Surveillance for incidence and etiology of early-onset neonatal sepsis in Soweto, South Africa.

Sithembiso C Velaphi,Jeannette Wadula,Nicole Wolter,Firdose Nakwa,Matthew Westercamp,Ziyaad Dangor,Tracy Pondo,Grace Okudo,Alicia Demirjian,Shabir A Madhi,Maureen H Diaz,Clare Cutland,Stephanie J Schrag,Malefu Moleleki,Nong Shang,Jonas M Winchell,Anne Von Gottberg,Shawn D Larson

doi:10.1371/journal.pone.0214077

Abstract

BackgroundGlobally, over 400,000 neonatal deaths in 2015 were attributed to sepsis, however, the incidence and etiologies of these infections are largely unknown in low-middle income countries. We aimed to determine incidence and etiology of community-acquired early-onset (<72 hours age) sepsis (EOS) using culture and molecular diagnostics.MethodsThis was a prospective observational study, in which we conducted a surveillance for pathogens using a combination of blood culture and a polymerase chain reaction (PCR)-based test. Blood culture was performed on all neonates with suspected EOS. Among the subset fulfilling criteria for protocol-defined EOS, blood and nasopharyngeal (NP) respiratory swabs were tested by quantitative real-time reverse-transcriptase PCR using a Taqman Array Card (TAC) with 15 bacterial and 12 viral targets. Blood and NP samples from 312 healthy newborns were also tested by TAC to estimate background positivity rates. We used variant latent-class methods to attribute etiologies and calculate pathogen-specific proportions and incidence rates.ResultsWe enrolled 2,624 neonates with suspected EOS and from these 1,231 newborns met criteria for protocol-defined EOS (incidence- 39.3/1,000 live-births). Using the partially latent-class modelling, only 26.7% cases with protocol-defined EOS had attributable etiology, and the largest pathogen proportion were Ureaplasma spp. (5.4%; 95%CI: 3.6–8.0) and group B Streptococcus (GBS) (4.8%; 95%CI: 4.1–5.8), and no etiology was attributable for 73.3% of cases. Blood cultures were positive in 99/1,231 (8.0%) with protocol-defined EOS (incidence- 3.2/1,000 live-births). Leading pathogens on blood culture included GBS (35%) and viridans streptococci (24%). Ureaplasma spp. was the most common organism identified on TAC among cases with protocol-defined EOS.ConclusionUsing a combination of blood culture and a PCR-based test the common pathogens isolated in neonates with sepsis were Ureaplasma spp. and GBS. Despite documenting higher rates of protocol-defined EOS and using a combination of tests, the etiology for EOS remains elusive.

Highlights

The minimal data set underlying is available upon request to the Respiratory and Meningeal Pathogens Research Unit Website, or by request to the ethics committee at HRECMedical@ResearchOffice.wits.ac.za, for researchers who meet the criteria for access to confidential data. This was a prospective observational study, in which we conducted a surveillance for pathogens using a combination of blood culture and a polymerase chain reaction (PCR)-based test
Among the subset fulfilling criteria for protocol-defined EOS, blood and nasopharyngeal (NP) respiratory swabs were tested by quantitative real-time reverse-transcriptase PCR using a Taqman Array Card (TAC) with 15 bacterial and 12 viral targets
Using a combination of blood culture and a PCR-based test the common pathogens isolated in neonates with sepsis were Ureaplasma spp. and group B Streptococcus (GBS)

Summary

Introduction

The yield from blood culture, the gold standard for determining sepsis etiology might be compromised due to inadequate blood volume sampling in newborns, challenges in timely processing of specimens and antecedent antibiotic therapy prior to sampling. In order to address this gap, we established a prospective surveillance for serious probable infections in neonates from a large academic hospital in Soweto, South Africa with the aim to evaluate the etiology and incidence of early-onset (first-three days of life) sepsis (EOS). Investigations included blood culture and molecular diagnostic assay on blood and nasopharyngeal respiratory samples in newborns with protocol-defined community-acquired EOS. Over 400,000 neonatal deaths in 2015 were attributed to sepsis, the incidence and etiologies of these infections are largely unknown in low-middle income countries. We aimed to determine incidence and etiology of community-acquired early-onset (

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