RESUMO
The fecundities and drug susceptibilities of Schistosoma mansoni isolates from Senegal, Puerto Rico, and Kenya have been examined in mice. The Senegal parasite, obtained from the field in 1993, was shown to have a longer prepatent period (eggs first recovered in the faeces on Day 46 after infection) than those of two isolates, from Puerto Rico and Kenya, that had been maintained for a long period in the laboratory (faecal eggs recovered on Days 38 and 36 after infection, respectively). A Kenyan isolate, also collected from the field in 1994, was shown to mature more slowly than the laboratory-maintained Kenyan isolate. Tissue egg counts confirmed that early in infection the fecundity of the recently collected isolates from Senegal and Kenya was significantly lower than that of the long-term laboratory-maintained Kenyan isolate. Praziquantel and oxamniquine treatment of 8-week-old infections caused a significant (P < 0.001) reduction in worm burden in all isolates tested. However, the reduction in worm burden after praziquantel treatment of infections of the Senegal isolate (50% reduction) was significantly lower than the > 90% reductions in worm burdens after praziquantel treatment of mice infected with either of the Kenyan isolates (P < 0.001). The study confirms that despite being tolerant to praziquantel, the Senegal isolate is fully susceptible to oxamniquine. The praziquantel tolerance of the Senegal parasite is not solely attributed to the state of maturation of the parasite at the time of drug administration.
Assuntos
Schistosoma mansoni/efeitos dos fármacos , Esquistossomose mansoni/parasitologia , Esquistossomicidas/farmacologia , Animais , Sistema Digestório/parasitologia , Resistência a Medicamentos , Fezes/parasitologia , Feminino , Fertilidade/efeitos dos fármacos , Quênia , Fígado/parasitologia , Masculino , Camundongos , Oxamniquine/farmacologia , Oxamniquine/uso terapêutico , Contagem de Ovos de Parasitas , Praziquantel/farmacologia , Praziquantel/uso terapêutico , Porto Rico , Schistosoma mansoni/crescimento & desenvolvimento , Schistosoma mansoni/fisiologia , Esquistossomose mansoni/tratamento farmacológico , Esquistossomicidas/uso terapêutico , Senegal , Razão de MasculinidadeRESUMO
Schistosoma mansoni infected Kenyan patients were treated and the intensities of their reinfections were followed over the next two years. In addition, their pre- and six month post-treatment serum levels of IgG1-4, IgM, and IgE, specific for schistosomula, egg and adult worm, were measured in ELISA. No reinfection took place before six months post-treatment. Reinfection intensities varied with age; the younger children becoming reinfected at significantly higher intensities than older individuals. When antibody and reinfection levels were compared, only the six month post-treatment IgE response against adult worm correlated negatively with intensities of reinfection and, therefore, was predictive of resistance or immunity to reinfection. IgE and IgG specific Western Blots were carried out. The adult worm antigens recognized by IgE were restricted compared with the IgG responses of the same patients, although no individual antigen was uniquely recognized by the IgE isotype. A dominant 22 kDa antigen was recognized by most but not all high IgE responders. Patients with IgE responses against this antigen suffered significantly lower subsequent levels of reinfection, compared with non-responders. A monospecific rabbit antiserum against the 22 kDa adult worm antigen showed that this antigen is specifically located in the tegument of the adult worm and of 'lung' and 'liver' stage schistosomula, but is absent from the early 'skin' schistosomula. It is possible that this antigen is a target for human IgE mediated immune effector mechanisms active against the post skin stage schistosomula and that this is boosted by the death of adult worms.
Assuntos
Anticorpos Anti-Helmínticos/imunologia , Imunoglobulina E/imunologia , Schistosoma mansoni/imunologia , Esquistossomose mansoni/imunologia , Adulto , Fatores Etários , Animais , Anticorpos Anti-Helmínticos/biossíntese , Especificidade de Anticorpos , Antígenos de Helmintos/imunologia , Antígenos de Superfície/imunologia , Criança , Pré-Escolar , Feminino , Proteínas de Helminto/imunologia , Humanos , Imunidade Inata , Imunoglobulina E/biossíntese , Quênia/epidemiologia , Masculino , Glicoproteínas de Membrana/imunologia , Especificidade de Órgãos , Recidiva , Schistosoma mansoni/crescimento & desenvolvimento , Esquistossomose mansoni/tratamento farmacológico , Esquistossomose mansoni/epidemiologiaRESUMO
After treatment young Kenyan schoolchildren are highly susceptible to reinfection with Schistosoma mansoni. Older children and adults are resistant to reinfection. There is no evidence that this age related resistance is due to a slow development of protective immunological mechanisms, rather, it appears that young children are susceptible because of the presence of blocking antibodies which decline with age, thus allowing the expression of protective responses. Correlations between antibody responses to different stages of the parasite life-cycle suggest that, in young children, antigen directed, isotype restriction of the response against cross-reactive polysaccharide egg antigens results in an ineffectual, or even blocking antibody response to the schistosomulum.
Assuntos
Anticorpos Anti-Helmínticos/imunologia , Antígenos de Helmintos/imunologia , Schistosoma mansoni/imunologia , Esquistossomose mansoni/imunologia , Fatores Etários , Animais , Criança , Suscetibilidade a Doenças , Humanos , Imunoglobulina G/imunologia , Isotipos de Imunoglobulinas/imunologia , Imunoglobulina M/imunologia , RecidivaRESUMO
Plasma samples from St. Lucians were tested for the presence of antibodies which cooperate in vitro with normal human leukocytes in causing cytotoxic damage to schistosomula of Schistosoma mansoni. The in vitro antibody activity, which has been previously shown to depend on eosinophil effector cells was detected in 56% of the individuals with known, current S. mansoni infections and in 14% of control subjects from the same endemic area. Quantitatively, eosinophil dependent cytotoxic antibody (EDCA) activity, when expressed as the maximum amount of damage to schistosomula induced at high plasma concentration, correlated significantly with the intensity of S. mansoni infection as determined by fecal egg count, the highest levels of activity occurring in patients with stool counts of 60 eggs/ml or greater. In addition, plasma EDCA activity was found to correlate with the in vitro blastogenic responsiveness of patients' lymphocytes to three different parasite antigen preparations. In contrast, titrations of EDCA activity failed to reveal a relationship between EDCA titer and the most recent egg count performed on each subject. However, a significant correlation was observed when titers were compared to egg counts averaged over a 3-year period. Neither maximal EDCA activity nor titer was found to correlate with the duration of known schistosome infection.
Assuntos
Anticorpos/análise , Testes Imunológicos de Citotoxicidade , Eosinófilos/imunologia , Esquistossomose/imunologia , Humanos , Ativação Linfocitária , Contagem de Ovos de Parasitas , Schistosoma mansoni , Fatores de Tempo , Índias OcidentaisRESUMO
Plasma samples from St. Lucians were tested for the presence of antibodies which cooperate in vitro with normal human luekocytes in causing cytotoxic damage to schistosomula of Schistosoma mansoni. The in vitro antibody activity, which has been previosly shown to depend on eosinophil effector cells was detected in 56 percent of the individuals with known, current S. mansoni infections and in 14 percent of control subjects from the same endemic area. Quantitatively, eosinophil dependent cytoxic antibody (EDCA) activity, when expressed as the maximum amount of damage to schistosomula induced at high plasma concentration, correlated significantly with the intensity of S.mansoni infection as detemined by fecal egg count, the highest levels of activity occuring in patients with stool counts of 60 eggs/ml or greater. In addition, plasma ECDA activity was found to correlate with the in vitro blastogenic responsiveness of patients' lympjocytes to three different parasite antigen preparations. In contrast, titrations of ECDA activity failed to reveal a relationship between ECDA titer and the most recent egg count performned on each subjects. However, a significant correlation was observed when titers were compared to egg counts averaged over a 3-year period. Neither maximal ECDA activity nor titer was found to correlate with the duration of known schistosome infection (AU)