Characterising Streptococcus pneumoniae Transmission Patterns in Malawi Through Genomic and Statistical Modelling

Controlling the carriage and transmission of Streptococcus pneumoniae in children from high- disease burden countries is crucial for disease prevention. To assess the rate of spread, and the factors associated with the high frequency of transmission despite pneumococcal conjugate vaccine (PCV) introduction, we measured evolution divergence time using the whole genome sequences of S. pneumoniae collected from 1,617 child participants from Blantyre, Malawi between 2015 and 2019. These children included both PCV13 vaccinated children aged 2 to 7 years and PCV13 unvaccinated children aged 5 to 10 years who were age ineligible when PCV was introduced. Using a generalized additive mixed model (GAMM) and relative risk (RR) frameworks, while accounting for household geospatial distances, we found that the spread of lineages became widespread across the population of Blantyre over approximately four years, with transmission being more likely between neighbouring households. Logistic regression and random forest models predicted a higher incidence of events among preschool children in densely populated, higher socioeconomic areas. Additionally, recent transmission was linked to recently expanding, non-vaccine serotype lineages that are penicillin non-susceptible. Our findings suggest that enhancing vaccine-mediated immunity among preschool-aged children in high density settings could reduce transmission of disease-causing and antimicrobial-resistant pneumococcal lineages, therefore strengthening herd protection for vulnerable individuals (e.g. very young children and people living with HIV).