Analysis of the effects of treatment of human Schistosoma mansoni infection on the immune response of patients from endemic areas.
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Adult↗
Biomedical subjects
A Prata
Publications and source records attributed to A Prata.
Yellow fever.
With the infestation by Aedes aegypti, urban yellow fever might already exist. This did not occur because of either the lacking of a sufficient contact between the diseased individual and the A. aegypti or perhaps because this, after sixty years without transmitting the virus, needs an adaptation phase to infecting again.
Adolescent↗
Infection and disease in human schistosomiasis mansoni are under distinct major gene control.
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Animals↗
Evolution of the clinical and epidemiological knowledge about Chagas disease 90 years after its discovery.
Three different periods may be considered in the evolution of knowledge about the clinical and epidemiological aspects of Chagas disease since its discovery: (a) early period concerning the studies carried out by Carlos Chagas in Lassance with the collaboration of other investigators of the Manguinhos School. At that time the disease was described and the parasite, transmitters and reservoirs were studied. The coexistence of endemic goiter in the same region generated some confusion about the clinical forms of the disease; (b) second period involving uncertainty and the description of isolated cases, which lasted until the 1940 decade. Many acute cases were described during this period and the disease was recognized in many Latin American countries. Particularly important were the studies of the Argentine Mission of Regional Pathology Studies, which culminated with the description of the Romaña sign in the 1930 decade, facilitating the diagnosis of the early phase of the disease. However, the chronic phase, which was the most important, continued to be difficult to recognize; (c) period of consolidation of knowledge and recognition of the importance of Chagas disease. Studies conducted by Laranja, Dias and Nóbrega in Bambuí updated the description of Chagas heart disease made by Carlos Chagas and Eurico Villela. From then on, the disease was more easily recognized, especially with the emphasis on the use of a serologic diagnosis; (d) period of enlargement of knowledges on the disease. The studies on denervation conducted in Ribeirão Preto by Fritz Köberle starting in the 1950 decade led to a better understanding of the relations between Chagas disease and megaesophagus and other visceral megas detected in endemic areas.
Brazil↗
Human Schistosomiasis mansoni: IL-10 modulates the in vitro granuloma formation.
Granuloma formation and modulation around Schistosoma mansoni eggs that are trapped in host tissues play a pivotal role during schistosomiasis. It has been demonstrated that the granuloma reactions differ in patients with the different clinical forms of the disease. The pathology during murine schistosomiasis has been correlated with a Th2 response while resistance to infection with a Th1 type response. In humans, very little is known about the role of different cytokines on the development of the disease. Here we demonstrate that IL-10 is an important cytokine regulating the in vitro granulomatous reactivity of PBMC from intestinal (INT) patients. This was evidenced by the fact that blockage of this cytokine in the in vitro granuloma assay lead to a significant increase in granuloma size with cells from INT patients but not with individuals in the acute phase or with the hepatosplenic (HS) form of schistosomiasis. These results demonstrate for the first time that, in context with the model, a Th2 cytokine in human schistosomiasis plays an important role in controlling morbidity.
Acute Disease↗
Cytokines as determinants of resistance and pathology in human Schistosoma mansoni infection.
The role of different cytokines in the peripheral blood mononuclear cell (PBMC) proliferative response and in in vitro granuloma formation was evaluated in a cross-sectional study with patients with the different clinical forms and phases of Schistosoma mansoni infection, as well as a group of individuals "naturally" resistant to infection named normal endemic (NE). The blockage of IL-4 and IL-5 using anti-IL-4 and anti-IL-5 antibodies significantly reduced the PBMC proliferative response to soluble egg (SEA) and adult worm (SWAP) antigens in acute (ACT), chronic intestinal (INT) and hepatosplenic (HS) patients. Similar results were obtained in the in vitro granuloma formation. Blockage of IL-10 had no significant effect on either assay using PBMC from ACT or HS. In contrast, the addition of anti-IL-10 antibodies to PBMC cultures from INT patients significantly increased the proliferative response to SEA and SWAP as well as the in vitro granuloma formation. Interestingly, association of anti-IL-4 and anti-IL-10 antibodies did not increase the PBMC proliferative response of these patients, suggesting that IL-10 may act by modulating IL-4 and IL-5 secretion. Addition of recombinant IL-10 decreased the proliferative response to undetectable levels when PBMC from patients with the different clinical forms were used. Analysis of IFN-gamma in the supernatants showed that PBMC from INT patients secreted low levels of IFN-gamma upon antigenic stimulation. In contrast, PBMC from NE secreted high levels of IFN-gamma. These data suggest that IL-10 is an important cytokine in regulating the immune response and possibly controlling morbidity in human schistosomiasis mansoni, and that the production of IFN-gamma may be associated with resistance to infection.
Animals↗
Evaluation of SPf66 malaria vaccine efficacy in Brazil.
This paper reports the efficacy results of the randomized, placebo-controlled, field trial of SPf66 malaria vaccine in Costa Marques, Rondonia, Brazil. This region is characterized by the seasonal distribution of Plasmodium falciparum and P. vivax infections, and the recent occupation by migrants from nonendemic areas. A total of 800 individuals of both sexes, ranging in age from seven to 60 years, were included in the study. Of the initial cohort, 572 participants completed the vaccination schedule. Clinical and parasitologic evaluations were obtained by active and passive searches on a periodic basis. The overall protective efficacy against P. falciparum infections was -1.6% (-32.9% to 22.4%), and 14.1% (-17.0% to 36.9%) for the first episode. The overall protective efficacy for P. vivax infections was -19.7% (-44.8% to 1.03%), and -10.8% (-41.1% to 12.8%) for the first episode. No statistical evidence of an overall significant protective effect of SPf66 malaria vaccine against P. falciparum and P. vivax malaria was obtained in this trial.
Adolescent↗
Genetic and environmental factors regulating blood pressure in childhood: prospective study from 0 to 3 years.
OBJECTIVES: Blood pressure (BP) regulation depends on the interaction between multiple environmental and genetic factors. Of these, BP sensitivity to dietary sodium intake has been one that has been investigated in adults but not in children. The aim of the present study was to investigate, prospectively, the BP profile in relation to different genetic and hormonal factors, in the first 3 years of life. POPULATION AND METHODS: Thirty-nine children born at term following normal pregnancies, with uncomplicated neonatal periods, were randomly selected to take part in the study. BP, weight and length were evaluated every 3 months from birth to 3 years. At the age of 12 months, haptoglobin phenotypes and plasma active renin concentration were determined as well as random urine evaluation of aldosterone, cAMP, dopamine and digoxin-like immunoreactive substances (DLIS). Family history of cardio-vascular diseases was also recorded. RESULTS: Systolic BP (SBP) demonstrated a gradual increase until the age of 6 months with little variation up to 36 months. Tracking of SBP values was also observed from the first year as infants with high values (above the 75 percentile) maintained this tendency up to, at least, the age of 36 months. The comparison between SBP and diastolic BP (DBP) according haptoglobin phenotypes demonstrated that SBP was systematically higher in allele 1, with apparently an increasing tendency with age, although the differences did not have statistical significance. The comparative study between haptoglobin phenotypes, with correction for the covariates fractional excretion of sodium and potassium, showed that allele 1 carriers had significantly lower plasma renin and urine aldosterone and cAMP concentrations than allele 2, but dopamine excretion was found to be higher in allele 1 than in allele 2. There were no differences among variables relating to family history of cardiovascular disease. CONCLUSIONS: There was an early tracking process of BP values from the first 6 months of life which persists through, at least, to the age of 36 months. Differences in sodium handling between haptoglobin 1 and 2 phenotypes were already present in early childhood, although no significant repercussion in BP values could be demonstrated in the 3-year duration of this study.
Age Factors↗
Flow cytometric study of blood leucocytes in clinical forms of human schistosomiasis.
The aim of this study was to examine three distinct groups of schistosomiasis patients and to determine whether cell phenotype profiles could be correlated with the different clinical forms of the disease. The data obtained indicate that Schistosoma mansoni infected patients have a lower percentage of CD3+ T cells than do non-infected individuals. Interestingly, infected patients presented more than twice the mean percentage of circulating activated T cells (CD3+HLA-DR+) when compared to the control group. Examination of T lymphocyte subpopulations showed that patients with the severe hepatosplenic form (HS) of the disease had lower levels of both CD8High+ and CD8Low+ cells when compared to the other groups of patients. All infected individuals had a higher percentage of circulating B cells, with an increase in the CD5+ B cell population that was more evident in the HS group. The data presented here are evidence to support a relationship between the hepatosplenic form of the disease, a decrease on the CD8+ cell population and an elevation on CD5+ B cells.
Adolescent↗
Cytokine regulation of human immune response to Schistosoma mansoni: analysis of the role of IL-4, IL-5 and IL-10 on peripheral blood mononuclear cell responses.
The role of cytokines on the in vitro proliferative response of peripheral blood mononuclear cells (PBMC) from Schistosoma mansoni infected patients to soluble egg (SEA) and adult worm antigens (SWAP) were evaluated. The results obtained demonstrated that the proliferative response of PBMC from chronic intestinal (INT) patients to SEA and SWAP is increased by the blockage of IL-10 with specific monoclonal antibodies (MAb). The effects of these antibodies were readily reversed by the addition of recombinant IL-10. In contrast, no effect was observed on the PBMC response of acute and hepatosplenic patients (HS) in the presence of anti-IL-10. Anti-IL-4 antibodies decreased the PBMC response of the intestinal (INT) and HS individuals to SEA and SWAP, and the PBMC response of acute patients to SEA but not to SWAP. Addition of anti-IL-5 MAb did not decrease the PBMC response of acute patients to SEA or SWAP. These results suggested that IL-10 has an important role in the modulation of the immune response in chronic asymptomatic patients and that this cytokine may be an important factor in controlling morbidity.
Acute Disease↗
Chagas' disease.
Chagas' disease is one of the most important public health problems in South America and Mexico. Migrations from rural areas into urban zones have contributed to the spread of the disease. The main targets of the disease within the body are the heart, the alimentary tract, and the nervous system. In the acute phase of the disease, the parasite responsible for the disease can be identified in the blood by direct examination. This article identifies the parasite responsible for transmission of the disease and discusses symptoms, means of identification in the patient, and treatment.
Chagas Disease↗
Influence of the host related factors in the development of the hepatosplenic form of schistosomiasis mansoni.
The frequency of hepatosplenomegaly in endemic areas is not proportional to the fecal ova count. This may be explained by epidemiological genetic. The occurrence of two or more cases of schistosomal hepatosplenomegaly in nuclear family is much higher than expected. The concentration is higher among siblings than it is among mothers and children of father and children. It is not significant between father and mother. If the mother, instead of the father, has hepatosplenic schistosomiasis the relative risk for the child to acquire hepatosplenomegaly is at least five times (the maternal affect). The inbreeding is higher in the hepatosplenic than in the hepato-intestinal patients. In some areas in Brazil the hepatosplenic form of the schistosomiasis mansoni occurs with much higher frequency in whites than in blacks. After treatment, reversion of hepatosplenic schistosomiasis occurs more frequently in non-whites. It seems that the resistance of blacks to the hepatosplenic form of schistosomiasis may be related to the glyoxalase system, perhaps associated to another genetic marker. The hepatosplenic schistosomiasis is less frequent in longilineal individuals. In some areas the hepatosplenic form of schistosomiasis is more frequent in A blood group of ABO system. The family heredograms do not suggest a single mendelian inheritance, but probably a multifactorial and possibly polygenic one.
ABO Blood-Group System↗
Phagocytic and bactericidal function of mouse macrophages to Salmonella typhimurium in schistosomiasis mansoni.
Patients infected with schistosomes may develop a clinical picture of chronic salmonellosis. We have investigated the altered function of macrophages capable of playing a role in the development of chronic salmonellosis associated with Schistosoma mansoni in an experimental model. The capacity of mouse peritoneal macrophages to ingest and kill Salmonella was assessed in mice infected with S. mansoni with or without concurrent Salmonella typhimurium infection. Schistosomiasis was associated with a significant decrease in the phagocytic index of macrophages, due to the reduced number of cells engaged in phagocytosis. However, the number of bacteria ingested by these cells was comparable to that of the control group. The bactericidal capacity of macrophages from S. mansoni-infected mice was also significantly lower than that of cells from normal mice. Macrophages from animals infected only with Salmonella typhimurium showed an increased phagocytic capacity. It was concluded that S. mansoni infection alters phagocytosis and intracellular destruction of salmonellae. This demonstration of a novel mechanism of survival of salmonellae represents a step forward in understanding the pathogenesis and management of chronic septicemic salmonellosis.
Analysis of Variance↗
Evidence for an association between human resistance to Schistosoma mansoni and high anti-larval IgE levels.
The anti-larval IgE antibody response of adolescents with high or low resistance to infection by Schistosoma mansoni was evaluated before parasitological cure with oxamniquine and over an extended post-treatment period during which the least resistant subjects regained high infections. IgE from most sera, taken at several bleeding times before and after treatment, reacted, on immunoblots, with a large number of antigens (Ag) in schistosomular tegument extract. A family of 120-165-kDa cross-reacting molecules and a 85-kDa Ag were the most prominent Ag. Some of these determinants were shown to be located on the outer tegumental membrane and to be accessible to IgE on living larvae. The comparison of IgE between the two study groups showed that IgE levels were on average six-to eightfold higher (p less than 0.01) in the sera of the most resistant adolescents whereas there was no difference in patterns of Ag recognition between study groups. In contrast to IgE, anti-larval IgG and IgM levels were either similar in both groups or higher in the least resistant subjects when these exhibited high reinfection levels. IgG that competed for the binding of IgE to larval Ag were detected in most sera and their levels were higher in the least resistant group after reinfection. Finally, the treatment had no observable long-lasting effects on the levels and on the specificity of the anti-larval IgE. Altogether, these observations can be taken as evidence supporting a role of IgE in human resistance to infection by S. mansoni.
Adolescent↗
Evidence for the segregation of a major gene in human susceptibility/resistance to infection by Schistosoma mansoni.
Severe clinical disease caused by the major human parasite Schistosoma mansoni is the consequence of high and prolonged infections. Epidemiological studies indicate that, for individuals having frequent contacts with cercaria-infested waters, both infection intensities and reinfection after treatment depend, in large part, on their intrinsic susceptibility/resistance to infection, suggesting the role of genetic factors in human resistance to S. mansoni. To investigate whether a major gene controls human susceptibility/resistance to infection by S. mansoni, segregation analysis of infection intensities, adjusted for the factors relevant in schistosomiasis (water contact, age, sex), was performed on 20 Brazilian pedigrees (269 individuals), using both the unified mixed model and the regressive model of analysis. The results are consistent with the hypothesis that there is a codominant major gene controlling human susceptibility/resistance to infection by S. mansoni. Parameter estimates indicate a frequency of .20-.25 for the deleterious allele; thus, about 5% of the population is predisposed to high infections, 60% is resistant, and 35% has an intermediate, although fairly good, level of resistance. These findings provide a genetic basis for earlier observations on the lower resistance and the predisposition to reinfection of certain individuals. In addition to the detection of a major gene effect, the data suggest that immunity to S. mansoni develops progressively during childhood to reach a maximum around the age of puberty. The implications of these results for the strategy to be used in endemic areas to reduce morbidity and to control parasite transmission are discussed.
Age Factors↗
Human resistance to Schistosoma mansoni is associated with IgG reactivity to a 37-kDa larval surface antigen.
The aim of this work was to determine whether human resistance to Schistosoma mansoni was associated with increased antibody reactivity to certain larval surface Ag. To this end, young residents of a hyperendemic area were selected for their low or high susceptibility to reinfection after parasitologic cure, and the reactivity of their sera to individual larval surface Ag was determined at different times before and after treatment. The data showed that six Ag: 202, 165, 90 to 92, 85, 72, and 37 kDa are the principal targets on the larva of IgG in the sera of resistant subjects. The comparative study, by immunoblotting and ELISA on purified Ag, of the sera from high and low susceptibility subjects indicates that IgG reactivity toward the 37-kDa Ag may be associated with resistance. This work and ongoing vaccination trials carried out in mice suggest that the 37-kDa Ag may have vaccinating potentials.
Adolescent↗
[Biometric data on adult patients with schistosomiasis, Bahia (Brazil)].
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Adult↗
[Cold lymphocytotoxins in schistosomiasis mansoni].
The serum of 134 patients infected with Schistosoma mansoni, including both acute and chronic forms of the disease, were tested for the presence of cold lymphocytotoxins. These were found in 4.5% of acute forms of the disease, in 88.4% of chronic infections and in only 9.8% of the uninfected control group (blood donors). An analysis of the results suggests a probable role for cold lymphocytotoxins in the immune response of the different phases of human schistosomiasis.
Adolescent↗