Pre- and post-treatment immunodiagnostic evaluation in human schistosomiasis mansoni

Schistosomiasis control seems to be different in countries were low parasitic burden and asymptomatic clinical patients are the features of majority of cases. Immunological methods must substitute the traditional coprologic techniques used for some decades in the Control Program. Circumoval Precipitin Test (COPT), intradermal test and ELISA with soluble egg antigen (SEA) are evaluated for using as tools for seroepidemiologic studies. COPT and ELISA were performed after treatment to known their utility when impact of chemotherapy must be assessed. One hundred sixty five persons were followed up 3, 6, 9 and 12 months after treatment. The mean sensitivity of CPT studied by age groups was 95.6% which is very important considering that 88.4% of the studied population excreted less than 100 egg/gr of feces, while sensitivity of intradermal test was 58.2%. Children showed the highest ractivity to COPT. When treatment is effective, COPT reactivity progressively disminish until become negative one year later. In the non cure group, the COPT reactivity disminished but never below 20%. ELISA-SEA did not modify one year after treatment. Effort should be made to isolate fractions of eggs Schistosoma mansoni whose antibodies disappear after treatment.

Interrelationship between Schistosomiasis and concomitant diseases

The biological literature contains many examples of mutual influences between different species of parasites, especially with respect to concomitant helminth infections. Several situations are known in wich the association of infection by Shistosoma mansoni with other pathogens in the same host results in a type of disease wich differs from the simple summation of the individual effects of each infection. The present study concerns concomitant infections involving S. mansoni and enterobacteriaceae; S. mansoni and other helmints such as Ascaris lumbricoides, Ancylostomids, Toxocara canis and species of the genus Hymenolepis; S. mansoni and different protozoa such as Trypanosoma cruzi, T. brucei, Toxoplasma gondii and Plasmodium berghei. The interaction between hepatitis B virus and S. mansoni, leading to prolonged viremia and worsening of liver damage, is also discussed. The paper also treats the simultaneous occurrence of schistosomiasis and other aggravating factors such as malnutrition and neoplasias wich may alter the host's response to the trematode.

Nutrition and acute schistosomiasis

In northeast Brazil, nutritional deficiency diseases and schistosomiasis mansoni overlap. An experimental model, wich reproduces the marasmatic clinical form of protein-energy malnutrition, was developed in this laboratory to study these interactions. Albino Swiss mice were fed with a food association ingested usually by human populations in northeast Brazil. This diet (Regional Basic Diet - RBD) has negative effects on the growth, food intake and protein utilization in infected mice (acute phase of murine schistosomiasis). Nitrogen balance studies have also shown that infection with Schistosoma mansoni has apparently no effect on protein intestinal absorption in well nourished mice. However, the lowest absorption ratios have been detected among RBD - fed infected animals, suggesting that suprerimposed schistosome infection aggravated the nutritional status of the undernourished host. The serum proteins electrophoretic pattern, as far as albumins are concerned, is quite similar for non-infected undernourished and infected well-fed animals. So, the significance of albumins as a biochemical indicator of the nutritional status of human populations residing in endemic foci of Manson's schistosomiasis, is discussable.

Seroepidemioplogy of schistosomiasis mansoni

In population surveys in wich the Schistosoma mansoni intensity of infection is low, or in localities where the schistosomiasis control program had success the parasitologic methods lack in sensitivity. Despite of some limitations the immunological methods are useful to provide valuable information in such field conditions. Thus, the prevalaence of schistosomiasis in untreated population can be determined by the detection of IgG or IgM antibodies, as well as the incidence by the IgA antibodies , employing mainly immunofluorescence (IF) and immunoenzymatic (ELISA), and in some extent hemagglutination (HA) or even skin test. The true prevalence and incidence of schistosomiasis can be estimated using a probabilistic model equation, since knowing before-hand the sensitivity and specificity of emploved test. The sensitivity and the specificity of serologic test become higher in low aged group, under 14. The geometric mean IF titers also gives a positive correlation with the intensity of infection. Presently there are need of serologic tests wich are economic and pratical in soroepidemiologic inquires, requiring no specialized personnel to collect population blood or serum and also easily interpret the test results. The reagents for such tests are desired to be stable and reproducible. Moreover, it is expected that the tests can distinguish an ative infection.

Parasitological diagnosis of schistosomiasis mansoni: fecal examination and rectal biopsy

Even with all progress in the search of sensitive and methods for the immunological diagnosis of schistosomiasis, the microscopic detection of eggs of the parasite in the stool still remains the most widely used tool for the actual diagnosis of active infection. Among the coproscopic methods, Kato's technic modified by Katz et al (Kato/Katz) has the advantages of higher sensitivity, the possibility of egg quantification, its low operational cost and its feasibility in areas with minimal infra-structure. The oorgram of the rectal mucosa is valuable in initial clinical trials of schistosomicides, when it is needed to observe egg morphology in tissue. It could be an alternative method for individual diagnosis, being more sensitive than a single stool exam in low intensity infection. However, the increased sensitivity of a higher number of fecal exams makes that invasiveprocedure unnecessary. In the assessment of cure of schistosomiasis, Kato/Katz method (three fecal samples in one, three and six months after treatment) and the rectal biopsy four months after treatment, are equally reliable.

Vaccine strategies against schistosomiasis

Schistosomiasis, the second major parasitic disease in the world after malaria affects at least 200 million people, 500 million being exposed to the risk of infection. It is widely agreed that a vaccine strategy wich could lead to the induction of effector mechanisms reducing the level of reinfection and ideally parasite fecundity would deeply affect the incidence of pathological manifestations as well as the parasite transmission potentialities. Extensive studies performed in the rat model have allowed the identification of novel effector mechanisms involving IgE antibodies and various inflammatory cell populations (eosinophils, macrophages and platelets) whereas regulation of immune response by blocking antibodies has been evidencial. Recent epidemiological studies have now entirely confirmed in human populations the the role of IgE antibodies in the acquisition of resistance and the association of IgG4 blocking antibodies with increased susceptibility. On the basis of these concepts, several schistosome glutathion S-transferase (Sm 28 GST) appears as a pronising vaccine candidate. Immunization experiments have shown that two complementary goals can be achieved: (a) a partial but significant reduction of the worm population (up to 60//in rats); (b) a significant reduction of parasite fecundity (up in the mice and 85//in cattle) and egg viability (up to 80//). At least two distinct immunological mechanisms account for these two effects. IgE antibodies appear as a major humoral component of acquired resistance whereas IgA antibodies appear as a major humoral factor affecting parasite fecundity. These studies seem to represent a parasite diseases through the identification of potentially protective antigens and of the components of the immune response which vaccination should aim at inducing.

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.

Diagnostic markers in schistosomiasis

In the present paper a brief overview will be given of the recent progress and trends in assaying diagnostic markers in schistosomiasis; only markers of the humoral immunological system and biochemical markers will be discussed, as markers for cellular immunological reactivity will be discussed by other authors. The following diagnostic markers will be reviewed: markers for infection, markers for immunity and markers for morbidity.

Factors conditioning the habitat and the density of Biomphalaria tenagophila (Orbigny, 1835) in an isolated schistosomiasis focus in Rio de Janeiro city

The present work was carried out in a watercress garden in Alto da Boa Vista, in the city of Rio de Janeiro, Brazil. The investigation was carried out in two phases. The first one (1985-86) involved the sampling of Biomphalaria tenegophila in two areas to determine its relative populational densities. The results showed that the populations presented similar densities and dynamics. The second phase (1988-89) involved the study of the influence of some environmental factors on the establishment of B. tenagophila in watercress garden. Two factors were identified as responsible for the establishment of B. tenagophila in the garden: (1) the quality of the water entering the irrigation system, to which domestic sewage is added, and (2) alterations in the nature of the substrate, due to inadequate fertilization techniques, which employ organic matter from adjacent pigsties. Aquatic plants and hydrological parameters of the irrigation system were subsidiary factors to the establishment of B. tenagophila in the garden.

Intestinal protein absorption in malnourished mice with acute schistosomiasis mansoni

Intestinal protein absorption was studied in undernourished albino Swiss mice with acute schistosomiasis mansoni. Undernutrition was induced by feeding mice with the Regional Basic Diet (RBD) ingested by human populations in Northeast Brazil, an experimental model previously developed in our laboratory. Weaning mice were infected with 40 cercariae and compared to undernourished non-infected mice and/or to infected mice fed a balanced control diet. Apparent and True Protein Absorption Coefficients were determined by nitrogen balance during five consecutive days ending at the 63rd day of the trial (acute phase of murine schistosomiasis). Fecal metabolic nitrogen (FMN) was determined after administration of a non-protein diet and was also calculated through linear regression. Our results showed a reduced protein absorption in non-infected RBD-fed mice as compared to mice fed a casein control diet. Infection with Schistosoma mansoni had apparently no effect on intestinal protein absorption in well-nourished mice. However, infection seemed to interfere with protein absorption in under-nourished animals, since the lowest absorption ratios have been detected among RBD-fed infected mice. A brief discussion is made on the advantages of using the method of linear regression for the determination of FMN.

Schistosomiasis mansoni in the region of the Triângulo Mineiro, State of Minas Gerais, Brazil

In order to reevaluate the possible presence of schistosomiasis mansoni in the Triângulo Mineiro, one of the areas of the State of Minas Gerais where this parasite is not commonly found, malacological survey and fecal examinations were undertaken in the region between October 1990 and June 1992. A sample of 7,032 1st grade school children from 29 counties had their feces examined using the Kato-Katz method. Amongst the children examined, two from Planura and one from each countie of Capinópolis, Conceição das Alagoas, Uberaba, Uberlândia, Prata and Gurinhatã were positive for Schistosoma mansoni. None of the children were identified as being autoctonous cases. In the malacological survey, 5,406 planorbid snails were examined. The specimens were identified morphologically and examined for S. mansoni by squashing between glass plates. The species were identified as Biomphalaria tenagophila in three counties, as B. straminea in ten and B. intermedia in 16. No snails were found in eight other counties studies. The snails were found to be negative for S. mansoni. The presence of intermediate hosts for S. mansoni, associated with parasitized individuals emphasizes the necessity of epidemiological surveillance for schistosomiasis in the region of Triângulo in the State of Minas Gerais.

Ultrasonography in Schistosomiasis in Africa

Approximately 50 publications have become available in the international literature on ultrasonography in schistosomiasis in Africa. Geographically these cover Congo, Egypt, Kenya, Mali, Mauritius, Niger, Senegal, Sudan, Tanzania and East African Islands as well as Zimbabwe. Further studies are ongoing in many countries, such as Burundi, Ghana, Madagaskar and Uganda. It was shown that ultrasonography is useful in the detection of morbidity induced by schistosomiasis on an individual basis and on the community level. There is indication for varying morbidity patterns in different African foci. Post-treatment monitoring has provided evidence for reversibility of pathological lesions induced by Schistosoma (S.) haematobium and S. mansoni, even though evidence for reversibility of periportal fibrosis in adults is not yet satisfactorily substantiated. A standardized set of criteria for ultrasonographical observations has been worked out and is presently in the process of being refined. It is thus hoped that standardization will contribute to render studies in different endemic settings comparable on a global basis.

Determination and control of schistosomiasis

The subject of this conference reflects the scientific community's interest in seeking to understand the complex causal web whose various social, economic, and biological components interact in the production and reproduction of schistosomiasis and its control in relation to community participation. From the onset, the author stresses the impossibility of dealing separately with community participation, as if social components were just one more "weapon" in the arsenal for schistosomiasis control. This study begins with a brief historical review of the 71 years of control activities with this endemic disease, stressing the enormous efforts and huge expenditures in this field vis-à-vis the limited results, despite the extraordinary technological development of specific, classical control inputs such as new treatment drugs and molluscicides. The article then discusses the various strategies used in control programs, emphasizing ideological consistencies and contradictions. Interactions at the macro and micro levels are discussed, as are the determinants and risk factors involved in producing the disease's endemicity. Unequal occupation of space leaves the segregated portion of the population exposed to extremely favorable conditions for transmission of the disease. This raises the issue of how to control an endemic disease which is so closely linked to the way of life imposed on the population. The study challenges the classical control model and suggests an alternative model now undergoing medium-term investigation in the States of Espirito Santo, and Pernambuco, Brazil. The author concludes that we do not need new strategies, but a new control model, contrary to the prevailing classical model in both concept and practice. From the conceptual point of view, the new model mentioned above is different from others in that schistosomiasis control is seen from a social perspective stressing the population's accumulated knowledge in addition to the building of shared knowledge. The model's praxis has the following characteristics: (1) it is integrated with and financed by research agencies and health services; (2) it operates at the local health services level; (3) use of molluscicides has been eliminated; (4) emphasis is given to individual medical treatment and improvement of sanitary conditions.

Treatment of schistosomiasis: gathering stones together

In this paper the treatment of schistosomiasis is examined under the following headings: cercarial dermatitis, Katayama fever, schistosomiasis in the immunosuppressed host and treatment of therapeutic failures.

Molluscicide control of snail vectors of schistosomiasis

A review of the methodology recommended by the World Health Organization for the use of molluscicides for the control of snail vectors of schistosomiasis is presented. Discussion of the principle molluscicides used, their advantages and disadvantages, the techniques and equipment required for their application and evaluation of effect as well as the biological control of snails is included.