Dataset Information

TsAg5, a Taenia solium cysticercus protein with a marginal trypsin-like activity in the diagnosis of human neurocysticercosis.

ABSTRACT: Neurocysticercosis is an endemic parasitic disease caused by Taenia solium larva. Although the mechanism of infection is not completely understood, it is likely driven by proteolytic activity that degrades the intestinal wall to facilitate oncosphere penetration and further infection. We analyzed the publicly available T. solium EST/DNA library and identified two contigs comprising a full-length cDNA fragment very similar to Echinococcus granulosus Ag5 protein. The T. solium cDNA sequence included a proteolytic trypsin-like-domain in the C-terminal region, and a thrombospondin type-1 adherence-domain in the N-terminal region. Both the trypsin-like and adherence domains were expressed independently as recombinant proteins in bacterial systems. TsAg5 showed marginal trypsin-like activity and high sequence similarity to Ag5. The purified antigens were tested in a Western immunoblot assay to diagnose human neurocysticercosis. The sensitivity of the trypsin-like-domain was 96.36% in patients infected with extraparenchymal cysts, 75.44% in patients infected with multiple cysts, and 39.62% in patients with a single cyst. Specificity was 76.70%. The thrombospondin type-1 adherence-domain was not specific for neurocysticercosis.

SUBMITTER: Rueda A

PROVIDER: S-EPMC3196780 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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TsAg5, a Taenia solium cysticercus protein with a marginal trypsin-like activity in the diagnosis of human neurocysticercosis.

Rueda Analiz A Sifuentes Cecilia C Gilman Robert H RH Gutiérrez Andrés H AH Piña Ruby R Chile Nancy N Carrasco Sebastián S Larson Sandra S Mayta Holger H Verástegui Manuela M Rodriguez Silvia S Gutiérrez-Correa Marcel M García Héctor H HH Sheen Patricia P Zimic Mirko M

Molecular and biochemical parasitology 20110826 2

Neurocysticercosis is an endemic parasitic disease caused by Taenia solium larva. Although the mechanism of infection is not completely understood, it is likely driven by proteolytic activity that degrades the intestinal wall to facilitate oncosphere penetration and further infection. We analyzed the publicly available T. solium EST/DNA library and identified two contigs comprising a full-length cDNA fragment very similar to Echinococcus granulosus Ag5 protein. The T. solium cDNA sequence includ ...[more]

PMID: 21893105

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Project description:BackgroundEstimating the burden of neglected tropical diseases is a valuable tool to support policymakers in the resource allocation for control and elimination of these diseases. Spatial analysis allows to identify the geographical distribution patterns of infectious and parasitic diseases within a country and allows to assess their possible correlation with other health disorders. Despite being neurocysticercosis (NCC) considered as the most important parasitic disease of the nervous system, few efforts have been addressed to assess the real burden of NCC in endemic countries, to date, there are no studies estimating the burden of NCC in South America. In this study we aimed to use the Disability Adjust Life Years (DALY) and spatial indicators as tools to measure the impact of human neurocysticercosis in Ecuador between 2013 and 2017.MethodsMortality, morbidity and spatial data from the national agency of statistics were used to estimate the burden of disease of NCC during a five-year period (2013-2017). NCC cases and its two main sequelae, epilepsy and migraine headache, were stratified by sex and age group to calculate the DALY associated to NCC using the DALY package in R. SATSCAN software was used to assess spatial clusters of NCC and its possible neurological sequelae as epilepsy, status epilepticus, migraine and hydrocephalus.Principal findingsThe burden of human neurocysticercosis ranged from 56201 [95% CI 29961-89333] to 59612 [95% CI 31854-94689] DALY per year, corresponding to 3.54 to 3.56 DALY per 1000 population. Average yearly incidence rates per 10 000 person-years were 0.23 [95% CI 0.21-0.26] for NCC, 4.89 [95% CI 4.78-5.00] for epilepsy, 0.130 [95% CI 0.11-0.15] for status epilepticus, 0.62 [95% CI 0.58-0.66] for migraine headache, and 1.02 [95% CI 0.98-1.07] for hydrocephalus. Most important significant spatial clusters (p<0.0001) were located in the southern region of the highlands of the country.Conclusion/significanceThis is the first study in South America to calculate estimates for burden of NCC and one of the few using spatial analysis to show the importance of sequelae other than epilepsy that play an important role in the impact of human neurocysticercosis.

Project description:BackgroundThe ability of Taenia solium to modulate the immune system likely contributes to their longevity in the human host. We tested the hypothesis that the nature of the immune response is related to the location of parasite and clinical manifestations of infection.MethodologyPeripheral blood mononuclear cells (PBMC) were obtained from untreated patients with neurocysticercosis (NCC), categorized as having parenchymal or subarachnoid infection by the presence of cysts exclusively within the parenchyma or in subarachnoid spaces of the brain, and from uninfected (control) individuals matched by age and gender to each patient. Using multiplex detection technology, sera from NCC patients and controls and cytokine production by PBMC after T. solium antigen (TsAg) stimulation were assayed for levels of inflammatory and regulatory cytokines. PBMC were phenotyped by flow cytometry ex vivo and following in vitro stimulation with TsAg.Principal findingsSera from patients with parenchymal NCC demonstrated significantly higher Th1 (IFN-?/IL-12) and Th2 (IL-4/IL-13) cytokine responses and trends towards higher levels of IL-1?/IL-8/IL-5 than those obtained from patients with subarachnoid NCC. Also higher in vitro antigen-driven TNF-? secretion was detected in PBMC supernatants from parenchymal than in subarachnoid NCC. In contrast, there was a significantly higher IL-10 response to TsAg stimulation in patients with subarachnoid NCC compared to parenchymal NCC. Although no differences in regulatory T cells (Tregs) frequencies were found ex vivo, there was a trend towards greater expansion of Tregs upon TsAg stimulation in subarachnoid than in parenchymal NCC when data were normalized for the corresponding controls.Conclusions/significanceT. solium infection of the subarachnoid space is associated with an enhanced regulatory immune response compared to infection in the parenchyma. The resulting anti-inflammatory milieu may represent a parasite strategy to maintain a permissive environment in the host or diminish inflammatory damage from the host immune response in the central nervous system.

Dataset Information

TsAg5, a Taenia solium cysticercus protein with a marginal trypsin-like activity in the diagnosis of human neurocysticercosis.

Publications

TsAg5, a Taenia solium cysticercus protein with a marginal trypsin-like activity in the diagnosis of human neurocysticercosis.

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