Sequential histological changes in Biomphalaria glabrata during the course of Schistosoma mansoni infection

Biomphalaria glabrata, highly susceptible to Schistosoma mansoni, were seen to shed less and less cercariae along the time of infection. Histological examination kept a close correlation with this changing pattern of cercarial shedding, turning an initial picture of no-reaction (tolerance) gradually into one of hemocyte proliferation with formation of focal encapsulating lesions around disintegrating sporocysts and cercariae, a change that became disseminated toward the 142nd day post miracidial exposure. Findings were suggestive of a gradual installation of acquired immunity in snails infected with S. mansoni.     

Characterization of the immunosuppressive state during Schistosoma mansoni infection.

Analysis of a murine model of schistosomiasis revealed that both the thymus (T)- and bursa (B)-derived compartments of the immune system are modified during acute infection. The functional capacity of T and B lymphocytes to respond to mitogenic stimuli and the humoral response to thymus-dependent (SRBC) and thymus-independent (DNP-Ficoll) antigens are severely depressed. In addition, it was found that suppressor cells capable of inhibiting the response of normal lymphocytes to SRBC arise during acute infection. Although the splenic frequency of T (theta) and B (Ig+) cells remained constant during chronic infection, quantitative changes were detected in each population. In the T cell pool there was a decrease in the percentage of Ly-1+ cells and a concomitant increase in Ly-1+, 2+, 3+, cells, whereas the B cell pool showed a progressive loss of complement receptor-bearing lymphocytes, which apparently was the result of inactivation of surface complement receptor by a serum factor specifically found in infected mice. Characterization of the serum factor strongly suggests it is an immune complex. Thus, it appears that both suppressor cells and immune complexes contribute to changes noted in the immune system during acute schistosomiasis. Additional studies carried out in mice after unisexual infection revealed that egg production is not a necessary prerequisite for several of the immunologic phenomena associated with acute schistosomiasis.     

Natural infection of wild rodents by Schistosoma mansoni

In Planalto, a small locality in the interior of the Bahia state, Brazil, 47% of sylvatic rodents were found to be naturally infected with Schistosoma mansoni, whereas the prevalence of the infection in the inhabitants of the area was 3.26%. The rodents (Nectomys) live near the houses, in contact with water, passing viable schistosome eggs in the stools. Worm burden is variable amongst such rodents. Periovular granulomas are small, especially in liver and intestines, and hepatic fibrosis is mild or absent, with no morphological evidence of portal hypertension being noted. Miracidia isolated from the eggs recovered from Nectomys readly infected laboratory-raised Bahia strain of Biomphalaria glabrata. Cercariae then obtained infected Swiss mice in a similar way as the human strains of S. mansoni kept in laboratory. Also, Swiss mice left in contact with water collections in Planalto were easily infected, which proved the transmissibility potential of the area. In conclusion: sylvatic rodents found in the area of Planalto tolerate well S. mansoni infection, eliminate viable eggs in the stools, are usually infected with a strain probably of human origin and therefore may play a role in maintaining parasite cycle in the area.     

Lysosomal enzyme activities in susceptible and refractory strains of Biomphalaria glabrata during the course of infection with Schistosoma mansoni

The distribution and abundance of the lysosomal enzyme markers, acid phosphatase (AP), peroxidase (PO), and nonspecific esterase (NE), within circulating blood cells (hemocytes) were examined in a schistosome-susceptible (PR albino M-line) and a resistant (10-R2) strain of Biomphalaria glabrata during the course of infection with Schistosoma mansoni. The dynamics of serum (cell-free hemolymph) AP activities and total hemocyte numbers in infected snails also were investigated. Hemocyte subpopulations, as determined by these enzyme markers, responded differently to parasite infection between snail strains. Generally, the hemocyte subpopulations within PR albino snails remained largely unchanged, whereas the same subpopulations in 10-R2 snails fluctuated considerably. The distribution of AP in the hemocytes of 10-R2 snails decreased by 1 hr postexposure (PE) to the parasite and remained low through 12 hr before increasing to control values at 24 hr and 2 wk PE. In comparison, PO activity increased by 1 hr PE and peaked at 12 hr before dropping to 0 hr values by 2 wk PE. The NE activity exhibited still another pattern with the percentage of NE-positive cells decreasing from 0 to 12 hr PE followed by a recovery to 0-hr values by 24 hr. The abundance of these hemocyte enzymes followed a similar pattern to that of their distribution, although some differences were observed. Serum AP values varied little in PR albino snails except for a significant increase at 2 wk PE, indicating a possible response to tissue damage resulting from migrating daughter sporocysts.(ABSTRACT TRUNCATED AT 250 WORDS)     

Experimental models of Schistosoma mansoni infection

Experimental models of Schistosoma mansoni infections in mammals have contributed greatly to our understanding of the pathology and pathogenesis of infection. We consider here hepatic and extrahepatic disease in models of acute and chronic infection. Experimental schistosome infections have also contributed more broadly to our understanding of granulomatous inflammation and our understanding of Th1 versus Th2 related inflammation and particularly to Th2-mediated fibrosis of the liver.     

Preventive effect of artemether in experimental animals infected with Schistosoma mansoni

The effect of artemether, an antimalarial drug developed from the plant Artemisia annua, has been tested against the larval stages of Schistosoma mansoni covering the time from skin penetration to the early adult liver-stage. The results show that the experimental animals used (hamster and mice) do not develop schistosomiasis mansoni if treated with artemether during the first month after infection. The parasite was found to be especially susceptible between the 3rd and 4th week after infection, resulting in worm reductions of 75.3-82.0% compared to non-treated controls. This level was boosted to 97.2-100% when the animals were subjected to various schedules of repeated treatment. Almost complete protection was also reached in parallel experiments with repeated infections carried out to mirror more closely the real situation of trickle infection.     

Metabonomic investigation of human Schistosoma mansoni infection

Schistosomiasis is a parasitic infection that is endemic in many developing countries in the tropics and subtropics afflicting more than 207 million people primarily in rural areas. After malaria, it is the second most important parasitic infection in terms of socio-economic and public health. Investigation of the host-parasite interaction at the molecular level and identification of biomarkers of infection and infection-related morbidity would be of value for improved strategies for treatment and morbidity control. To this end, we conducted a nuclear magnetic resonance (NMR) based metabonomics study involving a well-characterized cohort of 447 individuals from a rural area in Uganda near Lake Victoria with a high prevalence of Schistosoma mansoni, a species predominantly occurring in Africa including Madagascar and parts of South America. Cohort samples were collected from individuals at five time-points, before and after (one or two times) chemotherapy with praziquantel (PZQ). Using supervised multivariate statistical analysis of the recorded one-dimensional (1D) NMR spectra, we were able to discriminate infected from uninfected individuals in two age groups (children and adults) based on differences in their urinary profiles. The potential molecular markers of S. mansoni infection were found to be primarily linked to changes in gut microflora, energy metabolism and liver function. These findings are in agreement with data from earlier studies on S. mansoni infection in experimental animals and thus provide corroborating evidence for the existence of metabolic response specific for this infection.     

Neuroinflammatory implication of Schistosoma mansoni infection in the mouse

Schistosomiasis is a parasitic disease due to Schistosoma mansoni. Schistosome infection is known to induce granulomas not only in the spleen, bladder, liver and intestine but also in the brain and spinal cord resulting in severe neuropathological and psychiatric disorders though the interaction between Schistosoma mansoni infection and the nervous system has received on the whole little attention. In the present review it has been discussed recent findings from experimental Schistosoma mansoni infection in mouse nervous system. We show that brain granulomas are associated with a significant alteration in the constitutive levels of nerve growth factor (NGF), a trophic factor playing an essential role in nerve growth and differentiation and in preventing neuronal damages. Animals infected with schistosomes suffered also of increased pain sensitivity which was inhibited by TNF-alpha antibody injections and not by anti-NGF. These findings suggest that the neuropathological dysfunctions in neuroschistosomiasis may be linked to changes in the basal levels and/or activity of neurotrophic factors caused by local formation of granulomas.     

Genetics of Biomphalaria glabrata and its effect on the outcome of Schistosoma mansoni infection

The genetics of the snail Biomphalaria glabrata is better characterized than that of any other intermediate host of schistosomes of humans. Using techniques of selective breeding, several snail stocks have been developed that consistently display resistant or susceptible phenotypes. Investigators using these stocks have learned that several snail and parasite genes influence the course of parasite development. Here, Charles Richards, Matty Knight and Fred Lewis discuss the importance of the snail's genetics in categorizing resistance in this complex invertebrate, some recent molecular evidence that may help us understand several of the problems that still remain, and some challenges lying ahead for investigators in this field.     

Effect of the administration of estrogen-antiestrogen combinations on the experimental infection of the hamster with Schistosoma mansoni

In the purpose of establishing if the antiestrogens may inhib the protective effects of the estrogens during an experimental infection with Schistosoma mansoni in golden female hamster, we have studied the following estrogen-anti-estrogen associations: 17 beta-estradiol + trans-tamoxifène, 17 beta-estradiol + trans-clomifène, hexestrol + trans-tamoxifène. The decrease of the number of worms in the animals under experiment shows that these associations still give a protective effect. This protection is however weaker than the one which is induced by estrogens administration only. The interpretation of these results agree with the intervention of an estrogen receptor.     

Desmin expression in fibroblasts of murine periovular granuloma during liver Schistosoma mansoni infection

We have studied the expression of the desmin gene, a muscle-specific intermediate filament protein in the granuloma cells of mouse liver infected with Schistosoma mansoni. In situ hybridization using a desmin DNA probe showed that fibroblastic cells in the granuloma strongly expressed desmin mRNAs, while in normal liver these cells did not express this mRNA to a detectable degree. The quantitative analysis of total RNAs demonstrated that the proportion of specific desmin mRNA increased from 14 to 18 weeks after infection and decreased at 20 weeks. The analysis of collagen gene expression indicated that the amount of type III collagen mRNAs was still increasing after 18 weeks from infection; in contrast, the amount of type I collagen mRNAs remained unchanged at that stage. A good correlation was observed between the detection of the specific mRNAs and the detection of both desmin and collagen molecules. Therefore, these data point to a coordinate induction of desmin and collagen gene expression during Schistosomal granuloma formation. They also suggest that the expression of the myofibroblast phenotype involves the induction of both genes.