Cysticercosis

Human cysticercosis occurs throughout the globe, particularly in regions where pig cysticercosis is common. Taenia solium is found worldwide, but is more common where pork is part of the diet and humans live in close contact with pigs. Both the forms of tapeworm infections – taeniasis and cysticercosis are prevalent in the rural areas of developing countries, especially which have poor sanitation, pigs roaming freely and eating human stools. Therefore, high prevalences are reported in Mexico, Latin America, West Africa, Russia, India, Pakistan, North-East China, and Southeast Asia.

International Scenario

About 50-100 million people are diagnosed with cysticercosis globally. This number is possibly underestimated as many infections do not present any symptoms and may go undiagnosed. World Health Organization (WHO) estimates that 2.56-8.30 million cases of neurocysticercosis occur globally. Neurocysticercosis is one of the most common cause of adult-onset seizures throughout the world. In the past decades, the diagnosis of neurocysticercosis has improved a lot, which can be attributed to the development of CT (Computed Tomography) and MRI (Magnetic Resonance Imaging) scan of the brain.

In Central and South America, Southeast Asia, India, China, and Sub-Saharan Africa, cysticercosis is characterised as an endemic disease. Studies indicate that in Latin America and India, almost half of the adult-onset seizures are caused due to neurocysticercosis. The seroprevalence rate in Latin America is about 4.9-24% and in some rural South American communities is between 10-25%. In rural Vietnam, the approximated true prevalence of both the tapeworm infections is 13%. Studies also indicate that taeniasis and cysticercosis occur in eastern European countries. In the United States, about 2,000 patients are hospitalized for neurocysticercosis every year. The cases are more prevalent in Latin American immigrants living in regions like Texas, Arizona, and California. Some cases occur because of travelling to the endemic areas.

Indian Scenario

Recent neuroimaging studies in India advocate that the disease burden in India exceeds several other developing countries. Cysticercosis is one of the neglected diseases in the country and systematic population-based studies for the disease are deficient. Hence, cysticercosis is most likely under-reported in India. Neurocysticercosis is considered as one of the most common single cause of epilepsy/seizures in India. About 50% of Indian patients with partial seizures are caused due to Cysticercosis. It appears to be more prevalent in northern states of India, such as Uttar Pradesh, Punjab, and Bihar. The prevalence of active epilepsy reported by a community survey of 50,617 people in South India was 3.83 per 1000 and neurocysticercosis was diagnosed in 28.4% of the cases by CT scanning. Pig or porcine cysticercosis is also prevalent in India. A study reported that the prevalence of pig cysticercosis in Lucknow district, Uttar Pradesh was as high as 26%, about 40% of them had cysts in the brain. Previous studies had also reported the detection of cysts in the pigs in Kolkata, Chandigarh and the surrounding regions.

The tapeworm infection-treatment gap, the difference in the number of people who need care and those who receive care, is above 90% in rural India. This gap could be attributed to lack of knowledge, deficiency of medical facilities, social preconception of modern medicine, and belief in alternative treatment methods. This needs to be addressed urgently by extensive use of treatment modalities, available preventive chemotherapeutic agents and vaccines as well as health education.

Risk factors of cysticercosis

Cysticercosis occurs due to swallowing of the tapeworm eggs excreted in the feces of people infected with adult tapeworm. Tapeworm infection is caused due to the consumption of food or water contaminated with tapeworm eggs and putting contaminated fingers in the mouth.

The following are the risk factors of cysticercosis:

• Eating pork, beef and other meat that are undercooked or cooked with improper methods
• Travelling to or living in regions with poor sanitation, where pigs roam freely and consume human feces
• Reinfection with the eggs due to poor personal hygiene
• Living with someone who has intestinal tapeworm infection

Cysticercosis is caused by the ingestion of the eggs of the tapeworm called Taenia solium. In this disease, the larval form of the tapeworm develops in an intermediate host. Usually, pigs are the intermediate host for T. solium, but sometimes humans can serve as accidental hosts. Cysticercosis only occurs when the tapeworm eggs are ingested (fecal oral route), not when the cysts in undercooked pork is eaten; the latter is associated with taeniasis.

Cysticercosis is caused by the ingestion of the eggs of the tapeworm called Taenia solium. In this disease, the larval form of the tapeworm develops in an intermediate host. Usually, pigs are the intermediate host for T. solium, but sometimes humans can serve as accidental hosts. Cysticercosis only occurs when the tapeworm eggs are ingested (fecal oral route), not when the cysts in undercooked pork is eaten; the latter is associated with taeniasis.

Lifecycle of Taenia solium (pork tapeworm)

The normal lifecycle of Taenia solium involves part development in pigs and another part in humans. The pigs ingest the feces of the individual infected with the tapeworm infection, which contain the tapeworm eggs. The eggs reach the pigs’ intestine, hatch into larvae, penetrate through the intestinal wall and move into the muscle tissue. In the tissue, they develop into larval cysts called cysticerci. When the meat of the pigs (pork) is eaten by a human, the cysticerci are released. Cysticerci attach themselves to the intestinal wall and mature into adult tapeworms that produce eggs. This is called as taeniasis or adult tapeworm infection. The ingested eggs move into the bloodstream, travel until they find their way into the subcutaneous tissues, muscle, brain, or other tissues. After 60 to 90 days, the eggs develop into larval cysts. These cysts stay in the tissue for an indefinite period, without proceeding to the next stage of the life cycle. During this period, the larvae ‘disguise’ and protect themselves from the immune system, while presenting only mild symptoms. This is the stage of cysticercosis. If humans ingest tapeworm eggs through food or water contaminated with human fecal matter, they may also develop cysticercosis. Some humans having taeniasis infect themselves with eggs by accidentally ingesting their own fecal matter through bad hygienic practices. Cysticercosis develops as the eggs mature to larval form in the intestine and go through development similar to that they undergo in pigs.

The symptoms of cysticercosis vary from case to case and depending on the tissues infected and the number of the cysts. Cysticerci can develop in the muscles, brain, and/or spinal cord, eyes, heart tissue, liver, lungs, subcutaneous tissue and other tissues. If the tapeworm larvae infect the brain, abnormalities such as seizures and headaches may occur. In some cases of cysticercosis, cysts may develop under the skin, resulting in small lumps, which typically do not cause any additional symptoms. Mostly, the cysticerci cause only a few symptoms and degenerate on their own. Cysts in the eyes may cause visual impairment. Similarly, cysts in the spinal cord may cause muscle weakness or paralysis. Although, eventually, the larvae die, they result in a strong immune defensive reaction when they get exposed to the host immune system. Such reactions can cause severe complications, especially if the cysticerci are in the central nervous system and can be mild to fatal.

Sign and symptoms of neurocysticercosis

In many cases of cysticercosis, the central nervous system is involved. This condition is known as neurocysticercosis. But in most cases, no symptoms develop. However, some individuals may develop serious epileptic and neurological manifestations.

The symptoms of neurocysticercosis are based on the type of neurocysticercosis. The common symptoms of neurocysticercosis include:

• Headache
• Nausea
• Vomiting
• Dizziness
• Changes in vision
• Hydrocephalous
• Blurred or double vision
• Confusion
• Difficulty in balance

The neurocysticercosis symptoms that vary depending on the type of neurocysticercosis based on the site of presence of the cysts are listed below.

Parenchymal disease: In this type, the cysticerci develop within the brain tissue and cause the following symptoms: Seizures, Headaches, Behavioural changes, Intellectual impairment, Hydrocephalus, Loss of the ability to coordinate voluntary movements (ataxia) and/ or Muscle weakness on one side of the body (hemiparesis).

Subarachnoid cysticercosis: In this type, the cysts develop in the subarachnoid space and present symptoms like: Chronic Meningitis (inflammation of meninges, membranes covering the brain), Seizures, Headaches and/ or Hydrocephalous.

Parenchymal and extra-parenchymal (cysts in meninges or subarachnoid space) cysticercosis can occur simultaneously in an individual.

A subtype of neurocysticercosis is the racemose cysticercosis, which occurs when the cysts accumulate in the base of the brain and cause coma, mental deterioration or life-threatening complication.

The cysts in the spinal cord occur rarely but may cause compression of the spinal cord or meningitis.

Heavy central nervous system infections can result in life-threatening complications like coma or stroke. The initial symptoms of heavy central nervous system infections include weakness, fever, and muscle pain (myalgia).

Ocular cysticercosis: In this type cysts occur in the eyes and cause the following Symptom: Eye pain, Loss of vision, Retinal detachment, parting of the retina from its underlying tissue. Sometimes, cysticercosis may only affect the eyes. This condition is known as isolated ocular cysticercosis.

The diagnosis of cysticercosis is based on clinical presentation, travel history, history of the type of food eaten recently, abnormal findings on neuroimaging, and serology. If anyone has been diagnosed with cysticercosis, they and their family members should be tested for taeniasis (intestinal tapeworm infection).

The diagnostic criteria for definitive and probable neurocysticercosis are listed below:

Absolute criteria

• Biopsy of brain or spinal cord lesion showing histological evidence of tapeworm cysts
• Visualization of subretinal cysts
• Neuroimaging studies showing a scolex (head part of the tapeworm) within a cystic lesion

Neuroimaging criteria

The main neuroimaging criteria include:

• Enhancing lesions
• Cystic lesions without an apparent scolex (head part)

Confirmative neuroimaging criteria include:

• Resolution of cystic lesions following cysticidal drug therapy
• Spontaneous resolution of single small enhancing lesions
• Sequential neuroimaging studies documenting migration of ventricular cysts

Minor neuroimaging criteria include:

• Obstructive hydrocephalus (symmetric or asymmetric)
• Abnormal enhancement of basal leptomeninges

Exposure/ clinical criteria

The main exposure/clinical criteria include:

• Finding specific cysticercal antigens or anticysticercal antibodies by well-standardized immunodiagnostic tests
• Proof of household contact with tapeworm infection
• Cysticercosis outside central nervous system

Minor exposure/clinical criteria include:

• Clinical manifestations indicating neurocysticercosis
• The patient lives in region where cysticercosis is endemic

Degrees of diagnostic certainty

One of the following criteria must be met to make a definitive diagnosis:

• One absolute criterion
• Two major neuroimaging criteria along with any exposure/clinical criterion
• One confirmative and one major neuroimaging criteria along with any exposure/clinical criterion
• One major neuroimaging criterion, two exposure/clinical criteria (including at least one major exposure/clinical criteria) and exclusion of other pathologies that produce similar results.

Probable diagnosis requires one of the following:

• One major neuroimaging criteria along with any two exposure/clinical criterion
• One minor neuroimaging criteria along with at least one major exposure/clinical criterion

PORCINE CYSTICERCOSIS

Porcine cysticercosis or cysticercosis in pigs, caused by Taenia solium is a globally emerging socio-economic and public health problem. Domesticated pigs are the natural host of the parasite. They play a major role in the transmission cycle as they are close to humans and there is increase in pig farming or raising and pork consumption in many developing countries. In fact, pork is the most widely eaten meat in the world accounting for over 36% of the world meat intake. Though pigs could have massive infections, the disease is rarely associated with symptoms since most pigs are slaughtered before nine months of age, a time too short for the cysts to reach the state of degeneration and result in visible manifestations. However, the fact that Taenia solium is a leading cause of acquired epilepsy in endemic areas and the parasite was ranked first on the global scale of foodborne parasites in 2014, proves the significance and quantum of the problem.

Porcine cysticercosis is mostly caused by the larval stage of tapeworm named T. solium. Taenia asiatica is a less widespread cause of cysticercosis in pigs, with the cysts locating in the liver and viscera. Most adult and larval tapeworm infections cause little or no disease. But T. solium cysticercosis is exceptional in that the cysts are also lodged in the brain/ CNS. The caseous form of cyst contains caseous exudate which may have some calcification and develop into scars looking like rice grains. Cysticercosis in pigs are not only problematic due to the risks to humans but also cause direct problem by economic loss through condemnation of infected meat and offal.

Pigs can become infected at any age. The gravid proglottids (segment of mature worm) are shed by infected humans along with their feces. Taenia solium segments, are often passed in chains. Each of these gravid segments (proglottids) liberate up to 60,000 eggs, the greater percentage of them infective. These eggs are immediately infective when passed. Pigs feed on these feces or vegetation contaminated with these and get infected. It is possible that pigs also acquire T. solium also by ingestion of the faeces of pigs that have eaten segments. In the intestine of these pigs, the eggs hatch by shedding their outer covering and develop into oncospheres. These oncospheres traverse the intestinal wall and enter blood and lymph vessels to be carried to muscles, brain and with lesser frequency to other organs where they develop into vesicular cysticerci. In experimentally infected pigs this process takes 4 to 6 weeks after which time the immature stage of the tape worm can be identified grossly as vesicles measuring about 0.4 cm x 0.3 cm. They contain a transparent fluid with a small white structure which is the scolex (head part). Humans, in turn, ingest undercooked infected pork and thus the cycle is completed from human to pigs and from pigs, back again to humans.

Cysticercosis in pigs can be prevented by the use of chemotherapeutic agents like Oxfenbendazole and use of TSOL18 (Cysvax®) vaccine that has been registered and available for sale since November 2016. Though vaccine is effective alone, combination of vaccination and chemotherapy in pigs (99% efficacy in protecting pigs against infection when the vaccine is used in conjunction with a single dose of Oxfenbendazole) is feasible and sustainable under field conditions, taking local pig management practices into account. What is required is widespread dissemination of knowledge and use of the chemotherapeutic agents and the vaccine.

Cysticercosis may not always need treatment. About 80% of the patients with cysticercosis do not present any symptoms and these patients may not require any treatment. Each case should be assessed thoroughly for deciding the treatment modalities. Patients with Subcutaneous or intramuscular cysticercosis that cause symptoms due to inflammation can be managed by administering anti-inflammatory agents or by excision of cysticerci. For a solitary symptomatic lesion, excision is preferred. In case of single extracranial lesion, excision may be considered only after neurocysticercosis is ruled out with brain imaging. Ocular cysticercosis which involves extraocular muscle may present recurrent eye pain and diplopia. Albendazole and corticosteroids are useful in the treatment of this condition. However, surgical removal is the choice of treatment for intraocular cysticerci, instead of antiparasitic drug therapy.

Treatment for neurocysticercosis:

Neurocysticercosis is managed as per the presenting symptoms. Patient presenting with seizures are treated with antiepileptic drug therapy. Patients with vasculitis or cerebral edema should be treated with anti-inflammatory drugs like methotrexate and corticosteroids. Those diagnosed with having hydrocephalus require a shunt surgery that reduces the intracranial pressure by channeling out cerebrospinal fluid from the brain. Although antiparasitic treatment is vital for treatment of cysticercosis, it should never be given emergently. This is because the antiparasitic drugs can further deteriorate cerebral edema and these drugs must be avoided in patients with high intracranial pressure caused by untreated hydrocephalus or diffuse cerebral edema.

Antiparasitic drugs given along with corticosteroids have better outcomes for patients with parenchymal cystic neurocysticercosis. The treatment for parenchymal neurocysticercosis is based on its form. For diffuse cerebral edema or untreated hydrocephalus, treatment involves management of increased intracranial pressure alone. For viable parenchymal cysticercosis, administration of antiparasitic drugs, only of there is no increased intracranial pressure. For a single enhancing lesion or 1-2 viable parenchymal cysts, monotherapy with albendazole at 15 mg/kg/day in 2 daily doses (up to 1200 mg/day) for 10-14 days is preferable. For more than two viable parenchymal cysts, combination of praziquantel (15 mg/kg/day in 3 daily doses) and albendazole (15 mg/kg/day in 2 daily doses up to 1200 mg/day) for 10-14 days is required. Antiparasitic drugs should always be given along with corticosteroids. All cases of seizures should be treated with antiepileptic drugs. Calcified parenchymal neurocysticercosis should not be managed with antiparasitic treatment and excision is the treatment of choice in this case.

PROGNOSIS

Most individuals with parenchymal cysticercosis either do not present any symptoms or develop a seizure disorder. Patients with intracerebral calcifications, often have recurrent seizures. These seizures can be easily controlled by anticonvulsant drugs. Ventricular neurocysticercosis is usually treated by shunting. Neurosurgery can have complications like focal neurologic damage. Often shunt revisions are required, unless corticosteroids or antiparasitic drugs are used for the treatment. However, some patients may still require subsequent revision despite the treatment. Subarachnoid disease was associated with a 90% 10-year fatality rate before the use of corticosteroids and antiparasitic drugs, even with shunting. With adaptation of current management guidelines, fatalities have become rare. Evidence suggests that, once a person has been infected with cysticercosis, they are immune to reinfection.

PREVENTION AND CONTROL OF CYSTICERCOSIS

The transmission of cysticercosis can be controlled by:

• Educating the population in endemic areas about the route of transmission of the tapeworm eggs.
• Organising meat inspection in regions with high prevalence.
• Cooking meat thoroughly and freezing it before cooking can kill the cysticerci.
• voiding undercooked pork in the areas of endemic cysticercosis.
• Identifying human carriers of tapeworm depending on the history of proglottid passage and initiating targeted treatment.
• Maintaining good sanitary conditions, especially by properly disposing human stool in endemic areas.
• Changing pig-raising methods in endemic areas, probably by confining the animals and stopping them from roaming freely to prevent them from contacting infectious ova excreted in human feces.
• Vaccinating the pigs.

Combination of mass treatment of pigs, mass treatment for tapeworm carriage, and vaccination of pigs have shown to be beneficial in interrupting the transmission of T. solium infection in endemic regions. Also, mass chemotherapy has shown to be effective in interrupting the transmission, but the infection usually recurs in a few years. Mass anthelminthic therapy have shown only limited success; but importantly, this method can cause adverse neurologic events in patients with undiagnosed neurocysticercosis.

The following precautions should be taken to prevent cysticercosis:

• Wash hands with water and soap after using the toilet, before handling food, after changing diapers.
• Explain the importance of washing hands to children.
• Wash thoroughly and peel all fruits and raw vegetables before eating.
• Follow safety measures while traveling to developing countries, where cysticercosis is prevalent; such as:
• Drink only boiled or bottled water or carbonated drinks in cans or bottles.
• Filter water if you feel that it is not clean with “absolute 1 micron or less” filters and add iodine tablets to the filtered water.
• Ensure that the meat or fish is properly cooked before eating.
• Eat vegetables and fruits that have been peeled by you.

The transmission of cysticercosis can be controlled by:

• Educating the population in endemic areas about the route of transmission of the tapeworm eggs.
• Organising meat inspection in regions with high prevalence.
• Cooking meat thoroughly and freezing it before cooking can kill the cysticerci.
• Avoiding undercooked pork in the areas of endemic cysticercosis.
• Identifying human carriers of tapeworm depending on the history of proglottid passage and initiating targeted treatment.
• Maintaining good sanitary conditions, especially by properly disposing human stool in endemic areas.
• Changing pig-raising methods in endemic areas, probably by confining the animals and stopping them from roaming freely to prevent them from contacting infectious ova excreted in human feces.
• Vaccinating the pigs.

Combination of mass treatment of pigs, mass treatment for tapeworm carriage, and vaccination of pigs have shown to be beneficial in interrupting the transmission of T. solium infection in endemic regions. Also, mass chemotherapy has shown to effective in interrupting the transmission, but the infection usually recurs in a few years.

Mass anthelminthic therapy have shown only limited success; but importantly, this method can cause adverse neurologic events in patients with undiagnosed neurocysticercosis.

Vaccines play a major role in preventing diseases and maintaining good health in animals. It has been effective in reducing disease burden in pets and farm animals. Vaccines contain antigens from bacteria, viruses, bacterial toxins, or parasites. They stimulate an immune response without causing the actual disease.

When vaccines are injected into a pig, its immune system responds to the vaccine and remembers the infectious agent. Thus, when the vaccinated animals are exposed to the same pathogen, the immune system will fight and prevent the disease by exerting anamnestic response. Some of the vaccines provide robust immunity especially with live vaccines while as the inactivated vaccines provide shorter immunity in vaccinated animals.

Pig vaccination can be done to provide protection against various diseases, including Classical Swine Fever, Foot and Mouth Disease, Porcine Parvovirus, Porcine Reproductive Respiratory Syndrome, Porcine Circovirus Associated Disease, and tape worm infections. The vaccines are usually administered in pigs by individual injection.

Indian Immunologicals Limited, Hyderabad, India has been the first manufacturing company to come out with a commercial vaccine against Porcine cysticercosis. The vaccine has been the research efforts and outcome with involvement of the University of Melbourne, Australia and IIL. The name of the vaccine is CYSVAX R and is available from the year 2016. Vaccinating pigs in endemic regions to prevent porcine cysticercosis along with administration of anthelminthics is a good strategy to improve animal health, meat yield and to break the parasite life cycle thus preventing porcine and human cysticercosis.

Cysvax^® – by IIL

IIL has collaborated with Professor Marshall Lightowlers of The University of Melbourne, to develop the vaccine Cysvax®. Development of this vaccine is the first step towards vaccine licensing for cysticercosis. The five-year public-private partnership of these esteemed institutes has focused on making the vaccine available to regions where porcine cysticercosis has a significant effect on human health and economy. Effective administration of the vaccine is believed to reduce the incidence of neurocysticercosis-related epilepsy in the developing world.

Cysvax® is a biotechnologically derived vaccine for porcine cysticercosis. The vaccine contains the antigen, Oncosphere protein of Taenia solium. This triggers the immune response in the vaccinated pigs and provides protection against the actual tapeworm infection. Cysvax® vaccine can be given along with Paranthic® – the only registered anthelmintic for porcine cysticercosis, to control the cystic stage of the parasite in pigs thus breaking the life cycle of the tapeworm.

Description:

Cysvax is a biotechnologically derived immunological veterinary vaccine. The vaccine antigen is the Oncosphere protein encoded by a specific gene (TSOL 18 gene) of Taenia Solium. This antigen is produced by Pichia Pastoris expression system and formulated with an oil adjuvant and recognized to be highly immunogenic.

Composition: Each dose 1 ml contains Taenia Solium oncosphere antigen (TSOL 18) greater or equal to 150 micro grams, Thiomersal (as preservative) ≥ 0.02 % w/v. Mineral oil (as adjuvant) and phosphate buffer diluent q.s.

Potency: Greater or equal to 500 Anti TSOL 18 IgG titre in 5 animals out of 6 by Elisa.

Indications: Cysvax vaccine is indicated for active immunization of pigs against porcine cysticercosis

Target species: Pigs

Dosage and administration: Pigs: 1 ml by deep Intramuscular injection behind the ear area. A sterile needle and syringe should be used for each vaccination.

Vaccination Regimen: Primary vaccination: Pigs approximately 2 months of age and above Booster dose: 3-4 weeks after primary vaccination Re-vaccination: 6 Months.

Immunity: Develops by 2 weeks post booster dose

Contraindications: Do not vaccinate unhealthy animals i.e. animals suffering from diseases, malnutrition, allergic conditions and extreme stress etc.

Precautions: In rare cases, hypersensitivity may occur, immediate treatment with adrenaline & antihistaminic is advocated.

Injection of mineral oil into humans can produce serious localized reactions and special care should be taken to avoid accidental inoculation. If it happens, consult a medical physician immediately.

Generally, corticosteroid therapy should be avoided 1-2 weeks before and after the vaccination for developing good immune response.

Side Effects: Generally, no significant side effects are noticed, however in some animals temporary pyrexia, lethargy for 1-2 days and local injection site reactions for up to 7 days may be observed after vaccination.

Effects with other vaccines: No information is available on the compatibility of this vaccine with any other vaccines. Therefore, the safety and efficacy of this product when used with other vaccines has not been demonstrated.

Withdrawal Period: Zero days.

Overdose: With administration of a 5-fold overdose of vaccine, no adverse reactions were observed under farm conditions other than those described under side effects.

Storage & Transport: The vaccine should be stored and transported between 2°C and8°C

DO NOT FREEZE. SHAKE WELL BEFORE USE. KEEP OUT OF REACH OF CHILDREN.

Shelf Life: 24 months from the date of manufacture when stored at recommended storage conditions.

Disposal of Used Containers: The empty containers of the vaccine, used syringes and needles should be disposed of properly and carefully according to local regulatory requirements.

Presentation: Cysvax is available as 1mL,5mL,10mL & 20mL vial