Background: Salmonella bacteraemia is an important public health problem in children from sub Saharan Africa (SSA). Understanding what constitutes natural acquired immunity to Salmonella is crucial for the development of Salmonella vaccine. It was hypothesized that natural Salmonella exposure within the GIT and peripheral blood induces the generation of specific-antibodies and T cells and these might provide protection to subsequent Salmonella infection. Methods: Natural acquisition of antibody and T cell immunity to Salmonella was investigated in healthy and Salmonella infected Malawian children. Acquisition of typhoid vaccine induced T cell immunity in healthy adults from the United Kingdom (UK) was investigated to model natural immunizing events occurring within the gut associated lymphoid tissues (GALTs) following Salmonella infection. Acquisition of immunity was examined using immunological tools including the intra-cellular cytokine staining assay (ICS), serum bactericidal activity (SBA) assay, ELISA and ELISpot. Exposure to Salmonella was examined using microbiological tools including standard culture and real-time PCR. Principal findings: CD4+ T cells and IgG antibodies to Salmonella develops sequentially in under-five children. Acquisition of Salmonella-specific CD4+ T cells and antibodies coincides with the decline in S. Typhimurium bacteraemia cases in older children. As much as 47% of Malawian children (aged 6-18 months) are exposed to Salmonella at least once within the gastrointestinal tract (GIT). Natural Salmonella exposure within the GIT is associated with development of potentially protective SBA in children. Invasive Salmonella infection elicits an increase in generation of Salmonella-specific CD4+T cells, IgG and IgA antibody secreting cells (ASC). Oral Ty21a vaccination (model of natural Salmonella infection) did not elicit an increase in generation of both CD4+Cytokine+ and CD8+Cytokine+ T cells in the peripheral blood and gut mucosa compartments at day 11, and day 18 post vaccination. Conclusion: Young children (<2 years of age) are more vulnerable to invasive Salmonella infection. Salmonella exposure within the GIT and peripheral blood compartments tissues facilitates acquisition of robust immunity (mediated by antibodies and T cells) in children and these might provide protection to subsequent Salmonella infection. Public health interventions are urgently required in SSA including vaccination with cross-protective Salmonella vaccine, improvements in sanitation, access to clean and safe water and food hygiene.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:666734 |
| Date | January 2015 |
| Creators | Nyirenda, Tonney |
| Publisher | University of Liverpool |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://livrepository.liverpool.ac.uk/2010084/ |
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