Comparative clinical and ultrasound study of egg-negative and egg-positive individuals from Schistosoma mansoni low morbidity endemic areas, and hospitalized patients with hepatosplenic disease

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.

Screening and fractionation of plant extracts with antiproliferative activity on human peripheral blood mononuclear cells

Three hundred and thirteen extracts from 136 Brazilian plant species belonging to 36 families were tested for their suppressive activity on phytohemaglutinin (PHA) stimulated proliferation of human peripheral blood mononuclear cells (PBMC). The proliferation was evaluated by the amount of [ H]-thymidine incorporated by the cells. Twenty extracts inhibited or strongly reduced the proliferation in a dose-dependent manner at doses between 10 and 100 æg/ml. Three of these extracts appeared to be non-toxic to lymphocytes, according to the trypan blue permeability assay and visual inspection using optical microscopy. Bioassay-guided fractionation of Alomia myriadenia extract showed that myriadenolide, a labdane diterpene known to occur in this species, could account for the observed activity of the crude extract. Using a similar protocol, an active fraction of the extract from Gaylussacia brasiliensis was obtained. Analysis of the H and13C NMR spectra of this fraction indicates the presence of an acetylated triterpene whose characterization is underway. The extract of Himatanthus obovatus is currently under investigation

Some aspects of idiopatyc regulation in Chagas disease and human schistosomiasis

We developed an approach for the examination of antiidiotypic cell-mediated reactivity during chronic human infections. Antibodies against Schistosoma mansoni egg antigens (anti-SEA) and against Trypanosoma cruzi epimastigotes (anti-EPI) prepared from pooled and individual sera from patients with either schistosomiasis mansoni or Chagas disease were immunoaffinity purified on appropriate columns and used to stimulate patients' T cells. These antibodies preparations and their F (ab)2 fragments stimulated in a dose-dependent assay the proliferations of peripheral blood mononuclear cells (PBMC) and T lymphocytes from some, but not all actively infected individuals. Anti-idiotypic T cells can recognize and respond to anti-SEA or anti-EPI idiotypes directly. We contend that the most likely explanation of this stimulations is that the idiotype expressed on these anti-SEA or anti-EPI antibodies are acting as immunogens to stimulate antiidiotypic T lymphocytes that develop during the course of the infection. Immunization of rabbits with these antibodies (anti-SEA or anti-EPI) preparations, followed by absorption of the rabbit antisera on absorbants of normal Ig, produced specific anti-id reagents. Use of these reagents in competitive ELISA distinguished the idiotypic expression on anti-SEA or anti-EPI preparations obtained from patients' sera with different clinical forms of schistosomiasis or Chagas disease, respectively. The anti-SEA Id-reactive T cells from S. mansoni infected patients were capable of regulating autologous in vitro granuloma formation.

Human immune responses during schistosomiasis mansoni

O estudo da resposta imune de pacientes com esquistossomose progride em funçäo do avanço tecnológico, apesar das dificuldades de manipulaçäo in vivo deste complexo sistema parasita-hospedeiro. A ênfase nos estudos tem sido mais freqüentemente dirigida para comparaçöes entre grupos característicos de indivíduos, tais como infectado/näo infectado, reinfectado/näo reinfectado, assintomático/hepato-esplênico, com intensidade de infecçäo alta/baixa, etc. Baseado nessas comparaçöes razoáveis com relaçäo à regulaçäo imunológica, susceptibilidade e resistência e até mesmo consideraçöes sôbre mecanismos, que têm sido mais apropriadamente analisados, entretanto, em sistemas experimentais. Tais estudos têm como finalidade a compreensäo das causas e eventos que levam à morbidade e ao desenvolvimento de uma vacina humana anti-esquistosoma

Immunological profiles of patients from endemic areas infected with Schistosoma mansoni

Crude extracts of eggs (SEA) adult worms (SWAP) or cercariae (Cerc) have been used to stimulate Peripheral Blood Mononuclear cells (PBMC) and have provided rather distinct profiles of responses in different types of patients. In genenral it is clear that patients with early infections respond strongly to SEA while response to SWAP are developed more slowly. As infection progresses into the more chronic phases, a general pattern is seen whic leads to lower anti-SEA proliferative responses in the face of higher responses to SWAP and variable anti-cerc responsiveness. Cured not re-exposed patients express very high levels of anti-SEA proliferation. It has recently been seen that those individuals who live in endemic areas and have continued water contact, but are reapeatedly stool-negative (who are presumed to have self-cured or be putatively resistant; endemic normals) are strongly responsive to antigenic extracts, particularly to SEA. Furthermore, our results show that endemic normal individuals have significantly higher IFN gamma production upon PBMC stimulation with schistosome antigens than infected individuals. With the emergence of more studies it is becoming apparent that both the intensity and the prevalence of a given area may influence or shape the general responsiveness of the population under study

Human schistosomiasis mansoni: studies on in vitro granuloma modulation

Infection with Schistosoma mansoni induces humoral and T cell mediated responses and leads to delayed hipersensitivity that results in granulomatous inflamatory disease around the parasite eggs. Regulation of these responses resulting in a reduction in this anti-egg inflamatory disease is appsrently determined by idiotypic repertoires of the patient, associated with genetic background and multiple external factors. We have previously reported on idiotype/anti-idiotype-receptor transactions in clinical human schistosomiasis. These findings support a hypothesis that anti-SEA cross-reactive idiotypes develop in some patients during the course of a chronic infection and participate in regulation of anti-SEA cellular immune responses. We repport here on experiments wich extend those observations to the regulation of granulomatous hypersensitivity measured by an in vitro granuloma model. T cells from chronic intestinal schistosomiasis patients were stimulated in vitro with anti-SEA idiotypes and assayed in an autologous in vitro granuloma assay for modulation of granuloma formation. These anti-SEA idiotype reactive T cells were capable of regulating autologous in vitro granuloma formation. This regulatory activity, initiated with stimulatory anti-SEA idiotypic antibodies, was antigenically specific and was dependent on the present of intact (F(ab')2 immunoglobulin molecules. The ability to elicit this regulatory activity appears to be dose dependent and is more easily demonstrated in chronically infected intestinal patients or SEA sensitized individuals. These data support the hypothesis that anti-SEA cross reactive idiotypes are important in regulating granulomatous hypersensitivy in chronic intestinal schistosomiasis patients and these cross-reactive idiotypes appear to play a major role in cell-cell interactions which result in the regulation of anti-SEA cellular immune responses

Fatores que podem afetar a criaçäo e manutençäo de caramujos infectados e a produçäo de cercárias de Schistosoma masoni / Factors that can affect the breeding and maintenance of infected snails and yield of cercariae of Schistosoma mansoni

Foram estudados fatores que afetam a produçäo em massa de cercárias do Schistosoma mansoni. Rotíferos e ostracodos causaram diminuiçäo de produçäo em nossa colônia. Os rotíferos foram erradicados facilmente lavando-se os aquários e a alface com ácido acético diluído. Já o ostracodo foi de difícil erradicaçäo, produzindo mortalidade nos caramujos infectados, que alcançou níveis de 50-60% por mês. Moluscos infectados mantidos na incubadora a temperatura constante e em total escuridäo apresentaram maior eliminaçäo quando iluminados, a aproximadamente 30-C. A eliminaçäo de cercárias foi praticamente a mesma entre os pHs 5-7. Traços de metais pesados adicionados à água destilada afetaram negativamente a eliminaçäo. Finalmente, a manutençäo em incubadora, embora apresenta-se maior mortalidade de moluscos, foi mais simples e eficiente para a produçäo em massa de cercárias que o sistema convencional com água corrente

Granulomatous hypersensitivity to Schistosoma mansoni egg antigens in human Schistosomiasis: I. Granuloma formation and modulation around polyacrylamide antigen-conjugated beads

We have developed an in vitro model of granuloma formation for the purpose of studying the immunological components of delayed type hypersensitivity granuloma formation in patients infected with Schistosoma mansoni. Our data show that 1) granulomatous hypersensitivity can be studied by examining the cellular reactivity manifested as multiple cell layers surrounding the antigen conjugated beads; 2) this reactivity is a CD4 cell dependent, macrophage dependent, B cell independent response and 3) the in vitro granuloma response is antigenically specific for parasite egg antigens. Studies designed to investigate the immune regulation of granulomatous hypersensitivity using purified populations of either CD4 or CD8 T cells have demonstrated the complexity of cellular interactions in the suppression of granulomatous hypersensitivity. The anti-S. mansoni egg immune responses of individual patients with chronic intestinal schistosomiasis can be classified either as soluble egg antigen (SEA) hypersensitive with maximal granulomatous hypersensitivity or SEA suppressive with activation of the T cell suppressor pathway with effective SEA granuloma modulation. Our data suggest that T cell network interactions are active in the generation of effective granuloma modulation in chronic intestinal schistosomiasis patients.