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.

Extramedullary hematopoiesis in murine schistosomiasis mansoni

During Schistosoma mansoni infection, there is morphological evidence of involvement of various hematopoietic growth factors, which cause eosinophil, neutrophil, megakaryocytic and erythroid extramedullary foci in the liver, lymph nodes and omental and mesenteric milky spots. While the eosinophil metaplasia in the periphery of hepatic granulomas roughly reproduced the intensity of the medullary eosinopoiesis, the neutrophil metaplasia, on the contrary, was more intense during the period of neutrophil depression in the bone marrow. This fact suggests that extramedullary hematopoietic foci are locally regulated, and amplify and/or compensate the systemic hematopoietic response during the infection.

The snail hosts of schistosomiasis: some evolutionary and ecological perspectives in relation to control

Despite opportunities for radiation provided by spatio-temporal isolation, the basic morphological plan of pulmonate snails has remained conservative. In consequence of the resulting dearth of morphological characters and their plasticity, there is a case for using biochemical characters such as exogenous chemicals released by the snails (e.g. amino acids) and their chemoreception niche as taxonomic aids to classify snails of medical importance. As these same chemicals are used by snails to distinguish conspecifics they could also be used as "environmental antibodies" in controlled release formulations (CRF's) designed to remove target snails in a specific, cost-effective and ecologically acceptable manner. The snails, surface-living bacteria, algae and macrophytic plants are considered as co-evolved, interactive modular systems with strong mutualistic elements. Recently, anthropogenic perturbations such as deforestation, and damming of flowing waters, have benefited these modules whereas others such as river canalization, acid deposition, accumulation of pesticide residues and eutrophication have harmed them. Research is needed to elucidate the factors which limit the growth of snails in primitive habitats, uninfluenced by man, as well as in those subject to harmful anthropogenic factors. The understanding thus gained could be applied to develop cost-effective primary health care strategies to reduce or prevent transmission of schistosomiasis and other water related diseases.

Opportunities and constraints in schistosomiasis vaccine development: infection characteristics and industry realities

The notes provided in this article relate to two components of the development of vaccines against schistosomiasis: (1) The characteristics of schistosome infections (eg. features of the schistosome life cycle), and the parasite itself, that have implications for vaccination strategies; (2) The characteristics of the biopharmaceutical industry that have implications for product development. As will be seen, these two topic areas are not vastly disparate.

Schistosomiasis vaccine development: approaches and prospects

Mounting evidence for acquired immunity to schistosomiasis in humans supports the case for immunological intervention. On the other hand, rapid reinfection poses a threat to younger age groups due to the slow maturation of natural resistance. However, rational approaches, based on advances in immunology and molecular biology, have substantially increased the odds of producing an effective vaccine. Since the parasite cannot replicate in the human host and serious morbidity generally occurs only after a relatively long period of heavy worm burden, complete protection against infection is not essential. The chances of success would increase if more than one of the various host/parasite interphases were targeted, for example reducing morbidity through decreased worm loads as well as through suppression of egg production. Several promising schistosome antigens have now reached an advanced phase of development and are currently undergoing independent confirmatory testing according to a standardized protocol. A few molecules are being contemplated for scaled-up production but, so far, only one has reached the stage of industrial manufacture and safety testing. Since schistosomiasis cannot realistically be controlled by a single approach, vaccination is envisaged to be implemented in conjunction with other means of control, notably chemotherapy.

Health education, public information, and communication in schistosomiasis control in Brazil: a brief retrospective and perspectives

In recent years, the strategy for the control of schistosomiasis has placed increased emphasis on the role of health education, public information, and communication. This should, not only bring about specific changes in behavior aiming at disease prevention, but also stimulate participation of the community in health programs. Beyond this, it is desirable that both community members and researchers should seek better life conditions through a transformative social action. The present paper addresses these concerns; first, by critically reviewing some health education programs that were developed in Brazil, and, secondly, by analyzing and suggesting ways to improve this area.

Development of a vaccine strategy against human and bovine schistosomiasis: background and update

Schistosomiasis is a chronic and debilitating parasitic disease that affects over 200 million people throughout the world and causes about 500,000 deaths annually. Two specific characteristics of schistosome infection are of primordial importance to the development of a vaccine: schistosomes do not multiply within the tissues of their definitive hosts (unlike protozoan parasites) and a partial non-sterilizing immunity can have a marked effect on the incidence of pathology and on disease transmission. Since viable eggs are the cause of disease pathology, a reduction in worm fecundity whether or not accompanied by a reduction in parasite burden is a sufficient goal for vaccine induced immunity. We originally showed that IgE antibodies played in experimental models a pivotal role for the development of protective immunity. These laboratory findings have been now confirmed in human populations. Following the molecular cloning and expression of a protein 28 kDa protein of Schistosoma mansoni and its identification as a glutathion S-transferase, immunization experiments have been undertaken in several animal species (rats, mice, baboons). Together with a significant reduction in parasite burden, vaccination with Sm28 GST was recently shown to reduce significantly parasite fecundity and egg viability leading to a decrease in liver pathology. Whereas IgE antibodies were shown to be correlated with protection against infection, IgA antibodies have been identified as one of the factors affecting egg laying and viability. In human populations, a close association was found between IgA antibody production to Sm28 GST and the decrease of egg output. The use of appropriate monoclonal antibody probes has allowed the demonstration that the inhibition of parasite fecundity following immunization was related to the inhibition of enzymatic activity of the molecule. Epitope mapping of Sm28 GST has indicated the prominent role of the N and C terminal domains. Immunization with the corresponding synthetic peptides was followed by a decrease of 70% of parasite fecundity and egg viability. As a preliminary step towards phase I human trials, vaccination experiments have been performed in cattle, a natural model for Schistosoma bovis. Vaccination of calves with the S. bovis GST has led to a reduction of ever 80% of egg output and tissue egg count. Significant levels of protection were also observed in goats after immunization with the recombinant S. bovis GST. Increasing evidence of the participation of IgA antibodies in protective immunity has prompted us toward the development of mucosal immunization. Preliminary results indicate that significant levels of protection can be achieved following oral immunization with live attenuated vectors or liposomes. These studies seem to represent a promising approach towards the future development of a vaccine strategy against one of major human parasitic diseases.

Vaccination against schistosomiasis and fascioliasis with the new recombinant antigen Sm14: potential basis of a multi-valent anti-helminth vaccine?

Molecular cloning of components of protective antigenic preparations have suggested that related parasite fatty acid binding proteins could form the basis of the well documented protective, immune cross reactivity between the parasitic trematode worms Fasciola hepatica and Schistosoma mansoni. We have now confirmed the cross protective potential of parasite fatty acid binding proteins and suggest that it may be possible to produce a single vaccine that would be effective against at least two parasites, F. hepatica and S. mansoni of veterinary and human importance respectively.

Control of schistosomiasis in Brazil: perspectives and proposals

Attempts to control schistosomiasis have hitherto involved the use of one or more of the following methods, either in isolation or in combination: (1) control of the intermediate host using molluscicides or biological methods; (2) basic sanitation and clean water supply; (3) health education; (4) individual or mass treatment; (5) protection of individuals in such a way as to prevent cercariae from penetrating the skin; (6) vaccine-based strategies against schistosomiasis. None of these methods is capable, on its own, of bringing about effective control of schistosomiasis, except in populations of a very limited size or under very special conditions. Molluscicides, besides expensive and toxic, have only a temporary effect. As for biological control, there is no effective method yet. Basic sanitation and clean water supply combined with health education potentially constitute the most effective approach, but only in the mid-to-long term. Mass treatment reduces morbidity, but does not control transmission. Protection of individuals has proved to be impracticable on a large scale. Vaccine-based strategies against schistosomiasis are still in the experimental stage. Experiments carried out in Brazil in the last 20 years have shown that mass treatment with single doses of oxamniquine or praziquantel can rapidly reduce levels of Shistosoma mansoni infection and morbidity in endemic areas. They have also shown that subsequent transmission and reinfection frequently occur in defined foci or "clusters", due to human contact with water, and in inverse proportion to the number and frequency of treatments carried out. On the basis of these experiments, the author suggests a multidisciplinary strategy for schistosomiasis control.

Acute human schistosomiasis mansoni

The acute schistosomiasis is the toxemic disease that follow the Schistosoma cercariae active penetration trough screen in the immunologicaly naive vertebrate host. The clinical picture starts two to eight weeks after the first contact with the contaminated water. Susceptible patients present a syndrome comprising fever, diarrhea, toxemia and hepatosplenomegaly. Diagnosis is based on epidemiological and clinical features, presence of Schistosoma eggs in the feces, enlargement of abdominal lymph nodes by ultrasonography and by detection of high antibodies levels against the antigen keyhole limpet haemocyanin. Different rates of cure have been observed with specific medication and for the most severe clinical presentations the use of steroids reduces the systemic and allergic manifestations.

Control of schistosomiasis transmission

Despite the success of control programmes, schistosomiasis is still a serious public health problem in the world. More than 70 countries where 200 million individuals are evaluated to be infected of a total 600 million at risk. Though there have been important local success in the control of transmission, globally the infection has increased. Economic constrains in developing countries, environmental changes associated with migration and water resources development have been blocking the progress. The main objective of schistosomiasis control is to achieve reduction of disease due to schistosomiasis. We discussed the control measures like: health education, diagnosis and chemotherapy, safe water supplies, sanitation and snail control. We emphasized the need to give priority to school-age children and the importance of integrating the measures of control into locally available systems of health care. The control of schistosomiasis is directly related to the capacity of the preventive health services of an endemic country. The strategy of control requires long-term commitment from the international to the local level.

Anti-embryonation immunity in murine schistosomiasis japonica (Philippines)

The hypothesis that granuloma modulation and disease abatement in chronic infection with Schistosoma japonicum could be ascribed to antibody-mediated effects on egg maturation and egg viability, arose from studies performed with mice in the Philippines. This novel hypothesis has not yet been integrated into the schistosomiasis literature despite being formulated more than a decade ago. One reason for this is that the phenomenon might be confined to S. japonicum, even S. japonicum (Philippines).

Schistosomiasis control in China

After three decades' efforts, schistosomiasis japonica were controlled in one-third (4/12) of endemic provinces and 68.2 (259/380) of endemic counties throughout the country. The remaining 121 endemic counties are located primarily in the lake and mountainous regions. The epidemiological and ecological features of the lake and mountainous areas are different from the other endemic areas. The major schistosomiasis control efforts in China can be characterized as follows: (1) Application of centralized leadership and management, since schistosomiasis control is a task not only of the Ministry of Public Health, but also of all local governments in the endemic areas; (2) Integration of actions taken by various departments or bureaus, such as agriculture, water conservation and public health; (3) Promotion of mass participation; (4) Organization of strong professional teams; (5) Raising sufficient funds. Strategies on schistosomiasis control applied in different areas are divided into three levels: (1) In the areas where the schistosomiasis has been successfully controlled, surveillance must be maintained and immediate action should be taken where new infections occur and/or vector snails are found, so that control can be reestablished quickly; (2) In the areas where schistosomiasis has been partially controlled, any residents and/or live-stock infected should be examined and treated promptly with due care, and environment modifying and/or mollusciding must be used to eliminate the remaining snails; (3) In the areas where transmission has not been controlled, the main strategy is to control morbidity. Mass or selective chemotherapy with praziquental should be applied to both infected persosns and the live-stock, and environment modification for the snail-ridden areas should be taken but should be coordinated with agriculture where possible. Advance cases must be treated; and epidemics of Katayama fever prevented; water supply and sanitation shoud be improved and health education emphasized. Annual mass or selective chemotherapy with praziquental both reduces the prevalence rate and decreases the intensity of the infection for inhabitants and live-stock. As a consequence of the therapy a low prevalence rate can be obtained in a short time. The length of such arrangement period can be decided in accordance with the prevalence of the infection before the drug program is begun. Therefore,a maintenance phase is urgently needed. As China's ecomony expands and people's living standard rises, schistosomiasis will be controlled more effectively and successfully.