[Show abstract][Hide abstract] ABSTRACT: Neurocysticercosis is caused by the establishment of Taenia solium cysticerci in the central nervous system. It is considered that, during coevolution, the parasite developed strategies to modulate host's immune response. The action mechanisms of T regulatory cells in controlling the immune response in neurocysticercosis are herein studied. Higher blood levels of T regulatory cells with CD4+CD45RO+FOXP3(high) and CD4+CD25(high) FOXP3+CD95(high) phenotype and of non-regulatory CD4+CD45RO+FOXP3(med) T cells were found in neurocysticercosis patients with respect to controls. Interestingly, T regulatory cells express higher levels of CTLA-4, LAG-3, PD-1, and GITR, suggesting a cell-to-cell contact mechanism with dendritic cells. Furthermore, higher IL-10 and Tr1 levels were found in neurocysticercosis patients' peripheral blood, suggesting that the action mechanism of T regulatory cells involves the release of immunomodulatory cytokines. No evidence of T regulatory cell role in inhibiting the proliferative response was found. Suppressive T regulatory cells from neurocysticercosis patients negatively correlated with late activated lymphocytes (CD4+CD38+). Our results suggest that during neurocysticercosis, T regulatory cells could control the immune response, probably by a cell-to-cell contact with dendritic cells and IL-10 release by Tr1, to create an immunomodulatory environment that may favor the development of T. solium cysticerci and their permanence in the central nervous system. This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Taenia solium cysticercosis is a major parasitic disease that severely affects
human health and the economy of undeveloped countries. Since pigs are obligate
intermediate hosts, it is plausible to curb human transmission by reducing pig
cysticercosis through effective vaccination. This article reviews the current knowledge
on the development of vaccines against porcine cysticercosis. It highlights the
development of plant-based, needle-free vaccine versions as a feasible and affordable
approach to reduce the logistic costs of injectable vaccines, while preventing the
digestive hydrolysis of vaccine antigens.
Frontiers in Medicinal Chemistry, 09/2015; Bentham., ISBN: 978-1-60805-971-3
[Show abstract][Hide abstract] ABSTRACT: Human neurocysticercosis (NC) is caused by the establishment of Taenia solium larvae in the central nervous system. NC is a severe disease still affecting the population in develop- ing countries of Latin America, Asia, and Africa. While great improvements have been made on NC diagnosis, treatment, and prevention, the management of patients affected by extraparenchymal parasites remains a challenge. The development of a T. solium NC experimental model in pigs that will allow the evaluation of new therapeutic alternatives is herein presented. Activated oncospheres (either 500 or 1000) were surgically implanted in the cerebral subarachnoid space of piglets. The clinical status and the level of serum anti- bodies in the animals were evaluated for a 4-month period after implantation. The animals were sacrificed, cysticerci were counted during necropsy, and both the macroscopic and microscopic characteristics of cysts were described. Based on the number of established cysticerci, infection efficiency ranged from 3.6% (1000 oncospheres) to 5.4% (500 onco- spheres). Most parasites were caseous or calcified (38/63, 60.3%) and were surrounded by an exacerbated inflammatory response with lymphocyte infiltration and increased inflamma- tory markers. The infection elicited specific antibodies but no neurological signs. This novel experimental model of NC provides a useful tool to evaluate new cysticidal and anti-inflam- matory approaches and it should improve the management of severe NC patients, refrac- tory to the current treatments.
[Show abstract][Hide abstract] ABSTRACT: Excretory/Secretory (ES) proteins play an important role in the host-parasite interactions. Experimental identification of ES proteins is time-consuming and expensive. Alternative bioinformatics approaches are cost-effective and can be used to prioritize the experimental analysis of therapeutic targets for parasitic diseases. Here we predicted and functionally annotated the ES proteins in T. solium genome using an integration of bioinformatics tools. Additionally, we developed a novel measurement to evaluate the potential antigenicity of T. solium secretome using sequence length and number of antigenic regions of ES proteins. This measurement was formalized as the Abundance of Antigenic Regions (AAR) value. AAR value for secretome showed a similar value to that obtained for a set of experimentally determined antigenic proteins and was different to the calculated value for the non-ES proteins of T. solium genome. Furthermore, we calculated the AAR values for known helminth secretomes and they were similar to that obtained for T. solium. The results reveal the utility of AAR value as a novel genomic measurement to evaluate the potential antigenicity of secretomes. This comprehensive analysis of T. solium secretome provides functional information for future experimental studies, including the identification of novel ES proteins of therapeutic, diagnosis and immunological interest.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: Taenia solium cysticercosis affects both humans and pigs. It has been considered an eradicable disease, and yet its prevalence remains stable in most endemic countries, due to the persistence of risk factors usually associated with the marginalization of an important sector of the population. In this chapter we will review key aspects of its epidemiology, clinical features, diagnosis, treatment, and prevention.
[Show abstract][Hide abstract] ABSTRACT: The seroprevalence of cysticercosis indicate that there is a high risk of contact with Taenia solium in Mexico, including both genders and all regions, socioeconomic group, and ages. There are some statistically significant differences in risk of contact, affecting principally the center and southeast of the country, rural areas, handicapped persons, children, old people and women. However, these differences are small. This study emphasizes the fact that the risks of infection by Taenia solium are important in all groups, and therefore, the programs for the control of this disease should be focused at the entire population and emphasize strategies for social development.
Salud publica de Mexico 09/2014; 34(2):197-210. · 0.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The progressive interest in transgenic plants as advantageous platforms for the production and oral delivery of vaccines has led to extensive research and improvements in this technology over recent years. In this paper, the authors examine the most significant advances in this area, including novel approaches for higher yields and better containment, and the continued evaluation of new vaccine prototypes against several infectious diseases. The use of plants to deliver vaccine candidates against viruses, bacteria, and eukaryotic parasites within the last 5 years is discussed, focusing on innovative expression strategies and the immunogenic potential of new vaccines. A brief section on the state of the art in mucosal immunity is also included.
[Show abstract][Hide abstract] ABSTRACT: Neurocysticercosis, a clinically and radiologically pleomorphic parasitic disease, is still endemic to most non-developed countries of Latin America, Africa, and Asia. Anti-helminthic drugs (AHD) are generally effective and rapidly destroy parenchymal cysticerci. In contrast, several cycles of AHD are frequently necessary to damage extraparenchymally located parasites. The present study was designed to evaluate whether differences in the immunological profile of the patients is involved in the diversity of the response to AHD. To this end, a global gene expression microarray and a cytokine analysis were made. Responder patients were those showing a radiological reduction greater than 50 % in the parasite burden following AHD treatment. Microarray pre- and post-treatment comparisons showed that a total of eighteen immune-related genes were up-regulated in the five responder patients with respect the expression profile seen in the four non-responder subjects. The function of up-regulated genes exerted pro-inflammatory (RORγC, Sema4A, SLAMF3, SLAMF6), anti-inflammatory (TGFβ, TNFRSF25, TNFRS18, SLAMF1, ILF2), or immunomodulatory effects (CXCL2, RUNX3, SLAMF9, TGFBR3). To further explore the causes of the heterogeneity in the response to treatment, a wide ELISA cytokine analysis was performed in serum, PBMC supernatants, and CSF samples from 39 responder and 26 non-responder patients. Responder patients showed higher CSF IL-17A levels (P = 0.04) and higher supernatant IL-6 levels (P = 0.03) 60 days after treatment. These results suggest a possible influence of pro-inflammatory cytokines on the response to AHD as observed by radiological methods, and thus the possible participation of the host immunity in the effectiveness of AHD treatment.
Medical Microbiology and Immunology 06/2014; 203(6). DOI:10.1007/s00430-014-0345-2 · 3.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The host-parasite relationship in cestode infections is complex. One feature of this bidirectional molecular communication is the uptake of host proteins by the parasite. Here we describe the presence of several host proteins in the vesicular fluid of Taenia solium cysticerci dissected from the central nervous system and the skeletal muscle of naturally infected pigs. Using two-dimensional electrophoresis we compared the protein patterns of vesicular fluids of cysticerci vs. the sera of cysticercotic pigs. We found that the vesicular fluids of both groups of cysts showed 17 protein spots matching with the pig's sera spots. After mass spectrometry sequencing of these spots, five host proteins were identified: hemoglobin, albumin, serpin A3-8, haptoglobin, rho GTPase-activating protein 36-like. Three of the 17 spots corresponded to host protein fragments: hemoglobin, albumin and serpin A3-8. IgG heavy and light chains were also identified by western blot using a specific antibody. Quantitative estimations indicated that the host proteins represented 11-13% of the protein content in the vesicular fluids. We also calculated the relative abundance of these host proteins in the vesicular fluids; all were represented in similar relative abundances as in host sera. This suggests that uptake of host proteins by cysticerci proceeds through an unspecific mechanism such as non-specific fluid pinocytosis.
[Show abstract][Hide abstract] ABSTRACT: Human cysticercosis is known since old historical times in Greece and China; however, human infections by tapeworms have accompanied human beings for more that hundred thousand years. The disease is tightly bound to poverty and lack of hygiene, and has been eradicated in developed countries, but continues being a public health problem in developing countries of Latin-American, Sub-Saharan Africa and Asia, and is also remerging in a number of non endemic countries. It is considered a neglected disease. Here we revise a number of key scientific contributions on taeniid biology that open new avenues for more effective approaches to the control of cysticercosis. The evolution of flatworms and class Cestoda is analyzed, with special emphasis on the emergence of taeniid parasites and the colonization of the human species by tapeworms. The complex molecular host-parasite interplay in this relationship as result of co-evolution between two distantly related organisms. The relevant host and parasite’s factors, in the prospect of identifying species-specific molecular markers useful in epidemiological studies carried out in endemic countries. The new possibilities arising with the characterization of the genomes for several species of tapeworms, including a deeper understanding of these organisms, as well as improved tools for diagnosis, vaccination and drug treatment. The need to revise the current control and management strategies for this tropical neglected disease.
Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 04/2014; 23. DOI:10.1016/j.meegid.2014.02.005 · 3.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives
To review neurological complications after the influenza A (H1N1) pdm09, highlighting the clinical differences between patients with post-vaccine or viral infection. DesignA search on Medline, Ovid, EMBASE, and PubMed databases using the keywords “neurological complications of Influenza AH1N1” or “post-vaccine Influenza AH1N1.” SettingOnly papers written in English, Spanish, German, French, Portuguese, and Italian published from March 2009 to December 2012 were included. SampleWe included 104 articles presenting a total of 1636 patient cases. In addition, two cases of influenza vaccine-related neurological events from our neurological care center, arising during the period of study, were also included. Main outcome measuresDemographic data and clinical diagnosis of neurological complications and outcomes: death, neurological sequelae or recovery after influenza A (H1N1) pdm09 vaccine or infection. ResultsThe retrieved cases were divided into two groups: the post-vaccination group, with 287 patients, and the viral infection group, with 1349 patients. Most patients in the first group were adults. The main neurological complications were Guillain-Barre syndrome (GBS) or polyneuropathy (125), and seizures (23). All patients survived. Pediatric patients were predominant in the viral infection group. In this group, 60 patients (4.7%) died and 52 (30.1%) developed permanent sequelae. A wide spectrum of neurological complications was observed. Conclusions
Fatal cases and severe, permanent, neurological sequelae were observed in the infection group only. Clinical outcome was more favorable in the post-vaccination group. In this context, the relevance of an accurate neurological evaluation is demonstrated for all suspicious cases, as well as the need of an appropriate long-term clinical and imaging follow-up of infection and post-vaccination events related to influenza A (H1N1) pdm09, to clearly estimate the magnitude of neurological complications leading to permanent disability.
Influenza and Other Respiratory Viruses 02/2014; 8(3). DOI:10.1111/irv.12241 · 2.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Neurocysticercosis (NC) is a clinically and radiologically heterogeneous parasitic disease caused by the establishment
of 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.
Memórias do Instituto Oswaldo Cruz 11/2013; 108(7):914-920. DOI:10.1590/0074-0276130308 · 1.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cysticercosis, caused by the larval stage of Taenia solium, is a zoonotic disease affecting pigs and humans that is endemic to developing countries in Latin America, Africa and South East Asia. The prevalence of infection in pigs, the intermediate host for T. solium, has been used as an indicator for monitoring disease transmission in endemic areas. However, accurate and specific diagnostic tools for porcine cysticercosis remain to be established. Using proteomic approaches and the T. solium genome sequence, seven antigens were identified as specific for porcine cysticercosis, namely, tropomyosin 2, alpha-1 tubulin, beta-tubulin 2, annexin B1, small heat-shock protein, 14-3-3 protein, and cAMP-dependent protein kinase. None of these proteins were cross-reactive when tested with sera from pigs infected with Ascaris spp., Cysticercus tenuicollis and hydatid cysts of Echinococcus spp. or with serum from a Taenia saginata-infected cow. Comparison with orthologues, indicated that the amino acid sequences of annexin B1 and cAMP-dependent protein kinase possessed highly specific regions, which might make them suitable candidates for development of a specific diagnostic assay for porcine cysticercosis.
The Veterinary Journal 09/2013; 198(3). DOI:10.1016/j.tvjl.2013.09.056 · 1.76 Impact Factor