Understanding the Dynamics and Spread of Pneumococcal Infection From Healthy Carriage to Pneumonia and Invasive Disease, in Kilifi, Kenya

Morpeth, Susan Claire (2015). Understanding the Dynamics and Spread of Pneumococcal Infection From Healthy Carriage to Pneumonia and Invasive Disease, in Kilifi, Kenya. PhD thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.0000efe8

Abstract

Streptococcus pneumoniae, the pneumococcus, is an important pathogen globally, especially among children <5 years old. Pneumococcus colonises the human nasopharynx, and carriage is a prerequisite to disease. Understanding the concentration of pneumococcal colonisation may help us to better understand the pathogenesis of pneumococcal disease.

We hypothesized that If increased nasopharyngeal pneumococcal concentration is important in the pathogenesis of pneumonia then the concentration would be lowest among well children, intermediate among children with symptomatic upper respiratory tract infection (URTI) and highest among children admitted to hospital with WHO-defined pneumonia. We found that in fact, the nasopharyngeal pneumococcal concentration was of similar distribution among all three groups of children, and was highest among the group with URTI.

We studied the nasopharyngeal concentration of pneumococcus among children <5 years old before, during and after episodes of symptomatic URTI with respiratory syncytial virus (RSV) or rhinovirus. Nasopharyngeal pneumococcal concentration increased 4-fold with onset of the viral infection, which may contribute to risk.

We examined the response of nasopharyngeal pneumococcal concentration to vaccination with the 10-valent pneumococcal conjugate vaccine (PCV-10) among children aged 12-23 months. Vaccine-type (VT) carriage concentration did not change, while nonvaccine-type (NVT) concentration increased over six months post vaccination, which may have been a vaccine effect on VT relative to NVT concentration. There were large differences in serotype-specific pneumococcal concentration within and between individuals.

We investigated the performance of quantitative lytA PCR (qPCR) on blood samples in the diagnosis of invasive pneumococcal disease (IPD) among children <13 years old at Kilifi County Hospital, and among children 1-59 months old in a seven-country case-control study of pneumonia aetiology. lytA qPCR was not specific for the diagnosis of IPD, being positive among 5% of control participants. Pneumococcal DNA is more commonly found in the bloodstream of children in low and lower-middle income countries than has been appreciated.

Studying nasopharyngeal concentration of pneumococcus demonstrated why it is difficult to diagnose pneumococcal disease among young children in high-burden countries. Total nasopharyngeal concentration of pneumococcus is similar in well children as in disease. Serotype-specific concentration varies widely within and between children. Pneumocodcal bloodstream invasion appears to be a frequent occurrence, without always leading to IPD.