A thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand,
Johannesburg, in fulfillment of the requirements for the degree of
Doctor of Philosophy
Johannesburg, South Africa 2016 / Introduction: Neonatal infections contribute to 25% of all neonatal deaths, which
account for approximately 44% of all under-5 childhood deaths globally. Pathogens
responsible for sepsis in neonates and young infants can be acquired vertically prior to
or during labour, or from the environment (community or hospital).
This project evaluated the burden and aetiology of sepsis in neonates and young
infants (≤90 days), and explored this association to in-utero exposure to human
immunodeficiency virus. The study also included a specific focus on the epidemiology
of invasive Group B Streptococcal disease in young infants.
Additionally, we assessed the efficacy of intrapartum chlorhexidine vaginal washes for:
(i) preventing early-onset neonatal sepsis; and (ii) vertical transmission of potentially
pathogenic bacteria to the newborns. Furthermore, we evaluated risk factors for poor
outcomes due to neonatal sepsis.
Materials and methods: (i) A bacterial surveillance system was established at Chris
Hani Baragwanath Academic Hospital (CHBAH) from 2004-2008 to identify young
infants with bacterial sepsis hospitalised in the neonatal and paediatric wards. Medical
and microbiological records were utilised to obtain clinical and laboratory data. Maternal
HIV results were obtained from antenatal testing records or admission records.
(ii) A blinded, randomised, placebo-controlled trial of 0.5% chlorhexidine maternal
vaginal intrapartum wipes and newborn skin wipes was conducted at CHBAH between
2004 and 2007. Consented, eligible participants were randomised during labour to
receive either chlorhexidine vaginal wipes or water external genitalia wipes. Newborns
received either chlorhexidine full-body wipes (intervention arm) or foot wipes (control
arm). Maternal and infant participants were followed up for admissions during the first
month after delivery/ birth. A subset of 5144 maternal participants had an intrapartum
lower vaginal swab collected, and skin swabs were collected from their newborns to
assess colonisation with potentially pathogenic bacteria (Group B streptococcus,
Escherichia coli and Klebsiella pneumoniae).
Results: Group B streptococcus (GBS) was the most commonly isolated bacterial
pathogen, causing 35.2% of culture-confirmed sepsis in infants ≤90 days, 41.6% of
early-onset disease (EOD, 0-6 days), 40.5% of late-onset neonatal disease (LOD, 7-27
days) and 18.7% of young-infant community-acquired disease (YI-CAD, 28-90 days).
Staphylococcus aureus (S. aureus), Escherichia coli (E. coli) and Klebsiella
pneumoniae (K. pneumoniae) contribute 16.2%, 12.2% and 3.4% to sepsis in young
infants.
Overall, incidence (per 1000 live births) of invasive GBS disease was 2.72 (95%
confidence interval [95% CI]: 2.46 to 3.01), including an incidence of 1.50 and 1.22,
respectively, in infants 0-6 days and 7-90 days of age. HIV-exposed infants were at
greater risk of EOD (Relative risk [RR]: 1.69; 95% CI: 1.28-2.24) and LOD (RR= 3.18;
95% CI: 2.34-4.36) than HIV-unexposed infants. GBS serotypes Ia and III caused
84.0% of invasive GBS disease in young infants.
Intrapartum chlorhexidine interventional wipes was not efficacious in prevention of any
of: (i) vertical transmission of pathogenic bacteria (54% vs. 55%; efficacy -0.05, 95% CI:
-9.5 to 7.9) to the newborns; (ii) sepsis in first 3 days of life (3% vs. 4%; p=0.65,); (iii)
sepsis in the later neonatal period (both <1%; p=0.4444); or (iv) maternal puerperal
sepsis(both <1%; p=0.56).
Conclusion: GBS, S. aureus, E. coli and K. pneumoniae are the most commonly
isolated bacterial pathogens in neonates and infants ≤90 days old. HIV-exposed infants
are at greater risk of GBS sepsis. Intrapartum chlorhexidine intervention was not
efficacious in reducing vertical transmission of pathogenic bacteria, neonatal or
maternal sepsis. Alternative interventions to prevent sepsis in young infants, including
maternal immunisation, need to be investigated in setting such as ours where there is a
high prevalence of maternal HIV infection. / MT2017
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/22516 |
| Date | January 2016 |
| Creators | Cutland, Clare Louise |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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