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Abstract 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: Identifying determinants of morbidity and mortality may help target future interventions for human immunodeficiency virus (HIV)-infected children., Methods: CD4(+) T-cell count, HIV viral load, and levels of biomarkers (C-reactive protein, tumor necrosis factor α [TNF-α], interleukin 6 [IL-6], and soluble CD14) and interleukin 7 were measured at antiretroviral therapy (ART) initiation in the ARROW trial (case-cohort design). Cases were individuals who died, had new or recurrent World Health Organization clinical stage 4 events, or had poor immunological response to ART., Results: There were 115 cases (54 died, 45 had World Health Organization clinical stage 4 events, and 49 had poor immunological response) and 485 controls. Before ART initiation, the median ages of cases and controls were 8.2 years (interquartile range [IQR], 4.4-11.4 years) and 5.8 years (IQR, 2.3-9.3 years), respectively, and the median percentages of lymphocytes expressing CD4 were 4% (IQR, 1%-9%) and 13% (IQR, 8%-18%), respectively. In multivariable logistic regression, cases had lower age-associated CD4(+) T-cell count ratio (calculated as the ratio of the subject's CD4(+) T-cell count to the count expected in healthy individuals of the same age; P < .0001) and higher IL-6 level (P = .002) than controls. Clustering biomarkers and age-associated CD4(+) and CD8(+) T-cell count ratios identified 4 groups of children. Group 1 had the highest frequency of cases (41% cases; 16% died) and profound immunosuppression; group 2 had similar mortality (23% cases; 15% died), but children were younger, with less profound immunosuppression and high levels of inflammatory biomarkers and malnutrition; group 3 comprised young children with moderate immunosuppression, high TNF-α levels, and high age-associated CD8(+) T-cell count ratios but lower frequencies of events (12% cases; 7% died); and group 4 comprised older children with low inflammatory biomarker levels, lower HIV viral loads, and good clinical outcomes (11% cases; 5% died)., Conclusions: While immunosuppression is the major determinant of poor outcomes during ART, baseline inflammation is an additional important factor, identifying a subgroup of young children with similar mortality. Antiinflammatory interventions may help improve outcomes., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.)