Functional genomics of pneumonia and pneumococcal disease
The syndrome of pneumonia is the most common infectious cause of death in children under five years of age across the globe. A large range of organisms can cause pneumonia, but the aetiology of each case of pneumonia is only rarely accurately diagnosed. Previous studies of the change in pneumonia following vaccination against Streptococcus pneumoniae (pneumococcus) suggest that approximately one third of severe pneumonia is caused by the pneumococcus. However, vaccination using pneumococcal conjugate vaccines (PCV, used in the UK since 2006) has only recently started to be introduced to low income settings with high pneumonia burdens, with the help of Gavi, the Vaccine Alliance.
As a paediatrician, I have spent the last 20 months working in Kathmandu, Nepal, developing new diagnostic methods for the pneumococcus in cases of severe pneumonia (Pneumonia Aetiology in Nepal: Diagnosis with Immunology and Transcriptomics – PANDIT). Nepal introduced PCV in August 2015. I am currently using RNA-sequencing methods to investigate whether differential regulation of genes (transcriptomics) can be used to develop a pathogen-specific signature for the pneumococcus in cases of pneumonia. Additionally, I am investigating the use of the immunological test, antibodies from lymphocyte supernatant, serotype-specific nasopharyngeal carriage of pneumococci, and more standard techniques (chest radiographs, inflammatory markers). We aim to use these data to create a model to accurately predict whether a child has pneumococcal pneumonia (or another aetiology of pneumonia) and thereby accurately assess the impact of PCV in Nepal. These data will be useful for health policy makers in Nepal and elsewhere in South Asia.
I am a paediatric trainee in the London School of Paediatrics, currently taking time out-of-programme. My work is supported by a Wellcome Trust Research Training Fellowship and the European Union Horizon 2020 programme. I am studying towards a DPhil in Paediatrics.
Keywords: pneumonia, pneumococcus, sepsis, Asia, transcriptomics, vaccines.