) Even though T.solium could be eliminated through mass treatment of human and
porcine population, it is not sustainable (14).
Moreover, both tapeworm carriers of humans and pigs tend to spread the
disease from endemic to non-endemic areas resulting in periodic outbreaks of
cysticercosis or outbreaks in new areas (14)(18)(19).
Vaccine against porcine cysticercosis
http://blogs.unimelb.edu.au/musse/files/2008/11/marshall-lightower_blog.JPG
Given the fact that pigs are part of
a life cycle, vaccination of pigs is another feasible intervention to eliminate
cysticercosis. Research studies have been focusing on vaccine against cestode
parasites, since many immune cell types are found to be capable of destroying cysticercus (20). Many vaccine candidates are extracted from
antigens of different cestodes such as T.solium,
T.crassiceps, T.saginata, T.ovis and target at oncospheres and/or
cysticerci (20-23). In 1983, Molinari et.al reported the first vaccine
candidate against porcine cysticercosis using antigen from cysticercus cellulosae drawn out from naturally infected (23). Recently, vaccines extracted from genetically
engineered 45W-4B antigens have been successfully tested to pigs in an
experimental condition. (22)This type of vaccine can protect against
cysticercosis in both Chinese and Mexican type of T.solium. However, it has not been tested in endemic field
conditions, which is important because the realistic condition in the field
differ greatly from experimental condition, and this can result in a great
difference in the chances of infection and immune reaction (20).
The S3PVAC Vaccine
The
vaccine constituted by 3 peptide synthetically produced (S3Pvac) has proven its
efficacy in natural conditions of transmission (24). The S3PVAC vaccine so far,
can be considered as the best vaccine candidate to be used in endemic areas
such as
Figure.
Three peptides present in different stages of T.solium
(http://www-lab.biomedicas.unam.mx/cistimex/Galeria/vacunas.jpg)
Non-infected
pigs from rural villages in
Limitations of vaccines
Even though vaccines have been
successfully generated, the feasibility of its production and usage in rural
free ranging pigs still remains a challenge. If a vaccine is to be injected,
the burden of work and the cost of vaccine administration to pigs will remain
high and unrealistic (20). The incentives of using vaccines by pig owners will
decrease if the vaccine administration to pigs takes time by injecting every
single pig in their livestock. An oral
vaccine is proposed to be more effective in this case as it can be easily
delivered to the pigs with the food, though no one has ever achieved it yet
(20).
Other types of interventions and Limitations
Cysticercosis can also be prevented
by routine inspection of meat and condemnation of measly meat by the local
government (28). However, in areas where food is scare, cyst-infected meat
might be considered as wasted since pork can provide high quality protein (29).
At times, infected pigs are consumed within the locality or sold at low prices
to traffickers who take the uninspected pigs at urban areas for sale. (30) 
Figure.
http://www-lab.biomedicas.unam.mx/cistimex/Galeria/Cap4_Page_22_Image_0001.jpg
Giving
health education about cysticercosis is a good strategy to change human’s
behavior. However, education does not result in dramatic changes in behavior,
since other social and economic factors also play a role (14).
Current
efforts to combat cysticercosis
Center for Disease Control (CDC) gives
support and collaboration in research and control activities through formal
designation of the Division of Parasitic Diseases (NCID, CDC) as WHO/CDC
Collaborating Center for Cysticercosis and Taeniasis (31). Moreover, the
cysticercosis working group in Europe works in collaboration with WHO/FAO
Collaborating Center for Parasitic Zoonoses in
Useful links
·
http://www.cdc.gov/ncidod/dpd/parasites/cysticercosis/default.htm
·
http://www.cdc.gov/mmwr/preview/mmwrhtml/00017648.htm
·
http://www.dpd.cdc.gov/dpdx/HTML/Cysticercosis.htm
http://www-lab.biomedicas.unam.mx/cistimex/s1.html#capitulo6
http://www.who.int/zoonoses/diseases/taeniasis/en/index.html
References
(1) http://www.cdc.gov/ncidod/dpd/parasites/cysticercosis/factsht_cysticercosis.htm
(2)
Markell EK, John DT, Krotoski WA. Medical
Parasitology Eighth Edition.
(3)
(4)
(5)
Cox, F.E.G. “History of Human Parasitology” Clinical
Microbiology Reviews. October
2002. 15(4) 595-612.
(6)
Küchenmeister, F. The Cysticercus cellulosus transformed within the
organism of man into Taenia solium. Lancet 1861 i:39.
(7)
http://www.ars.usda.gov/is/AR/archive/may01/worms0501.htm
(8)
Wortman PD. “Subcutaneous cysticercosis” J Am
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(9) Dimitrios K. Matthaiou,
Georgios Panos, Eleni S. Adamidi,Matthew E. Falagas “Albendazole versus
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(12) WHO, “Global Plan to
Combat Neglected Tropical Diseases 2008-2015. World Health Organization 2007.
(13) CDC, International Task
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(16) Garcia, H.H.,
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(21) Flisser A, Gauci CG, Zoli A, Martinez-Ocana J, Garza-Rodriguez A, Dminguez-Alpizar J L, Maravilla P, Canul RP, Avila G, Aguilar-Vega L, Kyngdon C Geerts S, Lightowlers MW. 2004 “Induction of Protection against Porcine Cysticercosis by Vaccination with Recombinant Oncosphere Antigens” Infect Immun. 72(9): 5292-5297.
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(23) Molinari J. L, Meza R, Suarez B, Palacios S, Tato P, Retana A. 1983 “Taenia solium : immunity in hogs to the Cysticercus.”Exp. Parasitol 55: 340-57.
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(28)http://www.cwgesa.org/CWGESA%20Action%20Plan/CWGESA%20Action%20Plan.aspx
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