Parasitology CNS Cestoda

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CNS Parasites: 

CNS Parasites Cestoidea

This presentation involves three types of cestodes: 

This presentation involves three types of cestodes Taenia solium Pork tapeworm Echinococcus granulosus Dogs and other canids tapeworm Taenia multiceps Dogs and other canids

What kind of diseases do they cause?: 

What kind of diseases do they cause? T. solium Neurocysticercosis E. granulosus Hydatid disease T. multiceps Coenurosis

What makes these parasites so important to the CNS?: 

What makes these parasites so important to the CNS? Two of the parasites are not supposed to be in humans at all Echinococcus granulosus Taenia multiceps T. solium is a human parasite, but the human ingests an egg, and not a cysticercoid larva The larvae wander around and may, and often do end up in the CNS

A possibly disastrous infection: 

A possibly disastrous infection Parasitic larvae go to places in the human body to wait to be eaten The cysts that they form can cause neurological symptoms in the victim Parasitic larvae in the CNS can kill the host in different ways

Slide6: 

In short, neurocysticercosis, hydatid disease, and coenurosis are the result of parasitic larvae

T. solium: 

T. solium Cysticercosis Involves various muscles in body Neurocysticercosis Same process as above The differecne is the cysticercoid larvae end up in the CNS Usually the brain Spinal cord infection not unknown

What’s supposed to happen: 

What’s supposed to happen Human has tapeworm Passes egg Pig ingests egg Oncosphere emerges, migrates to muscles Grows into a cysticercus Humans eat poorly cooked infected pork Cysticercus develop into a tapeworm

Slide9: 

Human ingests egg Cysticerci go to places most Likely to be eaten

Neurocysticercosis: 

Neurocysticercosis Cosmopolitan – just like the pork tapeworm Endemic wherever both pigs are present and poor hygiene is practiced Virtually unknown in USA, however it is becoming increasingly prevalent with travel and immigration Emergency Rooms and Clinics in New Mexico and Southern California are seeing more of these patients

How Neurocysticercosis is Acquired: 

How Neurocysticercosis is Acquired Blowflies can carry eggs mechanically from feces to uninfected meat Autoreinfection of the host of a mature tapeworm Poor sanitary practices in original host, ingest eggs from tapeworm that they already have From intestine to duodenum Movement of mature proglottid Reverse peristalsis Accidental infection by family member with tapeworm Eggs on surfaces/food that are eaten by other family members

Symptoms of NCC vary: 

Symptoms of NCC vary Location Number Size Of larvae present Symptoms may vague and many cases are only diagnosed at autopsy

Pressure Necrosis May Cause: 

Pressure Necrosis May Cause Severe CNS malfunction Blindness Paralysis Disequilibrium Obstructive hydrocephalus Disorientation Sudden adult-onset epilepsy with no childhood history of epilepsy

Racemose: 

Racemose Aberrant cysticerci Grapelike clusters of cysticerci These larvae form no scolex Cyst wall grows in an irregular, branching and budding fashion Diameter of several centimeters Poor prognosis Doesn’t respond to drugs Must be surgically removed

When cysticerci die: 

When cysticerci die Cysticerci may not cause any problems while they are alive However, an intense inflammatory reaction may arise when the cysticerci die

Reasons for the Symptoms When Cysticerci Die: 

Reasons for the Symptoms When Cysticerci Die Release of antigenic substances released by the dead or dying worm Cessation of their active immunosuppression that: Depletes complement Suppresses lymphocyte activity Reduces activity of eosinophils Has an active cytotoxic effect

Nausea and Vomiting: 

Nausea and Vomiting Intraventricular cysts may block the flow of CSF Intracranial pressure builds and causes persistent headache, papilledema, progressive loss of vision Increased intracranial pressure causes nausea and vomiting too

Diagnosis of NCC: 

Diagnosis of NCC Surgical removal of intracranial cysts with demonstration of the organism Signs and symptoms of a space-occupying lesion is suggestive of NCC Visualization of cysticercus in the orbit of the eye socket Presence of demonstrable cysticerci in other parts of the body

Serologic Diagnosis of NCC: 

Serologic Diagnosis of NCC A positive serologic test for cysticercus may be helpful However, serologic tests are often negative in NCC

Radiographic Diagnosis of NCC: 

Radiographic Diagnosis of NCC Plain skull radiographs may reveal calcified cysts in the brain CT shows both calcified and uncalcified cysts Considered the tool of choice for detecting / diagnosing NCC Using contrast medium may show inflammatory changes Active versus inactive cysticerci

What About Magnetic Resonance Imaging (MRI)?: 

What About Magnetic Resonance Imaging (MRI)? Is inferior to CT for detecting parenchymal calcifications However, MRI is superior for demonstrating ventricular cysts not seen on CT

Treatment: 

Treatment Albendazole and Praziquantel frequently mentioned Albendazole is the drug of choice since it kills cerebral cysts in both humans and pigs But according to autopsy data from Mexico City, most cases of NCC are asymptomatic and require no treatment

Treatment -- Historically: 

Treatment -- Historically Anticonvulsants to relieve seizures Corticosteroids to control symptoms secondary to meningitis and cerebral edema Surgery in select cases Direct excision of ventricular cysts Shunting procedures to relieve hydrocephalus Removal of cysts by stereotaxic endoscopy

NCC – Treat or Not Treat?: 

NCC – Treat or Not Treat? Some experts say “No” There are immediate risks of neurologic symptoms because of the inflammation caused by the death of cysts Underlying reason for the seizures may worsen because of scarring due to acute inflammation Treatment is unnecessary because cysts die within a short period anyway

Garcia et al – NEJM Jan. 2004: 

Garcia et al – NEJM Jan. 2004 Double-blind, placebo controlled trial of 120 people with active parenchymal cysts Treatment group received 800 mg of albendazole per day and 6 mg of dexamethasone per day Followed both groups for 30 months

Garcia’s Results: 

Garcia’s Results Treatment group had a 67% reduction of seizures with generalization Incidence of partial seizures similar in both groups More of the intracranial lesions resolved in the albendazole group Conclusion: Treatment with albendazole decreased the parasitic load and risk of seizures with generalization

Echinococcus granulosus: 

Echinococcus granulosus Dog tapeworm Most important intermediate host is sheep Common parasite of goats, swine, cattle and horses

Echinococcus granulosus: 

Echinococcus granulosus Endemic in areas where humans have close contact with dogs Sheep raising areas of the world So. Brazil, Argentina, Uruguay, Chile, Peru, Yugoslavia, Bulgaria, Sardinia, Cyprus, Turkey, and Lebanon, N. Africa, Iraq, Iran, China, New Zealand, and Australia A number of cases have been reported from California, Arizona, Utah, New Mexico and lower Mississippi valley

Slide29: 

Life Cycle of E. granulosus

E. Granulosus is also known as Hydatid Cyst Disease: 

E. Granulosus is also known as Hydatid Cyst Disease A section of a hydatid cyst at low power.  The cyst consists of a thick outer layer (*), several thinner internal layers, and many protoscolices.  The protoscolices are often called "hydatid sand." Hydatid cysts in brain have 3 layers.

Hydatid Sand: 

Hydatid Sand Individual larvae Notice the hooklets on the individual organisms Each one of these can hook onto the intestinal wall of the host and develop into adults

Hydatid Cyst Formation: 

Hydatid Cyst Formation Intermediate Host eats egg oncosphere/ Hexacanth embryo released by digestive juices Embryo bore into intestinal wall, ride bloodstream to lodge in any organ, but prefer liver and lungs Form hydatid cyst, which grows slowly over time Cysts have a thick outer (limiting) membrane and an inner germinal membrane Cysts become vacuolated and become brood capsules which produce protoscolices, which are infective if released

Hydatid Disease Transmission: 

Hydatid Disease Transmission Usually transferred to adults by uncooked foods In children infection commonly takes place via accidental contamination by direct contact with contaminated feces The larvae reach the brain after passing through the liver and lung filters

CNS Involvement: 

CNS Involvement Only 2-3% of patients Most of the larvae go to the liver Mainly affects the cerebral hemispheres But infection may be located in the Extradural space Cavernous sinus Intradiploic or eyeball

Clinical Manifestations of Hydatid Cyst Disease: 

Clinical Manifestations of Hydatid Cyst Disease Affects adults in the 3rd to 5th decade of life Equal sex distribution Clinical manifestations are dependent on: Organ involved Site of organ involvement Stage of cyst development Viability of cyst contents

Symptoms of Hydatid Disease Are Related To:: 

Symptoms of Hydatid Disease Are Related To: Expanding mass Pressure on adjacent structures Infection Rupture of cyst contents into surrounding body cavities In the brain, one sees Raised intracranial pressure Focal epilepsy

Diagnosis – Serology: 

Diagnosis – Serology Serology – detecting specific antibodies ELISA employing hydatid fluid antigen for detecting echinococcal antibodies (IgG) Sensitivity for CNS 25% -- 56% Limitations to test after surgery or drainage Titers increase for 3 months Negative after 12 – 24 months post surgery

Diagnostic Imaging: 

Diagnostic Imaging Computerized tomography is the method of choice for hydatid cyst disease in the brain, lung, and bone CT has better documentation of: size, site and structure of cyst Monitoring lesions during chemotherapy Daughter cysts and detachment of membranes following surgery

Treatment – Surgery: 

Treatment – Surgery Cystectomy with complete removal germinal and laminated layers and preservation of the pericyst Can lead to a complete cure Contraindicated in Extremes of age Pregnancy Multiple cysts and cysts difficult to access

Surgical Risks: 

Surgical Risks Operative mortality rates: 0.5% – 4.0% Cyst fluid spillage can result in anaphylaxis (extreme immune response) and/or secondary echinococcosis from protoscolices being let loose

Chemotherapy: 

Chemotherapy Mebendazole Albendazole Praziquantel Praziquantel increases the scolicidal activity of mebendazole and albendazole Chemo cyst disappearance rates Complete: 30% Partial: 30% No response 40%

New Treatment Technique: 

New Treatment Technique PAIR Puncture of hydatid cyst Aspiration Installation of scolicidal agent Reaspiration Popular in Europe Shown to be treatment of choice in hydatid liver disease

Coenurosis: 

Coenurosis Organisms: Taenia -- multiceps serialis brauni glomerata

T. multiceps Is The Focus Of This Presentation: 

T. multiceps Is The Focus Of This Presentation Definitive hosts: Dogs, foxes and other canids Intermediate hosts: Sheep, Goats, Cattle, Horses Accidental intermediate host: Humans Larvae develops in various tissues, commonly in the brain

Coenurus: 

Coenurus The larval stage of a tapeworm (Taenia coenurus) which forms bladder-like sacs in the brain of sheep, causing the fatal disease known as water brain, vertigo, staggers or gid Sheep ingest eggs from feces dropped on the pasture Humans ingest these eggs from contaminated fruits and vegetables

Slide46: 

A coenurus is a white, translucent structure varying from 2-10 cm in the largest dimension, filled with clear, watery fluid or a collapsed membrane with many protoscolices on its internal surface.  The cysts from subcutaneous tissues are often unilocular (having a single compartment or cavity). Those from the central nervous system are frequently multilocular (with many compartments or cavities), sometimes with multiple irregular vesicles and with a grape-like appearance.  Viable cysts have many (often hundreds) protoscolices.  The bladder of the coenurus has budding-off daughter bladders, either internally, floating in the cystic fluid, or externally, attached by stalks.

Slide47: 

Coenurus

Coenurosis Development: 

Coenurosis Development Eggs are ingested by intermediate host Oncospheres (tapeworm embryos) escape from eggs Form fluid filled, bladder-like cysts called coenurus While the coenurus develop in any organ, most settle in the brain No one knows why the larvae have such an affinity for CNS tissue

Human Coenurus Cases: 

Human Coenurus Cases Only about 100 have been reported Most cases involve CNS Order of importance Brain Subcutaneous or intermuscular tissues Eye Spinal cord

Human Coenurus - Symptoms: 

Human Coenurus - Symptoms When in the brain, patients may complain of occipital headaches (headaches in the lower part of the skull), vomiting, seizures, hemiplegia (paralysis affecting only one side of the body), monoplegia (paralysis that involves one limb), and cerebellar ataxia (loss of ability to coordinate muscular movements).

Human Coenurus - Symptoms: 

Human Coenurus - Symptoms Cysts in the spinal canal can cause arachnoiditis.  Arachnoiditis is a term used to describe a pain caused by inflammation of one of the membranes that surrounds and protects the nerves of the spinal cord.  This membranes is called the arachnoid, hence the name arachnoiditis

Human Coenurus - Symptoms: 

Human Coenurus - Symptoms In the eye, the coenurus cyst is usually located in the posterior chamber, causing decreased vision. In the subcutaneous and intermuscular tissues, the lesion presents as a mass which is sometimes painful

Human Coenurus – Clinical Findings: 

Human Coenurus – Clinical Findings Papilledema (swelling of the optic nerve head) in the back of the retina during eye examination Moderate hypoglycorrhachia (low concentrations of blood sugar in the cerebral spinal fluid) with glucose concentrations below 40 mg/dl occurs in about half the cases; Occasionally the glucose levels fall to values as low as 10 mg/dl

Slide54: 

Papilledema: The edges of the optic nerve (the yellow disc in the center) appear blurred and indistinct when swollen 

Human Coenurus – Clinical Findings: 

Human Coenurus – Clinical Findings Raised intracranial pressure caused by ventricular obstruction Cerebral spinal fluid (CSF) examination showing nonspecific profile indicating subacute (between acute and chronic) nonbacterial inflammation.  Ventriculography, CT, or MRI may show dilatation of the ventricles

Slide56: 

CT scan showing enlarged lateral ventricles

Human Coenurus – Clinical Findings: 

Human Coenurus – Clinical Findings Imaging reveals a cystic mass, often in the ventricles or in the subarachnoid space, suggesting the differential diagnosis of a parasitic infection.  More specifically, on CT scans viable cysts appear as lucent lesions surrounded by a contrast-enhanced peripheral rim.  Multiple echo MRI sequences reveal that the intensity of the cyst contents is similar to that of the CSF.

Slide58: 

However, a definitive diagnosis of coenurosis can only come from a gross microscopic examination of the morphologic appearance of the cyst. 

Treatment: 

Treatment The only recognized treatment for coenurosis is surgical removal of cysts.  However, although their effectiveness has not been proven, Glucocorticoids and Anthelmintics have been used to treat coenurosis.

Treatment – Anhelmintics: 

Treatment – Anhelmintics Praziquantel (Biltricide): Causes cell membranes of worms to become permeable. In this way the worm loses intracellular calcium.  This in turn causes the worm to become paralyzed. Niclosamide (Niclocide): By causing the death of cells in the head and adjoining segments, this drug causes the worm to let go of whatever it is attached to in the human body.  The worm is then excreted in the feces. Albendazole (Albenza): Causes the worm to produce less ATP eventually leading to its death.

Treatment -- Glucocorticoids: 

Treatment -- Glucocorticoids Glucocorticoids are usually used for patients with elevated intracranial pressure. Dexamethasone (Decadron)- an anti-inflammatory

Prevention: 

Prevention Since transmission of this infection to humans occurs via an oral fecal route (ingestion of eggs in feces of dogs), the best prevention would be to avoid eating fruits and vegetables that were grown on fields fertilized with dog manure (or to avoid using dog manure in general).  In addition, since dogs become infected by eating infected sheep, uncooked sheep should not be fed to dogs.  Sheep offal (trimmings or waste of sheep) and sheep brain should especially be avoided.  This is because the brain is part of the CNS and sheep offal tends to contain parts of the CNS were coenuri are more prevalent.  Also, dogs should be treated immediately if they are suspected of having any sort of tapeworm.

Epidemiology: 

Epidemiology The incidence of coenurosis are very low with only about 100 cases ever being reported in humans. Therefore there is no real “endemic” area but there are areas were coenurosis is most common. Coenurosis is very rare in the Western Hemisphere with the majority of cases (65%) occurring in Europe and Africa.  The distribution of the different species that cause coenurosis are as follows. Taenia multiceps: France, Africa, England, Brazil, and the United States. Taenia serialis: Canada and the United States Taenia brauni: North Africa, Rwanda, and the Democratic Republic of Congo. Taenia glomerata: Nigeria and the Democratic Republic of Congo.

References: 

References Coenurosis. http://www.stanford.edu/class/humbio103/ParaSites2005/Coenurosis Miabi Z, Hashemi H, Ghaffarapour M, Ghelichnia H, Media r. Clinicoradiological findings and treatment outcome in patients with intracranial hydatid cyst. Actas Medica Iranica, 43(5): 359-364; 2005 Khuroo MS. Hydatid disease: current status and recent advances. Annals of Saudi Medicine, Vol 22, Nos. 1-2, 2002 John DT, Petri, WA jr. Markell and Voges Medical Parasitology, 9th edition. Saunders/Elsevier. 2006 Ansari JA, Karki P, Dwivedi S, Ghotekar LH, Rauniyar RK, Ripal S. Neurocysticercosis – a review. Kathmandu University Medical Journal. Vol. 1, No.1, 48-50. 2003. Garcia HH, Pretell EJ, Gilman RH, Martinez SM, Moulton LH, Del Brutto OH, Hererra G, Evans CAW, Gonzalez, AE. A trial of antiparasitic treatment to reduce the rate of seizures due to cerebral cysticercosis. N Engl J Med 350;3 January 15, 2004 Garcia HH, Del Brutto OH, Nash TE, White AC Jr, Tsang VCW, Gilman RH. New concepts in the diagnosis and management of neurocysticercosis (Taenia solium). Am J Trop Med. Hyg., 72(1), 2005, pp. 3-9