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Introduction: Offspring of Schistosoma mansoni-infected women in schistosomiasis-endemic areas may be sensitised in-utero. This may influence their immune responsiveness to schistosome infection and schistosomiasis-associated morbidity. Effects of praziquantel treatment of S. mansoni during pregnancy on risk of S. mansoni infection among offspring, and on their immune responsiveness when they become exposed to S. mansoni, are unknown. Here we examined effects of praziquantel treatment of S. mansoni during pregnancy on prevalence of S. mansoni and immune responsiveness among offspring at age five years., Methods: In a trial in Uganda (ISRCTN32849447, http://www.controlled-trials.com/ISRCTN32849447/elliott), offspring of women treated with praziquantel or placebo during pregnancy were examined for S. mansoni infection and for cytokine and antibody responses to SWA and SEA, as well as for T cell expression of FoxP3, at age five years., Results: Of the 1343 children examined, 32 (2.4%) had S. mansoni infection at age five years based on a single stool sample. Infection prevalence did not differ between children of treated or untreated mothers. Cytokine (IFNγ, IL-5, IL-10 and IL-13) and antibody (IgG1, Ig4 and IgE) responses to SWA and SEA, and FoxP3 expression, were higher among infected than uninfected children. Praziquantel treatment of S. mansoni during pregnancy had no effect on immune responses, with the exception of IL-10 responses to SWA, which was higher in offspring of women that received praziquantel during pregnancy than those who did not., Conclusion: We found no evidence that maternal S. mansoni infection and its treatment during pregnancy influence prevalence and intensity of S. mansoni infection or effector immune response to S. mansoni infection among offspring at age five years, but the observed effects on IL-10 responses to SWA suggest that maternal S. mansoni and its treatment during pregnancy may affect immunoregulatory responsiveness in childhood schistosomiasis. This might have implications for pathogenesis of the disease.

Background: Offspring of women with schistosomiasis may exhibit immune responsiveness to schistosomes due to in utero sensitisation or trans-placental transfer of antibodies. Praziquantel treatment during pregnancy boosts maternal immune responses to schistosome antigens and reduces worm burden. Effects of praziquantel treatment during pregnancy on responses among offspring are unknown., Methods: In a trial of anthelminthic treatment during pregnancy in Uganda (ISRCTN32849447; http://www.controlled-trials.com/ISRCTN32849447/elliott), offspring of women with Schistosoma mansoni were examined for cytokine and antibody responses to schistosome worm (SWA) and egg (SEA) antigen, in cord blood and at age one year. Relationships to maternal responses and pre-treatment infection intensities were examined, and responses were compared between the offspring of women who did, or did not receive praziquantel treatment during pregnancy., Results: Of 388 S. mansoni-infected women studied, samples were obtained at age one year from 215 of their infants. Stool examination for S. mansoni eggs was negative for all infants. Cord and infant samples were characterised by very low cytokine production in response to schistosome antigens with the exception of cord IL-10 responses, which were substantial. Cord and infant cytokine responses showed no association with maternal responses. As expected, cord blood levels of immunoglobulin (Ig) G to SWA and SEA were high and correlated with maternal antibodies. However, by age one year IgG levels had waned and were hardly detectable. Praziquantel treatment during pregnancy showed no effect on cytokine responses or antibodies levels to SWA or SEA either in cord blood or at age one year, except for IgG1 to SWA, which was elevated in infants of treated mothers, reflecting maternal levels. There was some evidence that maternal infection intensity was positively associated with cord blood IL-5 and IL-13 responses to SWA, and IL-5 responses to SEA, and that this association was modified by treatment with praziquantel., Conclusions: Despite strong effects on maternal infection intensity and maternal immune responses, praziquantel treatment of infected women during pregnancy had no effect on anti-schistosome immune responses among offspring by age one year. Whether the treatment will impact upon the offspring's responses on exposure to primary schistosome infection remains to be elucidated., Trial Registration: ISRCTN: ISRCTN32849447.

Background: Praziquantel treatment of schistosomiasis during pregnancy was only recommended in 2002; hence the effects of treatment during pregnancy are not fully known. We have therefore evaluated the effects on infection intensity and the immunological effects of praziquantel treatment against Schistosoma mansoni during pregnancy, compared with treatment after delivery., Methods: A nested cohort of 387 Schistosoma mansoni infected women was recruited within a larger trial of de-worming during pregnancy. Women were randomised to receive praziquantel or placebo during pregnancy. All women were treated after delivery. Infection intensity after treatment was assessed by a single Kato-Katz examination of stool samples with duplicate slides and categorised as undetected, light (1-99 eggs per gram (epg)), moderate (100-399 epg) or heavy (>or=400 epg). Antibodies against S. mansoni worm and egg antigens were measured by ELISA. Results were compared between women first treated during pregnancy and women first treated after delivery., Results: At enrollment, 252 (65.1%) of the women had light infection (median (IQR) epg: 35 (11, 59)), 75 (19.3%) moderate (median (IQR) epg: 179(131, 227)) and 60 (15.5%) had heavy infection (median (IQR) epg: 749 (521, 1169)) with S. mansoni. At six weeks after praziquantel treatment during pregnancy S. mansoni infection was not detectable in 81.9% of the women and prevalence and intensity had decreased to 11.8% light, 4.7% moderate and 1.6% heavy a similar reduction when compared with those first treated after delivery (undetected (88.5%), light (10.6%), moderate (0.9%) and heavy (0%), p = 0.16). Parasite specific antibody levels were lower during pregnancy than after delivery. Praziquantel treatment during pregnancy boosted anti-worm IgG isotypes and to a lesser extent IgE, but these boosts were less pronounced than in women whose treatment was delayed until after delivery. Praziquantel had limited effects on antibodies against egg antigens., Conclusion: S mansoni antigen-specific antibody levels and praziquantel-induced boosts in antibody levels were broadly suppressed during pregnancy, but this was not associated with major reduction in the efficacy of praziquantel. Long-term implications of these findings in relation to resistance to re-infection remain to be explored.

Background: Praziquantel treatment of schistosomiasis boosts antischistosome responses, with type 2 helper T cell bias that may contribute to immunologically mediated killing and to protection against reinfection. Praziquantel treatment during pregnancy was recommended in 2002, but the immunological effects of the treatment had not been investigated., Methods: A cohort of 387 Schistosoma mansoni-infected women were recruited from a larger trial of deworming during pregnancy. Women were randomized to receive either praziquantel or placebo during pregnancy. Six weeks after delivery, all women received praziquantel. Cytokine responses to S. mansoni worm and egg antigens were measured in whole blood culture before and 6 weeks after each treatment., Results: Schistosome-specific cytokine responses were suppressed during pregnancy. Praziquantel treatment during pregnancy caused significant boosts in interferon-gamma (IFN-gamma), interleukin (IL)-2, IL-4, IL-5, IL-13, and IL-10 responses to schistosome worm antigen and in IFN-gamma, IL-5, and IL-13 responses to schistosome egg antigen, but these boosts were not as substantial as those seen for women treated after delivery., Conclusion: Pregnancy suppresses a potentially beneficial boost in cytokine responses associated with praziquantel treatment. Further studies are needed on the long-term effects that treatment of schistosomiasis during pregnancy have on morbidity and resistance to reinfection among treated women and their offspring.

Background: Studies showing that helminths stimulate type 2 cytokine responses and influence responses to unrelated antigens suggest that helminths may accelerate human immunodeficiency virus type 1 (HIV-1) disease progression in coinfected individuals and that antihelminthic therapy may be beneficial. By the same logic, however, the increase in type 2 cytokines occurring immediately after antischistosomal treatment might increase viral replication and be detrimental., Methods: To assess the effect of antischistosomal therapy on immune responses and HIV-1 replication, a cohort of 163 Ugandans coinfected with Schistosoma mansoni and HIV-1 was treated with praziquantel. CD4(+) T lymphocyte counts, eosinophil counts, and plasma HIV-1 RNA concentrations were measured before treatment and 1 month and 5 months after treatment. Schistosoma mansoni- and Mycobacterium tuberculosis-specific cytokine responses and serum interleukin (IL)-10 concentrations were analyzed., Results: Transient increases in viral load and sustained decreases in CD4(+) T lymphocyte count were observed, especially in subjects with higher-intensity infections. Despite enhanced posttreatment S. mansoni-specific type 2 responses, no increase in eosinophils or in M. tuberculosis-specific type 2 responses nor any decline in M. tuberculosis-specific interferon (IFN)-gamma responses were seen. A significant decline in circulating IL-10 concentrations was observed., Conclusion: Although the mechanisms underlying the increase in viral load after treatment with praziquantel are unclear, these results do not support the hypothesis that treating schistosomiasis is beneficial in the management of HIV-1 disease in Africa.

We show that Ugandan adults coinfected with Schistosoma mansoni and human immunodeficiency virus type 1 (HIV-1) are able to mount S. mansoni-specific immune responses but that few such responses increase after treatment with praziquantel (PZQ). Levels of soluble worm antigen (SWA)-specific immunoglobulin (Ig) G1, IgG2, IgG3, IgG4, interleukin (IL)-4, and IL-5 increased significantly in HIV-negative participants after treatment with PZQ, whereas most soluble egg antigen-specific antibody responses and levels of interferon- gamma were unaltered. Only levels of SWA-specific IL-5 increased in HIV-1-coinfected participants after treatment. These deficiencies in immune responses may account for the previously reported increased susceptibility to infection and reinfection with S. mansoni in individuals coinfected with HIV-1.

Introduction: Offspring of Schistosoma mansoni-infected women in schistosomiasis-endemic areas may be sensitised in-utero. This may influence their immune responsiveness to schistosome infection and schistosomiasis-associated morbidity. Effects of praziquantel treatment of S. mansoni during pregnancy on risk of S. mansoni infection among offspring, and on their immune responsiveness when they become exposed to S. mansoni, are unknown. Here we examined effects of praziquantel treatment of S. mansoni during pregnancy on prevalence of S. mansoni and immune responsiveness among offspring at age five years. Methods: In a trial in Uganda (ISRCTN32849447, http://www.controlled-trials.com/ISRCTN32849447/elliott), offspring of women treated with praziquantel or placebo during pregnancy were examined for S. mansoni infection and for cytokine and antibody responses to SWA and SEA, as well as for T cell expression of FoxP3, at age five years. Results: Of the 1343 children examined, 32 (2.4%) had S. mansoni infection at age five years based on a single stool sample. Infection prevalence did not differ between children of treated or untreated mothers. Cytokine (IFNγ, IL-5, IL-10 and IL-13) and antibody (IgG1, Ig4 and IgE) responses to SWA and SEA, and FoxP3 expression, were higher among infected than uninfected children. Praziquantel treatment of S. mansoni during pregnancy had no effect on immune responses, with the exception of IL-10 responses to SWA, which was higher in offspring of women that received praziquantel during pregnancy than those who did not. Conclusion: We found no evidence that maternal S. mansoni infection and its treatment during pregnancy influence prevalence and intensity of S. mansoni infection or effector immune response to S. mansoni infection among offspring at age five years, but the observed effects on IL-10 responses to SWA suggest that maternal S. mansoni and its treatment during pregnancy may affect immunoregulatory responsiveness in childhood schistosomiasis. This might have implications for pathogenesis of the disease. [ABSTRACT FROM AUTHOR]

In 1994 and 2002, respectively, the World Health Organisation proposed that treatment for hookworm and schistosomiasis could be provided during pregnancy. It was hoped that this might have benefits for maternal anaemia, fetal growth and perinatal mortality; a beneficial effect on the infant response to immunisation was also hypothesised. Three trials have now been conducted. Two have examined the effects of benzimidazoles; one (the Entebbe Mother and Baby Study) the effects of albendazole and praziquantel. All three were conducted in settings of high prevalence but low intensity helminth infection. Results suggest that, in such settings and given adequate provision of haematinics, the benefit of routine anthelminthics during pregnancy for maternal anaemia may be small; none of the other expected benefits has yet been demonstrated. The Entebbe Mother and Baby Study found a significant adverse effect of albendazole on the incidence of infantile eczema in the whole study population, and of praziquantel on the incidence of eczema among infants of mothers with Schistosoma mansoni. Further studies are required in settings that differ in helminth species and infection intensities. Further research is required to determine whether increased rates of infantile eczema translate to long-term susceptibility to allergy, and to explore the underlying mechanisms of these effects. The risks and benefits of routine anthelminthic treatment in antenatal clinics may need to be reconsidered. [ABSTRACT FROM PUBLISHER]