Uptake of Human Papilloma Virus vaccine among young women living in fishing communities in Wakiso and Mukono districts, Uganda.

Human Papilloma Virus (HPV) is a preventable cause of cervical cancer, the commonest cancer among women in Uganda. The Uganda Ministry of Health included the HPV vaccine in the free routine immunization schedule since 2015. Five years after this policy, we assessed the uptake of the HPV vaccine and associated socio-demographic factors among young women living in fishing communities in Central Uganda in 2020. We analyzed secondary data from 94 young women aged 9-25 years who were recruited from the two fishing communities (Kasenyi landing site and Koome Island) in a primary study that aimed to promote awareness of maternal and childhood vaccines. We assessed uptake of the HPV vaccine as the proportion of participants who self-reported to have ever received at least one dose of the HPV vaccine. We assessed the socio-demographic factors associated with HPV vaccine uptake using a modified Poisson regression model adjusted for clustering by study site in STATA version 17. The mean (standard deviation) age of study participants was 21.1 (3.1) years and most (81.9%) of them were from Kasenyi landing site. The uptake of the HPV vaccine was 10.6% [95% Confidence Interval (CI) 5.6, 18.9]. After adjusting for covariates, being 13-19 years old (adjusted prevalence ratio [aPR] 5.52, 95%CI 1.69, 18.00) and of Catholic religion (aPR 5.55, 95%CI 1.53, 20.16) were significantly associated with HPV vaccine uptake. The HPV vaccine uptake was very low, despite the reported 99% national coverage of HPV vaccination program for the first dose at the end of 2019. Age and religion showed to be important determinants of the HPV vaccine uptake. Reasons for such very low uptake of HPV vaccinations need to be carefully assessed to find effective strategies to improve it.

HIV specific Th1 responses are altered in Ugandans with HIV and Schistosoma mansoni coinfection.

BACKGROUND: Fishing communities surrounding Lake Victoria in Uganda have HIV prevalence of 28% and incidence rates of 5 per 100 person years. More than 50% of the local fishermen are infected with Schistosoma mansoni (S. mansoni). We investigated the role of S. mansoni coinfection as a possible modifier of immune responses against HIV. Using polychromatic flow cytometry and Gran-ToxiLux assays, HIV specific responses, T cell phenotypes, antibody-dependent cell-mediated cytotoxic (ADCC) potency and titres were compared between participants with HIV-S. mansoni coinfection and participants with HIV infection alone. RESULTS: S. mansoni coinfection was associated with a modified pattern of anti-HIV responses, including lower frequency of bifunctional (IFNγ + IL-2 - TNF-α+) CD4 T cells, higher overall CD4 T cell activation and lower HIV ADCC antibody titres, compared to participants with HIV alone. CONCLUSIONS: These results support the hypothesis that S. mansoni infection affects T cell and antibody responses to HIV in coinfected individuals.

Schistosoma mansoni infection alters the host pre-vaccination environment resulting in blunted Hepatitis B vaccination immune responses.

The impact of endemic infections on protective immunity is critical to inform vaccination strategies. In this study, we assessed the influence of Schistosoma mansoni infection on host responses in a Ugandan fishing cohort given a Hepatitis B (HepB) vaccine. Concentrations of schistosome-specific circulating anodic antigen (CAA) pre-vaccination showed a significant bimodal distribution associated with HepB titers, which were lower in individuals with high CAA. We established that participants with high CAA had significantly lower frequencies of circulating T follicular helper (cTfh) subpopulations pre- and post-vaccination and higher regulatory T cells (Tregs) post-vaccination. Polarization towards higher frequencies of Tregs: cTfh cells can be mediated by changes in the cytokine environment favoring Treg differentiation. In fact, we observed higher levels of CCL17 and soluble IL-2R pre-vaccination (important for Treg recruitment and development), in individuals with high CAA that negatively associated with HepB titers. Additionally, alterations in pre-vaccination monocyte function correlated with HepB titers, and changes in innate-related cytokines/chemokine production were associated with increasing CAA concentration. We report, that by influencing the immune landscape, schistosomiasis has the potential to modulate immune responses to HepB vaccination. These findings highlight multiple Schistosoma -related immune associations that could explain abrogated vaccine responses in communities with endemic infections. Author Summary: Schistosomiasis drives host immune responses for optimal pathogen survival, potentially altering host responses to vaccine-related antigen. Chronic schistosomiasis and co-infection with hepatotropic viruses are common in countries where schistosomiasis is endemic. We explored the impact of Schistosoma mansoni ( S. mansoni ) infection on Hepatitis B (HepB) vaccination of individuals from a fishing community in Uganda. We demonstrate that high schistosome-specific antigen (circulating anodic antigen, CAA) concentration pre-vaccination, is associated with lower HepB antibody titers post-vaccination. We show higher pre-vaccination levels of cellular and soluble factors in instances of high CAA that are negatively associated with HepB antibody titers post-vaccination, which coincided with lower frequencies of circulating T follicular helper cell populations (cTfh), proliferating antibody secreting cells (ASCs), and higher frequencies of regulatory T cells (Tregs). We also show that monocyte function is important in HepB vaccine responses, and that high CAA is associated with alterations in the early innate cytokine/chemokine microenvironment. Our findings suggest that in individuals with high CAA and likely high worm burden, schistosomiasis creates and sustains an environment that is polarized against optimal host immune responses to the vaccine, which puts many endemic communities at risk for infection against HepB and other diseases that are preventable by vaccines.