Ecology of malaria vectors in the Americas and future direction

The resurgence of malaria in the Americas has renewed interest in Anopheles biology. Anopheles darlingi, An. albimanus, An. nuneztovai and An aquasalis are reconfirmed as major malaria vectors and other species are playing important roles in regional malaria transmission. Adultbiting activity and larval ecology are discussed in detail. Seasonal abundance and daily biting activity of Anopheles vary considerably among species and geographically for the same species. Anopheles albimanus has the least amount of variation in biting activity over its range and An. darlingi has the greatest. All species studied are more exophilic and exophagic than endophilic and endophagic. Anopheles darling is more antropophilic, endophilic and endophagic than other Anophelines. Larval studies remain more descriptive than comprehensive. Research on Anophelines is becoming more integrated and biologists are using new biochemical techniques and ecological principles to answer critical questions. This "pluralization" will help us understand species complexes, population dynamics and malaria transmission. integrated control programs will require more regional, in-depth ecological studies.

Harmonization of research and control in schistosomiasis

I have been employed by several different organizations during over 30 years working on schistosomiasis, the majority spent in endemic areas of Caribean, South America, Africa and the Western Pacific. Much of the work is best classified as applied research but sometimes it strayed to the extremes of either public health control programmes or pure research. Over this period, there have been several significant research developments that have altered our whole approach to control. Ideally, research and control should complement each other but, in reality, they sometimes have conflicting objectives. Public health workers understandably wish to provide immediate, shot-term protection to the communities in their care, but research workers may, within ethical limits, reasonably want to observe untreated communities for extended periods in order to understand the underluing process of transmission, disease pathogenesis and immunity to help develop more effective control measures. An example of this situation has occured recently in Senegal where water development projects seem to have favoured the introduction and spreed of Schistosoma mansoni in the Senegal River Basin. I have been asked to be the scientific consultant to the newly formed ESPOIR programme, linking European research organizations and the Senegal Ministry of Health, to reconcile the conflictiong aims of public health workers, wishing to use whatever funds can be obtained for an immediate chemotherapy to try to eliminate the focus, at present confined to the vicinity of a relatively small, commercially run sugar irrigation scheme; and research workers who see a rare chance to study the development of immune mechanisms in a adults in a community not previously exposed to the infection. This information could prove invaluable in understanding the development of immunity and the pathogenesis of disease, leading eventually to the development of vaccines to revolutionise the future approach to schistosomiasis...

The role of egg antigens, cytokines in granuloma formation in murine schistosomiasis mansoni

The induction of granuloma formation by soluble egg antigens (SEA) of Schistosoma mansoni is accompanied by T cell-mediated lymphokine production that regulates the intensity of the response. In the present study we have examined the ability of SDS-PAGE fractioned SEA proteins to elicit granulomas and lymphokine production in infected and egg-immunized mice. At the acute stage of infection SEA fractions (<21, 25-30, 32-38, 60-66, 70-90, 93-125, and > 200 kD) that elicited pulmonary granulomas also elicited IL-2, IL-4 lymphokine production. At the chronic stage a diminished number of fractions (60-66, 70-90, 93-125, and > 200 kD) were able to elicit granulomas with an overall decrease in IL-2, IL-4 production. Granulomas were elicited by larval-egg crossreactive and egg-specific fractions at both the acute and chronic stage of the infection. Examination of lymphokine production from egg-immunized mice demonstrated that as early as 4 days IL-2 was produced by spleen cells stimulated with <21, 32-38, 40-46, 93-125, and >200 kD fractions. By 16 days, IL-2production was envoked by 8 of 9 fractions. IL-4 production at 4 days in response to all fractions was minimal while at 16 days IL-4 was elicited with the < 21, 25-30, 50-56, 93-125, and > 200 kD fractions. The present study reveals differences in the range of SEA fractions able to elicit granulomas and IL-2, IL-4 production between acute and chronic stages of infection. Additionally, this study demonstrates sequential (IL-2 followed by IL-4) lymphokine production during the primary egg antigen response.

Molecular and cellular basis of hepatic fibrogenesis in experimental schistosomiasis mansoni infection

Morbidity in schistosomiasis mansoni occurs primaryly as a result of the complications of hepatic fibrosis. Yet, the pathogenesis of schistosomal hepatic fibrosis is poorly understood. The fact that hepatic egg granuloma is the hallmark of this infection suggests a potential role for granulomatous inflamation in hepatic fibrogenesis. Our studies in a murine schistosomiasis model indicate that hepatic granuloma cells secrete a variety of fibrogenic cytokines that may initiate the scarring process. Among these cytokines, we identified a novel protein that we designated fibroplast stimulating factor-1 (FsF-1). FsF-1 is a lymphokine that can stimulate fibroplast growth and matrix synthesis. A notable feature of hepatic fibrosis in this model is that production of FsF-1 and other granuloma-derived fibrogenic cytokines is down-regulated in chronic infection, an event that may be under immunological control. The spontaneous reduction of FsF-1 secretion presumably accounts for reduced scar formation late in infection of mice. In the context of relevant clinical studies, our findings engender the hypothesis that Symmer's fibrosis may develop in a small suppopulation of individuals as a result of immunogenetically-determined dysregulation of fibrogenic cytokine production.

Morphological features of collagen degradation in advanced hepatic schistosomiasis of man

Optical and electron microscopical evidences of focal matrix degradation were frequently seen in liver sections taken from patients with periportal ("pipe-stem") fibrosis caused by schistosomiasis mansoni. Besides present of focal areas of rarefaction, fragmentation and dispersion of collagen fibers, the enlargend portal spaces also showed hyperplasia of elastic tisue and disarray of smooth muscle fibers following the destrution of portal vein branches. Ultrastructural cahnges represented by focal lytic and/or electron dense alterations of colagen fibrils were similar to those first seen in experimental material and designated as "chronic collagen degradation". Elastin and related microfibrils were also affected by focal condensation, fragmentation, distorsion and dissolution. Schistosome eggs were scanty in the tissue sections examined. Matrix degradation represented involuting changes related to the progressive diminution of parasite aggression, which occurs spontaneously with age or after cure by chemotherapy. Changes of focal matrix degradation now being described represent the basic morphological counterpart of periportal fibrosis involution documented clinically, especially by ultrasonography, in patients with hepatosplenic schistosomiasis submitted to curative chemotherapy.

The value of ultrasonography in assessment of portal hypertension in hepatosplenic schistosomiasis

Ultrasonography can reveal most of the manifestations of portal hypertension complicating hepatosplenic, schistosomiasis. However, direct demonstration of gastroesophageal varices by ultrasonography is still very difficult. An attempt was done to correlate sonographic features of portal hypertension with the degree of fibrosis to screen patients having varices and predicting their chance of bleeding. The results obtained were found to be consistent with the esophagogastric endoscopy and with history of hematemesis. Four parameters were used, size of spleen, degree of periportal fibrosis, presence of collaterals and portal vein diameter. A pilot field survey was also done adopting the same principle.

Duplex Hemodinamic evaluation of hepatosplenic mansoni schistosomiasis

Conventional ultrasonography highly contributes to a non invasive diagnosis of HS schistosomiasis (Cerri et al., 1984). The introduction of Dopple allowed new advances in the knowledge of the portal dinamics of this disease (Taylor et al., 1985; Moriyasu et al., 1986). The aim of this paper was to analize the hemodinamic behavior of the portal vessels, considering caliper, maximum flow speed, direction of flow and preferential disposition of the collateral vessels. Thirty two patients with schistosomiasis mansoni with confirmed hepatosplenic form (HSSM), were analyzed. Fourteen patients with the intestinal form, have been analyzed as a control group. The results demonstrated that the maximum speed of the portal vein in the two groups has not been significantly diferent. Nevertheless, the diameter of the PV in the hepatosplenic group has been larger. The splenic vein presented speed and caliper larger than the superior mesenteric vein. The hepatic artery has been detectly in only 40% of the cases. The hepatic veins presented normal caliper and spectral pattern. The duplex proved to be an useful technich complementar and non-invasive, in the study of the HSSM.

Effector functions of eosinophils in schistosomiasis

The dual function of eosinophils is clearly illustred in schistosomiasis. Well equipped in membrane receptors for immunoglobulins and complement, and due to the presence of granule basic proteins, eosinophils can become cytotoxic for parasite larvae and thus participate to protective immunity. However mediators can also exert their cytolytic effect on normal cells or tissues, inducing therefore pathology. Through ADCC mechanisms against schistosome larvae in vitro involving different antibody isotypes (IgG, IgE and IgA) and also in experiments performed in vivo, eosinophils have been clearly involved in protective immunity. Although no direct evidence of the protective role of eosinophils were brought in humans, the striking association of eosinophil-dependent cytotoxic antibody isotypes with resistance to reinfection (for instance IgE and IgA antibodies), whereas in vitro blocking antibody isotypes (IgG4, IgM) were detected in susceptible subjects, strongly, suggested the participation of eosinophils in antibody-dependent protective immune response. However eosinophils could also participate to granuloma formation around S. mansoni eggs and consequently to the pathological reactions induced by schistosomiasis.

Experimental murine schistosomiasis mansoni: estabilishment of the chronic phase of the disease

After the acute hyperergic phase of schistosomal infection, the chronic phase of the disease corresponds to the estabilishment of a relative equilibrium between the host and the parasite. This involves: (1) A shift from the predominance of the TH2 response observed in the acute phase, to the predominance of the TH1 response in the chronic phase of the disease, with modification of lymphokine and immunoglobulin secretions patterns. (2) Redistribution of hosts responses to parasite, with predominance of systemic controls in the acute phase, and a shift towards local tissue responses in the chronic phase. This redistribution relieves the hyperergic responses involving the whole body of the host, and delimits cellular and molecular reactions to parasites to only those tissues that are directly involved by the adult parasites and their eggs. Mobilization of eosinophil granulocytes in schistosomal periovular granulomas is one of examples of this redistribution.

Ecological studies on the intermediate host snails and the relevance to schistosomiasis control

A detailed knoledge of distribution patterns schistosome intermediate hsts and their populations dynamics and factors affecting these patterns will provide useful information about the possibilities and desirability of conducting snail control measures in various transmission situations. On the basis of various case studies the association between the occurence of human water contacts and the presence of schistosome intermediate hosts or infections in the intermediate hosts is illustrated. Other parameters affecting snail distribution patterns and density fluctuations are discussed. It is concluded that ecological studies on the intermediate host are extremely relevant, either to optimally apply existing control measures or to develop alternative measures of snail control, such as ecological or biological control.

Further development of the baboon as a model for acute schistosomiasis

Baboons develop a syndrome, including eosinophilia and transient fever, after infection with carcariae of Schistosoma mansoni that is consistent with the human syndrome of acute schistosomiasis. Radiotelemetry can be used to follow the course of fever in infected baboons. Individual variations in intensity of disease were noted in baboons. These symptoms and signs were more closely linked to the onset of oviposition by the newly matured worms than they were to the presence of migrating schistosoma or maturing worms. The baboon is concluded to be a suitable and useful model for human acute schistosomiasis mansoni.

Efficient gene delivery and selective transduction of astrocytes in the mammalian brain using viral vectors.

Astrocytes are now considered as key players in brain information processing because of their newly discovered roles in synapse formation and plasticity, energy metabolism and blood flow regulation. However, our understanding of astrocyte function is still fragmented compared to other brain cell types. A better appreciation of the biology of astrocytes requires the development of tools to generate animal models in which astrocyte-specific proteins and pathways can be manipulated. In addition, it is becoming increasingly evident that astrocytes are also important players in many neurological disorders. Targeted modulation of protein expression in astrocytes would be critical for the development of new therapeutic strategies. Gene transfer is valuable to target a subpopulation of cells and explore their function in experimental models. In particular, viral-mediated gene transfer provides a rapid, highly flexible and cost-effective, in vivo paradigm to study the impact of genes of interest during central nervous system development or in adult animals. We will review the different strategies that led to the recent development of efficient viral vectors that can be successfully used to selectively transduce astrocytes in the mammalian brain.

Morphological characterization of the hemocytes of the pulmonate snail Biomphalaria tenagophila

The blood cells of the pulmonate snail Biomphalaria tenagophila, an important transmiter of the trematode Schistosoma mansoni in Brazil, were examined by ligth and transmission electron microscopy (TEM). Two hemocyte types were identified: hyalinocytes and granulocytes. Hyalinocytes are small young (immature), poorly spreading cells, which have a high nucleocytoplasmic ratio and are especially rich in free ribosomes. They do not appear to contain lysosome-like bodies and represent less than 10% of the circulating hemocytes. Granulocytes are larger hemocytes which readily spread on glass surface and which strongly react to the Gomori substrate, indicating the enzyme acid phosphatase usually found in lysosomes. Ultra-structurally, they contain a well-developed rough endoplasmic reticulum, dictyosomes and some some lysosome-like dense bodies. Granulocytes do not exhibit a characteristic granular aspect and the few granules observed in the cytoplasm should correspond to a lysosome system. They were named granulocytes instead of amoebocytes to use the same terminology adopted for Biomphalaria glabrata in order to make easier comparative studies. This is a preface study for more specific investigations on the functional activities of the blood cells of B. tenagophila and their interactions with the trematode parasite.

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.

Factors influencing predation of the Waterbugs Sphaerodema annulatum (Fab.) and S. rusticum (Fab.) on the Disease Transmitting Snail Lymnaea (Radix) luteola (Lamarck)

Variations in the rate of predation of the waterbugs Sphaerodema annulatum and S. rusticum on the snails Lymnaea (Radix) luteola have been noted in respect to the morphs of the waterbugs, size of the prey individuals, densities of prey and predators, temperature and surface area of the waterbody concerned and the seasons. Consumption rate was highest (7.2 and 2.2 individuals per day per individual of S. annulatum and S. rusticum, respectively) in prereproductive ages of the waterbugs. This was followed by a gradual decline with the increase in age of the predators. The consumption rate was gradually higher with the increase of temperature from 20 °C to 35 °C. The bugs failed to survive beyond 35 days at 35 °C. Though the bugs prey upon the snails of all sizes preference for 6.5 ÷ 4.5 mm to 8 ÷ 5 mm individuals by S. annulatum and for 5 ÷ 3 mm to 6.5 ÷ 4.5 mm individuals belonged to 3 ÷ 2 - 4 ÷ 3 mm size group maximum when supplied separately. The rate of predation gradually declined with the rise of predator's desity irrespective of waterbug species. Predation rate increased with increasing prey density. This was level off when the prey snails were 1100 and 700 in number for S. annulatum and S. rusticum respectively. An adult S. annulatum and S. rusticum consumed 5.04, 3.7, 1.43 and 3.36, 2.49, 1.04 snails per day respectively in summer, monsoon and winter.