Host glucose metabolism mediates T4 and IL-7 action on Schistosoma mansoni development

Interleukin (IL-)7 and thyroxin (T4) favor Schistosoma mansoni development. Their effect is similar, rather than identical; moreover, cotreatment acts synergistically on parasites. This questioned a common mediator to their action, which we hypothesized was host glucose metabolism. Infection with S. mansoni resulted in an early peak in glycemia immediately followed by a peak of insulinemia (D7-21). In IL-7 + T4 cotreated infected animals, the peak of insulin was abrogated. We further assessed the consequences of experimentally induced glucose- or insulin-level variations on parasite development. Insulin treatment from day 14 to day 21 post-infection (PI) led to increased worm burden and parasite size, thus mimicking the effect of T4 on schistosome development. Interestingly, insulin treatment did not modify glycemia yet abrogated the hyperinsulinemia, normally occurring during infection. Finally, these treatments were associated with an alteration of the expression of parasite genes involved in glucose uptake. These experiments characterize the elaborate links between parasite and host metabolism and their reciprocal influences.     

Host mouse strain is not selective for a laboratory adapted strain of Schistosoma mansoni

We genotyped pooled adult worms of Schistosoma mansoni from infected CF1, C57BL/6, BALB/c, and BALB/c interferon gamma knockout mice in order to establish if mouse strain differences selected for parasite genotypes. We also compared differentiation in eggs collected from liver and intestines to determine if there was differential distribution of parasite strains in the vertebrate host that might account for any genotype selection. We found that mouse strains with differing immune responses did not differ in resistance to infection and did not select for parasite genotypes. Schistosoma mansoni egg allele frequencies were also equally distributed in tissues and the difference between adult and egg allele frequencies was negligible.     

Effect of chemotherapy on the Schistosoma mansoni eggs

Praziquantel administered to mice with Schistosoma mansoni infection (50 cercarias/8 weeks) was observed to cause death of adult worms and disintegration of the eggs trapped within granulomas, sometimes with calcification, after the 4th day of treatment. Combined administration of oxamniquine/hycanthone to animals similarly infected, although quite effective in killing adult worms, did not interfere with the eggs in the tissue. The miracidium eclosion test was positive up to the 15th day after the curative treatment of these animals. Since praziquantel treatment causes a rapid destruction of eggs, possible serological and pathogenic effects are expected that may enable a faster reabsorption of granulomas by the host tissues than that produced by other equally effective drugs.     

Influence of a menhaden oil diet on cercarial penetration of Schistosoma mansoni.

The ability of a menhaden oil (MO) diet to influence cercarial penetration into mouse tail skin was evaluated. Male CD-1 mice 4-6 wk old (15.2 g average weight) were fed a 0, 10%, or 20% MO-supplemented diet for 2 wk. After this time mice were infected with either 65 +/- 3 or 145 +/- 3 [35S]methionine/cysteine-labeled cercariae for 1 hr by tail immersion. Twenty-four hours and 7 days later groups of mice were killed and their tail skin removed and autoradiographed. At 24 hr postinfection, mice fed a 20% MO diet had significantly higher cercarial penetration than controls and 10% MO diets (56% +/- 5.2 vs. 44% +/- 2.9, P = 0.02, 1-tailed t-test). After 7 days mice fed a 20% MO diet retained more radioactive foci than controls or 10% MO diets (21% +/- 2.0 vs. 15% +/- 1.3, P = 0.01, 1-tailed t-test).     

Influence of intramolluscan larval stages of Echinostoma liei on the infectivity of Schistosoma mansoni cercariae

During co-infection of Biomphalaria glabrata with Schistosoma mansoni and Echinostoma liei, S. mansoni cercariae released before the complete resorption of S. mansoni sporocysts show a very strong decrease of their infectivity in mice. Under conditions of high interspecific competition (i.e. when the snails are infected by E. liei 8 days after infection by S. mansoni), the mean overall worm return is five times lower than that of the control experiment. A marked decrease of the infectivity of cercariae is also noted when snails, infected exclusively with either sporocysts of S. mansoni or rediae of E. liei, are associated in the same tank.     

Influence of Schistosoma mansoni and Hookworm Infection Intensities on Anaemia in Ugandan Villages

BackgroundThe association of anaemia with intestinal schistosomiasis and hookworm infections are poorly explored in populations that are not limited to children or pregnant women.MethodsWe sampled 1,832 individuals aged 5–90 years from 30 communities in Mayuge District, Uganda. Demographic, village, and parasitological data were collected. Infection risk factors were compared in ordinal logistic regressions. Anaemia and infection intensities were analyzed in multilevel models, and population attributable fractions were estimated.FindingsHousehold and village-level predictors of Schistosoma mansoni and hookworm were opposite in direction or significant for single infections. S. mansoni was found primarily in children, whereas hookworm was prevalent amongst the elderly. Anaemia was more prevalent in individuals with S. mansoni and increased by 2.86 fold (p-value<0.001) with heavy S. mansoni infection intensity. Individuals with heavy hookworm were 1.65 times (p-value = 0.008) more likely to have anaemia than uninfected participants. Amongst individuals with heavy S. mansoni infection intensity, 32.0% (p-value<0.001) of anaemia could be attributed to S. mansoni. For people with heavy hookworm infections, 23.7% (p-value = 0.002) of anaemia could be attributed to hookworm. A greater fraction of anaemia (24.9%, p-value = 0.002) was attributable to heavy hookworm infections in adults (excluding pregnant women) as opposed to heavy hookworm infections in school-aged children and pregnant women (20.2%, p-value = 0.001).ConclusionCommunity-based surveys captured anaemia in children and adults affected by S. mansoni and hookworm infections. For areas endemic with schistosomiasis or hookworm infections, WHO guidelines should include adults for treatment in helminth control programmes.     

Effect of mutagen on cultured Schistosoma mansoni

Although lightly homogenized three-week-old Schistosoma mansoni incubated in Mitsuhashi and Maramorosch insect tissue culture medium or the medium of Weller and Wheeldon produced adherent cell layers, continued growth of these cells did not occur. Non-adherent cells obtained by trypsinization also failed to produce long term cell cultures even after the addition of a range of growth factors. The possibility of producing tumour-like schistosome cells by the use of the mutagen ethyl methane sulphonate was therefore examined. Four-hour exposure of three-week-old schistosomes caused in some worms (a) large fluid filled 'ballooning', which also occurred in adult males, (b) enlargement of the gut, (c) increase in numbers of large round cells within the worms and (d) tissue outgrowths. It is suggested that these effects of mutagen offer new approaches to obtaining permanent schistosome cell cultures.     

Proteomic Analysis of the Schistosoma mansoni Miracidium

Despite extensive control efforts, schistosomiasis continues to be a major public health problem in developing nations in the tropics and sub-tropics. The miracidium, along with the cercaria, both of which are water-borne and free-living, are the only two stages in the life-cycle of Schistosoma mansoni which are involved in host invasion. Miracidia penetrate intermediate host snails and develop into sporocysts, which lead to cercariae that can infect humans. Infection of the snail host by the miracidium represents an ideal point at which to interrupt the parasite’s life-cycle. This research focuses on an analysis of the miracidium proteome, including those proteins that are secreted. We have identified a repertoire of proteins in the S. mansoni miracidium at 2 hours post-hatch, including proteases, venom allergen-like proteins, receptors and HSP70, which might play roles in snail-parasite interplay. Proteins involved in energy production and conservation were prevalent, as were proteins predicted to be associated with defence. This study also provides a strong foundation for further understanding the roles that neurohormones play in host-seeking by schistosomes, with the potential for development of novel anthelmintics that interfere with its various life-cycle stages.     

Influence of saccharose on the development of cercariae from Schistosoma mansoni strains BH and SJ.

The development of cercariae from Schistosoma mansoni strains BH and SJ in Biomphalaria glabrata and Biomphalaria tenagophila treated with saccharose was studied. The molluscs were maintained in dechlorinated tap water containing 0.01% saccharose. After one week of treatment with saccharose, B. glabrata and B. tenagophila were exposed to ten S. mansoni miracidia, from BH and SJ strains respectively. Control snails of both species were maintained in dechlorinated tap water without saccharose and exposed to the same number of miracidia. There was no significant difference between the infection rates of snails treated or not with saccharose. However, the two groups of B. glabrata had significantly greater infection rates than the corresponding B. tenagophila groups. Molluscs treated with saccharose had a lower survival rate, with the greatest mortality occurring immediately before and at the beginning of cercariae release. Treatment with saccharose did not result in the release of more cercariae, but larvae from molluscs so treated showed a greater capacity to penetrate mouse skin, which was attributed to the greater energy supply during larval development in the mollusc.     

Host reproductive fitness: the influence of increasing parasite pressure in a Biomphalaria glabrata/Schistosoma mansoni system

Summary

Host life history traits are often shaped by trade-offs between the current and potential future costs of parasitism. Reproductive tissues are not normally essential for host survival and diversion of resources elsewhere is a common effect of parasitic infection. Variations in reproductive output may therefore indicate overall fitness correlated to the host response to parasite pressure. Here, we investigated reproductive fitness in a Biomphalaria glabrata—Schistosoma mansoni system, a laboratory model for schistosomiasis. Five matched groups of unselected B. glabrata snails were individually exposed to doses of 1, 2, 5, 10 or 20 S. mansoni miracidia, respectively. A sixth group remained unexposed providing a control. Fertility (defined as actual reproductive performance, measured as the number of offspring produced) and fecundity (defined as potential reproductive capacity, measured as number of eggs and embryos formed) were monitored for each group at weekly intervals. Our results revealed that both parasite dose and infection status had a significant effect on the potential reproductive capacity of the host, but this was not always reflected in the actual reproductive success. Egg mass production showed a negative association with increasing parasite dose in patently infected snails. In contrast, snails exposed to the parasite, but within which infection did not establish, demonstrated a positive association between egg mass production and parasite dose. This suggests the existence of a fecundity compensation mechanism occurring within the post-patent period of infection. This is, to our knowledge, the first report of such an effect in a snail-trematode system and, indeed, in any host-parasite association.