A review on diagnostic and preventive aspects of cystic echinococcosis and human cysticercosis.

Cystic echinococcosis and human cysticercosis have recently been included in the list of "neglected tropical diseases" by the World Health Organization (WHO). Both are zoonoses which are prevalent throughout the world and lead to considerable mortality, morbidity, and economic losses as well. This review deals with the disease burden of these two neglected cestode infections. Diagnostic modalities with their specific advantages and disadvantages have also been discussed. Recent developments in immunodiagnostic assays for the two diseases have been dealt with. Various control strategies including the use of veterinary vaccines have been highlighted.

INTRODUCTION

The neglected tropical diseases (NTD) are diseases which affect the world's poorest. The term “NTD” is a collective term used for diseases sharing a few common characteristics like being more common in tropical countries and the fact that most of them have been neglected by researchers and health policy makers alike.[1] Although effective chemotherapy and other treatment options are available for many of these diseases, these diseases still prevail amongst the poorest populations in the world. Recently, the World Health Organization (WHO) included human cysticercosis and cystic echinococcosis (CE) in the list of NTDs. These larval cestode infections cause considerable morbidity and mortality and socio-economic loses in many developing countries.[2] Cysticercosis in humans is the larval stage infection of the pork tapeworm Taenia solium whereas CE, otherwise known as hydatid disease is the larval form of the dog tapeworm Echinococcus granulosus. Both these conditions are responsible for considerable morbidity and socio-economic losses as well in many regions of the world.

CE, in the strictest sense, is not a tropical disease and is quite prevalent in temperate regions as well. However, since it results in considerable loss of disability adjusted life years (DALYs) in many underdeveloped parts of the world (many of them in the tropics), is not easy to diagnose because of the chronic course of the disease and lack of proper diagnostic facilities, it is justified to include it among the NTDs.

Human cysticercosis and CE have now been grouped under a separate group known as “neglected zoonotic diseases” (NZDs). NZDs can be considered a subset of NTDs. NZD is a comparatively new terminology which has been used for diseases such as anthrax, bovine tuberculosis, brucellosis, cysticercosis, CE (hydatid disease), and rabies.[3] According to WHO, these diseases are called “neglected” as these have not been given enough importance at national or international levels.

Although both human cysticercosis and CE lead to considerable mortality and morbidity, these conditions were only recently included in the WHO strategic plan (2008-2015) for the control of NTDs and were put under the neglected zoonosis subgroup.[2] CE and human cysticercosis have often been referred to as the “neglected NTDs.”[2] This is because even among the NTDs, these two conditions have not received much attention as compared with other public health problems like lymphatic filariasis or even intestinal helminthic infections. There are many reasons for this. The major reason is that the diagnostic modalities required to detect these conditions are not yet widely available, especially in the areas where these infections are most prevalent. Besides, many of the diagnostic techniques like imaging methods are not affordable. CE and cysticercosis in humans are both chronic conditions and clinical signs may be evident only after many years. Therefore, these conditions are grossly under-reported, ironically in areas where they are most prevalent.[2]

EPIDEMIOLOGY

CE and human cysticercosis are both diseases with a cosmopolitan spread with cases being seen in both the developed as well as the developing countries. However, the data regarding the geographic spread of these conditions is not complete. According to some data, CE due to E. granulosus has been reported from over 100 countries.[4] Only a few countries like Ireland and Iceland are believed to be free of CE.[5] However, it is in the developing countries that these are major problems and not only cause morbidity and mortality, but are also responsible for considerable socio-economic loss. According to statistics given out by WHO, the annual societal cost of CE amounts to US $150 million in the subcontinent of India alone.[3]

Cystic echinococcosis

Three forms of echinococcosis are seen in human beings- CE caused by E. granulosus, alveolar echinococcosis caused by Echinococcus multilocularis, and polycystic echinococcosis caused by Echinococcus vogeli and Echinococcus oligarthus. CE is of special importance due to its wide geographic distribution and socioeconomic impact, not only with respect to the medical costs associated with it but also with regard to the loss of livestock because of this condition in them.[4] As many as nine different strains or genotypes of E. granulosus have been described out of which at least seven of which are infective to humans.[4] These strains are named after their ideal intermediate hosts as G1(common sheep strain), G3(buffalo strain), G5 (cattle strain), G7 (pig strain) etc., Most important among these with regards to human infection are the sheep (G1) and the cattle (G5) strains.[6] Humans act as dead-end hosts.

CE is not strictly a tropical disease as it is quite prevalent in temperate regions of the world like Eurasia and Central Asia. High rates of infection have been reported from northern Russia and Siberia.[7] High incidences of this condition has been reported from many other parts of the world like China and parts of Africa and South America.[89] CE is reported to be endemic in countries such as Iran, Iraq, Turkey, Morocco, and Egypt.[9] In the last two decades, there has been a considerable increase in the number of cases of CE in parts of Central Asia like Kyrgystan and Kazhakhstan and also an increase in the number of imported cases of CE in Russia from these areas.[10]

Human cysticercosis

Cysticercosis in humans is an ancient disease and has even been detected in Egyptian mummies by paleoparasitologists.[11] Cysticercosis is now a major public health problem in much of the developing world. Neurocysticercosis (NCC) is the commonest parasitic infection of the central nervous system (CNS) and the single most common cause of epilepsy in the developing countries.[1213] NCC is endemic in many parts of the world including India, Mexico, parts of Central and South America, and Africa.[14] In Asia, NCC is a major cause of epilepsy in many countries like India, Indonesia, Vietnam, Nepal and China.[1516] Prevalence of cysticercosis is comparatively lower in countries like Japan and Singapore which can boast of improved infrastructure and sanitation conditions. But there are few studies from developed countries which have reported significant economic burden due to NCC. In a study from California, NCC was found to cause appreciable disease and a considerable economic burden among hospitalized cases, most of whom were Latino.[17]

SOCIOECONOMIC IMPACT OF THE LARVAL CESTODE DISEASES

It is difficult to gauge the socioeconomic loss due to human cysticercosis and CE as these conditions cause more of morbidity than mortality. According to some estimates, echinococcosis may be responsible for loss of upto 3.6 million DALYs worldwide.[18] Also, many of the measures like surgery or puncture, aspiration injection and re-aspiration (PAIR) may be associated with complications which add to the hospitalization and treatment costs due to these diseases. It has been estimated that irreversible damage due to CE may make the cost of treatment of this condition comparable to that of surgical treatment of some malignancies.[6] Like CE, cysticercosis, especially NCC, has been found to cause significant economic burden in some countries. A recent study from Mexico reported that 25,341 DALYs were lost due to NCC associated epilepsy and severe chronic headaches.[19] In another study from Peru, it was found that treatment costs and productivity losses due to NCC consume 54% of an annual minimum wage salary during the first year of treatment and 16% during the second year.[20]

Data on porcine cysticercosis is lacking in many developing and underdeveloped countries because there are no uniform policies which are followed in these countries to screen for infected pigs. There is a paucity of official slaughter houses in most of these countries and as a result porcine cysticercosis is grossly underestimated. One of the common ways of screening pigs for cysticercosis is the palpation of their tongues where cysticerci can be detected.[15] In recent years, serological tests have also become available to detect porcine cysticercosis.[21]

DIAGNOSIS

The major modalities of diagnosis of both CE and cysticercosis in humans, especially NCC, are imaging techniques and the detection of serum antibodies by various immunodiagnostic tests. Detection of specific antigens in various clinical specimens like serum, saliva, and urine has also been evaluated by some authors.

Imaging methods as diagnostic modalities

Imaging methods play very important roles in the diagnosis of both human cysticercosis as well as CE.

The diagnosis of CE relies heavily on imaging techniques like ultrasonography (USG) and computed tomography (CT). USG is the imaging tool most commonly used for diagnosis and follow-up of CE. USG findings are quite accurate, especially for abdominal and hepatic CE. Apart from that, the test is non-invasive, results are obtained quickly and there is no exposure to non-ionizing radiation.[22] In recent years, “portable USG” has been used in many areas of the world that are endemic for CE like Peru in South America for the detection of CE in even far flung areas.[23] These portable ultrasound scanners are powered by batteries or generators and are used in peripheral centers to screen for CE.[22] In CE, imaging methods are not only useful in diagnosis of the condition, but have also been evaluated in its treatment. It is now commonplace to use ultrasound guidance when carrying out treatment modalities like PAIR or percutaneous puncture with drainage and curettage (PPDC).[22] Since there are many types of CE cysts, many researchers have tried to classify them based on the clinical findings.[24] In 1995, a WHO working group proposed a standardized classification system where the hydatid cysts are grouped into three different groups- active, transitional and inactive.[25] Cysts belonging to these groups differ with respect to the stage at which the cyst is and the ideal treatment options for them.

CT findings are especially helpful in the diagnosis of hepatic hydatidosis. Few studies have indicated that CT is superior to USG in the diagnosis of CE of the liver.[26] CT scan is also the best imaging method to detect cyst calcification or infected cysts and also comes in useful when the patient is obese or there are abdominal wall deformities.[27] CT scan is also very useful in the diagnosis of hydatid cyst of the lungs. There are a few CT scan findings that are characteristic of hydatid cyst of the lungs- the “water-lily sign” created because of collapsed endocysts floating in the dependent part of the pericyst cavity, the “onion peel sign” which occurs because of the presence of air between the endocyst and pericyst, and the “meniscus sign” which is a very common finding in CE of the lungs.[28]

Magnetic resonance imaging (MRI) is useful in the diagnosis of cerebral hydatid cyst which is a rare entity and comprises only 2% of all intracranial space occupying lesions (ICSOL). It is especially helpful in detecting multiple cysts and detecting the cyst capsule.[29]

For the diagnosis of human cysticercosis, especially NCC, CT and MRI findings are at many times crucial. In fact, some characteristic neuroimaging findings are included in the “absolute criteria” for diagnosis of NCC. The characteristic appearance of the scolex within a cyst known as “hole-in-dot” sign is considered pathognomonic for cystic lesions of NCC.[30] The different findings by neuro-imaging methods depend on a number of variables like the number and location of cysts, stage and viability of the cysts, etc. While CT is considered to have the best sensitivity for detection of calcified lesions, MRI outperforms all the other neuro-imaging methods when it comes to detecting viable cysticerci.[12] MRI is very useful in detecting perilesional edema associated with NCC and also cysticerci in locations like ventricles and brainstem.[31]

Although imaging methods are extremely useful in the diagnosis of both human cysticercosis as well as CE, their major shortcoming is their cost and the fact that facilities and infrastructure for these imaging techniques is for the most part not available in rural areas and underdeveloped areas where the major disease burden lies.

Immunodiagnosis of cystic echinococcosis and cysticercosis

Antibody detection

Among the various immunodiagnostic tests available, enzyme-linked immunosorbent assays (ELISA) using crude hydatid cyst fluid antigen are most commonly used for the diagnosis of CE. Such assays are quite sensitive (95% sensitivity), but the specificity is often low.[4] When other techniques like immunoblot are used, the specificity is improved but that is at the cost of the sensitivity. In case of hydatid cysts at specific sites like the brain, bone and ocular cysts, false-negative results are common.[4] Serological assays like indirect hemagglutination (IHA) and intradermal skin test (Casoni's test) were quite popular couple of decades back but are rarely performed now.[3233] Other antibody detection formats which have been evaluated are dot-ELISA, latex agglutination, etc.[3334] Siavashi et al.,[34] reported dot-ELISA to have 100% sensitivity and 98.7% specificity in diagnosing surgically proven cases of CE and found the performance to be better than a sandwich ELISA.

Among the serological tests available for detecting antibodies against T. solium for diagnosis of cysticercosis, both human and porcine, ELISA formats are preferred in developing countries because of their simplicity and lower cost as compared to other more specific tests like enzyme linked immunoelectrotransfer blot (EITB).[35] EITB, however, has been found to be much more specific and in some studies, specificity of up to 100% has been reported.[35] But in one study by Michelet et al.,[36] it was found that the sensitivity and specificity of antibody detection from cerebrospinal fluid (CSF) samples in cases of NCC by ELISA and EITB were not significantly different. The same study also advocated the use of ELISA for antibody detection in the diagnosis of NCC in poor countries due to lower cost. Older assays for cysticercosis include IHA for demonstration of antibodies.[37] Apart from IgG, detection of IgA antibodies against cysticercus has been found to be useful in particular scenarios. Sahu et al.,[38] reported the detection of IgA antibodies in tear samples by IgA ELISA as a sensitive method for diagnosis of ophthalmic cysticercosis in humans.

Antigens used for designing diagnostic assays

Antigens used for diagnosis of cystic echinococcosis

One of the major shortcomings in the field of immunodiagnosis of parasitic diseases in general and hydatid cyst in particular is the lack of proper immunogenic antigens which can be used to design antibody assays. Many researchers in the field make use of native antigens from either human or animal source. Antigen prepared from hydatid cyst fluid obtained from humans has, however, been found to contain host immunoglobulins and is therefore not a good choice. Hydatid cyst fluid derived from various animal sources like sheep, cattle, and even camel have been evaluated by different authors and have been found to give better results than antigen derived from human hydatid cysts.[39] For example, immunoblot assay using bovine hydatid cyst fluid as the antigen has been found to perform quite well (sensitivity of 80% for hydatid cysts of the liver) even in areas endemic for hydatid cyst disease like in parts of Peru.[23]

Apart from hydatid cyst fluid, other components of hydatid cyst have also been evaluated like cyst-wall antigen and protoscolex antigen.[334041] Swarna et al.,[33] evaluated the diagnostic potential of different components of hydatid cyst like the cyst wall antigen, hydatid cyst fluid and protoscoleces in a DOT-ELISA format and found no significant difference in the performance of assay using any of these antigens. Some scientists have even evaluated the potential of adult E. granulosus antigen in immunodiagnostic assays.[42]

The major disadvantage of using crude hydatid cyst fluid as the source of antigen for antibody detection assays is that cross-reactivity is seen with sera of patients infected with other helminths. Antibody detection assays using crude hydatid cyst fluid antigen are however useful for screening purposes as the sensitivity of the assays is quite high.[43]

Because of the low specificity of hydatid cyst fluid, many antigenic components of the hydatid cyst fluid have been evaluated for designing immunodiagnostic assays for CE. Among them, antigen 5 (Ag5) and antigen B (AgB), both of which are lipoproteins, are the most widely used.[39] Ag5 is a high molecular weight lipoprotein whereas AgB is a 120 kDa oligomeric lipoprotein.[44] AgB dissociates into its subunits under reducing conditions and one of its smallest subunits of 8 kDa size has been found to be very reliable in immunoblot detection.[43]

The disadvantage of using native antigens in the diagnosis of any helminthic infection is that these antigens are limited in availability. The same problem is faced by researchers trying to design immunodiagnostic assays using native antigens in case of CE. Another problem in the use of native antigens is batch to batch variation in the antigens. Synthetic peptides derived from antigen B have been evaluated and have been found to perform better than AgB or Ag5 in ELISA.[44] Other antigens which have been evaluated include protoscolex and adult somatic antigens. Crude forms of these antigens as well as components derived from them have been used. Recently, researchers have made use of the tools of genomics and proteomics to discover diagnostically relevant peptides.[45] Recombinant DNA technology has revolutionized the development of new antigens which can be used in immunodiagnostic assays. Compared to native antigens, these antigens show much less cross-reactivity and can be obtained in large quantities. In case of CE, recombinant antigens derived from various components like protoscolex and Ag5 have been evaluated. Two recombinant forms of Ag5, i.e., rAg5 and rAg5-38S have been used for developing serological tests. Compared to the native antigens these recombinant antigens showed better performance.[43]

Recently, a recombinant antigen B8/1 based on the native antigen B was found to show an excellent specificity as compared to native antigens like antigen B and hydatid cyst fluid antigen.[46] Other antigens which have been evaluated include adult excretory secretory products and protoscolex antigens. These antigens, however, have mostly been evaluated as antigenic sources in the serodiagnosis of intestinal echinococcosis in dogs.[43]

Antigens used for diagnosis of human cysticercosis

Among the somatic antigens of T. solium cysticerci used in serological tests for cysticercosis are the cyst fluid, whole cyst homogenate, cyst-wall antigen, and protoscolex antigen.[47] All these antigens have been evaluated with varying degrees of sensitivity and specificity.[48] As compared to crude antigens, various purified antigenic components have been found to perform better in immunodiagnostic assays.[3549] For many parasitic diseases like malaria, amoebiasis, etc., excretory-secretory (ES) antigens have been found to perform much better than the crude somatic antigens. There are a few studies on use of ES antigens for developing antibody ELISA. A study by Sahu et al.,[50] evaluating an ELISA using ES antigens however showed a much lower sensitivity of 64.28% although the specificity was good (96.96%). Many peptides derived from the ES antigen of cysticercus metacestode like the 43-kDa peptide have been evaluated.[51] An advantage of using ES antigens instead of somatic antigens for detection of antibodies against T. solium cysticerci is that it is possible to determine whether the parasite larva is living, dead or degenerated.[52] Heterologous antigenic peptides derived from Taenia crassiceps have also been evaluated for immunodiagnosis of NCC.[53]

Synthetic peptides have also been evaluated for the detection of antibodies against T. solium cysticerci. Fleury et al.,[54] evaluated the diagnostic utility of five synthetic peptides cloned from a Taenia saginata oncosphere cDNA library and got encouraging results. Scheel et al.,[55] performed ELISA using four synthetic lentil lectin purified glycoprotein peptide (LLGP) antigens derived from T. solium metacestodes and found that although the ELISA did not perform well, EITB using these synthetic peptides gave results comparable with that obtained when native antigens were used for the assay.

Many scientists have developed and used recombinant antigens in immunodiagnostic assays in the past decade. Hancock et al., evaluated recombinant GP50 in a Western blot assay and reported a sensitivity of 90% and specificity of 100%. Many other recombinant antigens have also been evaluated showing very high specificity although the sensitivity is somewhat lower as compared to assays using native antigens.[35]

Despite so many developments with regard to antigens for immunodiagnostic use in human cysticercosis and CE, the fact remains that most commercially available assays as well as most in house standardized assays still utilize native antigens rather than the synthetic or recombinant ones. This makes the immunodiagnosis of these cestode infections cumbersome and for many populations inaccessible because of the cost involved. There is an urgent need to develop diagnostic tests using synthetic and recombinant assays in order to make antibody detection assays more widely and cheaply available.

ANTIGEN DETECTION

Detection of antigens in cystic echinococcosis

One of the major disadvantages of using antibody detection for diagnosis of helminthic infections like CE is that these antibodies might persist for a long time even after clinical and parasitological cure.[56] It is therefore not possible to differentiate between recent and past infections by antibody detection. Besides, it has been seen that up to 40% of peroperatively confirmed cases of hydatid cyst may be negative for hydatid specific antibodies.[57] Detection of circulating hydatid antigen in the serum has been evaluated to be useful in the diagnosis of active infection as these antigen levels decrease after chemotherapy or surgical resection of the hydatid cysts. ELISA, countercurrent immunoelectrophoresis (CIEP), reverse passive haemagglutination (RPHA) and latex agglutination have all been evaluated for hydatid antigen detection in serum and other samples.[58-60] Sheela Devi et al.,[56] standardized and evaluated a simple latex agglutination test for hydatid antigen detection from human serum and reported a high specificity of 98% for the assay although the sensitivity was comparatively low. An antigen-based ELISA was developed and evaluated by Sadjjadi et al.,[61] The authors found that when compared to antibody detection, the sensitivity of the antigen ELISA was very low (25.7%), although the specificity was found to be 98%. Co-agglutination test has also been found to be a rapid and cheap method of hydatid antigen detection in serum as well as urine samples.[586263]

The relevance of detecting circulating antigens in the serum of treated patients has been evaluated by many authors.[6465] Ferragut et al., studied the profile of circulating antigens and anti-hydatid antibodies in experimentally infected mice and found that an early circulating antigen peak was followed by large antibody peak which is followed by periods when antibody levels were very high but no circulating antigens were detected. They also evaluated the levels of circulating antigen levels in patients with hydatid cysts who had undergone surgical resection for the cysts and found that all patients who did not show any recurrence of the cysts were negative for circulating hydatid antigen.[64]

Antigen detection in the diagnosis of human cysticercosis

Antigen detection for cysticercosis has been performed on both serum as well as CSF samples.[66] Positive CSF ELISA for detection of cysticercal antigens is included as minor criteria in Del Brutto's criteria for diagnosis of NCC. Antigen detection ELISA with CSF samples has been found to be useful in demonstrating ES antigens in CSF.[3067] In a study from Mexico, Fleury et al., reported a sensitivity of 100% and specificity of 97.7% for detection of antigens against T. solium cysticerci from CSF samples by ELISA.[68] Detection of the secreted metacestode antigen HP10 in CSF samples is a very sensitive and specific method for the diagnosis of cases of NCC. A study found HP10 Ag-ELISA to have a specificity of 100% in CSF specimens, accompanied by high sensitivity for the detection of ventricular parasites located in the subarachnoid space or in ventricles in cases of NCC.[36] Another study by Fleury et al., found the detection of HP10 antigen in serum to be a useful tool in the diagnosis and follow-up of patients with severe clinical manifestations of NCC.[69] Apart from antigen ELISA, other techniques for cysticercus antigen detection have also been evaluated. Parija et al.,[70] evaluated the co-agglutination test for diagnosis of cases of cysticercosis and found it to be moderately sensitive and specific.

Non-invasive samples like urine, saliva have been used for detection of hydatid and cysticercus antigen with varying degrees of success.[6062] The major advantages of being able to detect parasite antigen in such samples is that it is easy to collect these specimens. However, the sensitivity and specificity of these tests varies widely. Among the antigen detection tests that have been evaluated for the detection of hydatid antigen in urine samples are the co-agglutination test, CIEP.[6271] Ravinder et al.,[62] evaluated the co-agglutination test for hydatid antigen detection in urine samples and reported a low sensitivity rate of 43.75% in surgically confirmed cases of hydatid cyst.

Similarly antigen detection in urine samples has also been evaluated for diagnosis of human NCC. Castillo et al., reported a sensitivity of 92% for detection of cysticercus antigen in cases where the parasites are viable. The sensitivity reported for patients with a single cyst is, however, quite low at only 62.5%. The authors also reported a strong correlation between the antigen level in the serum and that in urine.[72] Parija et al.,[73] have reported a sensitivity of 62.5% and a specificity of 91% for detection of cysticercus antigen in urine specimens by using a polyclonal antibody-based ELISA format.

TREATMENT

Both surgical intervention and chemotherapy play important roles in the treatment of human cysticercosis and CE. The mode of treatment depends on a lot of variables like the number of lesions (cysts), location and stage of cysts etc., Treatment of cysticercosis and CE is beyond the scope of this review. The reader may refer any of the excellent reviews available on the subject.[74-76]

PREVENTION AND CONTROL

General measures

There are many environmental, economic and social factors involved in the transmission of both human cysticercosis and CE, both of which are zoonoses and are more commonly seen in populations lacking basic sanitation facilities and living in close proximity to livestock.[77]

Some of the newer approaches for the control of these conditions include use of effective livestock vaccines, porcine vaccines in case of cysticercosis and ovine vaccines in case of CE. Other measures which will come in useful are development of better diagnostic assays to detect the parasite in both the human cases as well as in the definitive hosts in case of CE. Coproantigen detection in dogs is one such diagnostic assay.[78]

Preventive chemotherapy is one of the pillars of control programs targeting NTDs and has been quite successful for problems like lymphatic filariasis.[79] Large scale administration of anthelminthic drugs to humans has been found to reduce the number of tapeworm carriers and the probability of cysticercosis infection.[80] Similarly, regular praziquantel administration to dogs has been found to lead to a substantial decrease in the number of hydatid cyst cases.[77]

Vaccination-role in control of larval cestode infections

Although pertinent lifestyle changes, improved socioeconomic conditions and anthelminthic therapy are important in reducing the prevalence of the cestode larval diseases, they are clearly not enough to eradicate them. In recent years, a different approach has been evaluated for reducing the transmission of these infections and that is vaccination of the intermediate hosts to interrupt the transmission cycle of the parasites. Considerable progress has been made in developing vaccines against CE in sheep and cysticercosis in pigs. Antigens derived from the parasite oncosphere of E. granulosus have been used to vaccinate sheep against the parasite.[81] Recombinant DNA technology has been used for large scale production of these antigens.

A cloned recombinant antigen EG95 has been found to be highly immunogenic in sheep and goats and vaccines using this antigen have entered clinical trials in many countries like Australia, Argentina, and China.[8182] This particular vaccine is very promising because two doses of the vaccine have been found to confer protection for atleast one year. It has also been demonstrated that this immunity is passively transferred to neonates as well.[81]

Similar to CE, several approaches have been used for developing a vaccine against porcine cysticercosis. Vaccination of pigs is one of the important measures to prevent the transmission of T. solium in endemic areas thereby reducing the incidence of human cysticercosis. Initially, it started out with development of cell-free antigen preparations obtained from in vitro culture of oncospheres of Taenia ovis and T. saginata. A major breakthrough came in 1989 when Johnson et al.,[83] developed a recombinant antigen vaccine against cysticercosis caused by T. ovis in sheep. A similar approach was subsequently adopted for development of a vaccine against T. solium cysticercosis in pigs. In one trial, two recombinant oncosphere antigens, TSOL18 and TSOL45 1A were found to confer complete protection to all vaccinated pigs.[8485] In another study by Assana et al.,[86] it was reported that combined application of TSOL18 vaccination and a single dose of oxfendazole was useful in preventing T. solium transmission in pigs in the endemic areas. A recent study by Gauci et al.,[87] found the recombinant antigen TSOL16 to be capable of inducing a high level of immunity in pigs against a challenge infection with T. solium. Other sources of antigen which have been evaluated for developing a vaccine against porcine cysticercosis include antigens derived from T. crassiceps, a rodent parasite.[8488]

CONCLUSION

CE and cysticercosis in humans are NTDs whose prevalence is grossly under estimated. Most of the NTDs including cysticercosis and CE are chronic diseases which have a low case fatality rate and are seen among the world's poorest. The major reason for the underestimation of the disease burden due to the larval cestode diseases is because of the non-availability of proper diagnostic facilities in many settings where these infections are common. The mainstay of diagnosis of both CE and human cysticercosis are imaging methods and immunodiagnostic tests for antigen and antibody detection. While the imaging methods are too expensive for the people who are most commonly affected by these cestode larval infections, many of the immunodiagnostic tests (especially those detecting antibodies) have very low specificities. It is imperative to develop better immunodiagnostic assays with better sensitivity and specificity profiles. For this, it is necessary to evaluate synthetic and recombinant antigens which can be used in serological assays. Recent studies have shown better sensitivity and specificity for recombinant and synthetic antigens as compared to native antigens. The development of vaccines against the cestode larval diseases could be the way to protect whole populations from the morbidity and socioeconomic loss associated with these diseases. A number of potential candidate animal vaccines have been studied especially for prevention of porcine cysticercosis, some of which have showed very promising results.