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Published on: September 11, 2020
Genomic and statistical models to characterize Streptococcus pneumoniae transmission patterns in Malawi
Rory Cave1, James Chirombo2,3, Uri Obolski4
1NIHR Global Health Research Group on Vaccines to Control Respiratory Pathogens and AMR across Africa, Institute of Infection, Immunity and Transplantation, University College London, London, UK.
Insights
Pneumococcal conjugate vaccine (PCV) introduction in Malawi reduced transmission of Streptococcus pneumoniae, especially between nearby homes. Higher transmission risk was seen in young children in crowded, wealthier areas, linked to resistant strains.
Area of Science:
- Microbiology
- Epidemiology
- Genomics
Background:
- Controlling Streptococcus pneumoniae carriage and transmission in children is vital for disease prevention in high-burden regions.
- Pneumococcal conjugate vaccines (PCVs) are key tools, but understanding transmission dynamics post-introduction is crucial.
Purpose of the Study:
- To investigate the rate and drivers of Streptococcus pneumoniae transmission after the introduction of pneumococcal conjugate vaccine (PCV) in Blantyre, Malawi.
- To identify factors influencing transmission, particularly in relation to vaccine use and population density.
Main Methods:
- Whole-genome sequencing of S. pneumoniae from 1,617 children (vaccinated and unvaccinated) in Blantyre (2015-2019).
- Analysis using generalized additive mixed models, relative risk frameworks, and logistic regression/random forest models incorporating geospatial data.
Main Results:
- Pneumococcal lineages spread widely within approximately 4 years, with transmission primarily occurring between neighboring households.
- Higher transmission risk was observed in preschool-aged children residing in densely populated, higher socioeconomic status areas.
- Recent transmission events were associated with expanding, non-vaccine serotype lineages resistant to penicillin.
Conclusions:
- Extended valency PCVs may reduce the spread of disease-causing and antimicrobial-resistant pneumococcal lineages among young children in high-density areas.
- These vaccines can enhance herd protection for vulnerable populations, including infants and individuals with HIV.
Abstract:
Controlling the carriage and transmission of Streptococcus pneumoniae in children from high-burden settings is critical for disease prevention. To investigate the rate and drivers of transmission following pneumococcal conjugate vaccine (PCV) introduction, we estimated evolutionary divergence times using whole-genome sequences of S. pneumoniae from 1,617 children in Blantyre, Malawi (2015-2019). The cohort included PCV13-vaccinated children aged 2-7 years and unvaccinated children aged 5-10 years who were vaccine ineligible at the time of rollout into routine use. Using generalized additive mixed models and relative risk frameworks that incorporated household geospatial distances, we found that pneumococcal lineages spread widely across Blantyre within ~4 years, with transmission most likely between neighbouring households. Logistic regression and random forest models identified higher transmission risk among preschool-aged children in densely populated, higher socioeconomic areas. Recent transmission events were primarily associated with expanding, non-vaccine serotype lineages that were non-susceptible to penicillin. These findings highlight the potential for extended valency PCVs to reduce the spread of disease-causing and antimicrobial-resistant pneumococcal lineages among preschool-aged children, particularly in high-density areas - thereby strengthening herd protection for vulnerable groups such as young infants and individuals living with HIV.
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