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Title: Childhood pneumococcal pneumonia in Nepal
Author: Carter, Michael
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2017
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Pneumonia is the greatest cause of childhood mortality outside the neonatal period, yet the pathogen-specific aetiology of childhood pneumonia remains poorly defined. Vaccine probe studies estimate that approximately one third of children <5 years of age with radiographic endpoint consolidation have pneumococcal pneumonia in settings prior to the introduction of pneumococcal conjugate vaccination (PCV), such as much of South Asia. 10-valent PCV was introduced to the Nepali infant immunisation schedule in August 2015. I investigated childhood pneumococcal pneumonia in Nepal. I aimed to describe the prevalence of pneumococcal infection in children with suspected invasive bacterial disease admitted to Patan Hospital, Kathmandu, Nepal; to assess the impact of 10- valent PCV on pneumococcal pneumonia; and to assess two potential diagnostic tests for pneumococcal pneumonia based on the childhood response to pneumococci - assay of antibodies from lymphocyte supernatant (ALS) and analysis of differential gene expression (transcriptomics) - in children with pneumonia at Patan Hospital. Pneumococci were the second-most most prevalent pathogen isolated from the blood of children between 2005 and 2016. Interrupted time series analyses of data from children admitted with pneumonia from March 2014 - December 2016, showed a small increase (approximately 4%) in the odds of admission with pneumonia in comparison to non-pneumonia admis- sions temporally associated with 10-valent PCV introduction. However, it was not possible to adjust these time series analyses for extreme events including earthquakes (April 2015) and clean fuel shortages/increased air pollution (winter 2015/2016). In contrast, the indirect cohort method (a case-control approach in vaccinated vs unvaccinated children) showed vaccine effectiveness of 84% on the odds of nasopharyngeal carriage of vaccine-type pneumococci, but no effectiveness on pneumonia in these early data. Assay of IgG ALS pneumococcal capsular polysaccharides was complicated by what appear to be non-specific binding to capsular polysaccharides (of both S. pneumoniae, particularly serotype 3, and H. influenzae). Assay of IgG ALS to the best-performing of five pneumococcal proteins assessed had a sensitivity of 88% and specificity of 71% for the discrimination of pneumococcal pneumonia from other bacterial pneumonia. A transcriptomic signature discriminated between pneumococcal pneumonia and other bacterial pneumonia with a sensitivity of 91% and specificity of 100%. This thesis therefore contributes to knowledge of the clinical epidemiology of pneumococcal disease in South Asia. These data may also contribute to public health policy-making in the region. In addition, the development of two diagnostic tests for the aetiology of childhood pneumonia may be useful for future studies of childhood pneumonia aetiology.
Supervisor: Pollard, Andrew ; Kelly, Dominic ; Knight, Julian Sponsor: Wellcome Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Transcriptomics ; Immunology ; Vaccines ; Paediatrics ; Pneumonia ; Epidemiology ; Diagnostic tests