RESUMEN

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was funded in 2008 to conduct research that would support country schistosomiasis control programs. As schistosomiasis prevalence decreases in many places and elimination is increasingly within reach, a sensitive and specific test to detect infection with Schistosoma mansoni and Schistosoma haematobium has become a pressing need. After obtaining broad input, SCORE supported Leiden University Medical Center (LUMC) to modify the serum-based antigen assay for use with urine, simplify the assay, and improve its sensitivity. The urine assay eventually contributed to several of the larger SCORE studies. For example, in Zanzibar, we demonstrated that urine filtration, the standard parasite egg detection diagnostic test for S. haematobium, greatly underestimated prevalence in low-prevalence settings. In Burundi and Rwanda, the circulating anodic antigen (CAA) assay provided critical information about the limitations of the stool-based Kato-Katz parasite egg-detection assay for S. mansoni in low-prevalence settings. Other SCORE-supported CAA work demonstrated that frozen, banked urine specimens yielded similar results to fresh ones; pooling of specimens may be a useful, cost-effective approach for surveillance in some settings; and the assay can be performed in local laboratories equipped with adequate centrifuge capacity. These improvements in the assay continue to be of use to researchers around the world. However, additional work will be needed if widespread dissemination of the CAA assay is to occur, for example, by building capacity in places besides LUMC and commercialization of the assay. Here, we review the evolution of the CAA assay format during the SCORE period with emphasis on urine-based applications.

Asunto(s)

Antígenos Helmínticos/inmunología , Glicoproteínas/inmunología , Proteínas del Helminto/inmunología , Schistosoma/inmunología , Esquistosomiasis/diagnóstico , Animales , Biomarcadores , Burundi/epidemiología , Niño , Pruebas Diagnósticas de Rutina , Heces/parasitología , Femenino , Humanos , Pruebas Inmunológicas , Masculino , Modelos Animales , Papio/parasitología , Recuento de Huevos de Parásitos , Prevalencia , Rwanda/epidemiología , Santa Lucia/epidemiología , Schistosoma/aislamiento & purificación , Schistosoma haematobium/inmunología , Schistosoma haematobium/aislamiento & purificación , Schistosoma japonicum/inmunología , Schistosoma japonicum/aislamiento & purificación , Schistosoma mansoni/inmunología , Schistosoma mansoni/aislamiento & purificación , Esquistosomiasis/epidemiología , Sensibilidad y Especificidad , Tanzanía/epidemiología , Orina/parasitología

RESUMEN

Molecular surveillance provides a powerful approach to monitoring the resistance status of parasite populations in the field and for understanding resistance evolution. Oxamniquine was used to treat Brazilian schistosomiasis patients (mid-1970s to mid-2000s) and several cases of parasite infections resistant to treatment were recorded. The gene underlying resistance (SmSULT-OR) encodes a sulfotransferase required for intracellular drug activation. Resistance has a recessive basis and occurs when both SmSULT-OR alleles encode for defective proteins. Here we examine SmSULT-OR sequence variation in a natural schistosome population in Brazil ∼40years after the first use of this drug. We sequenced SmSULT-OR from 189 individual miracidia (1-11 per patient) recovered from 49 patients, and tested proteins expressed from putative resistance alleles for their ability to activate oxamniquine. We found nine mutations (four non-synonymous single nucleotide polymorphisms, three non-coding single nucleotide polymorphisms and two indels). Both mutations (p.E142del and p.C35R) identified previously were recovered in this field population. We also found two additional mutations (a splice site variant and 1bp coding insertion) predicted to encode non-functional truncated proteins. Two additional substitutions (p.G206V, p.N215Y) tested had no impact on oxamniquine activation. Three results are of particular interest: (i) we recovered the p.E142del mutation from the field: this same deletion is responsible for resistance in an oxamniquine selected laboratory parasite population; (ii) frequencies of resistance alleles are extremely low (0.27-0.8%), perhaps due to fitness costs associated with carriage of these alleles; (iii) that four independent resistant alleles were found is consistent with the idea that multiple mutations can generate loss-of-function alleles.

Asunto(s)

Mutación , Oxamniquina/farmacología , Schistosoma mansoni/efectos de los fármacos , Esquistosomiasis/parasitología , Esquistosomicidas/farmacología , Alelos , Animales , Brasil , Niño , Preescolar , Resistencia a Medicamentos/genética , Exones/genética , Heces/parasitología , Frecuencia de los Genes , Estudio de Asociación del Genoma Completo , Humanos , Lactante , Conformación Molecular , Reacción en Cadena de la Polimerasa , Polimorfismo de Nucleótido Simple , Schistosoma mansoni/genética

RESUMEN

BACKGROUND: Immunoepidemiologic studies have shown a relationship between IgE and IgG4 antibodies with age and with resistance and susceptibility to infection. It is believed that the IgE and IgG4 responses to soluble egg antigen (SEA) can be used for serological analysis of infection and post-treatment status. This study aimed to evaluate the association between Schistosoma mansoni infection and anti-SEA IgG4 and IgE reactivities, and determine whether these reactivities could be used as biomarkers of infection. METHODS: Between 2001 and 2009, a longitudinal study was performed in which parasitologic and blood specimens and socioeconomic and water-contact information were collected from 127 individuals. All patients positive for S. mansoni infection were treated. RESULTS: Schistosomiasis prevalence and the geometric mean of the egg count in 2001 were 59% and 61.05, respectively, decreasing to 26.8% and 8.78 in 2009. IgG4 anti-SEA reactivity in infected individuals was significantly higher than that in uninfected individuals at all time points. Analysis of receiver-operating characteristic (ROC) area showed that the IgG4 anti-SEA antibodies were able to predict infection by S. mansoni at each time point. CONCLUSION: IgG4 anti-SEA reactivity can be used as a biomarker for immune monitoring of the presence of infection with S. mansoni in endemic areas.

Asunto(s)

Anticuerpos Antihelmínticos/sangre , Antígenos Helmínticos/inmunología , Biomarcadores/sangre , Schistosoma mansoni/inmunología , Esquistosomiasis mansoni/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Anticuerpos Antihelmínticos/análisis , Anticuerpos Antihelmínticos/inmunología , Brasil/epidemiología , Niño , Susceptibilidad a Enfermedades/inmunología , Femenino , Humanos , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Enfermedades Desatendidas , Estudios Seroepidemiológicos , Adulto Joven

RESUMEN

SMYB1 is a Schistosoma mansoni protein highly similar to members of the Y-box binding protein family. Similar to other homologues, SMYB1 is able to bind double- and single-stranded DNA, as well as RNA molecules. The characterization of proteins involved in the regulation of gene expression in S. mansoni is of great importance for the understanding of molecular events that control morphological and physiological changes in this parasite. Here we demonstrate that SMYB1 is located in the cytoplasm of cells from different life-cycle stages of S. mansoni, suggesting that this protein is probably acting in mRNA metabolism in the cytoplasm and corroborating previous findings from our group that showed its ability to bind RNA. Protein-protein interactions are important events in all biological processes, since most proteins execute their functions through large supramolecular structures. Yeast two-hybrid screenings using SMYB1 as bait identified a partner in S. mansoni similar to the SmD3 protein of Drosophila melanogaster (SmRNP), which is important in the assembly of small nuclear ribonucleoprotein complexes. Also, pull-down assays were conducted using immobilized GST-SMYB1 proteins and confirmed the SMYB1-SmRNP interaction. The interaction of SMYB1 with a protein involved in mRNA processing suggests that it may act in processes such as turnover, transport and stabilization of RNA molecules.

Asunto(s)

Proteínas del Helminto/metabolismo , ARN de Helminto/metabolismo , ARN Mensajero/metabolismo , Schistosoma mansoni/metabolismo , Animales , Anticuerpos Antihelmínticos/sangre , Anticuerpos Antihelmínticos/inmunología , Transporte Biológico , Citoplasma/metabolismo , Femenino , Biblioteca de Genes , Proteínas del Helminto/genética , Inmunohistoquímica , Masculino , ARN de Helminto/genética , ARN Mensajero/genética , Conejos , Schistosoma mansoni/genética , Técnicas del Sistema de Dos Híbridos

RESUMEN

Schistosoma mansoni is responsible for schistosomiasis, a parasitic disease that affects 200 million people worldwide. Molecular mechanisms of host-parasite interaction are complex and involve a crosstalk between host signals and parasite receptors. TGF-ß signaling pathway has been shown to play an important role in S. mansoni development and embryogenesis. In particular human (h) TGF-ß has been shown to bind to a S. mansoni receptor, transduce a signal that regulates the expression of a schistosome target gene. Here we describe 381 parasite genes whose expression levels are affected by in vitro treatment with hTGF-ß. Among these differentially expressed genes we highlight genes related to morphology, development and cell cycle that could be players of cytokine effects on the parasite. We confirm by qPCR the expression changes detected with microarrays for 5 out of 7 selected genes. We also highlight a set of non-coding RNAs transcribed from the same loci of protein-coding genes that are differentially expressed upon hTGF-ß treatment. These datasets offer potential targets to be explored in order to understand the molecular mechanisms behind the possible role of hTGF-ß effects on parasite biology.

Asunto(s)

Perfilación de la Expresión Génica , Regulación de la Expresión Génica/efectos de los fármacos , Schistosoma mansoni/efectos de los fármacos , Schistosoma mansoni/genética , Factor de Crecimiento Transformador beta/metabolismo , Animales , Helmintos/efectos de los fármacos , Helmintos/genética , Interacciones Huésped-Patógeno , Humanos , Análisis por Micromatrices , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de Señal

RESUMEN

BACKGROUND: MicroRNAs (miRNAs) constitute a class of single-stranded RNAs which play a crucial role in regulating development and controlling gene expression by targeting mRNAs and triggering either translation repression or messenger RNA (mRNA) degradation. miRNAs are widespread in eukaryotes and to date over 14,000 miRNAs have been identified by computational and experimental approaches. Several miRNAs are highly conserved across species. In Schistosoma, the full set of miRNAs and their expression patterns during development remain poorly understood. Here we report on the development and implementation of a homology-based detection strategy to search for miRNA genes in Schistosoma mansoni. In addition, we report results on the experimental detection of miRNAs by means of cDNA cloning and sequencing of size-fractionated RNA samples. RESULTS: Homology search using the high-throughput pipeline was performed with all known miRNAs in miRBase. A total of 6,211 mature miRNAs were used as reference sequences and 110 unique S. mansoni sequences were returned by BLASTn analysis. The existing mature miRNAs that produced these hits are reported, as well as the locations of the homologous sequences in the S. mansoni genome. All BLAST hits aligned with at least 95% of the miRNA sequence, resulting in alignment lengths of 19-24 nt. Following several filtering steps, 15 potential miRNA candidates were identified using this approach. By sequencing small RNA cDNA libraries from adult worm pairs, we identified 211 novel miRNA candidates in the S. mansoni genome. Northern blot analysis was used to detect the expression of the 30 most frequent sequenced miRNAs and to compare the expression level of these miRNAs between the lung stage schistosomula and adult worm stages. Expression of 11 novel miRNAs was confirmed by northern blot analysis and some presented a stage-regulated expression pattern. Three miRNAs previously identified from S. japonicum were also present in S. mansoni. CONCLUSION: Evidence for the presence of miRNAs in S. mansoni is presented. The number of miRNAs detected by homology-based computational methods in S. mansoni is limited due to the lack of close relatives in the miRNA repository. In spite of this, the computational approach described here can likely be applied to the identification of pre-miRNA hairpins in other organisms. Construction and analysis of a small RNA library led to the experimental identification of 14 novel miRNAs from S. mansoni through a combination of molecular cloning, DNA sequencing and expression studies. Our results significantly expand the set of known miRNAs in multicellular parasites and provide a basis for understanding the structural and functional evolution of miRNAs in these metazoan parasites.

Asunto(s)

Genoma de los Helmintos/genética , MicroARNs/genética , Schistosoma mansoni/genética , Animales , Biología Computacional

RESUMEN

This study examines the relative contribution of age-specific total IgE levels, eosinophils and water contact behavior to the prevalence and intensity (geometric mean egg counts) of Schistosoma mansoni infection in the poor rural population of Virgem das Graças in northern Minas Gerais State. In bivariate analysis, age was strongly correlated with both prevalence and intensity of infection, while eosinophil levels with prevalence only (p<0.0001); IgE levels and 5 demographic and socioeconomic variables were moderately correlated with prevalence (p<0.05), as were number of persons per room and TBM (total body minutes) with egg counts. In multivariate analysis, after controlling for demographic and socioeconomic factors, only total IgE levels were significantly correlated with both prevalence (p=0.248, 95% CI=1.01-1.11) and intensity (p=0.0217, 95% CI=0.01-0.14) of infection and eosinophil levels with prevalence (p=0.0005, 95% CI=1.07-1.24). Although any causal relationship cannot be confirmed by a cross-sectional study, we demonstrated an associated decrease in prevalence and intensity of S. mansoni infection with increased IgE levels.

Asunto(s)

Eosinófilos/inmunología , Inmunoglobulina E/sangre , Schistosoma mansoni/inmunología , Esquistosomiasis mansoni/epidemiología , Esquistosomiasis mansoni/inmunología , Adolescente , Adulto , Animales , Anticuerpos Antihelmínticos/sangre , Especificidad de Anticuerpos , Brasil/epidemiología , Niño , Exposición a Riesgos Ambientales , Femenino , Humanos , Inmunoglobulina E/inmunología , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Recuento de Huevos de Parásitos , Prevalencia , Riesgo , Factores de Riesgo , Población Rural , Esquistosomiasis mansoni/sangre , Agua/parasitología

RESUMEN

The eggs produced by sexually mature female Schistosma mansoni are responsible for the pathogenesis of the disease. The eggshell precursor gene p14 is expressed only in the vitelline cells of sexually mature female worms in response to a yet unidentified male stimulus. Herein, we report the identification of a novel nuclear receptor response element in the upstream region of the p14 gene. This element contains the canonical hexameric DNA core motif, 5'-PuGGTCA, composed of an atypically spaced direct repeat (DR17). Schistosome nuclear receptors SmRXR1 and SmNR1 specifically bound to the p14-DR17 element as a heterodimer. SmRXR1, but not SmNR1, bound to the motif as a monomer. Introduction of mutations in the TCA core sequence completely abolished the binding by SmRXR1/SmNR1 heterodimer. This finding supports our hypothesis that the expression of Schistosoma mansonip14 gene is regulated through the nuclear receptor signaling pathway.

Asunto(s)

Regulación de la Expresión Génica , Genes de Helminto , Proteínas del Helminto/metabolismo , Receptores de Glutamato/metabolismo , Secuencias Repetitivas de Ácidos Nucleicos , Receptores X Retinoide/metabolismo , Schistosoma mansoni/genética , Animales , Secuencia de Bases , Dimerización , Femenino , Datos de Secuencia Molecular , Secuencias Reguladoras de Ácidos Nucleicos , Schistosoma mansoni/metabolismo , Transducción de Señal

RESUMEN

The SCF (Skp1-Cul1-F-box) complex is one of the several E3 ligase enzymes and it catalyzes protein ubiquitination and degradation by the 26S proteasome. Rbx1 is a member of the SCF complex in humans and HRT1 is its yeast orthologue. A cDNA encoding a Schistosoma mansoni Rbx1 homolog was cloned and functionally characterized. Heterologous functional complementation in yeast showed that the worm SmRbx gene was able to complement the HRT1yeast null mutation. Gene deletion constructs for N- and C-termini truncated proteins were used to transform hrt1(-) yeast mutant strains, allowing us to observe that regions reported to be involved in the interaction with cullin1 (Cul1) were essential for SmRbx function. Yeast two-hybrid assays using SmRbx and yeast Cul1 confirmed that SmRbx, but not the mutant SmRbxDelta24N, lacking the N-terminus of the protein, was capable of interacting with Cul1. These results suggest that SmRbx protein is involved in the SCF complex formation.

Asunto(s)

Proteínas del Helminto/genética , Schistosoma mansoni/genética , Ubiquitina/metabolismo , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Proteínas Portadoras/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas Cullin/genética , Proteínas Cullin/metabolismo , ADN Complementario/química , ADN de Helmintos/química , Etiquetas de Secuencia Expresada , Femenino , Prueba de Complementación Genética , Vectores Genéticos , Proteínas del Helminto/química , Humanos , Masculino , Datos de Secuencia Molecular , Mutación , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteínas Ligasas SKP Cullina F-box , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Schistosoma mansoni/metabolismo

RESUMEN

The objective of this paper is to identify and quantify socioeconomic determinants of Schistosoma mansoni infection in the rural area of Virgem das Graças in Minas Gerais State of Brazil. A cross-sectional study was carried out to examine the prevalence and intensity of schistosomiasis in relation to socioeconomic characteristics of the households. Log-binomial regression analysis was used to examine the data on both the household and individual levels, analyzing the prevalence ratios for the association of schistosomiasis and socioeconomic variables related to the head of the household. Multiple comparisons through mixed effect modeling were used to examine the relationship between intensity of infection (geometric mean egg counts) and different levels of socioeconomic variables, respectively. In the univariate analysis, place of residence, number of persons per room, and lack of motorized transport were associated with schistosomiasis at the household level and age and unsafe water contact at the individual level. Age, unsafe water contact, number of persons per room, household possessions and lack of education of head of household remained significant predictors of schistosomiasis in the multivariable analysis. Only age was significantly associated with intensity of infection of individuals. It is concluded that widespread poverty, the rural environment, and weak socioeconomic differentiation that result in intense contact with infective water appear to minimize the protective effect of piped water supply and other socioeconomic parameters on schistosomiasis found in other studies. The potential role of socioeconomic development in conjunction with schistosomiasis control is described and areas for further studies are identified.

Asunto(s)

Schistosoma mansoni/crecimiento & desarrollo , Esquistosomiasis mansoni/epidemiología , Adolescente , Adulto , Anciano , Animales , Brasil/epidemiología , Niño , Preescolar , Estudios Transversales , Composición Familiar , Heces/parasitología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recuento de Huevos de Parásitos , Pobreza , Prevalencia , Población Rural , Esquistosomiasis mansoni/parasitología , Factores Socioeconómicos , Abastecimiento de Agua

RESUMEN

Schistosomiasis prevalence and egg counts remained low one year after chemotherapy in most households in a hyperendemic rural area in northern Minas Gerais but several distinct spatial patterns could be observed in relation to IgE levels and to a lesser extent to exposure risk (TBM) and type of water supply. An inverse relationship between pre-treatment household prevalence and egg counts on the one hand and post-treatment IgE levels on the other were noted in two of the five communities. Low exposure risk was associated with the low pre-treatment infection rates in the central village but did not contribute to the decline of infection rates after chemotherapy in the study area, as indicated by the significant increase in water contact during the posttreatment period (p < 0.0001). Distance between households and the streams and socioeconomic factors were also unimportant in predicting the spatial distribution of infection. These results are consistent with the production and antiparasitic effect of high levels of IgE in Schistosoma mansoni infection.

Asunto(s)

Adolescente , Adulto , Animales , Niño , Preescolar , Femenino , Humanos , Masculino , Albendazol/administración & dosificación , Antihelmínticos/administración & dosificación , Praziquantel/administración & dosificación , Schistosoma mansoni/aislamiento & purificación , Esquistosomiasis mansoni/tratamiento farmacológico , Brasil/epidemiología , Heces/parasitología , Inmunoglobulina E/sangre , Recuento de Huevos de Parásitos , Esquistosomiasis mansoni/epidemiología , Esquistosomiasis mansoni/inmunología , Agua/parasitología

RESUMEN

Schistosomiasis prevalence and egg counts remained low one year after chemotherapy in most households in a hyperendemic rural area in northern Minas Gerais but several distinct spatial patterns could be observed in relation to IgE levels and to a lesser extent to exposure risk (TBM) and type of water supply. An inverse relationship between pre-treatment household prevalence and egg counts on the one hand and post-treatment IgE levels on the other were noted in two of the five communities. Low exposure risk was associated with the low pre-treatment infection rates in the central village but did not contribute to the decline of infection rates after chemotherapy in the study area, as indicated by the significant increase in water contact during the posttreatment period (p < 0.0001). Distance between households and the streams and socioeconomic factors were also unimportant in predicting the spatial distribution of infection. These results are consistent with the production and antiparasitic effect of high levels of IgE in Schistosoma mansoni infection.

Asunto(s)

Albendazol/administración & dosificación , Antihelmínticos/administración & dosificación , Praziquantel/administración & dosificación , Schistosoma mansoni/aislamiento & purificación , Esquistosomiasis mansoni/tratamiento farmacológico , Adolescente , Adulto , Animales , Brasil/epidemiología , Niño , Preescolar , Heces/parasitología , Femenino , Humanos , Inmunoglobulina E/sangre , Masculino , Recuento de Huevos de Parásitos , Esquistosomiasis mansoni/epidemiología , Esquistosomiasis mansoni/inmunología , Agua/parasitología

RESUMEN

Two hundred and twenty three subjects from a Schistosoma mansoni low morbidity endemic area and nine hospitalized hepatosplenic patients were submitted to stool test and clinical examination and abdomen ultrasound assessments. According to stool examination and ultrasound results, they were grouped as follows: G1 -- 63 Schistosoma mansoni egg-negative individuals; G2 -- 141 egg-positive patients and without evidence of periportal fibrosis; G3 -- 19 egg-positive patients with periportal echogenicity (3-6 mm); and G4 -- 9 hepatosplenic patients with periportal echogenicity (> 6 mm). Hepatomegaly detected by physical examination of the abdomen evaluated in the midclavicular line was verified in G1, G2 and G3, respectively, in 11.1, 12.1 and 26.3%. In G1, G2 and G3, periportal thickening occurred only in schistosomal patients (8.5%). Mild pathological alterations in patients that cannot yet be detected by clinical examination were detectable in the liver by ultrasound and can be due to fibrosis. The degree of mild periportal fibrosis was diminished in 57.9% of patients 12 months after treatment of schistosomiasis with oxamniquine. At ultrasonography, the mean liver left lobe measurement of G3 was larger than that of G1, and that of G4 larger than that of G1 and G2. The mean size of the spleen of G4 was significantly larger than that of the other three groups, and that of G3 larger than that of G1 and G2.

Asunto(s)

Parasitosis Hepáticas/diagnóstico , Esquistosomiasis mansoni/diagnóstico , Enfermedades del Bazo/diagnóstico , Adolescente , Adulto , Anciano , Animales , Estudios de Casos y Controles , Niño , Enfermedades Endémicas , Heces/parasitología , Femenino , Humanos , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/parasitología , Parasitosis Hepáticas/diagnóstico por imagen , Parasitosis Hepáticas/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Oxamniquina/uso terapéutico , Recuento de Huevos de Parásitos , Vena Porta/diagnóstico por imagen , Vena Porta/parasitología , Esquistosomiasis mansoni/diagnóstico por imagen , Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomicidas/uso terapéutico , Índice de Severidad de la Enfermedad , Enfermedades del Bazo/diagnóstico por imagen , Enfermedades del Bazo/tratamiento farmacológico , Ultrasonografía

RESUMEN

Duzentos e vinte e três indivíduos de área endêmica de baixa morbidade para esquistossomose e nove pacientes hospitalizados com a forma hepatoesplênica foram submetidos ao exame de fezes e clínico e à ultra-sonografia do abdômen. De acordo com os resultado dos exames de fezes e do ultra-som eles foram agrupados do seguinte modo: G1 - 63 indivíduos sem ovos de Schistosoma mansoni nas fezes; G2 - 141 indivíduos apresentando ovos de Schistosoma mansoni nas fezes, sem ecogenicidade periportal. G3 — 19 indivíduos com ovos de Schistosoma mansoni nas fezes e ecogenicidade periportal entre 3-6mm.; G4 — 9 pacientes hepatesplênicos com ecogenicidade periportal > 6mm. Pelo exame físico do abdômen, a hepatomegalia na linha hemiclavicular direita foi constatada em G1, G2 E G3, respectivamente, em 11,1, 12,1 e 26,3%. Nos grupos G1, G2 e G3, houve espessamento periportal somente em esquistossomáticos (8,5%). Alterações patológicas leves em pacientes, as quais não puderam ser detectadas pelo exame clínico, foram evidenciadas no fígado pelo ultra-som e podem ser devidas à fibrose. O grau de fibrose periportal leve foi diminuído em 57,9% dos pacientes 12 meses após tratamento da esquistossomose com oxamniquine. Na ultra-sonografia, a média da medida do lobo esquerdo do fígado dos indivíduos de G3 foi maior que a de G1 e, a de G4 maior que a de G1 e G2. O tamanho médio do baço de G4 foi significativamente maior que o dos outros grupos e o de G3 foi maior que o de G1 e G2.

Asunto(s)

Adolescente , Adulto , Anciano , Animales , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Parasitosis Hepáticas/diagnóstico , Esquistosomiasis mansoni/diagnóstico , Enfermedades del Bazo/diagnóstico , Estudios de Casos y Controles , Enfermedades Endémicas , Heces/parasitología , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/parasitología , Cirrosis Hepática , Parasitosis Hepáticas/tratamiento farmacológico , Parasitosis Hepáticas , Oxamniquina/uso terapéutico , Recuento de Huevos de Parásitos , Vena Porta/parasitología , Vena Porta , Índice de Severidad de la Enfermedad , Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomiasis mansoni , Esquistosomicidas/uso terapéutico , Enfermedades del Bazo/tratamiento farmacológico , Enfermedades del Bazo

RESUMEN

This paper examines the distribution and infection of Biomphalaria glabrata with Schistosoma mansoni in all aquatic snail habitats in a rural area in the state of Minas Gerais, Brazil, in relation to physico/biotic and behavioral factors. Snail and environmental surveys were carried out semi-annually between July 2001 and November 2002 at 106 sites. Collected snails were examined in the laboratory for infection. B. glabrata densities were highest in overflow ponds, irrigation ponds, springs, canals and wells, and lowest in fishponds and water tanks. Snail densities were higher during the hot, rainy season except for streams and canals and were statistically associated with the presence of fish, pollution, and vegetation density. Tilapia fish and an unidentified Diptera larva were found to be predators of B. glabrata but ducks were not. Twenty-four of the 25 infected snails were collected in 2001(1.4 percent infection rate) and only one in 2002, after mass chemotherapy. The occurrence of B. glabrata in all 11 snail habitats both at and away from water contact sites studied indicates widespread risk of human infection in the study area. In spite of the strong association between B. glabrata and tilapia in fishponds we do not recommend its use in schistosomiasis control for ecological reasons and its relative inefficiency in streams and dams.

Asunto(s)

Animales , Masculino , Bovinos , Biomphalaria , Vectores de Enfermedades , Ambiente , Schistosoma mansoni , Brasil , Densidad de Población , Factores de Riesgo , Población Rural , Esquistosomiasis mansoni , Estaciones del Año

RESUMEN

Schistosoma mansoni, an intravascular parasite, lives in a hostile environment in close contact with host humoral and cellular cytotoxic factors. To establish itself in the host, the parasite has evolved a number of immune evasion mechanisms, such as antioxidant enzymes. Our laboratory has demonstrated that the expression of antioxidant enzymes is developmentally regulated, with the highest levels present in the adult worm, the stage least susceptible to immune elimination, and the lowest levels in the larval stages, the most susceptible to immune elimination. Vaccination of mice with naked DNA constructs containing Cu/Zn cytosolic superoxide dismutase (CT-SOD), signal-peptide containing SOD or glutathione peroxidase (GPX) showed significant levels of protection compared to a control group. We have further shown that vaccination with SmCT-SOD but not SmGPX results in elimination of adult worms. Anti-oxidant enzyme vaccine candidates offer an advance over existing vaccine strategies that all seem to target the larval developmental stages in that they target adult worms and thus may have therapeutic as well as prophylactic value. To eliminate the potential for cross-reactivity of SmCT-SOD with human superoxide dismutase, we identified parasite-specific epitope-containing peptides. Our results serve as a basis for developing a subunit vaccine against schistosomiasis.

Asunto(s)

Glutatión Peroxidasa/inmunología , Schistosoma mansoni/inmunología , Esquistosomiasis mansoni/inmunología , Superóxido Dismutasa/inmunología , Vacunas de ADN/inmunología , Animales , Anticuerpos Antihelmínticos/inmunología , Antígenos Helmínticos/inmunología , Reacciones Cruzadas , Glutatión Peroxidasa/administración & dosificación , Humanos , Ratones , Ratones Endogámicos BALB C , Esquistosomiasis mansoni/prevención & control , Superóxido Dismutasa/administración & dosificación , Vacunas de ADN/administración & dosificación

RESUMEN

Schistosoma mansoni, an intravascular parasite, lives in a hostile environment in close contact with host humoral and cellular cytotoxic factors. To establish itself in the host, the parasite has evolved a number of immune evasion mechanisms, such as antioxidant enzymes. Our laboratory has demonstrated that the expression of antioxidant enzymes is developmentally regulated, with the highest levels present in the adult worm, the stage least susceptible to immune elimination, and the lowest levels in the larval stages, the most susceptible to immune elimination. Vaccination of mice with naked DNA constructs containing Cu/Zn cytosolic superoxide dismutase (CT-SOD), signal-peptide containing SOD or glutathione peroxidase (GPX) showed significant levels of protection compared to a control group. We have further shown that vaccination with SmCT-SOD but not SmGPX results in elimination of adult worms. Anti-oxidant enzyme vaccine candidates offer an advance over existing vaccine strategies that all seem to target the larval developmental stages in that they target adult worms and thus may have therapeutic as well as prophylactic value. To eliminate the potential for cross-reactivity of SmCT-SOD with human superoxide dismutase, we identified parasite-specific epitope-containing peptides. Our results serve as a basis for developing a subunit vaccine against schistosomiasis.

Asunto(s)

Humanos , Animales , Ratones , Glutatión Peroxidasa , Schistosoma mansoni , Esquistosomiasis mansoni , Superóxido Dismutasa , Vacunas de ADN , Anticuerpos Antihelmínticos , Antígenos Helmínticos , Reacciones Cruzadas , Ratones Endogámicos BALB C

RESUMEN

The effect of the intensity of infection (eggs per gram faeces, epg) on the production of interferon-gamma (INF-gamma), interleukin (IL)-10 and IL-13 by peripheral blood mononuclear cells (PBMCs) from individuals living in a Schistosoma mansoni-endemic area was evaluated. In vitro stimulation of PBMCs with soluble egg antigen (SEA) resulted in significantly higher secretion levels of IFN-gamma in egg-negative individuals compared with those with an intensity of infection of more than 100 epg. In contrast, the egg-positive group produced significantly higher amounts of IL-10. Levels of IL-13 did not differ significantly between egg-positive and egg-negative groups. These findings suggest that IL-10 is an important cytokine in the control of the T helper cell (Th) type 1 responses during human S. mansoni infection, shifting the immune response from Th0 in egg-negative individuals from an endemic area to a Th2 polarization in chronic infected individuals.

Asunto(s)

Antígenos Helmínticos/inmunología , Interferón gamma/biosíntesis , Interleucina-10/biosíntesis , Interleucina-13/biosíntesis , Esquistosomiasis mansoni/inmunología , Adulto , Factores de Edad , Animales , Brasil/epidemiología , Células Cultivadas , Susceptibilidad a Enfermedades/inmunología , Enfermedades Endémicas , Humanos , Interferón gamma/inmunología , Interleucina-10/inmunología , Interleucina-13/inmunología , Leucocitos Mononucleares/inmunología , Schistosoma mansoni/inmunología , Esquistosomiasis mansoni/epidemiología , Índice de Severidad de la Enfermedad

RESUMEN

Much research points to the importance of the household in the study of water-borne diseases such as schistosomiasis. An important aspect of the household is the clustering of domestic activities associated with water collection, storage and usage. Such activities can result in the sharing of water-contact sites and water-contact behaviour, which expose household members to similar risks of infection. In previous studies, we determined that shared residence accounted for 28% of the variance in Schistosoma faecal egg excretion rates. We now quantify the effect of shared residence on the variation in water-related health behaviours. We found that shared residence accounted for 30% of the variation in total water contacts per week. It also accounted for a large proportion of the variation in individual water-contact behaviour: e.g. agricultural contacts (63%), washing limbs (56%) or bathing (41%). These results implicate the household as an important composite measure of the complex relationships between socioeconomic, environmental and behavioural factors that influence water-contact behaviour and, therefore, the transmission of schistosomiasis. Our results also support a focus on the household in the implementation of schistosomiasis prevention and control efforts.

Asunto(s)

Exposición a Riesgos Ambientales/efectos adversos , Conductas Relacionadas con la Salud , Esquistosomiasis mansoni/epidemiología , Abastecimiento de Agua , Actividades Cotidianas , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Brasil/epidemiología , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Análisis de Regresión , Factores de Riesgo , Salud Rural , Esquistosomiasis mansoni/transmisión

RESUMEN

This paper examines the distribution and infection of Biomphalaria glabrata with Schistosoma mansoni in all aquatic snail habitats in a rural area in the state of Minas Gerais, Brazil, in relation to physico/biotic and behavioral factors. Snail and environmental surveys were carried out semi-annually between July 2001 and November 2002 at 106 sites. Collected snails were examined in the laboratory for infection. B. glabrata densities were highest in overflow ponds, irrigation ponds, springs, canals and wells, and lowest in fishponds and water tanks. Snail densities were higher during the hot, rainy season except for streams and canals and were statistically associated with the presence of fish, pollution, and vegetation density. Tilapia fish and an unidentified Diptera larva were found to be predators of B. glabrata but ducks were not. Twenty-four of the 25 infected snails were collected in 2001(1.4% infection rate) and only one in 2002, after mass chemotherapy. The occurrence of B. glabrata in all 11 snail habitats both at and away from water contact sites studied indicates widespread risk of human infection in the study area. In spite of the strong association between B. glabrata and tilapia in fishponds we do not recommend its use in schistosomiasis control for ecological reasons and its relative inefficiency in streams and dams.

Asunto(s)

Biomphalaria/parasitología , Vectores de Enfermedades , Ambiente , Schistosoma mansoni/aislamiento & purificación , Animales , Brasil , Bovinos , Humanos , Densidad de Población , Factores de Riesgo , Población Rural , Esquistosomiasis mansoni/transmisión , Estaciones del Año