Edda Sciutto

The genomes of four tapeworm species reveal adaptations to parasitism.

Tapeworms (Cestoda) cause neglected diseases that can be fatal and are difficult to treat, owing to inefficient drugs. Here we present an analysis of tapeworm genome sequences using the human-infective species Echinococcus multilocularis, E. granulosus, Taenia solium and the laboratory model Hymenolepis microstoma as examples. The 115- to 141-megabase genomes offer insights into the evolution of parasitism. Synteny is maintained with distantly related blood flukes but we find extreme losses of genes and pathways that are ubiquitous in other animals, including 34 homeobox families and several determinants of stem cell fate. Tapeworms have specialized detoxification pathways, metabolism that is finely tuned to rely on nutrients scavenged from their hosts, and species-specific expansions of non-canonical heat shock proteins and families of known antigens. We identify new potential drug targets, including some on which existing pharmaceuticals may act. The genomes provide a rich resource to underpin the development of urgently needed treatments and control.

Taenia solium disease in humans and pigs: an ancient parasitosis disease rooted in developing countries and emerging as a major health problem of global dimensions

This article reviews current knowledge on human and porcine cysticercosis caused by Taenia solium. It highlights the conditions favorable for its prevalence and transmission, as well as current trends in research on its natural history, epidemiology, immunopathology, diagnosis, treatment and prevention. Our opinions on the most urgent needs for further research are also presented.

High Prevalence of Calcified Silent Neurocysticercosis in a Rural Village of Mexico

Human neurocysticercosis (NC) is a parasitic disease caused by Taenia solium when its larvae lodge in the central nervous system. NC prevalence estimates are obscured by the variable and often asymptomatic clinical picture. While infection depends on exposure, severity is possibly related with various host factors (immunity, genes and gender). This epidemiological study of cranial CT scans in an endemic rural community found that 9.1% of apparently healthy subjects had calcified lesions and were completely asymptomatic. Silent NC cases did not correlate with the exposure factors tested but showed family aggregation and higher rates of positive serology. Thus, NC prevalence may be higher than currently considered and host-related factors appear to be involved in infection and pathogenesis.

Symptomatic human neurocysticercosis: Age, sex and exposure factors relating with disease heterogeneity

Abstract.Objective:To evaluate the relevance of exposure and host biological factors in the heterogeneity of the clinical, radiological and inflammatory picture of neurocysticercosis (NCC).Methods:105 Mexican symptomatic NCC patients confirmed by imaging were studied before they received any specific treatment. The relationships studied were those between a) the patients’ characteristics (gender, age and level of exposure), b) the type of clinical picture and c) the radiological and inflammatory characteristics of the disease (number, aspect, localization of the parasites, and CSF leukocytecounts).Results:Results Seizures were the most frequent symptom and multiple subarachnoid cysticerci the most frequent localization. Symptomatology related to the developmental stage, number and localization of the parasites as well as the CSF leukocyte-counts. The total number of cysticercal lesions and of vesicular cysticerci increased with age,whereas the number of colloidal cysticerci decreased. CSF leukocyte-counts were higher in women than in men. Levels of exposure did not correlate with the clinical and radiological pictures.Conclusions:The variability found in the number, stage, localization and inflammation in the parasite lesions is strongly associated with the heterogeneity of NCC symptoms. The increased number of vesicular cysticerci and the decreased number of degenerating cysticerci with aging, as well as the prominence of inflammation in women suggest that immuno-endocrinological factors may play a role in susceptibility and pathogenesis. The data also show that with increasing age and exposure there is no increment in severity, a suggestion that there might be ways of regulating pathogenicity.

Characterization of S3Pvac Anti-Cysticercosis Vaccine Components: Implications for the Development of an Anti-Cestodiasis Vaccine

Background Cysticercosis and hydatidosis seriously affect human health and are responsible for considerable economic loss in animal husbandry in non-developed and developed countries. S3Pvac and EG95 are the only field trial-tested vaccine candidates against cysticercosis and hydatidosis, respectively. S3Pvac is composed of three peptides (KETc1, GK1 and KETc12), originally identified in a Taenia crassiceps cDNA library. S3Pvac synthetically and recombinantly expressed is effective against experimentally and naturally acquired cysticercosis. Methodology/Principal Findings In this study, the homologous sequences of two of the S3Pvac peptides, GK1 and KETc1, were identified and further characterized in Taenia crassiceps WFU, Taenia solium, Taenia saginata, Echinococcus granulosus and Echinococcus multilocularis. Comparisons of the nucleotide and amino acid sequences coding for KETc1 and GK1 revealed significant homologies in these species. The predicted secondary structure of GK1 is almost identical between the species, while some differences were observed in the C terminal region of KETc1 according to 3D modeling. A KETc1 variant with a deletion of three C-terminal amino acids protected to the same extent against experimental murine cysticercosis as the entire peptide. On the contrary, immunization with the truncated GK1 failed to induce protection. Immunolocalization studies revealed the non stage-specificity of the two S3Pvac epitopes and their persistence in the larval tegument of all species and in Taenia adult tapeworms. Conclusions/Significance These results indicate that GK1 and KETc1 may be considered candidates to be included in the formulation of a multivalent and multistage vaccine against these cestodiases because of their enhancing effects on other available vaccine candidates.

Cysticercosis vaccine : cross protecting immunity with T. Solium antigens against experimental murine T. Crassiceps cysticercosis

Summary Vaccination of mice with an antigen extract from Taenia solium cysticerci induced protection against challenge with T. crassiceps cysticerci as successfully as did antigen extracts from T. crassiceps. Vaccination was more effective in male than in female mice and in the resistant strain (BALB/B) more so than in the susceptible strain (BALB/c). While only the resistant strain was completely protected by vaccination, the parasite load of the susceptible strain was significantly reduced by vaccination. Cross immunity between the human and murine parasites establishes murine T. crassiceps cysticercosis as a convenient laboratory model in which to test promising T. solium antigens aimed at vaccine development against T. solium cysticercosis. Further, results point to strong interactions of the immune system with sexual and histocompatibility factors in the hosts dealing with cysticercosis.

Limitations of current diagnostic procedures for the diagnosis of Taenia solium cysticercosis in rural pigs

The aim of the present study was to evaluate diagnostic procedures for porcine cysticercosis. Sera were obtained from 32 pigs reared in commercial farms, 47 pigs before and after experimental infection, 42 carefully necropsied rural pigs and 191 slaughtered pigs from rural communities in which the presence of the Taenia solium metacestode was assessed by tongue dissection. Sera were analyzed by ELISA to detect antibodies against T. solium antigens and to detect parasite antigens. Most sera from the necropsied rural pigs were also evaluated by the Western blot method. Antigen and antibody ELISA detection assays showed high sensitivity and specificity when applied to sera from pigs reared in commercial farms. In contrast, all methods (Ag-ELISA, Ab-ELISA assays, EITB and tongue inspection) showed lower sensitivity and specificity when applied to the generally lightly infected rurally reared pigs. The probability distribution of cysts in carcasses were also determined. These results emphasize the difficulties in detecting cysticercosis in rural pigs with low levels of cyst burdens.

Two Epitopes Shared by Taenia crassiceps and Taenia solium Confer Protection against Murine T. crassiceps Cysticercosis along with a Prominent T1 Response

ABSTRACT Taenia crassiceps recombinant antigens KETc1 and KETc12 have been shown to induce high level of protection against experimental murine T. crassiceps cysticercosis, an experimental model successfully used to test candidate antigens for use in vaccination against porcine Taenia solium cysticercosis. Based on the deduced amino acid sequence, KETc1 and KETc12 were chemically synthesized in linear form. Immunization with KETc1 induced 66.7 to 100% protection against murine cysticercosis, and immunization with KETc12 induced 52.7 to 88.1% protection. The elicited immune response indicated that both peptides contain at least one B-cell epitope (as demonstrated by their ability to induce specific antibodies) and one T-cell epitope that strongly stimulated the proliferation of T cells primed with either the free peptide or total cysticercal T. crassiceps antigens. The high percentage of spleen cells expressing inflammatory cytokines points to the likelihood of a T1 response being involved in protection. The protective capacity of the peptides and their presence in all developmental stages of T. solium point to these two epitopes as strong candidates for inclusion in a polyepitopic synthetic vaccine against T. solium pig cysticercosis.

CYSTICERCOSIS: IDENTIFICATION AND CLONING OF PROTECTIVE RECOMBINANT ANTIGENS

We describe the cloning and the evaluation of the protective capacity of 5 recombinant antigens expressed during the cysticercus stage of both Taenia crassiceps and Taenia solium. A cDNA library was constructed in bacteriophage lambda ZAP using mRNA isolated from larvae of T. crassiceps of the ORF strain. The recombinant phage library was screened with polyclonal antibodies against 56- and 74-kDa protective antigen fractions. This screening identified 13 recombinant clones, 5 of which were also strongly recognized by pooled sera from pigs experimentally infected with T. solium. The native antigens are proteins of 56 (clones KETcl, 4, 7) and 74 and 78 kDa (clones KETc11, 12) of T. crassiceps cysticerci. Vaccination experiments using these 5 recombinant clones against murine cysticercosis point to the relevance of KETcl, 4, 7, and 12 in host protection, whereas immunization with the clone KETc11 does not modify the parasite load in females and facilitates the parasitosis in males. We report here the DNA and the deduced amino acid sequence (100 amino acids) of the first protective antigen (KETc7) of potential interest for T. solium pig cysticercosis prevention.

MurineTaenia crassiceps cysticercosis: H-2 complex and sex influence on susceptibility

Several inbred strains of mice were infected by intraperitoneal injection of tenTaenia crassiceps cysticerci per mouse. Genes linked with the major histocompatibility complex (H-2) were found to influence parasite growth greatly, as demonstrated by the different parasite loads of H-2 congenic mice with BALB background: BALB/c (H-2d) mice were the most susceptible, whereas BALB/k (H-2k) and BALB/b (H-2b) animals were comparatively resistant. Non-H-2 genes had no significant effect on susceptibility in H-2d strains, as reflected by the similar parasite loads in BALB/c, DBA/2, and (BALB/cxDBA/2)F1 mice. Using the H-2b (BALB/b, C57BL/6J) and H-2k (C3H/HeJ, BALB/k, and C3HeB/FeJ) strains, we found that non-H-2 background genes caused a small but significant influence on parasite load. A recombinant mouse strain alleles (Kk, Ik, Sd, Dd) was also susceptible, indicating that S and/or D regions of the H-2d complex are probably involved in the control of resistance to murine cysticercosis. Females of all mouse strains were more susceptible than males. The same effects were observed for H-2 genes and sex, with two strains ofT. crassiceps differing in their rate of growth.