4 research outputs found

    Schistosome and malaria exposure and urban-rural differences in vaccine responses in Uganda: a causal mediation analysis using data from three linked randomised controlled trials.

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    BACKGROUND: Vaccine immunogenicity and effectiveness vary geographically. Chronic immunomodulating parasitic infections including schistosomes and malaria have been hypothesised to be mediators of geographical variations. METHODS: We compared vaccine-specific immune responses between three Ugandan settings (schistosome-endemic rural, malaria-endemic rural, and urban) and did causal mediation analysis to assess the role of Schistosoma mansoni and malaria exposure in observed differences. We used data from the control groups of three linked randomised trials investigating the effects of intensive parasite treatment among schoolchildren. All participants received the BCG vaccine (week 0); yellow fever (YF-17D), oral typhoid (Ty21a), human papillomavirus (HPV; week 4); and HPV booster and tetanus-diphtheria (week 28). Primary outcomes were vaccine responses at week 8 and, for tetanus-diphtheria, week 52. We estimated the total effect (TE) of setting on vaccine responses and natural indirect effect (NIE) mediated through current or previous infection with S mansoni or malaria, and baseline vaccine-specific responses. FINDINGS: We included 239 (43%) participants from the schistosomiasis-endemic setting, 171 (30%) from the malaria-endemic setting, and 151 (27%) from the urban setting. At week 8, vaccine responses were lower in rural settings: schistosomiasis-endemic versus urban settings (TE geometric mean ratio for YF-17D plaque reduction neutralisation at 50% (PRNT50) titres 0路58 [95% CI 0路37 to 0路91], for S Typhi O-lipopolysaccharide-specific IgG 0路61 [0路40 to 0路93], and for tetanus-specific IgG 0路33 [0路22 to 0路51]); malaria-endemic versus urban settings (YF-17D 0路70 [0路49 to 0路99], S Typhi O-lipopolysaccharide-specific IgG 0路29 [0路20 to 0路43], and tetanus-specific IgG 0路53 [-0路35 to 0路80]). However, we found higher BCG-specific IFN纬 responses in the malaria-endemic versus urban setting (1路54 [1路20 to 1路98]). The estimated NIEs of setting on vaccine responses mediated through previous and current S mansoni and malaria were not statistically significant. For malaria-endemic versus urban settings, baseline vaccine-specific responses contributed to some but not all differences: S Typhi O-lipopolysaccharide-specific IgG at week 8 (57.9% mediated [38路6 to 77路2]) and week 52 (70路0% mediated [49路4 to 90路6]) and BCG at week 52 (46.4% mediated [-4路8 to 97路7]). INTERPRETATION: We found significant variation in vaccine response between urban and rural settings but could not confirm a causal role for schistosome or malaria exposure. Other exposures require consideration. FUNDING: UK Medical Research Council

    Afri-Can Forum 2

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    Afri-Can Forum 2

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    CITATION: Mukudu, H., et al. 2016. Afri-Can Forum 2. BMC Infectious Diseases, 16:315, doi:10.1186/s12879-016-1466-6.The original publication is available at https://bmcinfectdis.biomedcentral.comENGLISH ABSTRACT: We are pleased to present peer reviewed forum proceedings of the 2nd synchronicity forum of GHRI/CHVIfunded Canadian and African HIV prevention and vaccine teams Forum objectives 鈭橤HRI-funded capacity building and HIV prevention research teams presented highlights of achievements 鈭橳eams discussed how to jointly build on achievements for sustainability 鈭橮rovided an opportunity for inter-team collaboration, synchronize best approach to capacity building, mentoring of new researchers and building leadership 鈭橮rovided opportunities for informal discussions and networking among the teams. 鈭橳eams learnt about recent advances in the area of African regulatory and ethics review process 鈭橳he forum proceedings was a special supplement in an openaccess journal was producedhttps://bmcinfectdis.biomedcentral.com/articles/supplements/volume-16-supplement-2Publisher's versio
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