Invasive bacterial disease trends and characterization of group B streptococcal isolates among young infants in southern Mozambique, 2001-2015

PLoS One. 2018 Jan 19;13(1):e0191193. doi: 10.1371/journal.pone.0191193. eCollection 2018.

Abstract

Background: Maternal group B streptococcal (GBS) vaccines under development hold promise to prevent GBS disease in young infants. Sub-Saharan Africa has the highest estimated disease burden, although data on incidence and circulating strains are limited. We described invasive bacterial disease (IBD) trends among infants <90 days in rural Mozambique during 2001-2015, with a focus on GBS epidemiology and strain characteristics.

Methods: Community-level birth and mortality data were obtained from Manhiça's demographic surveillance system. IBD cases were captured through ongoing surveillance at Manhiça district hospital. Stored GBS isolates from cases underwent serotyping by multiplex PCR, antimicrobial susceptibility testing, and whole genome sequencing.

Results: There were 437 IBD cases, including 57 GBS cases. Significant declines in overall IBD, neonatal mortality, and stillbirth rates were observed (P<0.0001), but not for GBS (P = 0.17). In 2015, GBS was the leading cause of young infant IBD (2.7 per 1,000 live births). Among 35 GBS isolates available for testing, 31 (88.6%) were highly related serotype III isolates within multilocus sequence types (STs) 17 (68.6%) or 109 (20.0%). All seven ST109 isolates (21.9%) had elevated minimum inhibitory concentration (MIC) to penicillin (≥0.12 μg/mL) associated with penicillin-binding protein (PBP) 2x substitution G398A. Epidemiologic and molecular data suggest this is a well-established clone.

Conclusion: A notable young infant GBS disease burden persisted despite improvements in overall maternal and neonatal health. We report an established strain with pbp2x point mutation, a first-step mutation associated with reduced penicillin susceptibility within a well-known virulent lineage in rural Mozambique. Our findings further underscores the need for non-antibiotic GBS prevention strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Bacterial Infections / epidemiology*
  • Female
  • Genome, Bacterial
  • Humans
  • Immunity, Maternally-Acquired
  • Incidence
  • Infant
  • Infant, Newborn
  • Male
  • Microbial Sensitivity Tests
  • Mozambique / epidemiology
  • Multiplex Polymerase Chain Reaction
  • Penicillin Resistance / genetics
  • Penicillin-Binding Proteins / genetics
  • Point Mutation
  • Pregnancy
  • Retrospective Studies
  • Serotyping
  • Streptococcal Infections / epidemiology*
  • Streptococcal Infections / microbiology*
  • Streptococcal Infections / prevention & control
  • Streptococcal Vaccines / pharmacology
  • Streptococcus agalactiae* / drug effects
  • Streptococcus agalactiae* / genetics
  • Streptococcus agalactiae* / isolation & purification
  • Virulence / genetics

Substances

  • Penicillin-Binding Proteins
  • Streptococcal Vaccines
  • PBP 2x protein, Streptococcus

Grants and funding

This study was funded by CISM core funding provided by the Spanish Agency for International Cooperation (AECI-Ministry of Foreign Affairs, Spain). This study was also partly supported by funds from PATH through to the pneumonia and pneumococcus surveillance study (GAT.770-790-01350-LPS), Bill & Melinda Gates Foundation through Center for Vaccine Development, University of Maryland School of Medicine (Grant: S00957) and the United States Agency for International Development mission in Mozambique through to Fixed Obligation Grant No. AID-656-F-12-00001, under RFA-656-12-000003. Johns Snow, Inc. currently provides support in the form of salary for author B.S. None of the funders have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.