Parasitology - Cestodes

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Cestodes (tapeworms)

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Tapeworms are obligate parasites in the gut tracts of various vertebrate hosts. Tapeworms are flat, segmented worms, composed of a head (scolex), and a series of segments, known as proglottids. Together, all proglottids are referred to as the strobila. The scolex is the point of attachment between the host and the parasite. It may be equipped with suckers, hooks, or grooves for attachment. The scolex contains nerves terminating in ganglia, while the segments contain only nerves. The neck region of the scolex is metabolically active, and is the site in most tapeworms from which new proglottids form.

Taenia saginata (beef tapework)
Taenia solium (pork tapeworm)
Echinococcus granulosus (dog tapeworm)

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Cestodes (tapeworms)

Nutrient acquisition

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Tapeworms do not have a function gut tract. Rather, the segments are enclosed in a special tegument covered by microvilli that actively transport nutrients into its segment.

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Cestodes (tapeworms)

Movement and Nervous system

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Each proglottid has two layers of muscle - longitudinal and transverse - enabling the segment to move. Segments are anatomically independent, but are all connected by a common nervous system emanating from cerebral ganglia located in the scolex.

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Cestodes (tapeworms)

Reproduction

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Mature proglottids possess both male and female sex organs, but self-mating within a segment is unusual. Typically, sperm are transferred between mature proglottids which lie next to each other. Gravid proglottids develop after mating and contain embryonated eggs. The proglottids then detach from the parent organism and exit via host feces. Eggs may remain viable in the external environ for weeks or months. Hatching occurs typically within the small intestine of the intermediate host. The oncosphere then penetrates the gut tract and lodges within the tissues, developing into metacestode. This stage is ingested by the definitive host and transforms to the adult in the lumen of the small intestine.

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Taenia saginata (beef tapeworm)
Taenia solium (pork tapeworm)

Infection

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Lives in the lumen of the upper half of the small intestine.

T. saginata is acquired by eating undercooked or raw beef containing the cysticercus stage, while infection with T. solium is contracted through the ingestion of raw or undercooked pork

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Taenia saginata (beef tapeworm)
Taenia solium (pork tapeworm)

Adult worm

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The adults live in the small intestine. The proglottids containing eggs are passed in the feces. The eggs are released as the segment disintegrates in the soil. When either a cow or pig ingests them, they acquirethe intermediate stage of the infection (cysticercus). Each parasite is specific to its host.

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Taenia saginata (beef tapeworm)

Pathology

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The adult worms typically cause no clinical symptoms

T. saginata occupies a large part of the lumen of the small intestine, but it is flexible and relatively fragile, therefore bowel obstruction does not occur. Adult worms are immunogenic but gut inflammatory responses are minimal.

No diarrhea or weight loss

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Taenia saginata (beef tapeworm)

Diagnosis

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Eggs can be found in feces or on the perianal region (sticky tape test). The eggs of all Taenia spp. look alike, so a definitive diagnosis based on finding them cannot be made. Often, however, a whole proglottid or series of connected proglottids is brought to the diagnostic lab by the patient. PCR or ELISA can also be done.

The two species of Taenia can be distinguished from each other by injecting the gravid proglottids wtih an opaque dye or india ink and counting either row of uterine branches.

T. saginata has 15-30 branches on each side, T. solium has only 7-12 branches

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Taenia saginata (beef tapeworm)


Lifecycle

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Infection begins when the cysticercus is ingested along with raw or undercooked beef. The cyst enters the small intestine and the wall of the cyst is digested away, freeing the worm inside. The parasite then everts its scolex and attaches to the intestinal wall wtih the aid of 4 sucker disks. A mature adult takes 3 months to grow to full length. The developing proglottids extend down the small intestine, sometimes reaching the ileum. All adult tapeworms feed by actively transporting nutrients across their tegumental surface, since they have no digestive tract. Segments mature as they progress towards the terminal end of the worm. Terminal proglottids, gravid with embryonated eggs, may detach from the colony and migrate out the anus where they are deposited on the ground. A cow then ingests the segment where the eggs lying inside the lumen of the uterine branches of the proglottid are freed from teh tapeworm tissue by the cow's digestive enzymes, stimulating the eggs to hatch in the small intestine. The oncosphere (6-hooked larvae) penetrates the intestinal wall, most likely aided by hooks and peptidases that is secretes. The larva enters the blood stream and is passively carried throughout the body. Oncospheres lodge in tissue, especially striated skeletal muscle tissue. There they encyst, and develop to the cysticercus (metacestode). Cysticerci live for several years before calcifying. Taenia saginata eggs will only hatch in stomach of cows, and adult parasites can only be harbored in humans.

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Taenia saginata (beef tapeworm)

Treatment

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Praziquantel

MOA: Interferes with invertebrate Ca2+ ion channels

Causes worm to release its hold

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Taenia saginata (beef tapeworm)

Prevention and Control

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1. Sanitory disposal of feces
2. Prevent cows from coming into contact with human feces - maintain good sanitary practices
3. Freeze and/or cook all beef until well-done
4. Federal meat inspection programs work

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Taenia solium (pork tapeworm)

Lifecycle

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Infection begins when the encapsulated cysticercus is ingested along with raw or undercooked pork. The capsule is digested in the stomach freeing the juvenile parasites. In the small intestine, the parasite then everts its scolex and attaches to the intestinal wall wtih the aid of 4 sucker disks and 2 rows of hooklets. A mature adult takes 3 months to grow to full length. The developing proglottids extend down the small intestine. All adult tapeworms feed by actively transporting nutrients across their tegumental surface, since they have no digestive tract. Segments mature as they progress towards the terminal end of the worm. Terminal proglottids, gravid with embryonated eggs, may detach from the colony and migrate out the anus where they are deposited on the ground. A pig then ingests the segment where the eggs lying inside the lumen of the uterine branches of the proglottid are freed from the tapeworm tissue by the pig's digestive enzymes, stimulating the eggs to hatch in the small intestine. The oncosphere (6-hooked larvae) penetrates the intestinal wall, most likely aided by hooks and peptidases that is secretes. The larva enters the blood stream and is passively carried throughout the body. Oncospheres lodge in tissue, especially striated skeletal muscle tissue. There they encyst, and develop to the cysticercus (metacestode). Cysticerci live for several years before calcifying. Taenia solium eggs can hatch in both pigs and humans, and adult parasites can only be harbored in humans. Thus, humans can auto-infect with the contaminated eggs of their own tapeworm.

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Taenia solium (pork tapeworm)

Prevention and Control

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1. Sanitory disposal of feces
2. Prevent pigs from coming into contact with human feces - maintain good sanitary practices
3. Freeze and/or cook all pork until well-done
4. Federal meat inspection programs work
5. Treat or vaccinate pigs

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Taenia solium (pork tapeworm)

Diagnosis

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1. Find eggs or proglottids in stool
2. Identify species based on proglottid morphology
3. Identify scolex
4. Stool PCR or ELISA

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Taenia solium (pork tapeworm)

Treatment

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Praziquantel
MOA: Interferes with invertebrate Ca2+ ion channels
Causes worm to release its hold

Niclosamide�
- Not absorbed systemically

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Taenia solium (pork tapeworm)

Aberrant lifecycle - Human cysticercosis

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Infection begins by ingesting embryonated eggs. Patents harboring adult worms typically have eggs on their exteriors, thus having plenty of opportunity to acquire cysticerci through autoinfection, as well as contaminate others in their immediate surroundings. When eggs are ingested, the larvae (oncospheres) inside survive the gastric acid of the stomach and enter the small intestine. They are stimulated to hatch, and then they penetrate the intestinal wall and enter the bloodstream. Eventually, the oncospheres could penetrate into one of many tissues and encyst there. The oncosphere rapidly differentiates into a cysticercus (juvenile stage), grows and develops, and creates a space filling lesion within 2-3 months, typically measuring approx 10 mm. Cysticerci achieve maximum growth about 3 weeks after entering a given tissue and then cease growing.

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Taenia solium (pork tapeworm)

Human cysticercosis

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Infection with the cysticercus (i.e. juvenile stage) of the pork tapework, exists in the regions where the following conditions are present:
1) the incidence of T. solium adult infections is high
2) pigs are allowed to roam freely within human habitats
3) improper disposal of human feces is the rule

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Taenia solium (pork tapeworm)

Pathology

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Regular lifecycle : The adult worms typically cause no clinical symptoms. No diarrhea or weight loss

Aberrant lifecycle - Extraneural (subcutaneous and intramuscular) cysticercosis and neurocysticercosis

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Taenia solium (pork tapeworm)

Pathology - Extraneural cysticercosis

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Usually asymptomatic, but patients may notice painless subcutaneous nodules in the arms or chest, or small discrete swellings of particular muscles. After several months, the nodules become swollen and tender, presumably because of the host inflammatory response. Subsequently the nodules disappear. Ultimately the lesions will calcify after death, and can persist for years.

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Taenia solium (pork tapeworm)

Pathology - Neuralcysticercosis

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Neurocysticercosis causes varying signs and symptoms. Cysts modulate host response (interfering with th-2 type protective immune responses), and are immunologically silent for the first 2 years, but when start to degrade, cause cerebral inflammation and seizures. It presents as a space occupying lesion, and may mimic a tumor. Thus seizures, hydrocephalus, epilepsy and focal neurological abnormalities may be presenting signs. Patients living in endemic areas may present with more complex disease such as elevated intracranial pressure, arachnoiditis, meningitis, encephalitis, or hydrocephalus. Opthalmic cysticercosis can also occur, and most typically manifests as intraocular cysts floating freely in the vitreous humor or the subretinal space. Patients complain of seeing shadows. Subsequent development of uveitis, retinitis, or choroidal atrophy can lead to visual loss.

On neuroimaging studies, the inflammation encircles the lesion, giving a "ring-enhancement".

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Neuralcysticercosis

Diagnosis

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MRI or CT scan

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Neuralcysticercosis

Immune response

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Immunomodulation occurs during the life of the parasite. Substances identified:
- Taeniastatin: protease inhibitor
- Paromycin: inhibits complement
- Other proteases: degrade IL-2, immunoglobulins and interferon

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Neuralcysticercosis

Pathogenesis

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Space-occupying lesion
Local Immunologic reaction

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Neuralcysticercosis

Clinical disease

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Vision impairment/blindness
Seizures/death
Obstructive Hydrocephalus/Coma/Death
Focal Neurologic deficits that depend upon location of mass and area affected.

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Cysticercosis

Clinical epidemiology

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• Est. 50 million people with Intestinal Taeniasis, world-wide�
• 20% have cysticercosis; at least half will be symptomatic (Sz)�
• Leading cause of adult-onset seizures worldwide (~40%)

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Cysticercosis

Diagnosis

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Must differentiate between cysticercosis and other
possible lesions (benign cysts, solid tumors, etc.) �
1. Biopsy whenever possible
2. Physical (palpation) and X-ray evidence
3. Enzyme-linked immunoblot serological test, can be as high as 98% sensitive, 100% specific.
4. MRI�

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Cysticercosis

Treatments

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1.Surgical removal of cysticercus when appropriate�
2.Steroids (e.g., dexamethazone) during time of neurological symptoms (suppresses immune response)
3.Anticonvulsants (e.g. Dilantin - Phenytoin)�
4.Anti-emetics if patient has intestinal taeniasis�
5.Antiparasitic antibiotics: Praziquantel or albendazole + steroids + anticonvulsants for multiple or symptomatic cysticerci, or for inoperable cysts - under study)

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Echinococcus granulosus
The Dog tapeworm
Hydatid Disease in Humans�

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Definitive host (adult parasite): Dog
Intermediate host: Sheep, human

Traditional sheep husbandry and framing practices help maintain the cycle in animals and humans. Sheep graze where the dogs defecate, and then dogs eat sheep meet, and cycle is complete.

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Echinococcus granulosus
The Dog tapeworm

Lifecycle

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Echinococcus granulosus adults live in the canine small intestine. Multiple infection is the rule with hundreds to thousands of adult worms occupying the greater portion of the upper half of the small intestine. THe gravid segment (one per adult tapeworm) breaks off and disintegrates in the large bowel, releasing hundreds of infective eggs, which then pass out with the feces. Sheep, as well as other domestic animcals, and humans acquire the larval stage by ingesting the embryonated egg. Each intermediate host species seems to have evolved a separate, genetically definable strain of parasite. The oncosphere hatches in the small intestine, enters the blood stream, and in the vast majority of cases, reaches the liver via the portal circulation. Other organs: brain, lung, kidney. ONce in the tissue, the larva synthesizes a hyaline membrane, and becomes surrounded by it. THis membrane differentiates into an outer, acellular laminate structure, and an inner germinal layer. The inner surface of the germinal layer gives rise to protoscolices (the infectious stage for the definitive host). The hydatid cyst requires several months to years in order to develop, mature and fill with fluid. The fluid is under pressure and the wall can rupture if severely traumatized. The entire cyst can contain millions of protoscolices. The cycle is complete when the dog ingests the sheep meat infected with the hydatid cysts. The hydatid cyst The protoscolex, released from the hydatid cyst, attaches itself to the wall of the small intestine aided by its 4 suckers and row of hooklets. New gravid proglottids are released when the parasite matures.

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Echinococcus granulosus
The Dog tapeworm

Hydatid cyst

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Outer layer of the hydatid cyst is immunologically silent.
Eggs and their oncospheres are immunogenic and can elicit a protecitve immunity.
Hydatid fluid in the cyst is highly immunogenic which can lead to immediate hypersensitivity and anaphylaxis

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Distribution of hydatid cysts

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Liver - 63%
Lungs - 25%
Muscles - 5%
Bone marrow - 3% (usually fatal)
Kidney - 2%
Spleen - 1%
Brain - 1% (usually fatal)

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Hydatid cysts

Pathogenesis and clinical disease

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• When intact, hydatid cysts are immunologically and
often clinically silent, especially in the liver.
• In other organs (e.g., brain, lung, bone marrow), �

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Hydatid cysts

Diagnosis

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A.Direct
1. NO BIOPSY!

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Hydatid cysts

Treatment

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•Surgical, whenever possible

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Hydatid cysts

Prevention and Control

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• Regularly treat all shepherding dogs with niclosamide. This drug kills the adult parasites (by inhibing ATPase).
• Avoid feeding hydatid cyst material (sheep offal) to dogs.�
• Public health education of sheep farmers.