Background Schistosoma infection is associated with immune modulation that can influence responses to non-schistosome antigens. Vaccine responses may be impaired in S . mansoni -infected individuals. We investigated effects of S . mansoni infection on responses to childhood measles catch-up immunisation and of praziquantel treatment on this outcome in a randomised trial. Methodology The Immune Modulation and Childhood Immunisation (IMoChI) study was based in Entebbe, Uganda. Children aged 3–5 years (193 S . mansoni -infected and 61 uninfected) were enrolled. Infected children were randomised in a 1:1:1 ratio to receive praziquantel 2 weeks before, at time of, or 1 week after, measles catch-up immunisation. Plasma anti-measles IgG was measured at enrolment, 1 week and 24 weeks after measles immunisation. Primary outcomes were IgG levels and percentage of participants with levels considered protective against measles. Results Anti-measles IgG levels increased following immunisation, but at 1 week post-immunisation S . mansoni -infected, compared to uninfected, children had lower levels of anti-measles IgG (adjusted geometric mean ratio (aGMR) 0.4 [95% CI 0.2–0.7]) and the percentage with protective antibody levels was also lower (adjusted odds ratio 0.1 [0–0.9]). Among S . mansoni -infected children, anti-measles IgG one week post-immunisation was higher among those treated with praziquantel than among those who were not yet treated (treatment before immunisation, aGMR 2.3 [1.5–4.8]; treatment at immunisation aGMR 1.8 [1.1–3.5]). At 24 weeks post-immunisation, IgG levels did not differ between the trial groups, but tended to be lower among previously-infected children who were still S mansoni stool-positive than among those who became stool-negative. Conclusions and significance Our findings suggest that S . mansoni infection among pre-school children is associated with a reduced antibody response to catch-up measles immunisation, and that praziquantel treatment improves the response. S . mansoni infection may contribute to impaired vaccine responses in endemic populations; effective schistosomiasis control may be beneficial for vaccine efficacy. This should be further explored. Trial registration ISRCTN87107592 .

Zidovudine/lamivudine/tenofovir has good virological efficacy in advanced HIV disease. In this population, who were infected with HIV-1 subtypes A, C or D, M184V with or without NAMs was the most common route to resistance, whereas K65R was identified less often.

BackgroundHuman noroviruses (HuNoVs) are a prominent cause of gastroenteritis, yet fundamental questions remain regarding epidemiology, diversity, and immunity in sub-Saharan African children. We investigated HuNoV seroprevalence and genetic and sociodemographic risk factors in Ugandan children.MethodsWe randomly screened 797 participants of a longitudinal birth cohort (Entebbe, EMaBS) and 378 from a cross-sectional survey (rural Lake Victoria, LaVIISWA), for antibodies against HuNoV genotypes by ELISA. We used linear regression modeling to test for associations between HuNoV antibody levels and sociodemographic factors, and with the human susceptibility rs601338 FUT2 secretor SNP and histo-blood group antigens (A/B/O).ResultsOf EMaBS participants, 76.6% were seropositive by age 1, rising to 94.5% by age 2 years. Seroprevalence in 1 year olds of the rural LaVIISWA survey was even higher (95%). In the birth cohort, 99% of seropositive 2 year olds had responses to multiple HuNoV genotypes. We identified associations between secretor status and genogroup GII antibody levels (GII.4 P = 3.1 × 10−52), as well as ABO and GI (GI.2 P = 2.1 × 10−12).ConclusionsHuNoVs are highly prevalent in Ugandan children, indicating a substantial burden of diarrhea-associated morbidity with recurrent infections. Public health interventions, including vaccination, and increased surveillance are urgently needed.

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How human genetic variation contributes to vaccine immunogenicity and effectiveness is unclear, particularly in infants from Africa. We undertook genome-wide association analyses of eight vaccine antibody responses in 2,499 infants from three African countries and identified significant associations across the human leukocyte antigen (HLA) locus for five antigens spanning pertussis, diphtheria and hepatitis B vaccines. Using high-resolution HLA typing in 1,706 individuals from 11 African populations we constructed a continental imputation resource to fine-map signals of association across the class II HLA observing genetic variation explaining up to 10% of the observed variance in antibody responses. Using follicular helper T-cell assays, in silico binding, and immune cell eQTL datasets we find evidence of HLA-DRB1 expression correlating with serological response and inferred protection from pertussis following vaccination. This work improves our understanding of molecular mechanisms underlying HLA associations that should support vaccine design and development across Africa with wider global relevance.