Drivers of Nasopharyngeal Pneumococcal Colonisation: Investigation Using an Experimental Human Challenge Model

Introduction Streptococcus pneumoniae (or pneumococcus) is a common commensal (coloniser) of the human upper respiratory tract. Colonisation is likely a prerequisite for respiratory tract infections and invasive pneumococcal disease. Colonisation also has a significant role in the horizontal spread of this pathogen within communities, but paradoxically could also lead to boosting of the host’s immune system. We use the unique experimental human pneumococcal challenge (EHPC) model to study pneumococcal transmission and colonisation in healthy adults. This novel study design allows us to investigate bacteriological and immune factors associated with colonisation and to examine the density and duration of colonisation episodes. Project Aims 1) Investigation of the transmission dynamics of Streptococcus pneumoniae. Can the hands can be a vector for transmission of S. pneumoniae into the nasopharynx, leading to colonisation? Does concurrent asymptomatic viral infection affect transmission? 2) Investigation of the propensity of two pneumococcal serotypes to cause experimental pneumococcal colonisation, to improve the generalisability of the model and to investigate if immunological responses to serotype 6B are similar to other serotypes. We also wanted to investigate if colonisation is an asymptomatic process in healthy adults? How do the host’s polysaccharide specific antibody responses affect colonisation? Main findings Using our unique controlled human pneumococcal challenge model, we have demonstrated the viability of transmission of pneumococcus from the hand into the nasopharynx, leading to colonisation. We were unable to investigate the relationship between colonisation acquisition and concurrent viral infection due to the absence of viral infection in our participants. The data presented in this thesis showed that the experimental human pneumococcal carriage model can successfully investigate transmission dynamics of pneumococcus. We also demonstrated the varying propensity of two pneumococcal serotypes, 23F and 15B to experimentally colonise the nasopharynx of healthy adults. Nasopharyngeal colonisation was shown not to cause nasal symptoms; however, the data suggested that colonisation may cause a cough in healthy adults. No relationship was found between the level of serum IgG to 15B capsular polysaccharide at screening and colonisation outcome after intranasal inoculation. Nasopharyngeal colonisation with 15B was however, found to boost polysaccharide specific immunity; colonisation positive participants had a significant increase in serum IgG levels to 15B capsular PS. Implications Data presented in this thesis suggest that good hand hygiene practices, already known to reduce enteric bacterial and viral disease, may also prevent the spread of pneumococcus which is thought to be spread primarily through aerosolisation. Results support epidemiological studies which have shown the varying propensity of different pneumococcal serotypes to cause colonisation. We can build upon this work by investigating serotypes in vitro and in vivo to understand bacterial factors that impact the pneumococcus’ ability to colonise the nasopharynx in humans. The EHPC model will be useful in further studies to better understand the dynamics and drivers of pneumococcal transmission, bacterial factors which support successful colonisation and host responses to pneumococcal exposure and colonisation