Epidemiology and transmission dynamics of Streptococcus pneumoniae in low and lower-middle income settings: implications for vaccination strategies

Disease due to Streptococcus pneumoniae is a major cause of mortality and morbidity globally. Pneumococcal conjugate vaccines (PCVs) are being routinely introduced in immunisation programmes with support from Gavi, the Vaccine alliance, in low-income countries but uncertainty remains around the impact of different PCV introduction strategies in such settings, and in particular catch-up campaigns (CCs), which so far have not been conducted in Gavi-supported countries due to supply constraints. This thesis explored the potential impact on nasopharyngeal carriage and disease of introducing PCV with and without CCs, in Nha Trang, Vietnam, through a dynamic transmission model. Vietnam is yet to introduce PCV vaccination, as are most South-East Asian countries. Additional studies on the vaccine efficacy against carriage (VEC) and its waning, social contact patterns relevant for pneumococcal transmission, and age-specific epidemiology of carriage and serotype distribution were also conducted, the results of which fed directly into the transmission model. A meta-analysis provided the first ever-global estimates of VEC and its waning, by serotype and schedule. A large survey in southwest Uganda, collecting data on both social contact patterns and carriage from the same participants, shed light on which social contacts are important for pneumococcal transmission, showing that the frequency of close contacts, but not casual contacts, increased the colonisation risk, thereby informing the parameterisation of the transmission model. Results from the latter predicted elimination of vaccine type (VT) serotypes with near-complete replacement by non-VT across all age groups, within 10 years of PCV introduction with 90% coverage. The predicted benefit of CCs to expanded age groups was most pronounced in the first three years after PCV introduction, insofar that CCs result in limited introduction delays. This thesis provided important insight into the epidemiology and transmission dynamics of pneumococci, to inform policy in countries that have not yet introduced PCV.