Paediatrics (RCH) - Theses
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ItemEpidemiology of pneumococcal carriage and transmission in Fiji, before and after the introduction of the ten valent pneumococcal conjugate vaccine( 2022)Streptococcus pneumoniae (the pneumococcus) is responsible for substantial global morbidity and mortality in children younger than five years. The burden of pneumococcal disease is highest in low and middle income countries. Nasopharyngeal carriage of pneumococci is common and primarily asymptomatic but is responsible for transmission and precedes pneumococcal disease. There are approximately 100 different pneumococcal serotypes distinguished by the presence and diversity of a polysaccharide capsule. Pneumococcal conjugate vaccines (PCV) protect against the transmission and carriage of common disease-causing serotypes. Differences in the pneumococcal carriage and disease burden by country, ethnicity, age, and social determinants of health have been reported. Little is known about transmission and whether risk factors vary by setting. Understanding the varied epidemiology of pneumococcal carriage risk factors and transmission routes is essential to developing, evaluating, and comparing public health intervention policies, including PCV. This thesis addresses some outstanding questions about pneumococcal carriage risk factors and transmission post-PCV introduction and is set in Fiji. The Fijian Government introduced the ten valent PCV (PCV10) into the Fijian infant immunisation program in October 2012. Before introducing PCV10, the odds of pneumococcal nasopharyngeal carriage were significantly greater among Indigenous (iTaukei) Fijian toddlers aged 3 – 13 months compared with their Fijian of Indian Descent counterparts. Similarly, the risk of developing invasive pneumococcal disease (IPD) was significantly greater among iTaukei than FID. My thesis consists of an Introduction (Chapter 1) and four studies: a systematic review of risk factors for pneumococcal carriage and a summary of pneumococcal carriage rates, stratified by country income classification; an analysis of factors associated with pneumococcal carriage and density in Fiji; an investigation of the social contact, ethnicity, and pneumococcal carriage and density in Fiji; and a comparison of pneumococcal carriage by infant mode of delivery among Fijian infants too young for PCV vaccination. The chapters of my thesis that focus on pneumococcal carriage epidemiology use data obtained from a PCV impact evaluation study. Chapter 2, a systematic review, found that although pneumococcal carriage rates were highest in low income classifications, risk factors for pneumococcal carriage were similar across income classifications. Most risk factors would not be modifiable directly. Rather, public health interventions aimed at mitigating the adverse impact of some social determinants of health would be of benefit. Chapter 2 contributes new information regarding pneumococcal carriage risk factors and proposes variables to consider for collection in future community pneumococcal carriage surveys. PCV reduces vaccine serotype carriage and disease. However, it is essential to contemplate interventions to reduce overall carriage, particularly in some low and middle income countries, where high vaccine type carriage rates may persist or where carriage of non-vaccine serotypes replaces that of vaccine serotypes following PCV introduction. Notably, there was an identified knowledge gap surrounding the impact of PCV on risk factors for pneumococcal carriage in low and middle income countries of the Asia-Pacific region. Chapter 3 describes the risk factors for pneumococcal carriage and density in Fiji, one year pre- and up to three years post-introduction of ten valent PCV (PCV10). This work showed that Indigenous iTaukei (iTaukei) ethnicity, compared with Fijian of Indian Descent (FID), was a key risk factor for pneumococcal carriage despite high PCV10 coverage rates across the groups. Higher median pneumococcal density was associated with upper respiratory tract infection symptoms and young age. The positive association between Indigenous Fijian ethnicity and pneumococcal carriage, coupled with anecdotal observations, led to the hypothesis that differences in pneumococcal carriage between the ethnic groups may be due to differences in social contact. Chapter 4 determined whether there were any differences in the frequency and intensity of social contact between the two main ethnic groups in Fiji; and if any differences in social contact were associated with differences in pneumococcal carriage. This analysis showed that iTaukei had a greater frequency and intensity of social contact than FID. Physical, not conversational, contact was associated with pneumococcal carriage. Ethnicity-based differences in social contact patterns did not explain differences in pneumococcal carriage rates by ethnicity observed in Chapter 3. While contact between and with young children is a risk factor for pneumococcal carriage via horizontal transmission, little is understood about transmission and early onset carriage and disease. Chapter 5 describes and compares pneumococcal carriage and density by infant mode of delivery in Fijian infants too young to be PCV10-vaccinated. Infants born by vaginal delivery had higher pneumococcal carriage prevalence, range of detected serotypes, and odds of pneumococcal carriage than those born by Caesarean section. These findings raise a vertical transmission hypothesis. This PhD fills several pneumococcal carriage knowledge gaps and has implications for future research. It has provided a global summary of hypothesis-generating studies that will be of value for future research into causal relationships between risk factors and carriage of pneumococci. Importantly, my PhD highlights that in addition to using PCVs to control pneumococcal disease, efforts to reduce and control respiratory virus transmission and address social determinants of health are essential. My PhD also shows that catch-up campaigns may be necessary to control vaccine serotypes in higher prevalence settings. In such settings, reducing vaccine serotype transmission may take a long time due to a relative shift in the higher carriage rate of vaccine serotypes to older age groups, resulting in ongoing circulation. The role of a catch-up campaign with PCV introduction needs to be determined, as vaccine serotype transmission may persist for some time with a birth cohort only roll out. Transmission of pneumococci is complex, and host factors also play a role. However, household size is a crucial consideration, as is ensuring infants too young to be vaccinated in low and middle income countries are protected by herd immunity or by an earlier first dose of PCV.