Neonatal sepsis in The Gambia: a genomic analysis of infection transmission pathways. Gambia Neonatal Sepsis Transmission Study

Bacterial infections remain an important cause of neonatal mortality in sub-Saharan Africa. These infections may be acquired by vertical transmission of endogenous bacteria that colonize the maternal vaginal tract either shortly before or during labour, or horizontal transmission of bacteria from an environmental or human source after birth. We used whole-genome sequencing (WGS) to analyse whether neonatal sepsis was primarily due to vertical transmission of maternal genital tract bacteria to neonates with microbiologically confirmed bloodstream infection.We carried out a cross-sectional study of newborns admitted with clinical signs of sepsis admitted on the neonatal wards of three large hospitals in The Gambia over a 17-month period between April 2015 and January 2017. Neonatal blood cultures and maternal vaginal-rectal swabs were obtained at the time of recruitment. We genome sequenced paired bacterial neonatal blood culture and maternal genital tract isolates that were phenotypically matched in terms of species and antibiogram.We enrolled 203 newborn-mother pairs. Bacteria were cultured from the blood of 45% (91/202) of neonates; 25% (51/202) of all cultures grew a clinically significant bacterial pathogen and 20% (40/202) grew a clinically non-significant pathogen. Among neonates with culture-confirmed sepsis for a clinically significant pathogen, only 25% (12/51) of bloodstream isolates phenotypically matched the paired maternal genital tract isolate. Comparative genomic analysis of phenotypically matched paired isolates suggests that vertical transmission occurred in one-third (4/12; 33%) of mother-new born pairs with phenotypically matched isolates representing 8% (4/51) of newborns with culture-confirmed bacterial sepsis due to a clinically significant pathogen. All four neonates presented with early-onset Staphylococcus aureus sepsis (days 0 – 2 after birth) and were vaginally delivered.