53 results on '"Ssetaala, Ali"'
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52. An assessment of fishing communities around Lake Victoria, Uganda, as potential populations for future HIV vaccine efficacy studies: an observational cohort study.
- Author
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Kiwanuka, Noah, Mpendo, Juliet, Nalutaaya, Annet, Wambuzi, Matthias, Nanvubya, Annet, Kitandwe, Paul K, Muyanja, Enoch, Ssempiira, Julius, Balyegisawa, Apolo, Ssetaala, Ali, and UVRI-IAVI Research Team
- Abstract
Background: An effective HIV vaccine is still elusive. Of the 9 HIV preventive vaccine efficacy trials conducted to-date, only one reported positive results of modest efficacy. More efficacy trials need to be conducted before one or more vaccines are eventually licensed. We assessed the suitability of fishing communities in Uganda for future HIV vaccine efficacy trials.Methods: A community-based cohort study was conducted among a random sample of 2191 participants aged 18-49 years. Data were collected on socio-demographic characteristics, HIV risky behaviors, and willingness to participate in future HIV vaccine trials (WTP). Venous blood was collected for HIV serological testing. Retention/follow rates and HIV incidence rates per 100 person years at-risk (pyar) were estimated. Adjusted prevalence proportion ratios (PPRs) of retention and odds ratios (ORs) of lack of WTP were estimated using log-binomial and logistic regression models respectively.Results: Overall retention rate was 76.9% (1685/2191), highest (89%) among participants who had spent 5+ years in the community and lowest (54.1%) among those with <1 year stay. Significant predictors of retention included tribe/ethnicity, baseline HIV negative status, and longer than 1 year stay in the community. Overall WTP was 89.1% (1953/2191). Lack of WTP was significantly higher among women than men [adj.OR = 1.51 (95% CI, 1.14- 2.00)] and among participants who had stayed in fishing communities for 10 or more years relative to those with less than one year [adj.OR = 1.78 (95% CI, 1.11 - 2.88)]. Overall HIV incidence rate per 100 pyar was 3.39 (95% CI; 2.55 - 4.49). Participants aged 25-29 years had highest incidence rates (4.61 - 7.67/100 pyar) and high retention rates between 78.5 and 83.1%. In a combined analysis of retention and incidence rates participants aged 30+ years had retention rates ~80% but low incidence rates (2.45 - 3.57 per 100 pyar) while those aged 25-29 years had the highest incidence rates (4.61 - 7.67/100 pyar) and retention rates 78.5 - 83.1%.Conclusions: There is high HIV incidence, retention and WTP among fishing communities around L. Victoria, Uganda which make these communities appropriate for future HIV prevention efficacy studies including vaccine trials. [ABSTRACT FROM AUTHOR]- Published
- 2014
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53. Schistosoma mansoni infection alters the host pre-vaccination environment resulting in blunted Hepatitis B vaccination immune responses.
- Author
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Muir R, Metcalf T, Fourati S, Bartsch Y, Lugemwa JK, Canderan G, Alter G, Muyanja E, Okech B, Namatovu T, Namara I, Namuniina A, Ssetaala A, Mpendo J, Nanvubya A, Kitandwe PK, Bagaya BS, Kiwanuka N, Nassuna J, Biribawa VM, Elliott AM, de Dood CJ, Senyonga W, Balungi P, Kaleebu P, Mayanja Y, Odongo M, Fast P, Price MA, Corstjens PLAM, van Dam GJ, Kamali A, Sekaly RP, and Haddad EK
- Abstract
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.
- Published
- 2023
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