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

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

doi:10.1371/journal.pone.0214077

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

PLoS One. 2019 Apr 10;14(4):e0214077. doi: 10.1371/journal.pone.0214077. eCollection 2019.

Authors

Sithembiso C Velaphi¹, Matthew Westercamp², Malefu Moleleki³, Tracy Pondo², Ziyaad Dangor¹, Nicole Wolter³, Anne von Gottberg³, Nong Shang², Alicia Demirjian², Jonas M Winchell², Maureen H Diaz², Firdose Nakwa¹, Grace Okudo¹, Jeannette Wadula⁴, Clare Cutland⁵, Stephanie J Schrag², Shabir A Madhi^{5

6}

Affiliations

¹ Department of Pediatrics, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
² Centers for Disease Control and Prevention, Atlanta, United States of America.
³ Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service (NHLS), and School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁴ Department of Clinical Microbiology and Infectious Diseases, NHLS, South Africa and School of Pathology, University of the Witwatersrand, Johannesburg, South Africa.
⁵ Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁶ Department of Science and Technology/National Research Foundation: South African Research Chair Initiative in Vaccine Preventable Diseases, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.

Abstract

Background: Globally, 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.

Methods: 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. 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.

Results: We 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.

Conclusion: Using 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.

Publication types

Research Support, U.S. Gov't, P.H.S.

MeSH terms

Age of Onset
Blood Culture
Female
Humans
Infant, Newborn
Neonatal Sepsis / blood*
Neonatal Sepsis / epidemiology
Neonatal Sepsis / microbiology
Neonatal Sepsis / pathology
Pregnancy
Pregnancy Complications, Infectious / blood*
Pregnancy Complications, Infectious / epidemiology
Pregnancy Complications, Infectious / microbiology
Pregnancy Complications, Infectious / pathology
South Africa
Streptococcal Infections / blood*
Streptococcal Infections / epidemiology
Streptococcal Infections / microbiology
Streptococcal Infections / pathology
Streptococcus agalactiae / genetics
Streptococcus agalactiae / isolation & purification*
Streptococcus agalactiae / pathogenicity
Ureaplasma / isolation & purification
Ureaplasma / pathogenicity

Grants and funding

Sithembiso C. Velaphi (SCV) was funded for this study by Centre for Disease Control and Prevention, Atlanta, USA through the South African Global Disease Detection Centre at National Institute of Communicable Diseases. The funder of the study contributed to the study design, data analysis, data interpretation and reviewing the report through its employees, authors MW, TP, MD, JW, NS, AD and SJS.