Taenia solium Metacestode Factor as Probable Cause of Temporal Lobe Epilepsy.

This article analyzes data from scientific publications (mainly reviews) concerning the link between human neurocysticercosis and epilepsy. Along with data from our own studies on experimental hippocampal sclerosis induced by a Taenia crassiceps metacestode factor in mice, it explores the connection between mechanisms that likely favor the development of epilepsy in cases of human neurocysticercosis. The data from both sources suggest the idea that the T. solium metacestode factor causes hippocampal sclerosis and later epilepsy in humans with neurocysticercosis.

Taenia solium and Taenia crassiceps: miRNomes of the larvae and effects of miR-10-5p and let-7-5p on murine peritoneal macrophages.

Neurocysticercosis (NCC), a major cause of neurological morbidity worldwide, is caused by the larvae of Taenia solium. Cestodes secrete molecules that block the Th1 response of their hosts and induce a Th2 response permissive to their establishment. Mature microRNAs (miRs) are small noncoding RNAs that regulate gene expression and participate in immunological processes. To determine the participation of Taenia miRs in the immune response against cysticercosis, we constructed small RNA (sRNA) libraries from larvae of Taenia solium and Taenia crassiceps. A total of 12074504 and 11779456 sequencing reads for T. solium and T. crassiceps, respectively, were mapped to the genomes of T. solium and other helminths. Both larvae shared similar miRNome, and miR-10-5p was the most abundant in both species, followed by let-7-5p in T. solium and miR-4989-3p in T. crassiceps, whereas among the genus-specific miRs, miR-001-3p was the most abundant in both, followed by miR-002-3p in T. solium and miR-003a-3p in T. crassiceps. The sequences of these miRs were identical in both. Structure and target prediction analyses revealed that these pre-miRs formed a hairpin and had more than one target involved in immunoregulation. Culture of macrophages, RT-PCR and ELISA assays showed that cells internalized miR-10-5p and let-7-5p into the cytoplasm and the miRs strongly decreased interleukin 16 (Il6) expression, tumor necrosis factor (TNF) and IL-12 secretion, and moderately decreased nitric oxide synthase inducible (Nos2) and Il1b expression (pro-inflammatory cytokines) in M(IFN-γ) macrophages and expression of Tgf1b, and the secretion of IL-10 (anti-inflammatory cytokines) in M(IL-4) macrophages. These findings could help us understand the role of miRs in the host-Taenia relationship.

Association of TRAF1/C5 Locus Polymorphisms with Epilepsy and Clinical Traits in Mexican Patients with Neurocysticercosis.

Neurocysticercosis is caused by the establishment of Taenia solium cysts in the central nervous system. Murine cysticercosis by Taenia crassiceps is a useful model of cysticercosis in which the complement component 5 (C5) has been linked to infection resistance/permissiveness. This work aimed to study the possible relevance for human neurocysticercosis of single nucleotide polymorphisms (SNPs) in the C5-TRAF1 region (rs17611 C/T, rs992670 G/A, rs25681 G/A, rs10818488 A/G, and rs3761847 G/A) in a Mexican population and associated with clinical and radiological traits related to neurocysticercosis severity (cell count in the cerebrospinal fluid [CSF cellularity], parasite location and parasite load in the brain, parasite degenerating stage, and epilepsy). The AG genotype of the rs3761847 SNP showed a tendency to associate with multiple brain parasites, while the CT and GG genotypes of the rs17611 and rs3761847 SNPs, respectively, showed a tendency to associate with low CSF cellularity. The rs3761847 SNP was associated with epilepsy under a dominant model, whereas rs10818488 was associated with CSF cellularity and parasite load under dominant and recessive models, respectively. For haplotypes, C5- and the TRAF1-associated SNPs were, respectively, in strong linkage disequilibrium with each other; thus, these haplotypes were studied independently. For C5 SNPs, carrying the CAA haplotype increases the risk of showing high CSF cellularity 3-fold and the risk of having extraparenchymal parasites 4-fold, two conditions that are related to severe disease. For TRAF1 SNPs, the GA and AG haplotypes were associated with CSF cellularity, and the AG haplotype was associated with epilepsy. Overall, these findings support the clear participation of C5 and TRAF1 in the risk of developing severe neurocysticercosis in the Mexican population.

In vitro model of postoncosphere development, and in vivo infection abilities of Taenia solium and Taenia saginata.

Taenia solium is known to cause human cysticercosis while T. saginata does not. Comparative in vitro and in vivo studies on the oncosphere and the postoncospheral (PO) forms of T. solium and T. saginata may help to elucidate why cysticercosis can occur from one and not the other. The aim of this study was to use in vitro culture assays and in vivo models to study the differences in the development of the T. solium and T. saginata oncosphere. Furthermore, this study aimed to evaluate the expression of cytokines and metalloproteinases (MMPs) in human peripheral blood mononuclear cells (PBMCs), which were stimulated by these oncospheres and PO antigens. T. solium and T. saginata activated oncospheres (AO) were cultured in INT-407 and HCT-8 intestinal cells for 180 days. The T. solium began to die while the T. saginata grew for 180 days and developed to cysticerci in INT-407 cells. Rats were inoculated intracranially with AO and PO forms of either T. saginata or T. solium. Rats infected with T. solium AO and PO forms developed neurocysticercosis (NCC), while those infected with the T. saginata did not. Human PMBCs were stimulated with antigens of AO and PO forms of both species, and the production of cytokines and metalloproteinases (MMPs) was measured. The T. solium AO antigen stimulated a higher production of IL-4, IL-5, IL-13, IFN-γ, and IL-2 cytokines compared to T. saginata AO. In the PO form, the T. saginata PO antigen increased the production of IL-4, IL-5, IL-13, IFN-γ, IL-1ß, IL-6, IL-10, TNF-α and IL-12 cytokines compared to T. solium, suggesting that this global immune response stimulated by different forms could permit survival or destruction of the parasite depending of their life-cycle stage. Regarding MMPs, T. solium AO antigen stimulated a higher production of MMP-9 compared to T. saginata AO antigen, which may be responsible for altering the permeability of intestinal cells and facilitating breakdown of the blood-brain barrier during the process of invasion of host tissue.

Neurocysticercosis among People Living Near Pigs Heavily Infected with Cysticercosis in Rural Endemic Peru.

Neurocysticercosis causes substantial neurologic morbidity in endemic regions around the world. In this cross-sectional study, we describe the frequency of neurocysticercosis among a presumed high-risk group of people in an endemic community in northern Peru. Participants who screened positive on a nine-question seizure survey were evaluated clinically to diagnose epilepsy using International League Against Epilepsy criteria. Those with epilepsy were offered a noncontrast computerized tomography (CT) of the head. We also tested sera from all participants using the lentil lectin-bound glycoprotein enzyme-linked immunoelectrotransfer blot (EITB) to detect anti-cysticercus antibodies and enzyme-linked immunosorbent assay (ELISA) B60/B158 to detect cysticercosis antigens. Participants with strongly positive ELISA (ratio ≥ 3) were offered a noncontrast magnetic resonance imaging (MRI) of the brain. We diagnosed 16 cases of epilepsy among 527 people screened (lifetime prevalence 30 per 1,000). Twelve with epilepsy accepted CT scan and five (41.7%) had parenchymal calcifications. None had viable cysts. Of the 514 who provided a blood sample, 241 (46.9%) were seropositive by EITB and 12 (2.9%) were strongly positive by ELISA (ratio ≥ 3). Eleven accepted MRI and eight (72.3%) had neurocysticercosis, including five with extraparenchymal cysts, five with parenchymal vesicular cysts, and two with parenchymal granulomas. These findings show that clinically relevant forms of neurocysticercosis and epilepsy can be found by applying screening interventions in communities endemic to Taenia solium. Longitudinal controlled studies are needed to better understand which subgroups are at highest risk and which are most likely to have improved prognosis as a result of screening.

Neuropsychiatric manifestations and epidemiology of neurocysticercosis / Manifestações neuropsiquiátricas e epidemiologia de neurocisticercose

Neurocysticercosis (NCC) is the brain infection caused by larval stages of the helminth Taenia solium. The embryos of Taenia travel through the bloodstream and can reach the brain, muscles, eyes, and various organs. In the brain, the psychiatric manifestations are mood disorders, depression and anxiety, which are commonly associated with epilepsy and sensory-motor deficits. Neurocysticercosis is a frequent parasitic disease in the world population; it is endemic in Central and South America, Asia and Sub-Saharan Africa. In the present review, we report the major symptoms and signals of neurocysticercosis common to neurological and psychiatric illnesses. We briefly present Epidemiology of those manifestations and analyze the relationship between pathological changes and NCC symptomatology. OBJECTIVES AND METHODOLOGY: A literature review was conducted to characterize epidemiological, neurological and psychiatric manifestations of NCC. The final 90 papers were selected of a set of 937 publications from 2010 to 2016. RESULTS: NCC is a major cause of epilepsy in endemic areas; further- more, leads to a diversity of motor and sensitive deficits, manifestations vary from headache to severe intracranial hypertension. Potentially fatal conditions include arteritis, encephalitis and hydrocephalus. Depression and cognitive decline remain among the most important psychiatric manifestations. Neuropsychiatric manifestations, Epidemiology, and neuroimaging provide diagnostic criteria. Brain scans may reveal one or diverse cysts filled with fluid within a scolex (parasite's head). CONCLUSION: NCC's diversity of presentations encourage health professionals to consider it in diagnoses, especially in endemic countries, and also in non-endemic areas because migrants and travelers are subject to contagious. Treatment consists in use of antiparasitic drugs (albendazol, praziquantel) and drugs to treat associated conditions (anticonvulsants, corticosteroids). Surgery is reserved to extirpate the parasite from particular locations (eyes, spinal cord, cerebral ventricles) or to differentiate NCC from tumors, tuberculosis, mycosis, etc. Prevention includes treatment of intestinal helminthiasis, sanitation in animal farming, food preparing hygiene, quality control of water and food.

Neurocisticercose é a infecção cerebral causada pelos estágios lar- vais do helminto Taenia solium. Os embriões da Taenia deslocam-se através da corrente sanguínea e podem atingir o cérebro, músculos, olhos e vários órgãos. No cérebro, as manifestações psiquiátricas são transtornos de humor, depressão e ansiedade, as quais estão comumente associados com epilepsia e deficiências sensório-motoras. Neurocisticercose é uma parasitose frequente na população mundial, é endêmica na América Central e do Sul, Ásia e África subsaariana. Na presente revisão, relatamos os principais sintomas e sinais de neurocisticercose pertinentes a doenças neurológicas e psiquiátricas. Nós brevemente apresentamos a Epidemiologia dessas manifestações, e analisamos a relação entre alterações patológicas e sintomatologia da NCC. OBJETIVOS E METODOLOGIA: Uma revisão da literatura foi conduzida para caracterizar a epidemiologia, as manifestações neurológicas e psiquiátricas de NCC. Os 90 artigos finais foram selecionados de um conjunto de 937 publicações entre 2010 a 2016. RESULTADOS: NCC é uma importante etiologia de epilepsia em áreas endêmicas, além disso causa uma diversidade de deficiências motoras e sensoriais, as manifestações variam de cefaleia a severa hipertensão intracraniana. Condições potencialmente fatais incluem arterites, encefalites e hidrocefalia. Depressão e declíneo cognitive permanecem entre as mais importantes manifestações psiquiátricas. Manifestações neuropsiquiátricas, epidemiologia e neuroimagem provêm os critérios de diagnóstico. As imagens cerebrais podem revelar um ou diversos cistos preenchidos com líquido e o escólex (cabeça) do parasito. CONCLUSÕES: A diversidade de apresentações da NCC encoraja os profissionais de saúde a considerá-la dentre os diagnósticos, especialmente em países endêmicos; e também em áreas não-endêmicas, pois migrantes e viajantes estão sujeitos ao contágio. O tratamento consiste no uso de antiparasíticos (albendazol, praziquantel) e medicamentos para tratar condições associadas (anticonvulsivantes, corticosteróides). Cirurgia é reservada para remoção do parasito de locais particulares (olhos, medula espinhal, ventrículos cerebrais) ou para diferenciar NCC de tumores, tuberculose, micose, etc. Prevenção inclui o tratamento de helmintíases intestinais, sanidade animal, higiene ao preparar alimentos, controle da qualidade da água e alimentos.

Reprint of "Neurocysticercosis-related mortality in Brazil, 2000-2011: Epidemiology of a neglected neurologic cause of death".

Neurocysticercosis (NCC) is an important cause of severe neurological disease mainly in low- and middle-income countries, but data on NCC mortality from endemic areas are scarce. Here we analysed the epidemiological patterns of NCC-related mortality in Brazil. We included all deaths recorded in Brazil between 2000 and 2011, in which NCC was mentioned on death certificates, either as underlying or as associated cause of death. NCC was identified in 1829/12,491,280 deaths (0.015%), 1130 (61.8%) as underlying cause, and 699 (38.2%) as associated cause. Overall age-adjusted mortality rate for the period was 0.97 deaths/1,000,000 inhabitants (95% confidence interval [CI]: 0.83-1.12). The highest NCC-related mortality rates were found in males, elderly, white race/colour and residents in endemic states/regions. Age-adjusted mortality rates at national level decreased significantly over time (annual percent change [APC]: -4.7; 95% CI: -6.0 to -3.3), with a decrease in the Southeast, South and Central-West regions, and a non-significant increasing trend in the North and Northeast regions. We identified spatial and spatiotemporal high-risk mortality clusters located mainly in NCC-endemic areas. Conditions related to the nervous system were the most commonly associated causes of death when NCC was mentioned as an underlying cause, and HIV/AIDS was the main underlying cause when NCC was an associated cause. NCC is a neglected and preventable cause of severe neurologic disease and death with high public health impact in Brazil. There is a clear need to strengthen nationwide epidemiological surveillance and control for the taeniasis/cysticercosis complex.

Pathogenesis of Taenia solium taeniasis and cysticercosis.

Taenia solium infections (taeniasis/cysticercosis) are a major scourge to most developing countries. Neurocysticercosis, the infection of the human nervous system by the cystic larvae of this parasite, has a protean array of clinical manifestations varying from entirely asymptomatic infections to aggressive, lethal courses. The diversity of clinical manifestations reflects a series of contributing factors which include the number, size and location of the invading parasites, and particularly the inflammatory response of the host. This manuscript reviews the different presentations of T. solium infections in the human host with a focus on the mechanisms or processes responsible for their clinical expression.

Neurocisticercosis racemosa subaracnoidea gigante y ventricular: a propósito de un caso / Giant racemose subarachnoid and intraventricular neurocysticercosis: A case report

La neurocisticercosis es la enfermedad parasitaria más frecuente del sistema nervioso central. Es causada por las larvas de Taenia solium, las cuales pueden estar alojadas en distintas localizaciones anatómicas. En países como España existe una prevalencia en ascenso debido, principalmente, a la inmigración desde regiones endémicas. Las formas extraparenquimatosas son menos frecuentes, pero más graves por su tendencia a producir complicaciones. La neuroimagen desempeña un papel primordial en el diagnóstico y seguimiento de esta enfermedad, apoyada en la serología y un contexto clínico-epidemiológico compatible. El tratamiento de elección son los fármacos cisticidas albendazol y praziquantel, habitualmente se asocian a estos corticoides y, cuando corresponde, la cirugía. Se presenta un caso de neurocisticercosis con afectación simultánea intraventricular y subaracnoidea en su forma racemosa gigante.

Neurocysticercosis is the most frequent parasitic disease of the central nervous system. It is caused by the larvae of Taenia solium, which can affect different anatomical sites. In Spain there is an increasing prevalence mainly due to immigration from endemic areas. The extraparenchymal forms are less common, but more serious because they usually develop complications. Neuroimaging plays a major role in the diagnosis and follow-up of this disease, supported by serology and a compatible clinical and epidemiological context. First-line treatments are cysticidal drugs such as albendazole and praziquantel, usually coadministered with corticosteroids, and in some cases surgery is indicated. We here report a case of neurocysticercosis with simultaneous intraventricular and giant racemose subarachnoid involvement.

Characterization of a Thioredoxin-1 Gene from Taenia solium and Its Encoding Product.

Taenia solium thioredoxin-1 gene (TsTrx-1) has a length of 771 bp with three exons and two introns. The core promoter gene presents two putative stress transcription factor binding sites, one putative TATA box, and a transcription start site (TSS). TsTrx-1 mRNA is expressed higher in larvae than in adult. This gene encodes a protein of 107 amino acids that presents the Trx active site (CGPC), the classical secondary structure of the thioredoxin fold, and the highest degree of identity with the Echinococcus granulosus Trx. A recombinant TsTrx-1 (rTsTrx-1) was produced in Escherichia coli with redox activity. Optimal activity for rTsTrx-1 was at pH 6.5 in the range of 15 to 25°C. The enzyme conserved activity for 3 h and lost it in 24 h at 37°C. rTsTrx-1 lost 50% activity after 1 h and lost activity completely in 24 h at temperatures higher than 55°C. Best storage temperature for rTsTrx-1 was at -70°C. It was inhibited by high concentrations of H2O2 and methylglyoxal (MG), but it was inhibited neither by NaCl nor by anti-rTsTrx-1 rabbit antibodies that strongly recognized a ~12 kDa band in extracts from several parasites. These TsTrx-1 properties open the opportunity to study its role in relationship T. solium-hosts.

Expression of Multiple Taenia Solium Immunogens in Plant Cells Through a Ribosomal Skip Mechanism.

Taenia solium cysticercosis is a major parasitic disease that affects the human health and the economy in underdeveloped countries. Porcine cysticercosis, an obligatory stage in the parasite life cycle, is a suitable target for vaccination. While several recombinant and synthetic antigens proved to be effective as vaccines, the cost and logistic difficulties have prevented their massive use. Taking this into account, a novel strategy for developing a multi-epitope low-cost vaccine is herein explored. The S3Pvac vaccine components (KETc1, KETc12, KETc7, and GK1 [KETc7]) and the protective HP6/TSOL18 antigen were expressed in a Helios2A polyprotein system, based on the 'ribosomal skip' mechanism mediated by the 2A sequence (LLNFDLLKLAGDVESNPG-P) derived from the Foot-and-mouth disease virus, which induces self-cleavage events at a translational level. This protein arrangement was expressed in transgenic tobacco cells. The inserted sequence and its transcript were detected in several Helios2A lines, with some lines showing recombinant protein accumulation levels up to 1.3 µg/g of fresh weight in leaf tissues. The plant-derived Helios2A vaccine was recognized by antibodies in the cerebral spinal fluid from neurocysticercosis patients and elicited specific antibodies in BALB/c immunized mice. These evidences point to the Helios2A polyprotein as a promising system for expressing multiple antigens of interest for vaccination and diagnosis in one single construction.

New insights in cysticercosis transmission.

Taenia solium infection causes severe neurological disease in humans. Even though infection and exposure to swine cysticercosis is scattered throughout endemic villages, location of the tapeworm only explains some of the nearby infections and is not related to location of seropositive pigs. Other players might be involved in cysticercosis transmission. In this study we hypothesize that pigs that carry nematodes specific to dung beetles are associated with cysticercosis infection and/or exposure. We carried out a cross-sectional study of six villages in an endemic region in northern Peru. We euthanized all pigs (326) in the villages and performed necropsies to diagnose cysticercosis. For each pig, we counted cysticerci; measured anti-cysticercus antibodies; identified intestinal nematodes; tabulated distance to nearest human tapeworm infection; and recorded age, sex, productive stage, and geographic reference. For the purpose of this paper, we defined cysticercosis infection as the presence of at least one cysticercus in pig muscles, and cysticercosis exposure as seropositivity to anti-cysticercus antibodies with the presence of 0-5 cysticerci. Compared to pigs without nematode infections, those pigs infected with the nematode Ascarops strongylina were significantly associated with the presence of cysticerci (OR: 4.30, 95%CI: 1.83-10.09). Similarly, pigs infected with the nematode Physocephalus sexalatus were more likely to have cysticercosis exposure (OR: 2.21, 95%CI: 1.50-3.28). In conclusion, our results suggest that there appears to be a strong positive association between the presence of nematodes and both cysticercosis infection and exposure in pigs. The role of dung beetles in cysticercosis dynamics should be further investigated.

Evans blue staining reveals vascular leakage associated with focal areas of host-parasite interaction in brains of pigs infected with Taenia solium.

Cysticidal drug treatment of viable Taenia solium brain parenchymal cysts leads to an acute pericystic host inflammatory response and blood brain barrier breakdown (BBB), commonly resulting in seizures. Naturally infected pigs, untreated or treated one time with praziquantel were sacrificed at 48 hr and 120 hr following the injection of Evans blue (EB) to assess the effect of treatment on larval parasites and surrounding tissue. Examination of harvested non encapsulated muscle cysts unexpectedly revealed one or more small, focal round region(s) of Evans blue dye infiltration (REBI) on the surface of otherwise non dye-stained muscle cysts. Histopathological analysis of REBI revealed focal areas of eosinophil-rich inflammatory infiltrates that migrated from the capsule into the tegument and internal structures of the parasite. In addition some encapsulated brain cysts, in which the presence of REBI could not be directly assessed, showed histopathology identical to that of the REBI. Muscle cysts with REBI were more frequent in pigs that had received praziquantel (6.6% of 3736 cysts; n = 6 pigs) than in those that were untreated (0.2% of 3172 cysts; n = 2 pigs). Similar results were found in the brain, where 20.7% of 29 cysts showed histopathology identical to muscle REBI cysts in praziquantel-treated pigs compared to the 4.3% of 47 cysts in untreated pigs. Closer examination of REBI infiltrates showed that EB was taken up only by eosinophils, a major component of the cellular infiltrates, which likely explains persistence of EB in the REBI. REBI likely represent early damaging host responses to T. solium cysts and highlight the focal nature of this initial host response and the importance of eosinophils at sites of host-parasite interaction. These findings suggest new avenues for immunomodulation to reduce inflammatory side effects of anthelmintic therapy.

[Cathepsin L cysteine protease from Taenia solium: its biological role in the infection and potential use for the immunodiagnosis of neurocysticercosis]. / Cisteínoproteasas catepsinas L de Taenia solium: rol biológico en la infección y potencial uso para el inmunodiagnóstico de la neurocisticercosis.

Taenia solium is a plane helminth responsible for taeniasis and human cysticercosis, the latter being the result of the consumption of infective eggs. Cysticerci can develop in different human tissues, often in the central nervous system, causing neurocysticercosis (NCC). For the diagnosis of NCC, an adequate interpretation of clinical data, neuroimaging results and serological tests are required. However, serological tests could be improved by developing candidate antigens able to increase their sensibility and specificity. In the last years, a series of surface and secretory proteins of T. solium essential for the parasite-host interaction have been described. One of these families is cathepsin L cysteine proteases, which have a predominant role in the development and survival of the parasite. They take part in the tissue invasion, immune response evasion, excystation and encystment of cysticercus. They are considered potential antigens for the immunodiagnosis of neurocysticercosis.

Cisteínoproteasas Catepsinas L de Taenia solium: Rol biológico en la infección y potencial uso para el inmunodiagnóstico de la neurocisticercosis / Cathepsin L Cysteine Protease from Taenia solium: Its biological role in the infection and potential use for the immunodiagnosis of neurocysticercosis

Taenia solium es un helminto aplanado responsable de la teniosis y de la cisticercosis humana, siendo esta última producida por el consumo de huevos infectivos. Los cisticercos pueden desarrollarse en diferentes tejidos del hombre, frecuentemente en el sistema nervioso central causando la neurocisticercosis (NCC). Para el diagnóstico de la NCC se requiere de una adecuada interpretación de datos clínicos, resultados de neuroimagen y pruebas serológicas. Sin embargo, las pruebas serológicas podrían mejorarse con el desarrollo de antígenos candidatos capaces de incrementar su sensibilidad y especificidad. En los últimos años se han descrito una serie de proteínas de superficie y de secreción de T. solium esenciales para la interacción parásito-hospedero. Una de estas familias son las cisteínoproteasas catepsinas L, las cuales cumplen un rol preponderante para el desarrollo y supervivencia del parásito, participando en la invasión tisular, la evasión de la respuesta inmune, el desenquistamiento y enquistamiento del cisticerco. Son consideradas como antígenos potenciales para el inmunodiagnóstico de la neurocisticercosis.

Taenia solium is a plane helminth responsible for taeniasis and human cysticercosis, the latter being the result of the consumption of infective eggs. Cysticerci can develop in different human tissues, often in the central nervous system, causing neurocysticercosis (NCC). For the diagnosis of NCC, an adequate interpretation of clinical data, neuroimaging results and serological tests are required. However, serological tests could be improved by developing candidate antigens able to increase their sensibility and specificity. In the last years, a series of surface and secretory proteins of T. solium essential for the parasite-host interaction have been described. One of these families is cathepsin L cysteine proteases, which have a predominant role in the development and survival of the parasite. They take part in the tissue invasion, immune response evasion, excystation and encystment of cysticercus. They are considered potential antigens for the immunodiagnosis of neurocysticercosis.

Human neurocysticercosis: immunological features involved in the host's susceptibility to become infected and to develop disease.

Human neurocysticercosis (NC) is a clinically and radiologically heterogeneous disease caused by the establishment of Taenia solium larvae in the central nervous system. Herein, the immunological and endocrinological features involved in resistance to infection and severe forms of the disease are reviewed, and their clinical relevance is discussed.

Mimotope peptides selected from phage display combinatorial library by serum antibodies of pigs experimentally infected with Taenia solium as leads to developing diagnostic antigens for human neurocysticercosis.

Neurocysticercosis is caused by penetration of the tapeworm Taenia solium larvae into the central nervous system resulting in a diverse range of neurologic complications including epilepsy in endemic areas that globalization spreads worldwide. Sensitive and specific immunodiagnosis is needed for the early detection and elimination of the parasite, but the lack of standardized, readily obtainable antigens is a challenge. Here, we used the phage display for resolving the problem. The rationale of the strategy rests on the concept that the screening of combinatorial libraries with polyclonal serum to pathogens reveals families of peptides mimicking the pathogen most immunodominant epitopes indispensable for the successful diagnosis. The screening of a 7mer library with serum IgG of four pigs experimentally infected with parasite followed by computer aided segregation of the selected sequences resulted in the discovery of four clusters of homologous sequences of which one presented a family of ten mimotopes selected by three infected pig serum IgGs; the common motif sequence LSPF carried by the family was considered to be the core of an immunodominant epitope of the parasite critical for the binding with the antibody that selected the mimotopes. The immunoassay testing permitted to select a mimotope whose synthetic peptide free of the phage with the amino acid sequence Leu-Ser-Fen-Pro-Ser-Val-Val that distinguished well a panel of 21 cerebrospinal fluids of neurocysticercosis patients from the fluids of individuals with neurological complications of other etiology. This peptide is proposed as a lead for developing a novel molecularly defined diagnostic antigen(s) for the neurocysticercosis.

Cysticercosis in experimentally and naturally infected pigs: parasitological and immunological diagnosis / Cisticercose em suínos infectados experimentalmente e naturalmente: diagnósticos parasitológico e imunológico

Our objective was to evaluate the diagnosis of swine cysticercosis by examining "ante mortem" (inspection of the tongue), "post mortem" (inspection and detailed necropsy) and ELISA for research in serum of antibodies (Ab-ELISA) and antigens (Ag-ELISA). Seven (7) pigs were experimentally infected orally with eggs of Taenia solium and another 10 were naturally infected. In the pigs experimentally infected, inspection of the tongue was negative in all animals, in the routine inspection detailed necropsy and cysticercis were identified in all of them. In pigs with heavy natural infection, inspection of the tongue identified cysticerci in two (20%), while at inspection with necropsy the parasites were identified in large quantities in all animals. In ELISA for antibody search (Ab-ELISA) TS-14 recombinant protein was used, and in search for antigen (Ag-ELISA) a monoclonal antibody against this protein. In animals experimentally infected, blood was collected weekly for 140 days. The Ab-ELISA identified an increase in titers of antibody to cysticerci 21 days after infection, and at the end of the experimental period six animals (86%) were positive to the test. The search for circulating antigens (Ag-ELISA) was positive in two pigs 28 to 91 days after infection. All naturally infected pigs were positive for Ag-ELISA and Ab-ELISA. The search for antibodies and antigens by ELISA in serum from 30 pigs of a local farm and without history of cysticercosis was negative. Thus, the use of TS-14 antigen in ELISA test (Ab-ELISA) can be useful for the diagnosis of cysticercosis in pigs with low infection.(AU)

Nosso objetivo foi avaliar o diagnóstico de cisticercose suína através do exame "ante mortem" (inspeção da língua), "post mortem" (inspeção e necropsia detalhada) e teste de ELISA para a pesquisa no soro de anticorpos (Ab-ELISA) e antígenos (Ag -ELISA). Sete (7) suínos foram infectados experimentalmente por via oral com ovos de Taenia solium e outros 10 eram portadores de infecção natural generalizada. Nos suínos experimentalmente infectados, a inspeção da língua foi negativa em todos os animais, na inspeção 4 (57%) estavam infectados, a necropsia detalhada identificou cisticercos em todos os animais. Nos animais com infecção natural generalizada, a inspeção da língua identificou cisticercos em 2 (20%), enquanto que a inspeção e a necropsia os parasitas foram identificados em grande quantidade em todos os animais. No teste de ELISA para a pesquisa de anticorpos (Ab-ELISA) foi utilizada a proteína recombinante TS-14 e para a pesquisa de antígenos (Ag-ELISA) um anticorpo monoclonal produzido contra esta proteína. Nos animais experimentalmente infectados o sangue foi coletado semanalmente por um período de 140 dias. O Ab-ELISA identificou um aumento nos títulos de anticorpos para cisticercos 21 dias após a infecção, sendo que no final do período experimental 6 animais (86%) foram positivos ao teste. A pesquisa de antígenos circulantes (Ag-ELISA), foi positiva em 2 animais, entre os dias 21 e 91 após a infecção . Todos os suínos com infecção natural generalizada foram positivos para Ag-ELISA e Ab-ELISA.A pesquisa de anticorpos e antígenos pelo ELISA realizada no soro de 30 suínos procedentes de uma criação local sem historia de cisticercose foi negativa. Assim o uso do antígeno TS-14 (Ac-ELISA), pode ser útil para o diagnóstico da cisticercose em suínos com baixa infecção.(AU)

Cysticercosis in experimentally and naturally infected pigs: parasitological and immunological diagnosis / Cisticercose em suínos infectados experimentalmente e naturalmente: diagnósticos parasitológico e imunológico

Our objective was to evaluate the diagnosis of swine cysticercosis by examining "ante mortem" (inspection of the tongue), "post mortem" (inspection and detailed necropsy) and ELISA for research in serum of antibodies (Ab-ELISA) and antigens (Ag-ELISA). Seven (7) pigs were experimentally infected orally with eggs of Taenia solium and another 10 were naturally infected. In the pigs experimentally infected, inspection of the tongue was negative in all animals, in the routine inspection detailed necropsy and cysticercis were identified in all of them. In pigs with heavy natural infection, inspection of the tongue identified cysticerci in two (20%), while at inspection with necropsy the parasites were identified in large quantities in all animals. In ELISA for antibody search (Ab-ELISA) TS-14 recombinant protein was used, and in search for antigen (Ag-ELISA) a monoclonal antibody against this protein. In animals experimentally infected, blood was collected weekly for 140 days. The Ab-ELISA identified an increase in titers of antibody to cysticerci 21 days after infection, and at the end of the experimental period six animals (86%) were positive to the test. The search for circulating antigens (Ag-ELISA) was positive in two pigs 28 to 91 days after infection. All naturally infected pigs were positive for Ag-ELISA and Ab-ELISA. The search for antibodies and antigens by ELISA in serum from 30 pigs of a local farm and without history of cysticercosis was negative. Thus, the use of TS-14 antigen in ELISA test (Ab-ELISA) can be useful for the diagnosis of cysticercosis in pigs with low infection.

Nosso objetivo foi avaliar o diagnóstico de cisticercose suína através do exame "ante mortem" (inspeção da língua), "post mortem" (inspeção e necropsia detalhada) e teste de ELISA para a pesquisa no soro de anticorpos (Ab-ELISA) e antígenos (Ag -ELISA). Sete (7) suínos foram infectados experimentalmente por via oral com ovos de Taenia solium e outros 10 eram portadores de infecção natural generalizada. Nos suínos experimentalmente infectados, a inspeção da língua foi negativa em todos os animais, na inspeção 4 (57%) estavam infectados, a necropsia detalhada identificou cisticercos em todos os animais. Nos animais com infecção natural generalizada, a inspeção da língua identificou cisticercos em 2 (20%), enquanto que a inspeção e a necropsia os parasitas foram identificados em grande quantidade em todos os animais. No teste de ELISA para a pesquisa de anticorpos (Ab-ELISA) foi utilizada a proteína recombinante TS-14 e para a pesquisa de antígenos (Ag-ELISA) um anticorpo monoclonal produzido contra esta proteína. Nos animais experimentalmente infectados o sangue foi coletado semanalmente por um período de 140 dias. O Ab-ELISA identificou um aumento nos títulos de anticorpos para cisticercos 21 dias após a infecção, sendo que no final do período experimental 6 animais (86%) foram positivos ao teste. A pesquisa de antígenos circulantes (Ag-ELISA), foi positiva em 2 animais, entre os dias 21 e 91 após a infecção . Todos os suínos com infecção natural generalizada foram positivos para Ag-ELISA e Ab-ELISA.A pesquisa de anticorpos e antígenos pelo ELISA realizada no soro de 30 suínos procedentes de uma criação local sem historia de cisticercose foi negativa. Assim o uso do antígeno TS-14 (Ac-ELISA), pode ser útil para o diagnóstico da cisticercose em suínos com baixa infecção.

Neurocysticercosis: a review.

Neuroysticercosis is the most common helminthic infection of the nervous system, and a leading cause of acquired epilepsy worldwide. The disease occurs when humans become intermediate hosts of Taenia solium by ingesting its eggs from contaminated food or, most often, directly from a taenia carrier by the fecal-to-oral route. Cysticerci may be located in brain parenchyma, subarachnoid space, ventricular system, or spinal cord, causing pathological changes that are responsible for the pleomorphism of neurocysticercosis. Seizures are the most common clinical manifestation, but many patients present with focal deficits, intracranial hypertension, or cognitive decline. Accurate diagnosis of neurocysticercosis is possible after interpretation of clinical data together with findings of neuroimaging studies and results of immunological tests. The introduction of cysticidal drugs have changed the prognosis of most patients with neurocysticercosis. These drugs have shown to reduce the burden of infection in the brain and to improve the clinical course of the disease in most patients. Further efforts should be directed to eradicate the disease through the implementation of control programs against all the interrelated steps in the life cycle of T. solium, including human carriers of the adult tapeworm, infected pigs, and eggs in the environment.