Despite indirect protection against vaccine serotype (VT) pneumococcal disease from widespread use of infant pneumococcal conjugate vaccines (PCV) in low/middle-income settings, a substantial disease burden remains among vulnerable adults, those living with human immunodeficiency virus (HIV+) or aged ≥55 years-old (y), composed of serotypes not targeted by childhood PCV and substantial residual VT circulation. In this thesis, I aimed to address this gap by reviewing the burden and risk factors for pneumococcal carriage and transmission, and assessing vaccination strategies against pneumococcal disease in vulnerable adults in the mature infant PCV era. I first assessed the contribution of HIV+ adults to household carriage transmission by developing a hidden Markov model fitted to intensively sampled longitudinal carriage study with 115,595 samples. I estimated that HIV+ adults transmit pneumococci similarly to healthy adults implying no greater herd immunity if directly vaccinated, in addition to their direct protection from pneumococcal disease. I further investigated the role of HIV infection status in social contacts relevant to pneumococcal spread, by designing and conducting a social contacts survey yielding 12,540 contact events, and showed that mixing patterns are also similar between HIV+ and healthy adults. I extended my study for pneumococcal carriage risk by using existing rolling cross-sectional carriage data, and identified male sex and living without a <5y child as key factors for persistent VT carriage in HIV+ adults in the infant PCV era. Finally, I showed that healthy adults ≥55y who are similarly at high-risk of pneumococcal disease should be vaccinated at 55y and 65y in considered low/middle- and high-income countries, respectively, to maximise prevented invasive pneumococcal disease burden at population-level. Overall, my work demonstrates persistent adult carriage risk and transmission, and provides crucial evidence of the likely impact, and particularly indirect effects, of vaccination strategies targeting pneumococcal disease burden in vulnerable adults in low/middle-income.
