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

Femoral Interference Screw Position In Transtibial Acl Reconstruction: How To Optimize Alignment With A Mathematical Model. A Cadaveric Study

Femoral interference screw divergence is a potential pitfall associated with ACL reconstruction through transtibial tunnel technique, as angles greater than 15 jeopardize graft fixation. Our mathematical model theorizes the proper degrees of knee flexion during femoral screw insertion and the correct screwdriver position to obtain a minimal divergence of the screw in the femoral tunnel. The cadaveric study confirms our method

Immunolocalization of the S3Pvac peptides in <i>E. granulosus</i> and <i>E. multilocularis</i>.

<p>Sections of larval specimens reveal a strong binding to the tegument (<b>T</b>) as well as in the parenchyma (<b>P</b>) of <i>E. multilocularis</i> and in tegument of <i>E. granulosus</i>. (<b>A</b>) Control labeled with rabbit pre immune serum. (<b>B</b>) Positive control labeled with polyclonal sera from rabbit immunized with a total extract of <i>Taenia crassiceps</i> ORF cysticerci.</p

Sequences used to model the 3D structure of KETc1, GK1 and KETc12.

1<p>GK1 and KETc1 3D models include more than just the peptide sequence because the HMMSTR-server requires sequences of at least 20 amino acids length. Upper case marks the sequences of peptides while lower caps mark the preceding sequence to them.</p>2<p>There is no “complete” sequence for any of the strains of <i>T. crassiceps.</i> However, considering the strong similarity between the <i>Taenia</i> species we decided to construct a hypothetical sequence for each strain assuming that the preceding regions to KETc1 in <i>T. crassiceps</i> spp. are identical to those preceding the peptide in the other <i>Taenia</i> species.</p

A tuberculose nas prisões do Rio de Janeiro, Brasil: uma urgência de saúde pública Tuberculosis in Rio de Janeiro prisons, Brazil: an urgent public health problem

Em 2004, a taxa de incidência da tuberculose nas prisões do Estado do Rio de Janeiro, Brasil, foi trinta vezes superior à da população geral do Estado. Essa taxa provavelmente é subestimada, especialmente pela dificuldade de acesso ao serviço de saúde nesse ambiente. Com o objetivo de melhor avaliar a situação, um primeiro inquérito radiológico sistemático foi realizado e mostrou taxa de prevalência de 4,6% (prisão A, n = 1.052). Dois inquéritos adicionais revelaram, nas unidades B (n = 590) e C (n = 1.372), taxas maiores (6,3% e 8,6%, respectivamente). A comparação das características sócio-demográficas das prisões A, B e C mostrou que a população encarcerada não é homogênea. Em comparação com prisão A, os indivíduos encarcerados nas prisões B e C são oriundos de comunidades mais desfavorecidas e têm mais freqüentemente história de encarceramento anterior e de tuberculose. Essas diferenças, coerentes com os dados de prevalência, implicam a adaptação das medidas de controle da tuberculose ao perfil epidemiológico e sócio-demográfico de cada unidade prisional.<br>The tuberculosis incidence rate in prisons in Rio de Janeiro State, Brazil, was 30 times higher in 2004 than in the general population and is probably underestimated, particularly given the difficult access to care in the prison setting. To obtain a better estimate, a survey used systematic X-ray screening and showed a prevalence rate of 4.6% in one such detention facility, A (n = 1,052). Two additional surveys, in facilities B (n = 590) and C (n = 1,372), showed even higher prevalence rates (6.3% and 8.6% respectively). A comparison of socio-demographic characteristics between A, B, and C showed a heterogeneous prison population. As compared to facility A, inmates in B and C come from poorer urban communities and have more frequent histories of incarceration and tuberculosis. These differences, consistent with the prevalence data, imply the necessary adaptation of tuberculosis control programs to each detention facility's epidemiological and socio-demographic profile

S3Pvac peptides were detected in the tegument of <i>Taenia</i> tapeworms and <i>T. solium</i> eggs.

<p>No reaction was detected in control sections, for which naive rabbit serum was used in place of the specific polyclonal rabbit serum. <b>S.</b>- Sucker; <b>Sc.</b> Scolex, <b>MP.</b>- Medullar parenchyma, <b>N.</b>- Neck; <b>DC.</b>- Distal cytoplasm region; <b>PE.</b>- perinuclear cytoplasm region. <b>O.</b>- oncospheres.</p

Multiple sequence alignment GK1 peptides.

<p>The DNA and amino acid sequences of GK1 in several species of the Taeniidae family were aligned. GK1 alignments of amino acids (A) and cDNA (B) are shown in the upper part of the figure; the region encoding the actual peptides is marked with a double-headed arrow on the top of the alignment. On every alignment, boxes corresponding to the regions subjected to dN/dS-ratio analysis are marked accordingly. Models of the 3D structure of the GK1 peptide are shown in panel C. The model in red corresponds to <i>T. solium</i>, <i>T. saginata</i> and <i>E. granulosus</i>' GK1 and in purple to <i>T. crassiceps</i> ORF and WFU and <i>E. multilocularis</i>. A very good fitting between the two structures is shown as expected from the strong similarity of the amino acid sequence.</p

Multiple sequence alignment of KETc1 peptides.

<p>The DNA and amino acid sequences of KETc1 of several species of the Taeniidae family were aligned. KETc1 alignments of amino acids (A) and cDNA (B) are shown in the upper part of the figure. On every alignment, boxes corresponding to the regions subjected to dN/dS-ratio analysis are marked accordingly. Panel C and D shows the 3D models of the complete and truncated version of KETc1. Panel D depicts the models corresponding to <i>T. solium</i> (red), <i>T. crassiceps</i> ORF and WFU (pink), <i>T. saginata</i> (light green) and <i>Echinococcus</i> group (dark green). Structures are aligned with very good general agreement. Panel D shows the alignment of the truncated KETc1 peptide where the yellow model corresponds to <i>T. solium</i> and <i>T. saginata</i>; blue corresponds to <i>T. crassiceps</i> ORF and WFU and brown to the <i>Echinococcus</i> group.</p