Last Updated: 02/10/2025
Intestinal Inflammation in Malaria and Malaria-Schistosomiasis Co-Infection
Objectives
Overall, this project seeks to understand the mechanistic basis of the gastrointestinal immunopathology of malaria and malaria-schistosomiasis coinfection which could lead to the development of new therapeutic strategies to restore intestinal health promoting childhood well-being.
Diarrhoea is a less-recognised feature of malaria, yet the underlying mechanism remains unknown. To investigate this, the cellular and immunological pathology of intestinal inflammation in malaria will be characterised using two murine models: P.chabaudi AS (‘uncomplicated’) and P.chabaudi CB (‘severe’). Changes in cellular populations and gene expression in the small intestine will be determined by flow cytometry and single-cell genomics. As co-infection with malaria and Schistosomiasis mansoni is found in >90% of Ugandan children, the impact of co-infection will be explored in a novel P.chabaudi/S.mansoni murine co-infection model. Serum cytokines and faecal biomarkers of inflammation will be assessed using Olink cytokine multiplexing, traditional ELISA and flow cytometry. While animal work is ongoing, a cross- sectional field study of Ugandan schoolchildren will be undertaken from an area with endemic malaria and schistosomiasis. For the first time, faecal biomarkers of inflammation will be assessed in acutely infected children to determine the clinical features associated with human malaria-induced diarrhoea and its impact on S.mansoni co-infection.
Oct 2024 — Sep 2027
