Prospective case-control study of systemic host molecular pathway responses in Gambian infants to pneumococcal pneumonia

We are looking for natural pathway signals in the body that respond to pneumonia infection. This will help provide more effective treatments.
At present pneumococcal pneumonia is one of the most prevalent bacterial pneumonia, killing up to one million children under five worldwide each year. More than 90% of pneumococcal pneumonia deaths in children occur in developing countries and there remains a critical need to improve child survival and stop the devastating impact of pneumonia.
Understanding the immune response to infection is vital for diagnostic treatment and improving vaccinations. In this application we investigate how and what immune reaction pathways take place in the blood of infants with severe pneumococcal pneumonia. To test this idea we plan to undertake a molecular study of gene activity using very small amounts of blood to identify and mathematically model specific immune response pathways to infection.
The study will explore a new approach using computational science for mapping and understanding the relationships of genes and proteins that can be used to build predictive models of response to an infection. These studies may lead to new insights toward the molecular basis of disease outcome and prediction of treatment response to infection.

Understanding the nature of early systemic host responses to pathogen infection is an urgent unmet clinical need that would help in designing better treatments and vaccination approaches for infection of infants. Streptococcus pneumoniae is the leading cause of bacterial pneumonia in children killing up to one million children under five worldwide each year. More than 90% of pneumococcal pneumonia deaths in children occur in developing countries. Here we propose to undertake a prospective case-control molecular profiling study in the Gambia to investigate specific systemic immune response pathways resulting from severe pneumococcal pneumonia in early infancy. This study will apply a computational pathway biology methodology for mapping and understanding the causal relationships in pathways of systemic response. Specifically, in this application we tackle the challenge of combining genome-wide gene expression profiling with bioinformatics with systems level analysis, providing an innovative approach for investigating systemic physiology, and which may lead to new insights toward the molecular basis of disease outcome and prediction of treatment response.