Paediatrics (RCH) - Theses
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ItemImpact of pneumococcal vaccination on carriage in a Fijian population( 2018)Streptococcus pneumoniae (the pneumococcus) causes a range of diseases including otitis media, pneumonia and meningitis, and is a major cause of morbidity and mortality in children under five years of age worldwide. Colonisation of the nasopharynx by S. pneumoniae (carriage) is generally asymptomatic and is considered a precursor for pneumococcal disease. S. pneumoniae has several important virulence factors which contribute to colonisation and disease. The most significant of these is the polysaccharide capsule which forms the outer protective layer of the bacterium, with over 90 known capsule types or serotypes. Current pneumococcal conjugate vaccine formulations target 10-13 of the most common serotypes. Pneumococcal vaccines have been effective at reducing pneumococcal disease both directly, by protecting vaccinated individuals, and indirectly through reducing carriage, which lowers transmission of S. pneumoniae to unvaccinated individuals. However, pneumococcal vaccine introduction has also led to serotype replacement whereby serotypes not included in pneumococcal vaccines have become more prominent in carriage and disease. There is some evidence to suggest that species replacement (whereby vaccine introduction leads to increases in other bacterial species sharing the same ecological niche) can also occur. In Fiji, pneumonia and meningitis are a significant burden and S. pneumoniae is a major cause of both diseases. There are two main ethnic groups in Fiji, indigenous Fijians (iTaukei) and Fijians of Indian descent (Indo-Fijian). Significant differences in the burden of disease between ethnic groups have been observed for a number of diseases including invasive pneumococcal disease, which is higher in iTaukei compared with Indo-Fijians. An earlier vaccine trial in Fiji (FiPP) examined reduced-dose schedules and the use of the polysaccharide vaccine (23vPPV) to reduce cost and provide greater serotype coverage. However, the use of 23vPPV in children at 12 months of age was associated with poorer immune responses when challenged at 17 months of age. In this thesis we examined whether 23vPPV use had any long-term effects on nasopharyngeal carriage in the same children now aged 5-7 years. We found no overall effect of 23vPPV on pneumococcal carriage or on carriage of respiratory pathogens (H. influenzae, S. aureus and M. catarrhalis). We found that the carriage rates of all four bacterial species were significantly different between the two ethnic groups. When data were stratified by ethnicity, we found that 23vPPV use in iTaukei children was associated with higher carriage of S. aureus but had no effect on S. pneumoniae carriage. In contrast, 23vPPV use in Indo-Fijian children was associated with lower carriage of S. pneumoniae and had no effect on S. aureus carriage. Given the previous immune hyporesponsiveness observed with the use of 23vPPV and these findings, we conclude that the current WHO recommendations against the use of 23vPPV in children less than 2 years of age are appropriate. Next, we examined whether the 7-valent pneumococcal vaccine (PCV7) had an effect on the microbiome of children of iTaukei and Indo-Fijian descent. No overall effect of PCV7 on the microbiome at 12 months of age was observed, however there were significant differences between iTaukei and Indo-Fijian children in the composition of bacteria within the nasopharynx. After stratifying by ethnicity, PCV7 was associated with lower relative abundance of Streptococcus in iTaukei children and higher relative abundance of Dolosigranulum in Indo-Fijian children. Given Dolosigranulum has been associated with a healthy microbiome, pneumococcal vaccination elicited generally positive effects in both ethnic groups. With the introduction of PCV10 into the infant immunisation program in Fiji, we next examined whether PCV10 had an indirect effect on carriage in adult caregivers. Firstly, we examined whether there was added benefit to sampling the oropharynx in addition to the nasopharynx when using molecular methods for identification and serotyping. Oropharyngeal (OP) samples were more complex than nasopharyngeal (NP) samples, and contained commensal streptococci which caused spurious identification and serotyping results. We found that the inclusion of OP samples did not significantly improve detection of pneumococci compared with NP sampling alone. We next examined the indirect effect of PCV10 introduction in adults using NP samples, finding evidence to suggest that PCV10 reduced vaccine-type carriage three years post-vaccine introduction, particularly in iTaukei adults. Fewer adults had low-density carriage of pneumococci following vaccine introduction, which underpinned an observed increase in pneumococcal density in adults over this time. We found that Indo-Fijian adults had lower carriage of pneumococci than iTaukei adults and carried very little vaccine-type pneumococci. Indirect effects of PCV10 introduction may not have been apparent 3 year after PCV10 introduction and an additional year or years of data would strengthen the evidence for an indirect effect of PCV10 in adults. Taken together, the studies included in this thesis examine direct and indirect effects of several pneumococcal vaccines on carriage in a middle-income setting.