Human Neurocysticercosis Case and an Endemic Focus of Taenia solium in Lao PDR

A male patient with neurocysticercosis was identified in Montai Village, Xay District, Oudomxay Province, Lao PDR in February 2004. He had a history of diagnosis for neurocysticercosis by a CT scan in Thailand after an onset of epileptic seizure in 1993. A pig in the same district was found to contain Taenia solium metacestodes (=cysticerci); the slaughtered pig body contained more than 2,000 cysticerci. In addition to morphological identification, molecular identification was also performed on the cysticerci by DNA sequencing analysis of the mitochondrial cox1 gene; they were confirmed as T. solium metacestodes. The patient is regarded as an indigenous case of neurocysticercosis infected in an endemic focus of T. solium taeniasis/cysticercosis in Oudomxay Province, Lao PDR.     

Taenia asiatica: the Most Neglected Human Taenia and the Possibility of Cysticercosis

Not only Taenia solium and Taenia saginata, but also Taenia asiatica infects humans. The last species is not included in the evaluation of the specificity of the immunodiagnostic techniques for taeniasis/cysticercosis. There is currently no specific immunodiagnostic method for T. asiatica available. Therefore, due to the fact that molecular techniques (the only tool to distinguish the 3 Taenia species) are normally not employed in routine diagnostic methods, the 2 questions concerning T. asiatica (its definite geographic distribution and its ability to cause human cysticercosis), remain open, turning T. asiatica into the most neglected agent of human taeniasis-cysticercosis.     

Serological responses in porcine cysticercosis: a link with the parasitological outcome of infection

An oral infection model with Taenia solium whole proglottids was used to study host-parasite relationships and the mechanisms underlying resistance to infection in pigs. In addition, an attempt was made to link the parasitological findings to serological data. Groups of six piglets aged 1, 3 and 5 months were infected and slaughtered 3 months p.i. Circulating antibody and antigen levels were monitored weekly. At autopsy total cyst counts were performed. Although the detailed carcass dissection at necropsy revealed a high variation in the number of cysts, the trend was that the number of viable cysts decreased with the age at which the animals were infected. The kinetics of the antigen levels throughout the course of the infection differed markedly between the three age groups of the experimental infection model. In the younger animals, a fast increase in titres of circulating antigen was observed in most animals, reaching a plateau as early as 2 weeks p.i. Besides its faster increase, antigen levels in pigs infected at younger ages also reached higher levels than in older animals and were associated with weaker antibody responses. Results also demonstrated that a relationship exists between the number of cysts and the titre of circulating antigen. This is promising in view of the development of an assay to quantify the progress of an active T. solium infection and would be a useful tool in epidemiological studies to assess the infection burden and the risk of transmission of the disease. The use of specific antibody-detection assays combined with circulating antigen detection could improve our understanding of this relationship.     

A seroepidemiological survey of Taenia solium cysticercosis in Nabo, Guangxi Zhuang Autonomous Region, China

We have observed the seropositive rate of Taenia solium cysticercosis in residents at Nabo Village, Tiandong County, Guangxi Zhuang Autonomous Region, China by enzyme linked immunosorbent assay. The village had been found to be a relatively high endemic area of porcine cysticercosis among roaming pigs. Of 202 persons examined four males aged 15, 25, 35 and 41 year-old exhibited absorbance (abs) at 0.18, 0.20, 0.35 and 0.55, respectively. In addition, two females whose ages were 35 and 39 years revealed specific antibody levels of abs 0.26 and 0.41 in their sera. Overall positive rate among the people was 2.97%. All of these persons agreed that they had ingested the pork infected with T. solium metacestode (TsM), while history of proglottid discharge was not noticed from all of them. Three males and one female complained of intermittent headache. Our findings reinforced not only that the prevalence of cysticercosis might be related with roaming pigs infected with TsM but also that behavioral and environmental practices in local community constituted risk factors for transmission of the infection.     

Human cysticercosis and Indian scenario: a review

Cysticercosis, caused by Taenia solium larva is a major public health problem, especially in the developing world and neurocysticercosis (NCC) is considered to be the most common parasitic infestation of the central nervous system. NCC is identified as the single most common cause of community acquired active epilepsy; 26.3% to 53.8% active epilepsy cases in the developing world including India and Latin America are due to NCC. It is also becoming more common in the developed world because of increased migration of people with the disease or Taenia solium carriers and frequent travel to the endemic countries. It is estimated that three quarters of the estimated 50 million people with active epilepsy live in the poor countries of the world. Recent Indian studies using neuroimaging techniques suggest that the disease burden in India surpasses many other developing countries. Hence it is important to know the epidemiology, pathogenesis and diagnostic criteria so as to assess the disease burden and adopt interventional strategies for its control. Literature search was done for this review with special emphasis on Indian studies to create awareness about the disease in India, since cysticercosis is preventable and potentially eradicable.     

Eradication of Taenia solium cysticercosis: A role for vaccination of pigs

Taenia solium is the causative agent of neurocysticercosis, a disease responsible for substantial human morbidity and mortality. It is a zoonotic parasite, involving pigs as intermediate hosts. The parasite’s full life cycle is restricted to poor people in developing countries. Attempts to date to control transmission of the parasite have been relatively poorly effective and not sustainable. Over the past decade research has been undertaken to develop practical vaccines for use in pigs to prevent transmission of T. solium. The most effective of these vaccines in controlled experimental trials has been the TSOL18 vaccine. More recently, TSOL18 has been proven to be highly effective against naturally acquired infection with T. solium in pigs. Application of TSOL18 together with a single treatment of pigs with oxfendazole achieved the complete elimination of transmission of the parasite by pigs involved in the field trial. This strategy may provide a relatively low cost and sustainable control tool which could assist towards the goal of achieving eradication of the parasite. An assessment is made of the potential value of various control measures that are available for T. solium, and two options are suggested as potential parasite control programs.     

Genetic variation in the Cytb gene of human cerebral Taenia solium cysticerci recovered from clinically and radiologically heterogeneous patients with neurocysticercosis

Neurocysticercosis (NC) is a clinically and radiologically heterogeneous parasitic disease caused by the establishmentof larval Taenia solium in the human central nervous system. Host and/or parasite variations may be related to this observed heterogeneity. Genetic differences between pig and human-derived T. solium cysticerci have been reported previously. In this study, 28 cysticerci were surgically removed from 12 human NC patients, the mitochondrial gene that encodes cytochrome b was amplified from the cysticerci and genetic variations that may be related to NC heterogeneity were characterised. Nine different haplotypes (Ht), which were clustered in four haplogroups (Hg), were identified. Hg 3 and 4 exhibited a tendency to associate with age and gender, respectively. However, no significant associations were found between NC heterogeneity and the different T. solium cysticerci Ht or Hg. Parasite variants obtained from patients with similar NC clinical or radiological features were genetically closer than those found in groups of patients with a different NC profile when using the Mantel test. Overall, this study establishes the presence of genetic differences in the Cytb gene of T. solium isolated from human cysticerci and suggests that parasite variation could contribute to NC heterogeneity.     

Protein and antigen diversity in the vesicular fluid of Taenia solium cysticerci dissected from naturally infected pigs

Cysticercosis caused by Taenia solium is a health threat for humans and pigs living in developing countries, for which there is neither a flawless immunodiagnostic test nor a totally effective vaccine. Suspecting of individual diversity of hosts and parasites as possible sources of the variations of the parasite loads among cysticercotic animals and of the limited success of such immunological applications as well as, we explored and measured both in nine cases of naturally acquired porcine cysticercosis. For this purpose, 2-Dimensional IgG immunoblots were performed by reacting the sera of each cysticercotic pig with the antigens contained in the vesicular fluid (VF) of their own cysticerci. We found an unexpectedly large diversity among the proteins and antigens contained in each of the nine VFs. Also diverse were the serum IgG antibody responses of the nine pigs, as none of their 2D- immunoblot images exhibited the same number of spots and resembled each other in only 6.3% to 65.3% of their features. So large an individual immunological diversity of the cysticercal antigens and of the infected pigs′ IgG antibody response should be taken into account in the design of immunological tools for diagnosis and prevention of cysticercosis and should also be considered as a possibly significant source of diversity in Taenia solium′s infectiveness and pathogenicity.     

Age-related infection and transmission patterns of human cysticercosis

Neurocysticercosis is recognised as an important but neglected cause of epilepsy in developing countries where the parasite occurs. Data on the transmission dynamics of the parasite in endemic areas are scarce. Individuals living in these areas are likely to be highly exposed to the parasite, but relatively few of them develop active infections. The present study aimed to describe and gain insights into changes in antibody responses and infection patterns related to age and/or gender in a south Ecuadorian rural population by combining antibody and antigen serological data with demographic characteristics. In 25% of the population, antibodies to Taenia solium cysticerci were detected whilst 2.9% had circulating parasite antigens. The proportion of antibody-positive individuals increased significantly until the age of 40 years to become stable in older individuals. A rule-based simulation model was developed to explain these variations and to reflect the dynamics of exposure to, and transmission of, the parasite. In contrast, the proportion of people presenting circulating parasite antigens, reflecting an active infection, was significantly higher in people older than 60 years. Immunosenescence could explain such an observation since a weaker immune system in the elderly would facilitate the establishment and maintenance of viable cysticerci compared with fully immunocompetent younger individuals. This work points out the role of the immune system in the development of cysticercosis within an exposed population and highlights new essential issues in understanding the transmission dynamics of the parasite, its incidence and the resulting immunological response at a population level.     

The Asian Taenia and the possibility of cysticercosis

In certain Asian countries, a third form of human Taenia, also known as the Asian Taenia, has been discovered. This Asian Taenia seems to be an intermediate between Taenia solium and T. saginata since in morphological terms it is similar to T. saginata, yet biologically, as it uses the same intermediate host (pigs), it is more akin to T. solium. Taenia solium causes human cysticercosis, while T. saginata does not. It is not known whether the Asian taeniid is able to develop to the larval stage in humans or not. The arguments proposed by those authors who consider it unlikely that the Asian Taenia causes human cysticercosis are: (a) its molecular similarities with T. saginata; (b) the absence of cases of human cysticercosis in populations where the Asian adult is highly prevalent; and (c) the unsupporting results derived from an experimental infestation study. These three arguments are debated, although bearing in mind that at present there is still no clear scientific data to support that human cysticercosis can be caused by the Asian Taenia.     

Current Status and Perspectives of Cysticercosis and Taeniasis in Japan

This mini-review describes recent epidemiological trends in cysticercosis and taeniasis in Japan. Some of the topics discussed herein were presented at the first symposium on "Current perspectives of Taenia asiatica researches", that was held in Osong in Chungbuk Province, South Korea, in October 2011 and organized by Prof. K. S. Eom, Chungbuk National University School of Medicine. To better understand the trends in the occurrence of cysticercosis and taeniasis in Japan, clinical cases reported in 2005 have been updated. In addition, the current status of Taenia asiatica infections successively occurring in Japan since 2010 is also discussed.     

Clinical and Pathological Characteristics of Intraocular Cysticercosis

This study aimed to explore the clinical, radiological, and pathological characteristics of intraocular cysticercosis due to Taenia solium metacestode infection. Total 8 patients diagnosed with intraocular cysticercosis at the Red Cross Hospital of Yunnan Province, China were examined retrospectively. Patients with clear dioptic media had undergone fundus chromophotography. All patients underwent B ultrasonography of the ocular region (CT) successive scanning of the orbit and cerebral tissues. Parasites were extracted surgically and then examined pathologically. The fundus chromophotography showed a white and condensing scolex package in the vesicle. The B ultrasonic examination showed a vesicle-like echogenic mass in the vitreous chamber, in which the high-level echo spot was the cysticercus scolex. The pathological examinations showed that the vesicle wall exhibited hyaline degeneration, inflammatory cell infiltration, neuroglial fiber, and glial cell proliferation layers from the inside to the outside. The scolex is round and is composed of the outer tissue (the body wall) and the inner furrow tissue; these tissues migrated together. Primordially differentiated sucking discs were found in one case, but no hooklets were found. The inner scolex tissue was folded like a paper flower. The severity of intraocular disease is closely correlated with the pathophysiological processes of the cysticercus worm. Pathological examination of the intraocular lesions can help to evaluate the course of the disease as well as to provide a scientific basis for effective antiparasitic medication.     

Population genetic structure of Taenia solium from Madagascar and Mexico: implications for clinical profile diversity and immunological technology

Taenia solium is a cestode parasitic of humans and pigs that strongly impacts on public health in developing countries. Its larvae (cysticercus) lodge in the brain, causing neurocysticercosis, and in other tissues, like skeletal muscle and subcutaneous space, causing extraneuronal cysticercosis. Prevalences of these two clinical manifestations vary greatly among continents. Also, neurocysticercosis may be clinically heterogeneous, ranging from asymptomatic forms to severely incapacitating and even fatal presentation. Further, vaccine design and diagnosis technology have met with difficulties in sensitivity, specificity and reproducibility. Parasite diversity underlying clinical heterogeneity and technological difficulties is little explored. Here, T. solium genetic population structure and diversity was studied by way of random amplified polymorphic DNA in individual cysticerci collected from pigs in Madagascar and two regions in Mexico. The amplification profiles of T. solium were also compared with those of the murine cysticercus Taenia crassiceps (ORF strain). We show significant genetic differentiation between Madagascar and Mexico and between regions in Mexico, but less so between cysticerci from different localities in Mexico and none between cysticerci from different tissues from the same pig. We also found restricted genetic variability within populations and gene flow was estimated to be low between populations. Thus, genetic differentiation of T. solium suggests that different evolutionary paths have been taken and provides support for its involvement in the differential tissue distribution of cysticerci and varying degrees of severity of the disease. It may also explain difficulties in the development of vaccines and tools for immunodiagnosis.     

State of the Art of Taenia solium as Compared to Taenia asiatica

Three species of tapeworms infect humans in their adult stage (Taenia solium, Taenia saginata and Taenia asiatica). The 3 are flat, opaque white or yellowish, and exceptional long segmented parasites, measuring 1 to 12 m in their adult stage. In this review, the development of the knowledge regarding the first species, mainly focused on understanding how the larval stage or cysticercus is transmitted to humans, is described. The second species is a cosmopolitan parasite that only causes taeniosis and not cysticercosis; therefore, it will not be included. Information on the third species, which is presently being produced, since this species was recognized as such only at the end of the 20th century, will be discussed at the end of this review.     

A Bayesian approach for estimating values for prevalence and diagnostic test characteristics of porcine cysticercosis

Several diagnostic techniques are used to estimate the prevalence of the zoonotic tapeworm Taenia solium in pigs, but none of these tests are perfect, making interpretation of results difficult. A Bayesian approach was used to estimate values for the prevalence and diagnostic test characteristic of porcine cysticercosis by combining results of four imperfect tests. Village pigs (N = 868) slaughtered in Lusaka (Zambia), were bled, and tongue and routine meat inspected; and serum antibody and parasite antigen concentrations were determined by ELISA. A model, based on a multinomial distribution and including all possible interactions between the individual tests required 31 parameters to be estimated, but actually allowed only 15 parameters (i.e. had 15 degrees of freedom) to be estimated. Therefore, prior expert opinion on specificity and (in)-dependence of the tests was entered in the model, resulting in a reduction of the number of parameters to be estimated. The estimated prevalence of porcine cysticercosis was 0.642 (95% confidence interval 0.54-0.91). The performances of the tests were (sensitivity (se)-specificity (sp)): tongue inspection (se 0.210-sp 1.000), meat inspection (se 0.221-sp 1.000), Ab-ELISA (se 0.358-sp 0.917), Ag-ELISA (se 0.867-sp 0.947). To validate the estimates obtained from the model we performed a second study: 65 randomly purchased Zambian village pigs were bled for serum antibody and antigen determination, their tongue and meat inspected; and in addition, the carcasses were dissected for total cysticercus counts (gold standard). Cysticerci were found in 31 pigs (prevalence 0.477, 95% confidence interval 0.35-0.60), overlapping with the estimated prevalence in the first study. Sensitivity and specificity values obtained for the aforementioned tests in this study were in agreement with those estimated. A Bayesian analysis framework offers the possibility to combine prior opinion with experimental data to more accurately estimate the real prevalence of porcine cysticercosis in the absence of a gold standard.     

TLR2 mediates immunity to experimental cysticercosis

Information concerning TLR-mediated antigen recognition and regulation of immune responses during helminth infections is scarce. TLR2 is a key molecule required for innate immunity and is involved in the recognition of a wide range of viruses, bacteria, fungi and parasites. Here, we evaluated the role of TLR2 in a Taenia crassiceps cysticercosis model. We compared the course of T. crassiceps infection in C57BL/6 TLR2 knockout mice (TLR2^-/-) with that in wild type C57BL/6 (TLR2^+/+) mice. In addition, we assessed serum antibody and cytokine profiles, splenic cellular responses and cytokine profiles and the recruitment of alternatively activated macrophages (AAMφs) to the site of the infection. Unlike wild type mice, TLR2^-/- mice failed to produce significant levels of inflammatory cytokines in either the serum or the spleen during the first two weeks of Taenia infection. TLR2^-/- mice developed a Th2-dominant immune response, whereas TLR2^+/+ mice developed a Th1-dominant immune response after Taenia infection. The insufficient production of inflammatory cytokines at early time points and the lack of Th1-dominant adaptive immunity in TLR2^-/- mice were associated with significantly elevated parasite burdens; in contrast, TLR2^+/+ mice were resistant to infection. Furthermore, increased recruitment of AAMφs expressing PD-L1, PD-L2, OX40L and mannose receptor was observed in TLR2^-/- mice. Collectively, these findings indicate that TLR2-dependent signaling pathways are involved in the recognition of T. crassiceps and in the subsequent activation of the innate immune system and production of inflammatory cytokines, which appear to be essential to limit infection during experimental cysticercosis.     

Progesterone induces mucosal immunity in a rodent model of human taeniosis by Taenia solium

More than one quarter of human world's population is exposed to intestinal helminth parasites. The Taenia solium tapeworm carrier is the main risk factor in the transmission of both human neurocysticercosis and porcine cysticercosis. Sex steroids play an important role during T. solium infection, particularly progesterone has been proposed as a key immunomodulatory hormone involved in susceptibility to human taeniosis in woman and cysticercosis in pregnant pigs. Thus, we evaluated the effect of progesterone administration upon the experimental taeniosis in golden hamsters (Mesocricetus auratus). Intact female adult hamsters were randomly divided into 3 groups: progesterone-subcutaneously treated; olive oil-treated as the vehicle group; and untreated controls. Animals were treated every other day during 4 weeks. After 2 weeks of treatment, all hamsters were orally infected with 4 viable T. solium cysticerci. After 2 weeks post infection, progesterone-treated hamsters showed reduction in adult worm recovery by 80%, compared to both vehicle-treated and non-manipulated infected animals. In contrast to control and vehicle groups, progesterone treatment diminished tapeworm length by 75% and increased proliferation rate of leukocytes from spleen and mesenteric lymph nodes of infected hamsters by 5-fold. The latter exhibited high expression levels of IL-4, IL-6 and TNF-α at the duodenal mucosa, accompanied with polymorphonuclear leukocytes infiltration. These results support that progesterone protects hamsters from the T. solium adult tapeworm establishment by improving the intestinal mucosal immunity, suggesting a potential use of analogues of this hormone as novel inductors of the gut immune response against intestinal helminth infections and probably other bowel-related disorders.     

Current Status of Human Taeniasis in Lao People's Democratic Republic

Human taeniasis was investigated in Lao People''s Democratic Republic (Lao PDR) between 2000 and 2011 as part of the nation''s helminthiasis survey. A total of 55,038 inhabitants, including 29,846 school children, were examined using the Kato-Katz and scotch-tape anal swab method, and morphological observation of adult worms. Molecular identification of Taenia tapeworms was performed by multiplex PCR or DNA sequence analysis of the mitochondrial cox1 gene. Taenia eggs were present at a rate of 1.5% (845/55,038) in the subject population. Adult tapeworms were identified as T. solium or T. saginata by analyzing the collectable stool specimens (n=126). Three specimens identified as T. solium were found in Luang Prabang, while the remaining 123 specimens, which were T. saginata, were found in Bokeo, Bolikhamxay, Champasak, Houaphan, Khammouane, Luang Namta, Luang Prabang, Oudomxay, Phongsaly, Saysomboune, Saravane, Savannakhet, Xayaboury, Xekong, Xieng Khouang Province, and Vientiane Municipality.     

Voltage-gated calcium channel subunits from platyhelminths: potential role in praziquantel action

Voltage-gated calcium (Ca2+) channels provide the pathway for Ca2+ influxes that underlie Ca2+ -dependent responses in muscles, nerves and other excitable cells. They are also targets of a wide variety of drugs and toxins. Ca2+ channels are multisubunit protein complexes consisting of a pore-forming alpha(1) subunit and other modulatory subunits, including the beta subunit. Here, we review the structure and function of schistosome Ca2+ channel subunits, with particular emphasis on variant Ca2+ channel beta subunits (Ca(v)betavar) found in these parasites. In particular, we examine the role these beta subunits may play in the action of praziquantel, the current drug of choice against schistosomiasis. We also present evidence that Ca(v)betavar homologs are found in other praziquantel-sensitive platyhelminths such as the pork tapeworm, Taenia solium, and that these variant beta subunits may thus represent a platyhelminth-specific gene family.     

Nanobodies, a promising tool for species-specific diagnosis of Taenia solium cysticercosis

Taenia solium cysticercosis is a major helminth zoonosis in developing countries. Pigs are the intermediate hosts mediating transmission of infection. Specific assays to diagnose living cysts in pigs are lacking. The monoclonal-based antigen detection ELISA is genus-specific and cross-reactions with Taenia hydatigena hamper the use of this test to screen pigs. We, therefore, aimed to introduce nanobodies, camelid-derived single-domain antibodies specific for T. solium cysticercosis, to develop unambiguous tests. Nanobodies were cloned following immunization of two dromedaries with T. solium antigen and eight T. solium-specific nanobodies were selected after phage display. Their binding characteristics and potential for the diagnosis of porcine cysticercosis were investigated. The nanobodies do not cross-react with T. hydatigena, Taenia saginata, Taenia crassiceps or Trichinella spiralis and were categorized into four epitope-binding groups. The target protein was identified as 14 kDa diagnostic glycoprotein (Ts14), but the nanobodies also reacted with other proteins of the same family. Nanobodies were tested in a sandwich ELISA with cyst fluid, and one particular nanobody detected its cognate serum antigens in a species-specific inhibition ELISA. Considering their beneficial production and stability properties, these highly specific nanobodies constitute a promising tool to diagnose cysticercosis after further improvement of the sensitivity and future assay validation.