Cysticcercosis

CYSTICERCOSIS
By:Palak Parikh

EPIDEMIOLOGY
* Found in approximately 50 million people worldwide (probably an underestimate)
* Endemic in several countries in Central and South America, sub-Saharan Africa, India, and Asia
* Prevalence in this country often higher in rural areas
* 221 deaths identified in the US from 1990-2002 (62% had emigrated from Mexico)

CYSTICERCOSIS TRANSMISSION
* Caused by the larval stage of Taenia solium, the pork tapeworm
* Humans develop by ingestion of T. solium eggs; they can spread infection by:
o Egg-containing feces contaminating water supplies in endemic areas
o Contaminating food directly, as eggs are sticky and can often be found under the fingernails of tapeworm carriers.

LIFE CYCLE
* Once eggs ingested, embryos are released in the small intestine and invade the bowel wall.
* They then disseminate hematogenously to other tissues and develop into cysticerci over 3 weeks to 2 months.
* Cysticerci – liquid-filled vesicles consisting of a membranous wall and a nodule containing the invaginated scolex.
* Scolex – head armed with suckers and hooks and a rudimentary body.

PATHOGENESIS
* Cysticerci initially viable but do not cause much inflammation in surrounding tissues – asymptomatic infection
* Host develops immune tolerance to cysticerci, which remain in this stage for several years.
o Postulated mechanisms of tolerance:
+ Taenia elaborate substances that inhibit or divert complement pathways away from parasite
+ Humoral antibodies do not kill mature taenia.
+ Poorly defined factors may interfere with lymphocyte proliferation and macrophage function, inhibiting normal cellular immune defenses.
* Clinical manifestations occur when inflammatory response develops around degenerating cysticercus.

SYMPTOMATIC DISEASE
* Divided into:
o Neurocysticercosis
o Extraneural cysticercosis

NEUROCYSTICERCOSIS
* 80% of infections are asymptomatic
* Symptoms mainly due to mass effect, inflammatory response, or obstruction of foramina and ventricular system of brain.
* Most common symptoms:
o Seizures
o Focal neurological signs
o Intracranial hypertension
* Peak estimated to occur 3-5 years after infection

NEUROCYSTICERCOSIS
* Increased risk of seizures with a single calcific granuloma.
* Risk of seizures highest when lesions are degenerating and are surrounded by inflammation.
* Encephalitis and diffuse brain edema most common in children and young females.
* 1-3% of cases involve the spinal cord, with thoracic lesions the most common.

NEUROCYSTICEROSIS IN ENDEMIC COUNTRIES
* Most common cause of adult-onset seizures
* Risk of seizures in seropositive individuals 2-3 times higher than seronegative controls.
* Punctate calcifications most frequent finding on neuroimaging of brain.

EXTRANEURAL CYSTICERCOSIS
* Typically involves:
o Eyes – in 1-3% of all infections
o Muscle
o Subcutaneous tissue – nodules most common in patients from Asia and Africa than from Latin America

DIAGNOSIS
* Serologic testing
* Peripheral eosinophilia only if cyst is leaking
* CT scan or MRI
o Pathognomonic Lesion: Scolex – mural nodule within a cyst
* Brain biopsy (only in symptomatic patients with equivocal serology and radiologic tests)

SEROLOGIC TESTING
* ELISA
* Complement fixation (CF)
* Radioimmunoassay
* Enzyme linked immunoelectrotransfer blot (EITB) assay – test of choice

EITB ASSAY
* Enzyme-linked immunoelectrotransfer blot assay
* Test of choice for detecting anticysticercal antibodies
* Uses affinity-purified glycoprotein antigens
* Higher sensitivity (83-100%) and specificity (93-98%) than ELISA
* Can be performed on serum or CSF but has a higher sensitivity on serum.
* Detected 94% of pathologically confirmed NCC with 2 or more lesions compared to only 28% with a single lesion in one study.

CT VS MRI
* MRI preferred since it is more sensitive in detecting:
o small lesions
o brainstem or intraventricular lesions
o perilesional edema around calcific lesions
o scolex
o degenerative changes in the parasite
* CT scan cheaper and better at detecting:
o small areas of calcifications.
o cysticercal infestation of extraocular muscles.

* Perform CT scan first followed by MRI in patients with inconclusive findings or in those with negative CT scans where strong clinical suspicion persists.

PERUVIAN STUDY
POTENTIAL TREATMENTS
* Albendazole (15 mg/kg/day) X 15 days + corticosteroids (30-40 mg prednisolone or 12-16 mg dexamethasone daily) – per UpToDate
* Praziquantel (50 mg/kg/day) X 15 days + corticosteroids (30-40 mg prednisolone or 12-16 mg dexamethasone daily) – per UpToDate
* Corticosteroids alone
* Anticonvulsants in patients who present with seizures or are at high risk for seizures
* Surgery

ALBENDAZOLE VS PRAZIQUANTEL
* Albendazole
o Destroys 75-90% of parenchymal brain cysts
o Does not interact with anticonvulsants
o Levels not adversely affected w/ co-administration of corticosteroids
* Praziquantel
o Destroys 60-70% of cysts 3 months after administration
o Decreased efficacy compared to Albendazole
o Available for oral administration
o Does not cross the blood-brain barrier well, so CSF levels only approx 20% of plasma levels.
o Involves cytochrome P-450 hepatic metabolism, which is induced by corticosteroids, phenytoin, and phenobarbital

* No blinded randomized controlled trials comparing albendazole to praziquantel.
Because of the above, praziquantel is generally considered second-line therapy.

TREATMENT
* One randomized, double-blind, placebo-controlled trial
o 120 pts with living cysticerci in the brain and seizures treated with antiepileptic drugs
+ Randomized to either albendazole (800 mg qd) and dexamethasone (6 mg qd X 10 days) or double placebo
+ Followed for 30 months or until they were seizure-free for 6 months after tapering of antiepileptic drugs
o Results:
+ Resolution of intracranial cystic lesions more common in treatment arm
+ Number of patients experiencing generalized seizures declined in the treatment arm
+ No significant change between the two groups in patients experiencing partial seizures

NEUROCYSTICERCOSIS
* Treatment in those with:
o 5-50 cysts (both antiparasitic and steroids)
o Steroids alone in patients w/ > 50 cysts
* No Treatment in those with:
o Asymptomatic nonviable neurocysticercosis
o Calcified cysts
o Single viable cysts
o Fewer than 5 cysts

ANTICONVULSANTS
* Recommended for patients who present with seizures
* Should be stopped if patient remains seizure-free during therapy to see if the patient remains asymptomatic
* Should be reinitiated chronically if the patient has recurrent seizures
* Should be considered in patients w/ multiple cysts who have no history of seizure activity

SURGICAL INTERVENTION
* Used in some patients with intracranial hypertension
* Shunting improves hydrocephalus, although recurrent blockages of shunts common
* Surgical intervention recommended for cysts:
o Located in the 4th ventricle
o Attached to middle cerebral artery
o Compressing the optic chiasm
o Located in the spine

TREATMENT OF EXTRANEURAL CYSTICERCOSIS
* None if pt asymptomatic
* Surgical excision for intraocular disease
* Medical therapy for involvement of extraocular muscles or optic nerve.
* NSAIDs for patients w/ symptomatic subcutaneous or intramuscular lesions.
* Excision of solitary lesions if NSAIDs fail or not tolerated.

BEFORE INITIATING MEDS…
* Apply PPD.
* Consider treating with a single dose of ivermectin before beginning corticosteroids, as many patients have risk factors for strongyloidiasis.
* Consult ophthalmology to rule out ocular cysticercosis.

PATIENT MONITORING
* Intermittent surveillance w/ imaging until cyst(s) resolve(s).
o Perhaps every 3-6 months if patient improving or earlier if patient symptomatic.
* Reimaging of brain 2 months after completion of treatment
* Consider antiparasitic therapy if cysts growing off therapy

POSSIBLE PREVENTION
* Human Tapeworm Infections
o Inspection of pork for cysticerci
o Freezing or adequately cooking meat to destroy cysticerci
o Administering antiparasitic agents to pigs
* Infection in Pigs
o Confining animals and not allowing them to roam freely
o Improved sanitary conditions
* Egg Transmission to Humans
o Good personal hygiene and hand washing prior to food preparation
o Identifying human carriers of tapeworms
o Mass community programs to treat tapeworm carriers.
* Possible Vaccine – porcine vaccine currently in the works

TAKE HOME POINTS
* Cysticercosis caused by the larval stage of Taenia solium, the pork tapeworm
* Pay special attention if pt from Central and South America, sub-Saharan Africa, India, and Asia, as neurocysticercosis is the most common cause of adult-onset seizures in these endemic areas.
* Order Head CT first to diagnose neurocysticercosis; if negative and suspicion still high, order Brain MRI.
* EITB test of choice for serology.
* Place PPD before starting treatment.
* Obtain Ophthalmology consult before starting treatment.
* Albendazole and Dexamethasone comprise first-line treatment for symptomatic cysticercosis. Consider concurrent anticonvulsants if pt presents with seizures.

REFERENCES
* aapredbook.aappublications.org
* UpToDate.
* www.dpd.cdc.gov
* www.e-radiology.net
* www.parasite-diagnosis.ch
* www.stanford.edu/class/cysticercosis/symptoms

CYSTICERCOSIS.ppt