Biomphalaria snails are instrumental in transmission of the human blood fluke Schistosoma mansoni. With the World Health Organization's goal to eliminate schistosomiasis as a global health problem by 2025, there is now renewed emphasis on snail control. Here, we characterize the genome of Biomphalaria glabrata, a lophotrochozoan protostome, and provide timely and important information on snail biology. We describe aspects of phero-perception, stress responses, immune function and regulation of gene expression that support the persistence of B. glabrata in the field and may define this species as a suitable snail host for S. mansoni. We identify several potential targets for developing novel control measures aimed at reducing snail-mediated transmission of schistosomiasis.

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The impact of intestinal helminth infection, i.e. Ascaris lumbricoides and Trichuris trichiura, on cellular responsiveness and cytokine production was investigated in young adults. Ascaris-specific cellular responsiveness was higher in parasite-free endemic controls than in patients infected with T. trichiura, or A. lumbricoides, or patients co-infected with both parasites. Also, mitogen-induced tumour necrosis factor (TNF)-alpha, interleukin (IL)-12 and interferon (IFN)-gamma secretion by peripheral blood mononuclear cells (PBMC) was higher in negative endemic controls than in infected individuals. Ascaris antigen-specific production of TNF-alpha, IL-12 and IFN-gamma was low in singly Ascaris as well as in co-infected patients, whereas secretion of IL-10 and IL-13 was elevated and similarly high in all patient groups. The detection of Trichuris-specific and Ascaris-specific IgG4 revealed significantly higher serum antibody levels in Trichuris or Ascaris patients when compared to endemic controls (P < 0.05), whereas parasite-specific IgE antibody levels were similarly high in infected individuals and in endemic controls. In summary, chronically infected Ascaris and Trichuris patients with a high parasite load presented reduced cellular reactivity and lower type 1 TNF-alpha, IFN-gamma and IL-12 responses when compared with endemic controls, whereas type 2 IL-10 and IL-13 productions were similar in all groups from the endemic area. The former may support parasite persistence, whereas substantial type 2 cytokine release may promote protective immunity, suggesting an adaptation of the host to control the parasite burden while minimizing immune-mediated host self-damage.

During human schistosomiasis host responses to antigens of various parasite life-cycle stages may contribute to whether the severe, hepatosplenic state develops or the patient remains relatively asymptomatic throughout infection, and may play a role in resistance. This study evaluated production of interferon gamma (IFN-gamma) in vitro by schistosome antigen-stimulated peripheral blood mononuclear cells (PBMCs) from asymptomatic patients, and by PBMCs from apparently uninfected, untreated persons living in areas endemic for Schistosoma mansoni ('endemic normals'). IFN-gamma production parallels PBMC proliferation in that schistosomal egg antigens stimulate patent patients' cells poorly, but strongly stimulate PBMCs from 'endemic normals'. This is proportionally true for antigens from adult worms and cercariae. Although asymptomatic patent patients' cells produced little or no IFN-gamma in response to the 3 schistosomal antigenic extracts, their PBMCs, and PBMCs from 'endemic normals', produced expected amounts of IFN-gamma when exposed to phytohaemagglutinin. This implies that persons with patent infections have schistosome antigen-specific defects in their ability to respond to IFN-gamma production that are not exhibited by putatively resistant 'endemic normals'.

Abstract. Cellular and humoral immune responses to Schistosoma mansoni antigen preparations were evaluated in individuals presumed to be susceptible or resistant to reinfection after chemotherapeutic cure. A consistent proliferative increase in the response to soluble egg antigen (SEA) was observed post-treatment in both the susceptible and resistant groups. However, this change was not related to resistance. Isotype studies showed that IgM antibody levels to soluble worm antigen preparation (SWAP) and cercariae antigens were significantly higher in the resistant group than in the susceptible group. Post-treatment, an increase in IgE anti-SWAP and anti-schistosomular tegument (STEG) responses and a decrease in IgG4 anti-SEA and anti-STEG responses were observed in the resistant group. These finding are similar to those we have reported previously for a putative resistant group termed endemic normals, and are compatible with immunologic studies in different endemic areas. Together, these findings indicate that even on the population level, high IgE specificities coupled with low IgG4 specificities correlate well with documented resistance to reinfection.Based on field studies following curative chemotherapy of either Schistosoma mansoni 1-3 or S. haematobium, 4,5 individuals are often categorized as being either susceptible or resistant to natural reinfection by schistosomes. These studies have shown that resistance to reinfection is an age-related phenomenon, with most people in endemic areas becoming resistant, or expressing their resistance during their second decade of life. When determined directly or by estimation, resistance appears to be unrelated to the degree of contact that the susceptible and resistant groups have with cercariaecontaining water, and is usually attributed to immunity rather than physiologic or behavioral changes with age. 4,6,7 These studies have cataloged a variety of humoral immune responses, and are in agreement with several of the correlations demonstrated between given immune responses and susceptible or resistant groups. 8,9 A number of studies have shown associations between resistance status and a balance between the level of effective anti-schistosomula antibodies and the presence of blocking antibodies. 5,[10][11][12] The latter are sometimes most easily demonstrated as antibodies to egg antigens that cross-react with epitopes present in the schistosomula tegument. 3,10The most common features that show relationships to resistance to reinfection include high levels of IgE against adult worm or larval antigens, while high levels of IgG4 and IgM antibodies against egg antigens generally parallel susceptibility. 5,9,[11][12][13][14][15] Recent studies have also reported correlations between resistance and elevated levels of IgA against a schistosome vaccine candidate (Sm 28 glutathione-S-transferase). 16,17 Further studies with other antigens have demonstrated that higher levels of IgE against a 22-kD schistosomula moiety 9 and higher levels of IgM against a 68-kD adult schistos...

The polymerase chain reaction and restriction fragment length polymorphism (RFLP)

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Sera from individuals living in 2 areas endemic for Schistosoma mansoni in Minas Gerais, Brazil were assayed for the presence of antibodies against paramyosin and glutathione-S-transferase (GST), molecules previously implicated as vaccine immunogens from studies in laboratory hosts. A group was identified consisting of subjects who were stool-negative and had no record of previous infection but who were seropositive by enzyme-linked immunosorbent assay against crude adult worm antigen (SWAP). These individuals had anti-paramyosin antibody levels which were dramatically elevated with respect to those measured in infected (stool-positive) individuals living in the same endemic area. In contrast, the same 2 groups of stool-positive and stool-negative subjects could not be distinguished on the basis of their seroreactivity to either GST or SWAP. After chemotherapy, anti-paramyosin antibodies rose above pre-treatment levels and remained elevated in those individuals who became stool-negative. In contrast, anti-paramyosin antibodies decreased to pretreatment values in drug-treated individuals who failed to show complete parasitological cure. These results suggest that the immune response of humans to paramyosin may play a role in natural resistance to schistosome infection, and that an elevated antibody level against this antigen may be a useful correlate of drug-induced cure.