Genetic characterisation of Malawian pneumococci prior to the roll-out of the PCV13 vaccine using a high-throughput whole genome sequencing approach

PLoS One. 2012;7(9):e44250. doi: 10.1371/journal.pone.0044250. Epub 2012 Sep 10.

Abstract

Background: Malawi commenced the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) into the routine infant immunisation schedule in November 2011. Here we have tested the utility of high throughput whole genome sequencing to provide a high-resolution view of pre-vaccine pneumococcal epidemiology and population evolutionary trends to predict potential future change in population structure post introduction.

Methods: One hundred and twenty seven (127) archived pneumococcal isolates from randomly selected adults and children presenting to the Queen Elizabeth Central Hospital, Blantyre, Malawi underwent whole genome sequencing.

Results: The pneumococcal population was dominated by serotype 1 (20.5% of invasive isolates) prior to vaccine introduction. PCV13 is likely to protect against 62.9% of all circulating invasive pneumococci (78.3% in under-5-year-olds). Several Pneumococcal Molecular Epidemiology Network (PMEN) clones are now in circulation in Malawi which were previously undetected but the pandemic multidrug resistant PMEN1 lineage was not identified. Genome analysis identified a number of novel sequence types and serotype switching.

Conclusions: High throughput genome sequencing is now feasible and has the capacity to simultaneously elucidate serotype, sequence type and as well as detailed genetic information. It enables population level characterization, providing a detailed picture of population structure and genome evolution relevant to disease control. Post-vaccine introduction surveillance supported by genome sequencing is essential to providing a comprehensive picture of the impact of PCV13 on pneumococcal population structure and informing future public health interventions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anti-Bacterial Agents / pharmacology
  • Base Sequence
  • Child
  • Child, Preschool
  • Drug Resistance, Bacterial / drug effects
  • Drug Resistance, Bacterial / genetics
  • Genetic Variation*
  • Genome, Bacterial / genetics*
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Infant
  • Malawi
  • Middle Aged
  • Phylogeny
  • Pneumococcal Vaccines / immunology*
  • Serotyping
  • Streptococcus pneumoniae / classification
  • Streptococcus pneumoniae / genetics*
  • Vaccines, Conjugate / immunology
  • Young Adult

Substances

  • 13-valent pneumococcal vaccine
  • Anti-Bacterial Agents
  • Pneumococcal Vaccines
  • Vaccines, Conjugate