Browsing by Department "Paediatrics and Child Health"

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    A multicentre neonatal interventional randomised controlled trial of nebulized surfactant for preterm infants with respiratory distress: Neo-INSPIRe trial protocol
    (BioMed Central, 2023-09-19) Lategan, Ilse; Durand, David; Harrison, Michael; Nakwa, Firdose; Van Wyk, Lizelle; Velaphi, Sithembiso; Horn, Alan; Kali, Gugu; Soll, Roger; Ehret, Danielle; Zar, Heather; Tooke, Lloyd
    Introduction Respiratory distress syndrome in preterm infants is an important cause of morbidity and mortality. Less invasive methods of surfactant administration, along with the use of continuous positive airway pressure (CPAP), have improved outcomes of preterm infants. Aerosolized surfactant can be given without the need for airway instrumentation and may be employed in areas where these skills are scarce. Recent trials from high-resourced countries utilising aerosolized surfactant have had a low quality of evidence and varying outcomes. Methods and analysis The Neo-INSPIRe trial is an unblinded, multicentre, randomised trial of a novel aerosolized surfactant drug/device combination. Inclusion criteria include preterm infants of 27–34+6 weeks’ gestational age who weigh 900-1999g and who require CPAP with a fraction of inspired oxygen (FiO2) of 0.25–0.35 in the first 2–24 h of age. Infants are randomised 1:1 to control (CPAP alone) or intervention (CPAP with aerosolized surfactant). The primary outcome is the need for intratracheal bolus surfactant instillation within 72 h of age. Secondary outcomes include the incidence of reaching failure criteria (persistent FiO2 of > 0.40, severe apnoea or severe work of breathing), the need for and duration of ventilation and respiratory support, bronchopulmonary dysplasia and selected co-morbidities of prematurity. Assuming a 40% relative risk reduction to reduce the proportion of infants requiring intratracheal bolus surfactant from 45 to 27%, the study will aim to enrol 232 infants for the study to have a power of 80% to detect a significant difference with a type 1 error of 0.05. Ethics and dissemination Ethical approval has been granted by the relevant human research ethics committees at University of Cape Town (HREC 681/2022), University of the Witwatersrand HREC (221112) and Stellenbosch University (M23/02/004). Trial registration PACTR202307490670785
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    Associations between prenatal alcohol and tobacco exposure on Doppler flow velocity waveforms in pregnancy: a South African study
    (BioMed Central, 2023-08-23) Jonker, Deborah; Melly, Brigitte; Brink, Lucy T.; Odendaal, Hein J.; Stein, Dan J.; Donald, Kirsten A.
    Background The negative impact of prenatal alcohol and tobacco exposure (PAE and PTE) on fetal development and birth outcomes are well described, yet pathophysiologic mechanisms are less clear. Our aim was to investigate (1) the associations between quantity, frequency and timing (QFT) of PAE and PTE with blood flow velocities in arteries of the fetal-placental-maternal circulation and (2) the extent to which combined effect of QFT of PAE and/or PTE and Doppler flow velocity waveforms (FWV) predict infant birth weight. Methods The Safe Passage Study is a cohort based in urban Cape Town, South Africa. Recruitment occurred between 2007 and 2015. Information on QFT of PAE and PTE was collected prospectively at up to 4 occasions during pregnancy using a modified Timeline Follow-Back approach. Ultrasound examinations consisted of Doppler flow velocity waveforms of the uterine, umbilical (UA) and fetal middle cerebral arteries for the pulsatility index (PI) at 20–24 and 34–38 weeks. Exclusion criteria included: twin pregnancies, stillbirths, participants exposed to other drugs. The sample was divided into three groups (controls, PAE and PTE) and included 1396 maternal-fetal-dyads assessed during the second trimester; 1398 assessed during the third trimester. Results PTE was associated with higher UA PI values in second and third trimesters (p < 0.001), compared to the PAE and control group. The total amount of cigarettes smoked during pregnancy was positively correlated with UA PI values (r = 0.087, p < 0.001). There was a positive correlation between cigarettes smoked per day in trimester one (r = 0.091, p < 0.01), and trimester two (r = 0.075, p < 0.01) and UA PI (in trimester two), as well as cigarettes smoked per day in trimester two (r = 0.058, p < 0.05) and trimester three (r = 0.069, p < 0.05) and the UA PI in trimester three. Generalized additive models indicated that PAE in trimester two, PTE in trimester one and Doppler FWV in trimester three were significant predictors of birth weight in this sample. Conclusion In our study, PTE in trimesters two and three resulted in increased vascular resistance of the placenta. These findings highlight nuance in associations between PAE, PTE and blood flow velocities in arteries of the fetal-placental-maternal circulation and birth weight, suggesting that quantity and timing are important factors in these relationships.
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    Clinical and Experimental Determination of Protection Afforded by BCG Vaccination against Infection with Non-Tuberculous Mycobacteria: A Role in Cystic Fibrosis?
    (Multidisciplinary Digital Publishing Institute, 2023-08-01) Warner, Sherridan; Blaxland, Anneliese; Counoupas, Claudio; Verstraete, Janine; Zampoli, Marco; Marais, Ben J.; Fitzgerald, Dominic A.; Robinson, Paul D.; Triccas, James A.
    Mycobacterium abscessus is a nontuberculous mycobacterium (NTM) of particular concern in individuals with obstructive lung diseases such as cystic fibrosis (CF). Treatment requires multiple drugs and is characterised by high rates of relapse; thus, new strategies to limit infection are urgently required. This study sought to determine how Bacille Calmette-Guérin (BCG) vaccination may impact NTM infection, using a murine model of Mycobacterium abscessus infection and observational data from a non-BCG vaccinated CF cohort in Sydney, Australia and a BCG-vaccinated CF cohort in Cape Town, South Africa. In mice, BCG vaccination induced multifunctional antigen-specific CD up sup T cells circulating in the blood and was protective against dissemination of bacteria to the spleen. Prior infection with M. abscessus afforded the highest level of protection against M. abscessus challenge in the lung, and immunity was characterised by a greater frequency of pulmonary cytokine-secreting CD4 T cells compared to BCG vaccination. In the clinical CF cohorts, the overall rates of NTM sampling during a three-year period were equivalent; however, rates of NTM colonisation were significantly lower in the BCG-vaccinated (Cape Town) cohort, which was most apparent for M. abscessus. This study provides evidence that routine BCG vaccination may reduce M. abscessus colonisation in individuals with CF, which correlates with the ability of BCG to induce multifunctional CD4T cells recognising M. abscessus in a murine model. Further research is needed to determine the optimal strategies for limiting NTM infections in individuals with CF.
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    Effects of the COVID-19 pandemic on the outcomes of HIV-exposed neonates: a Zimbabwean tertiary hospital experience
    (BioMed Central, 2024-01-05) Gannon, Hannah; Chappell, Elizabeth; Ford, Deborah; Gibb, Diana M.; Chimwaza, Anesu; Manika, Ngoni; Wedderburn, Catherine J.; Nenguke, Zivai M.; Cowan, Frances M.; Gibb, Tom; Phillips, Andrew; Mushavi, Angela; Fitzgerald, Felicity; Heys, Michelle; Chimhuya, Simbarashe; Bwakura-Dangarembizi, Mutsa
    Abstract Introduction The COVID-19 pandemic has globally impacted health service access, delivery and resources. There are limited data regarding the impact on the prevention of mother to child transmission (PMTCT) service delivery in low-resource settings. Neotree ( www.neotree.org ) combines data collection, clinical decision support and education to improve care for neonates. Here we evaluate impacts of COVID-19 on care for HIV-exposed neonates. Methods Data on HIV-exposed neonates admitted to the neonatal unit (NNU) at Sally Mugabe Central Hospital, Zimbabwe, between 01/06/2019 and 31/12/2021 were analysed, with pandemic start defined as 21/03/2020 and periods of industrial action (doctors (September 2019-January 2020) and nurses (June 2020-September 2020)) included, resulting in modelling during six time periods: pre-doctors’ strike (baseline); doctors’ strike; post-doctors’ strike and pre-COVID; COVID and pre-nurses’ strike; nurses’ strike; post nurses’ strike. Interrupted time series models were used to explore changes in indicators over time. Results Of 8,333 neonates admitted to the NNU, 904 (11%) were HIV-exposed. Mothers of 706/765 (92%) HIV-exposed neonates reported receipt of antiretroviral therapy (ART) during pregnancy. Compared to the baseline period when average admissions were 78 per week (95% confidence interval (CI) 70–87), significantly fewer neonates were admitted during all subsequent periods until after the nurses’ strike, with the lowest average number during the nurses’ strike (28, 95% CI 23–34, p < 0.001). Across all time periods excluding the nurses strike, average mortality was 20% (95% CI 18–21), but rose to 34% (95% CI 25, 46) during the nurses’ strike. There was no evidence for heterogeneity (p > 0.22) in numbers of admissions or mortality by HIV exposure status. Fewer HIV-exposed neonates received a PCR test during the pandemic (23%) compared to the pre-pandemic periods (40%) (RR 0.59, 95% CI 0.41–0.84, p < 0.001). The proportion of HIV-exposed neonates who received antiretroviral prophylaxis during admission was high throughout, averaging between 84% and 95% in each time-period. Conclusion While antiretroviral prophylaxis for HIV-exposed neonates remained high throughout, concerning data on low admissions and increased mortality, similar in HIV-exposed and unexposed neonates, and reduced HIV testing, suggest some aspects of care may have been compromised due to indirect effects of the pandemic.
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    Reconstitution of antimycobacterial immune responses in HIV-infected children receiving HAART
    (2006) Kampmann, B; Tena, G; Nicol, MP; Levin, M; Eley, BS
    Objective: Recent epidemiological studies in adults suggest that HAART can prevent the development of tuberculosis in HIV-infected individuals, but the mechanisms are incompletely understood and no data exist in children. We investigated whether changes in mycobacterial-specific immune responses can be demonstrated in children after commencing antiretroviral therapy. Design: We measured mycobacterial growth in vitro using a novel whole-blood assay employing reporter-gene tagged bacillus Calmette–Guérin (BCG) in a prospective cohort study in the tuberculosis-endemic environment of South Africa. Key cytokines were measured in supernatants collected from the whole-blood assay using cytometric bead array. Patients: A cohort of 15 BCG-vaccinated HIV-infected children was evaluated prospectively for in-vitro antimycobacterial immune responses before and during the first year of HAART. All children had advanced HIV disease. Nine children completed all study timepoints. Results: Before HAART, blood from children showed limited ability to restrict the growth of mycobacteria in the functional whole-blood assay. The introduction of HAART was followed by rapid and sustained reconstitution of specific antimycobacterial immune responses, measured as the decreased growth of mycobacteria. IFN-γ levels in culture supernatants did not reflect this response; however, a decline in TNF-α was observed. Conclusion: This is the first study using a functional in-vitro assay to assess the effect of HAART on immune responses to mycobacteria in HIV-infected children. Our in-vitro data mirror the in-vivo observation of decreased susceptibility to tuberculosis in HIV-infected adults receiving antiretroviral agents. This model may be useful for further characterizing immune reconstitution after HAART.