Serious bacterial infections among Ugandan neonates: Aetiology, clinical findings and one year outcomes

Burgoine, Kathy ORCID: 0000-0001-7975-745X
(2021) Serious bacterial infections among Ugandan neonates: Aetiology, clinical findings and one year outcomes. PhD thesis, University of Liverpool.

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Title: Serious bacterial infections among Ugandan neonates: Aetiology, clinical findings and one year outcomes. Author: K L Burgoine Background: Globally, serious bacterial infections, such as sepsis, pneumonia and meningitis, are a leading cause of neonatal mortality. In sub-Saharan Africa (SSA) there are believed to be up to 2.6 million cases of pSBI every year, leading to an estimated 250,000 deaths. Diagnosis is challenging since signs and symptoms are often non-specific and laboratory facilities are limited. In low-resource settings, the diagnosis of a possible serious bacterial infection (pSBI) relies on clinical algorithms. Cranial ultrasound (cUS) is a relatively cheap, safe and portable method of assessing the neonatal brain that could be used to detect findings indicative of CNS involvement. There are also limited data on the outcomes of pSBI survivors. This is one of the first studies in SSA to assess the role of cUS in the evaluation of infants with pSBI and the early developmental outcome of infants admitted with pSBI. Aims: In term neonates presenting with pSBI to a neonatal unit in eastern Uganda: • Describe the clinical presentation, aetiology and neonatal outcomes • Describe findings on cUS scans at presentation and correlate the imaging findings with presentation, CSF analysis and neonatal mortality • Compare cUS findings to a cohort of similar aged well term neonates. • Describe findings on serial cUS scans up to 28 days • Evaluate mortality, growth and developmental impairment up to 12 months of age and compare it to the contemporaneous control cohort • Investigate the risk factors that contribute to poor early childhood outcome in term-born infants that experienced a possible severe bacterial infection (pSBI) during the neonatal period. Methods: Over a 1-year period, any term neonates presenting to the neonatal unit at Mbale Regional Referral Hospital who met the definition of pSBI were screened for inclusion. We described the microbiological aetiology using blood and CSF culture, the presenting clinical features and the neonatal outcomes. Each neonate had a standard cUS examination performed. The images were interpreted systematically by one of two experts blinded to the clinical details. A contemporaneous cohort of well term neonates were recruited. They underwent the same clinical and cUS examination. We followed-up surviving infants at 2, 6 and 12 months of age to evaluate survival, growth and development. The Bayley Scales of Infant Development-3rd edition (BSID-III) was used and developmental impairment was defined as a scaled-score <-1SD below the mean. Poor outcome was defined as either death, hydrocephalus, post-neonatal seizures or developmental impairment at 12 months of age. Results: 214 neonates with pSBI were recruited. Definite or possible pathogens were identified in 5.6% (12/214) of blood cultures. The most common pathogens isolated were Staphylococcus Aureus, Klebsiella and Escherichia coli. Potential pathogens were isolated in 0% (0/189) of CSF cultures. The overall neonatal mortality was 9.3% (20/214). The neonatal mortality from neonatal meningitis was 22.2% (6/27). Early cUS scans were available for 196/214 (91.6%) neonates with pSBI. There was no observed association between cUS findings at presentation and neonatal mortality. Moderate and severe cortical and/or white matter (WM) echogenicities were significantly associated with abnormal CSF analysis. The presence of signs suggestive of encephalopathy or meningism were associated with abnormal cortical, WM, and basal ganglia and thalami (BGT) echogenicity, ventricular dilatation and bright ventricular lining. At 12 months 164/187 survivors of pSBI were available for assessment; 4/187 infants had died during the post-neonatal period. Developmental impairment was evident across all domains of the BSID-III and the rates of impairment ranged from 7.9% to 14.6%. 24/44 control infants were available for assessment and none of these infants were impaired in any of the 5 domains. The raw scores and the scaled scores for all five neurocognitive domains were significantly lower for survivors of pSBI compared to control infants. Survivors of neonatal meningitis, had the highest rates of developmental impairment, being 24%, 35% and 24% in cognitive, language and motor domains respectively. Survivors of neonatal meningitis had a 12 to 18-fold increased risk of developmental impairment across all domains. By 12 months of age 30.5% (54/177) of infants had a poor outcome. After adjustment for sex, age and weight, the following factors increased the risk of poor outcome: age <48 hours at presentation, respiratory distress (aOR 2.7, 95%CI 1.2-6.2), neonatal seizures (aOR 13.0 (5.2-32.4)), opisthotonus (aOR 9.5 (3.5-27.0)), hypotonia (aOR 3.0 (1.1-8.3)) and raised CSF protein (aOR 9.5 (2.3-38.6)). cUS findings at presentation, significantly associated with poor outcome were abnormal cortex (aOR 6.9 (2.0-23.5)), abnormal white matter (aOR 2.0 (1.0-3.9)), abnormal basal ganglia (aOR 13.6 (2.7-68.2)) and abnormal thalami (aOR 5.28 (1.8-15.2)). Conclusion: It is clear that serious bacterial infections during the neonatal period, even without meningitis, may have a substantial public health and economic burden in SSA. Presentation before 48 hours of age, lower weight, several readily recognisable clinical signs as well as raised CSF protein and cortical, white matter, and central grey matter abnormalities seen on cUS, were all significant predictors of poor outcome. These risk factors will enable us to better consider which infants need more intensive follow-up, early intervention and support. Improving our understanding of the specific aetiologies associated with mortality, developmental impairment and post-infectious hydrocephalus, is now necessary to inform prevention strategies and treatment approaches.

Item Type: Thesis (PhD)
Divisions: Faculty of Health and Life Sciences
Depositing User: Symplectic Admin
Date Deposited: 13 Jan 2022 14:22
Last Modified: 18 Jan 2023 21:25
DOI: 10.17638/03142928