Schistosomiasis does not contribute to death or recurrence of nontyphoid Salmonella bacteremia in human immunodeficiency virus-infected Malawian adults.

Nontyphoid Salmonella (NTS) bacteremia has a very high mortality and recurrence rate among human immunodeficiency virus (HIV)-infected Malawian adults. Concurrent schistosomal infection might cause persistence of NTS infection and poor response to antibiotic therapy. Therefore, we tested serum samples for Schistosoma-specific circulating anodic antigen to diagnose coinfection with schistosomiasis among consecutive HIV-positive adults with NTS bacteremia. The results suggest that active schistosomiasis is not associated with adverse outcome of NTS bacteremia in this population, in contrast to other groups.

Associations between specific antibody responses and resistance to reinfection in a Senegalese population recently exposed to Schistosoma mansoni.

We examined associations between schistosome-specific antibody responses and reinfection in Senegalese individuals recently exposed to Schistosoma mansoni. The effects of treatment, age, intensity of infection and duration of exposure on schistosome-specific antibody responses were also investigated by comparing immune responses in individuals exposed for less than 3 years with responses in people exposed for more than 8 years. All individuals were bled before treatment as well as 6 and 12 weeks after. We used a statistical model that included interaction terms between time, age, infection intensity and duration of exposure. The overall patterns of most specific antibody responses by age were similar to those previously published for S. mansoni, Schistosoma japonicum and Schistosoma haematobium infections in different endemic areas. In general, a boost in specific antibody responses against adult worm antigen (SWA) was observed at 6 weeks after treatment whereas the majority of isotype responses against egg antigen (SEA) were not affected by treatment. Our analysis showed that the effect of treatment on schistosome-specific antibody responses is influenced by age, infection intensity and duration of exposure. We found no evidence that treatment matures the specific antibody response of children recently infected with S. mansoni. Our results indicate that the build-up of potentially protective immunoglobulin E (IgE) responses was associated with duration of exposure, or, in other words, experience of infection. Interestingly, in recently exposed individuals there was a significant association between IgA responses to SWA and resistance to reinfection. Resistance to reinfection and production of IgA-SWA was associated with adulthood independently of exposure patterns, suggesting that susceptibility to S. mansoni and the development of protective immune responses is age-dependent.

Specific antibody responses to three schistosome-related carbohydrate structures in recently exposed immigrants and established residents in an area of Schistosoma mansoni endemicity.

By the use of surface plasmon resonance spectroscopy, immunoglobulin G (IgG) subclass and IgM antibodies against three schistosome-derived carbohydrate structures, FLDN (Fucalpha1-3GalNAcbeta1-4GlcNAcbeta1-3Galalpha1), LDN-DF [GalNAcbeta1-4(Fucalpha1-2Fucalpha1-3)GlcNAcbeta1], and LDNF [GalNAcbeta1-4(Fucalpha1-3)GlcNAcbeta1-3Galalpha1], were measured in 184 previously unexposed Kenyan immigrants who moved into the Masongaleni area, where Schistosoma mansoni is endemic. They were sampled within their first year of exposure and again 2 years later. A cohort selected out of the original residents of the area, who had been exposed for many years, served as controls. Associations with responses to S. mansoni worm, egg (SEA), and cercarial (CERC) antigens were examined. In addition, we measured responses to keyhole limpet hemocyanin, a glycoprotein which carries glycan epitopes that are also expressed by schistosomes. Specific IgG1 responses were most pronounced against FLDN and LDN-DF and strongly associated with those previously measured to SEA and CERC. Similarly to previously published age profiles of IgG1 and IgG2 responses to SEA, levels of IgG1 against LDN-DF decreased with age. In contrast, specific IgM responses against the three schistosome-derived carbohydrate structures were most marked against LDNF. Our results indicate that, of the three glycan structures tested, the acute response against schistosome glycoconjugate antigens in young children is mainly directed against the LDN-DF epitope. The response to LDN-DF in older individuals and the responses to the two other epitopes were similar in the two cohorts, suggesting that these antigens are recognized in the early stages of infection and that the immune response persists. The biological significance of these observations needs further elucidation.

Serological responses among individuals in areas where both schistosomiasis and malaria are endemic: cross-reactivity between Schistosoma mansoni and Plasmodium falciparum.

We examined specific immunoglobulin G1 (IgG1) and IgG3 responses to Plasmodium falciparum schizont and Schistosoma mansoni egg and worm antigens in individuals from Kenya, Uganda, and the Sudan who had been exposed to malaria and schistosomiasis. A strong correlation between malaria- and schistosome-specific IgG3 responses was observed. This association appears to result from the presence of cross-reactive components of the 2 parasites that bind IgG3 antibodies, rather than to be mediated by immunological cross-regulation or specific regulatory mechanisms induced by either parasite. Cross-reactivity of IgG3 antibodies was confirmed in a Brazilian cohort of individuals living in an area where schistosomiasis is endemic but no malaria occurs and in a Pakistani cohort from an area where malaria is endemic but no schistosomiasis occurs. An IgG3 interaction with antigens from both parasites was observed in individuals from both cohorts, but not in uninfected European control subjects. The immunological and biological implications of this observation require further exploration.

Associations between anti-Schistosoma mansoni and anti-Plasmodium falciparum antibody responses and hepatosplenomegaly, in Kenyan schoolchildren.

Schoolchildren from 2 areas of Kenya, Kangundo and Kambu, have contrasting prevalences of hepatosplenomegaly, despite having similar prevalences and intensities of Schistosoma mansoni infection. However, in individual children, S. mansoni infection intensity is positively correlated with organomegaly. In a previous study, hepatosplenomegaly was associated with Th1-type anti-schistosome cytokine responses. Although the high-morbidity Kambu area had higher malaria transmission than did low-morbidity Kangundo, hepatosplenomegaly was not associated with clinical malaria or with patent malarial parasitemia. However, chronic exposure to malaria might be involved. Here, retrospectively, we assayed plasma from this original study, for anti-Plasmodium falciparum and anti-S. mansoni antibodies, to test whether greater exposure to Plasmodium was a cofactor for hepatosplenomegaly. We found that hepatosplenic children had significantly higher levels of anti-P. falciparum antibodies, compared with nonhepatosplenic children, a finding that strongly suggests that some experience of P. falciparum influenced the development of hepatosplenomegaly in these S. mansoni-infected children.

The relationship between age, sex, egg-count and specific antibody responses against Schistosoma mansoni antigens in a Ugandan fishing community.

In schistosomiasis endemic areas, antibody isotype responses against Schistosoma mansoni antigens vary with host age, sex and duration or intensity of infection, and are associated with susceptibility or resistance to infection. Identifying the quality and quantity of these responses is important to our understanding of the host-parasite relationship; however, the various host and parasite factors have a strong tendency to confound each other. We investigated the relationships and interactions between age, sex, faecal egg-counts and specific antibody isotype (IgA, IgG1, IgG2, IgG3, IgG4, IgE, IgM) responses to S. mansoni worm (SWA) and egg (SEA) antigens, amongst 380 individuals aged 5-59 from a fishing community from Uganda. This community was characterized by high levels of exposure, and high infection intensities, with higher infection intensities in males than in females. Multivariate anova was conducted with interaction terms between the three categorized explanatory variables. Most anti-SWA responses increased with age, whereas anti-SEA responses tended to decline with age, especially after puberty. IgG1-SWA, IgG4-SWA, IgG4-SEA, IgE-SWA responses increased with egg count, whereas IgG2-SEA decreased with egg count. IgG1-SWA, IgG4-SWA, IgE-SWA and IgG4-SEA responses were independently higher in males, whereas IgG2-SEA responses were independently higher in females. The significant effects of sex on isotype responses to adult worm antigens may be partly because of different levels of cumulative exposure. IgG4-SEA and IgG4-SWA were both strongly correlated with egg count. Patterns of IgE-SWA responses were qualitatively different to IgG4 responses, suggesting independent pathways of regulation.