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Cysticercosis 

Cysticercosis

Chapter:
Cysticercosis
Author(s):

Hector H. Garcia

and Robert H. Gilman

DOI:
10.1093/med/9780199204854.003.071003_update_001

February 27, 2014: This chapter has been re-evaluated and remains up-to-date. No changes have been necessary.

Update:

Epidemiology—seroprevalence in highlands of Papua, Indonesia.

Ocular cycticercosis.

Updated on 31 May 2012. The previous version of this content can be found here.
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Essentials

Cysticercosis, infection by larvae of the pork tapeworm Taenia solium (see Chapter 7.10.2), is the commonest helminthic infection of the human central nervous system. It accounts for up to 30% of all seizures and epilepsy in endemic countries, and travel and immigration now lead to its more frequent presentation in industrialized countries.

Ingestion of raw or undercooked pork can lead to infection with the T. solium cysticercus, formerly known as ‘Cysticercus cellulosae’, which is an immature tapeworm. Once attached to the person’s small intestine, the cysticercus develops segments (proglottids) to become an adult tapeworm. Proglottids discharged in the faeces contain tens of thousands of ova that can autoinfect the human host or pigs and other susceptible mammals. Ingestion of T. solium ova, for example by the faecal-oral route in those infected with adult tapeworms or their close contacts, or by eating food contaminated with raw sewage, can result in development of cysticerci in various tissues, but not an adult tapeworm. The ingested ova release embryos that penetrate the intestinal mucosa and migrate in the blood stream to the brain (causing neurocysticercosis), muscles, and subcutaneous tissues. Only by ingesting T. solium ova can humans develop cysticercosis.

Clinical features and diagnosis—manifestations of neurocysticercosis depend on the number, location, size, and stage of the parasite cysts in the brain, as well as on the immunological response of the host. The commonest syndromes are late-onset epilepsy or intracranial hypertension. Diagnosis is based on brain imaging studies (CT or MRI) and supported by highly specific serology.

Treatment and prognosis—treatment is (1) symptomatic—e.g. anticonvulsants; shunts for intracranial hypertension in patients with hydrocephalus; and (2) antiparasitic—albendazole or praziquantel, which are generally given with steroids to control cerebral oedema; but there is no role for these drugs in inactive neurocysticercosis (i.e. calcifications with or without enhancement on CT scan). Prognosis depends mainly on whether the cysts are intraparenchymal (better prognosis) or extraparenchymal (subarachnoid or intraventricular, poorer prognosis).

Introduction

Known since the Hippocratic era, cysticercosis is the commonest helminthic infection of the human central nervous system. It is probable that the suspicion of its origins led some religions expressly to forbid the consumption of pork. Socioeconomic improvements eradicated the infection in Europe and North America. However, endemic Taenia solium taeniasis/cysticercosis persists in most developing countries, where human cysticercosis is an important cause of epilepsy and other neurological morbidity, and porcine infections cause considerable economic losses to peasant farmers.

Aetiology

Cysticercosis is infection with the larval stage (cysticercus) of T. solium, the pork tapeworm (Chapter 7.10.2). In the life cycle of this two-host zoonotic cestode(Fig. 7.10.3.1), humans are the only definitive host and harbour the adult tapeworm, whereas pigs are intermediate hosts. The hermaphroditic adult T. solium inhabits the small intestine. Its head or scolex bears four suckers and a double crown of hooks, connected by a narrow neck to a large body (strobila) between 2 and 4 m long, composed of several hundred proglottids (Chapter 7.10.2, Fig. 7.10.3.1b, c). Gravid proglottids, each containing 50 000 to 60 000 fertile eggs, detach from the distal end of the worm and are excreted in the faeces. The cycle is completed when pigs ingest stools contaminated with T. solium eggs. Once ingested by the pig, the invasive oncospheres in the eggs are liberated by the action of gastric acid and intestinal fluids and actively penetrate the bowel wall, enter the bloodstream, and are carried to the muscles and other tissues where they develop into larval cysts (Chapter 7.10.2, and see Fig. 7.10.3.5). When humans ingest undercooked pork containing cysticerci, the larva evaginates in the small intestine, its scolex attach to the intestinal mucosa, and it begins forming proglottids. By accidentally ingesting taenia eggs, humans may also act as intermediate hosts for T. solium and develop cysticercosis.

Fig. 7.10.3.1 Life cycle of T. solium.

Fig. 7.10.3.1
Life cycle of T. solium.

Fig. 7.10.3.5 (a) Histopathology of a complete hydatid cyst removed by brain biopsy in a patient with recent onset of focal epilepsy (×4). (b) Structure of the cyst wall (×40). (c) Cerebral imaging CT enhanced. (d) MRI T2-weighted. (e) MRI T1-weighted with and without gadolinium enhancement. (Copyright DA Warrell.)

Fig. 7.10.3.5
(a) Histopathology of a complete hydatid cyst removed by brain biopsy in a patient with recent onset of focal epilepsy (×4). (b) Structure of the cyst wall (×40). (c) Cerebral imaging CT enhanced. (d) MRI T2-weighted. (e) MRI T1-weighted with and without gadolinium enhancement. (Copyright DA Warrell.)

Epidemiology

The availability of neuroimaging studies and the subsequent development of specific serodiagnostic tests has resulted in the identification of neurocysticercosis as a frequent neurological disorder in Latin America, Africa, and Asia, where the prevalence of active epilepsy is almost twice that in Western countries. Cysticercosis was introduced from Bali to the highlands of Papua, Indonesia nearly 40 years ago. Its seroprevalence is more than 20% in many communities. Neurocysticercosis is also an emerging problem in industrialized countries, seen mainly in immigrants from endemic areas, some of whom may spread the infection as tapeworm carriers. This applies to California and other southern areas of United States of America bordering Mexico.

The main sources of human cysticercosis are faecal–oral contamination in those carrying the tapeworm or their contacts and ingestion of food contaminated with T. solium eggs. Epidemiological studies suggest that almost every newly diagnosed patient with cysticercosis has been infected by someone in their close environment who is harbouring a T. solium and the tendency is to dismiss the role of environment or water in transmission. Airborne transmission of T. solium eggs and internal autoinfection by regurgitation of proglottids into the stomach have been suggested but not proved.

Pathogenesis

Any organ may be infected, but parasites survive more frequently in the nervous system, possibly because the immune response there is limited. Signs and symptoms are caused by perilesional inflammation and oedema, mass effect, or obstruction of cerebrospinal fluid circulation. Although complete development of cysts takes 2 to 3 months, symptoms usually develop years after the initial infection. This clinically silent period, and finding inflammation around cysts in symptomatic cases, suggests that in many cases symptoms are due to inflammatory processes associated with the recognition of the parasite by the immune system of the host (presumably progressing towards the death of the parasite) rather than to the presence of the parasite itself.

Subarachnoid cysticerci elicit an intense inflammatory reaction causing thickening of basal leptomeninges. The optic chiasma and other cranial nerves are usually entrapped within this dense exudate, resulting in visual field defects and other cranial nerve dysfunctions. The foramens of Luschka and Magendie may be occluded by the thickened leptomeninges, leading to hydrocephalus. Blood vessels may be affected by the inflammatory reaction. The walls of small penetrating arteries are invaded by inflammatory cells, leading to a proliferative endarteritis with occlusion of the lumen, and which may result in cerebral infarction.

Clinical features

Neurocysticercosis is a pleomorphic disease, whose manifestations vary with the number, size, and topography of the lesions and the intensity of the host’s immune response to the parasites. Patients can be classified by the number, stage, and location of the cysticerci, and the presence or absence of associated inflammation or calcifications.

Epilepsy, the most common presentation of neurocysticercosis, is usually the primary or sole manifestation of the disease. Seizures occur in 50 to 80% of patients with parenchymal brain cysts or calcifications but are less common in other forms of the disease. Other focal signs are less frequent and include pyramidal tract signs, sensory deficits, signs of brainstem dysfunction, and involuntary movements. These manifestations usually follow a subacute or chronic course, making neurocysticercosis difficult to differentiate clinically from neoplasms or other infections of the central nervous system. Focal signs may occur abruptly in patients who develop a cerebral infarct as a complication of subarachnoid neurocysticercosis. Subarachnoid cysticerci may reach 10 cm or more in diameter (‘giant’ cysticercosis, Fig. 7.10.3.2), and exert a mass effect.

Fig. 7.10.3.2 Giant cysticercotic cyst (brain CT).

Fig. 7.10.3.2
Giant cysticercotic cyst (brain CT).

Neurocysticercosis may present with increased intracranial pressure, usually from hydrocephalus secondary to basal subarachnoid cysticercosis or intraventricular cysts, cysticercotic arachnoiditis, or granular ependymitis. In these cases, intracranial hypertension develops subacutely and progresses slowly. An encephalitic picture may result from overwhelming inflammation around many parasitic cysts, a syndrome that occurs more frequently in younger people, especially women. In contrast, some patients may tolerate hundreds of intraparenchymal cysticerci with only minor symptoms.

Ocular cysticercosis can involve the posterior segment, retina, vitreous, subconjunctiva, orbit or eyelid (Fig. 7.10.3.3).

Fig. 7.10.3.4 Heavy cysticercal infection of skeletal muscles.

Fig. 7.10.3.4
Heavy cysticercal infection of skeletal muscles.

(Courtesy of the late Professor Sornchai Looareesuwan.)

Fig. 7.10.3.3 Intraocular cysticercosis: cysticercus in the anterior chamber of a Thai patient.

Fig. 7.10.3.3
Intraocular cysticercosis: cysticercus in the anterior chamber of a Thai patient.

(Courtesy of the late Professor Sornchai Looareesuwan.)

Muscular pseudohypertrophy, a rare presentation, is caused by heavy cysticercal infection of skeletal muscles (Fig. 7.10.3.4) giving a ‘Herculean’ appearance. The few cases reported are all from India. Other apparent differences in clinical manifestations between Asia and Latin America include a high frequency of subcutaneous cysts and single degenerating brain lesions in Asia.

Pathology

The cysticerci are liquid-filled vesicles consisting of vesicular wall and scolex (Fig. 7.10.3.5). The vesicular wall is composed of an outer or cuticular layer, a middle or cellular layer with pseudoepithelial structure, and an inner or reticular layer. The invaginated scolex has a head or rostellum armed with suckers and hooks, and a rudimentary body or strobila that includes the spiral canal.

The macroscopic appearance of cysticerci varies in different locations within the central nervous system. Cysticerci within the brain parenchyma are usually small and tend to lodge in the cerebral cortex or basal ganglia (Fig. 7.10.3.6). Subarachnoid cysts may be small if located in the depths of cortical sulci, or grow to 5 cm or more in the basal cisterns or sylvian fissures. Ventricular cysticerci are usually single, may or may not have a visible scolex, and may be attached to the choroid plexus or float freely in the ventricle. Spinal cysticerci are usually located in the subarachnoid space (rarely intramedullary). Their morphology is similar to cysts located within the brain.

Fig. 7.10.3.6 Uncontrasted T1 MR image showing two intraparenchymal cysticerci with visible scolices.

Fig. 7.10.3.6
Uncontrasted T1 MR image showing two intraparenchymal cysticerci with visible scolices.

Basal cysticerci may undergo a disproportionate growth of their membrane, with extension processes, resembling a brunch of grapes (racemose cysticercosis, Fig. 7.10.3.7). In these cases, the scolex is frequently unidentifiable even by microscopy.

Fig. 7.10.3.7 Basal ‘racemose’ cysticercosis.

Fig. 7.10.3.7
Basal ‘racemose’ cysticercosis.

Viable vesicular cysticerci elicit little inflammatory change in surrounding tissues because of active immune evasion mechanisms. The appearance of symptoms is interpreted as the result of immunological attack from the host, in a process of degeneration that ends with the death of the parasite. Inflammatory changes in the parasite membrane and increased density of cyst fluid mark the transition between four defined stages: viable, colloidal, granular nodular, and calcified cyst. Viable cysts may coexist with degenerating cysts or calcifications.

Laboratory/imaging diagnosis

The pleomorphism of neurocysticercosis makes it impossible to diagnose on clinical grounds alone. In endemic regions, late-onset seizures in otherwise healthy individuals are highly suggestive of neurocysticercosis. Most of these patients are normal on neurological examinations. Routine neuroimaging and serological studies are therefore mandatory. Finding cysticerci outside the central nervous system (eye, subcutaneous tissue, muscle) assists the diagnosis of neurocysticercosis. Muscular and subcutaneous cysticerci are far less common in American than in African or Asian patients with neurocysticercosis.

Neuroimaging

CT and MRI have drastically improved diagnostic accuracy by providing objective evidence about the topography of the lesions and the degree of the host inflammatory response to the parasite. Imaging findings in parenchymal neurocysticercosis depend on the stage of involution of cysticerci. Viable cysticerci appear as rounded cystic lesions on CT (Fig. 7.10.3.2), hypointense on T1 and FLAIR sequences on MRI (Fig. 7.10.3.6), without associated enhancement, whereas degenerating parasites are seen as focal enhancing lesions surrounded by oedema (Fig. 7.10.3.4c–e), and calcifications as hyperdense dots or nodules (Fig. 7.10.3.8). Disappearance of cyst fluid signals the degenerative phase and calcified nodules the residual phase. Single or multiple ring-like or nodular enhancing lesions are non-specific and present a diagnostic challenge. Pyogenic brain abscesses, fungal abscesses, tuberculomas, toxoplasma abscesses, and primary or metastatic brain tumours may produce similar findings on CT or MRI.

Fig. 7.10.3.8 Calcified neurocysticercosis.

Fig. 7.10.3.8
Calcified neurocysticercosis.

CT and MRI findings in subarachnoid neurocysticercosis are less specific. They include hydrocephalus, abnormal meningeal enhancement, and subarachnoid cysts. Cerebral angiography may show segmental narrowing or occlusion of major intracranial arteries in patients with cerebral infarcts secondary to parasitic vasculitis. In neurocysticercosis there is rarely fever or signs of meningeal irritation; glucose levels in cerebrospinal fluid are usually normal. MRI is generally better than CT for the diagnosis of neurocysticercosis, particularly in patients with basal lesions, brainstem or intraventricular cysts, and spinal lesions. MRI is, however, less sensitive than CT for the detection of calcifications.

Immunological tests

Immunoblot (western blot) using purified antigens is the best available serological test for T. solium antibodies. It performs well with serum samples and is 98% sensitive in cases with more than one active lesion, and 100% specific. Its sensitivity may drop in patients with a single cyst. Other assays using unfractionated antigens (e.g. enzyme immunoassay, ELISA) suffer from poor specificity but are more reliable when performed with cerebrospinal fluid than serum. Antigen-detection tests may provide a tool for serological monitoring of antiparasitic therapy. Although results of serology and imaging studies may be similar, they evaluate different aspects of the disease and may be discordant in some patients. Intestinal tapeworm carriers, naturally cured patients, or non-neurological infections may have normal brain images but be positive serologically. Those with only inactive lesions or a single cerebral lesion may be seronegative.

Parasitological diagnosis

A proportion (c.10–15%) of patients with neurocysticercosis are tapeworm carriers at the time of diagnosis, and in another 10% or so a carrier can be detected in the household. Parasitological diagnosis is difficult: eggs and proglottids are shed only intermittently in stool and are usually missed by routine stool examination. Stool assays to detect parasite antigens are more sensitive than microscopy, but are not widely available. A recently described serological test for tapeworm carriers may improve detection.

Diagnostic criteria

A set of diagnostic criteria based on neuroimaging studies, serological tests, clinical presentation, and exposure history has been proposed by Del Brutto and colleagues. Besides absolute demonstration of the presence of the parasite, ‘major’ criteria (including typical findings on neuroimaging, demonstration of specific anticysticercal antibodies, or the presence of typical cigar-shaped calcifications in muscle) are combined with ‘minor’ criteria and epidemiological data to suggest a probable or possible diagnosis. Application of these criteria should improve the consistency of diagnosis.

Treatment

Because of the clinical and pathological pleomorphism of neurocysticercosis, precise assessment of the viability and size of cysts, the location of parasites, and the severity of the host’s immune response is important before planning treatment.

Symptomatic treatment is very important. Seizures secondary to parenchymal neurocysticercosis can usually be controlled with anticonvulsants. However, the optimal duration of anticonvulsant therapy in patients with neurocysticercosis has not been determined, and it is difficult to withdraw this treatment. Prognostic factors associated with recurrence of seizures include the development of parenchymal brain calcifications, and occurrence of recurrent seizures or multiple brain cysts before starting antiparasitic therapy.

Antiparasitic agents destroy viable cysts and are associated with fewer seizures (particularly seizures with generalization) in the long term follow up. Antiparasitic or steroid treatments in patients with a single enhancing lesion seem to independently improve radiological resolution and decrease the chance of seizure relapses, albeit the magnitude of this effect is small. Albendazole is the drug of choice for antiparasitic treatment of cerebral cysticercosis (15 mg/kg per day for 7 days, with steroids), although a recently described single-day praziquantel regimen (75–100 mg/kg, in three doses at 2-h intervals, followed by steroids 6 h later) demonstrated similar cestocidal activity in patients with few cysts. Longer courses may be required in patients with many lesions or subarachnoid cysticercosis. Transient worsening of neurological symptoms can be expected during antiparasitc therapy, secondary to the perilesional inflammatory reaction. There is no role for antiparasitic drugs in inactive neurocysticercosis (i.e. calcifications with or without enhancement on CT scan) since the parasites are dead.

Between the second and fifth day of antiparasitic therapy there is usually an exacerbation of neurological symptoms, attributed to local inflammation caused by the death of the larvae. For this reason, albendazole or praziquantel is generally given simultaneously with steroids in order to control the oedema and intracranial hypertension. Serum levels of praziquantel decrease when steroids are administered simultaneously, an effect that does not occur with albendazole. However, there is no evidence that cysticidal efficacy is decreased. Serum levels of praziquantel or albendazole may be lowered by simultaneous antiepileptic drug (phenytoin or carbamazepine) administration.

Some forms of neurocysticercosis should not be treated with antiparasitic agents. In patients with severe cysticercotic encephalitis, these drugs may result in worsening cerebral oedema and fatal herniation. In this case, the mainstay of therapy is high doses of corticosteroids or mannitol to decrease the inflammatory response. In patients with both hydrocephalus and parenchymal brain cysts, antiparasitic drugs should be started only after placement of a ventricular shunt in case the intracranial pressure increases as a result of drug therapy. Antiparasitic drugs must be used with caution in patients with giant subarachnoid cysticerci. In such patients, concomitant steroid administration is mandatory to avoid cerebral infarction. Albendazole can successfully destroy ventricular cysts, but the surrounding inflammatory reaction may cause acute hydrocephalus if the cysts are located within the fourth ventricle or near the foramens of Monro and Luschka.

Surgery is limited to ventriculoperitoneal shunts to relieve obstructive hydrocephalus, and excision of single cysts (in the fourth ventricle or giant intraparenchymal cysts). However, shunts frequently dysfunction. The protracted course in these patients and their high mortality rates (up to 50% in 2 years) is directly related to the number of surgical interventions required to change the shunts. Recently, neuroventriculoscopy has been employed as a less invasive option for resection of ventricular cysticerci.

Prognosis

Parenchymal cysticercosis has a good prognosis. Appropriately managed, seizures usually subside in time without sequelae. In contrast, extraparenchymal cysticercosis and especially racemose cysticercosis have a poor prognosis, responding poorly to antiparasitic therapy, and leading to progressively deteriorating disease and death. Multiple courses of antiparasitic treatment and careful, prolonged follow-up are crucial in this type of patients.

Prevention and control

Cysticercosis would not exist if pigs had no access to human faeces. However, this approach is hampered in endemic zones by the lack of sanitary facilities and veterinary inspection, and more importantly, because farmers tend to raise pigs under free-range conditions in order to reduce the cost of feeding them. Intervention programmes have concentrated on mass chemotherapy to eliminate human taeniasis, but their results have not been sustained. New tools for control are oxfendazole, an effective and cheap single-dose therapy for porcine cysticercosis, and the candidate porcine vaccines under trial by several groups. TSOL18, an oncosphere-based vaccine developed in Australia, may provide over 99% protection.

Monitoring the effect of an intervention requires suitable indicators. Human seroprevalence does not reflect changes in infection patterns because antibodies persist for years, even after successful treatment. Studies in Peru have shown that serological monitoring of porcine infection is a useful marker for both prevalence and changes in infection intensity over time. Similarly, the rate of infection in uninfected (sentinel) pigs over time can be used to estimate intensity of T. solium infection in the community. The prevalences of human and porcine infection are strongly correlated.

Possible future developments

Although most cysts disappear after antiparasitic treatment, the antiparasitic efficacy of currently available regimes is incomplete. Data is missing on whether new drugs, combination therapy, or different schemes of albendazole of praziquantel can improve this efficacy.

Schemes and doses of antiparasitic and steroid therapy need to be assessed in controlled trials targeted to specific types of neurocysticercosis. Some authors suggested an association between brain calcifications secondary to cysticercosis and glial neoplasms. This has not yet been confirmed or rejected. Systematic long-term evaluation is needed to determine whether hydrocephalus is a late complication of anti-parasitic therapy. The efficacy and costs of comprehensive human–porcine eradication programmes must be assessed.

Further reading

Del Brutto OH, et al. (2001). Proposed diagnostic criteria for neurocysticercosis. Neurology, 57, 177–83. [A guide to systematic diagnosis.]Find this resource:

Del Brutto OH, et al. (2006). Albendazole and praziquantel therapy for neurocysticercosis: a meta-analysis of randomized trials. Ann Intern Med, 145, 43–51.Find this resource:

Evans C, et al. (1997). Controversies in the management of cysticercosis. Emerg Infect Dis, 3, 403–5.Find this resource:

Garcia HH, et al. (2003). Taenia solium cysticercosis. Lancet, 362, 547–56.Find this resource:

Garcia HH, et al. (2004). A trial of anti-parasitic treatment to reduce the rate of seizures due to cerebral cysticercosis. N Engl J Med, 350, 249–58.Find this resource:

Garcia HH, et al. (2005). Neurocysticercosis: updated concepts about an old disease. Lancet Neurol, 4, 653–61.Find this resource:

Garcia HH, et al. (2011). Cysticercosis of the central nervous system: how should it be managed? Curr Opin Infect Dis, 24, 423–7.Find this resource:

Gonzalez AE, et al. (1997). Treatment of porcine cysticercosis with oxfendazole: a dose–response trial. Vet Record, 141, 420–2.Find this resource:

Gonzalez AE, et al. (2005). Vaccination of pigs to control human neurocysticercosis. Am J Trop Med Hyg, 72, 837–9.Find this resource:

Montano SM, et al. (2005). Neurocysticercosis: association between seizures, serology and brain CT in rural Peru. Neurology, 65, 229–33.Find this resource:

Nash TE, et al. (2006). Treatment of neurocysticercosis—current status and future research needs. Neurology, 67, 1120–7.Find this resource:

Salim L, et al. (2009). Seroepidemiologic survey of cysticercosis-taeniasis in four central highland districts of Papua, Indonesia. Am J Trop Med Hyg, 80, 384–8.Find this resource:

Wender JD, et al. (2011). Intraocular cysticercosis: case series and comprehensive review of the literature. Ocul Immunol Inflamm, 19, 240–5.Find this resource: