Faculty of Health Sciences (ETDs)

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    Virological response in children and adolescents switching to dolutegravir based regimens in Johannesburg, South Africa – A Longitudinal Cohort Study
    (University of the Witwatersrand, Johannesburg, 2023) Mafora, Tshiamo; Technau, Karl
    Introduction: Dolutegravir (DTG) was introduced into South African HIV management guidelines in November 2019, and has since been the mainstay of both adult and paediatric first line antiretroviral treatment (ART) regimens. Following its rapid and widespread introduction we assessed the rate of virological suppression over two years in paediatric patients switching to DTG as part of first line treatment. Methods: We performed a retrospective cohort study at Rahima Moosa Mother and Child Hospital in Johannesburg, South Africa. Children and adolescents already on first line ART who switched to DTG (between November 2019 and November 2021) were included. Baseline characteristics (at DTG switch) included age, weight, gender, viral load (VL), CD4, and pre-switch regimen. Past ART exposure and past viraemic periods (years VL >1000 copies/ml) were assessed and VL suppression rates (< 50 copies/ml) were calculated at 6, 12 and 24 months post-switch. Associations with non-suppression were assessed using uni- and multivariate analysis. Results: Of the 747 participants that were switched to DTG, 724 (97%) qualified for a VL and 697 (96%) of those had at least one VL done after switch. Overall, 83% (450/543) were suppressed at 6 months, 86% (434/504) at 12, 91% (487/534) at 24 months. Overall, at a median of 637 days after switch, 90% (624/697) were suppressed at their last VL. Factors associated with not being suppressed at the last VL included: missing a follow-up visit by more than 90 days post-switch to DTG (OR: 3.2 [CI:1.5-6.8], p=0.003), switching to DTG with a VL of 50-1000 rather than <50 copies/ml (OR 2.0 [CI:1.1-3.9], p=0.042), having the blood test done during July December (OR 2.0 [CI:1.2-3.4], p=0.011), and having had exposure to viraemia ≥1000 copies/ml for more than two years between first ART start and DTG switch (OR: 1.9 [CI: 0.9-3.7], p=0.071). Conclusion: In our population, similar to other studies, VL suppression was effectively maintained in the majority of patients after switching to DTG. The switch did however result in a loss of suppression in some patients and caution is needed in children and adolescents with missed visits and extensive prior viraemia
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    Correlation of maternal age to their children born with orofacial cleft treated at Wits Oral Health Centre
    (2024) Ravat, Naseeba
    Objectives: Orofacial Clefts (OFC) are the most common congenital malformations of the craniofacial complex. OFC affects 1/700 live births globally with extensive variability across geographic origin, racial and ethnic populations. In South Africa the prevalence of OFC is 0.3 per 1000 live births. Advanced maternal age has been associated with cell division errors, that can predispose to the occurrence of OFC. This study evaluated the correlation of advanced maternal age with the occurrence of OFC and the types of OFC. Methods: A retrospective cross-sectional study was conducted to review records of 105 children with OFC from 1 January 2013 to 31 December 2019. The clinical information reviewed included the child’s sex, race and type and laterality of OFC. The mother’s demographic information including the age at birth to the child with OFC, race, marital status, education level, number of children that the mother gave birth to as well as the familial history of OFC was documented. Stata version 17.0 was used to analyse the data and statistical tests were conducted at a 5% significance level. Results: The mean maternal age at the birth of a child with OFC was 26 years, with a range of 17-46 years. The majority of the mothers were Black (64.76%) followed by White (14.29%), Indian (11.43%) and Coloured (9.52%). There were more female children with OFC (51.43%) compared to male children (48.57%). Most of the children were Black (63.81%) followed by White (12.38%), Indian (11.43%) and Coloured (10.48%). The predominant type of OFC was the unilateral cleft lip and palate (CLP) occurring on the left side of the face (39.05%) compared to the right side (23.81%). Bilateral CLP was observed in 28.67% of children, and 0.57% of children had a cleft palate only. Mothers who gave birth to children with right CLP were older (over 30 years old) compared to those who gave birth to children with left CLP (under 25 years old). No statistical significance was found between maternal age and OFC. Conclusions- The clinical appearance of OFC highlighted the maternal age differences to type of OFC in our study sample. Children with right CLP were born to older mothers whilst the youngest mothers had children with CP. The majority of the mothers were unemployed, single parents with low level of education. This signified the burden of care these single parents have in caring for their children with OFC.
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    Surveillance of gastrointestinal infections in individuals over the age of 5 years in South Africa
    (2024) Johnstone, Siobhan Lindsay
    Gastrointestinal infections cause significant mortality and morbidity, especially in Africa. While children ≤5 years of age bear the brunt of diarrhoeal disease, there is a significant burden in older age groups. Limited data on aetiology in these older age groups limits appropriate interventions. Diarrhoeal surveillance is important for monitoring disease trends in a population and should inform testing and treatment guidelines, and interventions. This body of work evaluated the epidemiology of diarrhoea at each level of the surveillance pyramid to assist in interpretation of routine health data and identify gaps in surveillance. A household survey was conducted in Soweto to estimate community diarrhoeal prevalence, associated risk factors and healthcare seeking behaviors. An analysis of diagnostic testing practices for diarrhoeal diseases was done, using a doctors’ survey, at three public hospitals in South Africa. Routine diagnostic data and enhanced surveillance data were compared to evaluate patient-related factors associated with requests for diagnostic investigation, type of diagnostic testing offered and the efficiency of available tests. A hospital surveillance study investigated the infectious causes of diarrhoea in hospitalised patients >5 years. Results indicated a high diarrhoeal burden across all age groups in South Africa (5.3% of respondents reported an episode in the preceding 2 weeks). While the majority of infections were mild, 40% required healthcare. Many of those requiring healthcare (34%), specifically adults, were unable to access the required care. Those that did access healthcare were treated empirically and seldom had stool samples collected for diagnostic investigations (approximately 10% of admitted cases). Available diagnostics in public health laboratories detected pathogens in only 13.7% of these submitted stools due to pre-analytical and analytical issues including not testing for all relevant pathogens. Diarrhoeal prevalence was particularly high among HIV-infected patients (67.5% of patients >5 years admitted for diarrhoea were HIV-infected) and these patients presented with a unique aetiology. This research highlights the need for diarrhoeal testing and treatment guidelines based on local epidemiological data with a focus on HIV-infected patients. Current diagnostics require optimisation including specimen collection, standardisation, pathogens included in routine testing panels, turnaround time and methods of detection. This will guide decisions on future public health interventions including vaccines.
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    Long-term outcomes of HIV infected, and uninfected children aged 1-59 months following inpatient management of severe acute malnutrition
    (2024) Bwakura-Dangarembizi, Mutsawashe
    Children with complicated severe acute malnutrition (SAM) are at a high risk for mortality and morbidity in the time after hospital discharge, and those with HIV are particularly vulnerable. What is not known is whether this higher risk for poor outcomes in children with HIV has improved in the era of treating all who are infected. The thesis' main aim was to characterize the 52-week outcomes of children aged 1 to 59 months who were hospitalized for complicated SAM and to identify the characteristics present at hospital discharge that were most predictive of these outcomes. The thesis utilised the HOPE SAM study, an observational cohort established in Zimbabwe and Zambia that enrolled children hospitalised for complicated SAM and followed them up for one year after discharge from hospital. The study outcomes were death, morbidity, nutritional recovery and body composition assessed using skinfold thickness and bioelectrical impedance analysis. There were 3 main findings from the thesis; nearly 1 in 10 children treated for SAM died and the risk of dying continued throughout the one year following discharge. Children living with HIV had an almost 4-fold higher mortality compared to those without HIV regardless of whether they were receiving antiretroviral therapy or not; wasted children and those with ongoing SAM had a 2-fold higher mortality compared to those who had oedema on admission; and cerebral palsy was associated with a nearly 6-fold higher mortality risk. Similar risk factors, with the exception of HIV infection and addition of stunting were associated with impaired anthropometric recovery and increased hospital readmission. In this cohort, the time to hospital readmission was correlated with low peripheral fat mass and low lean mass. Overall, this thesis emphasizes the vulnerability of children treated for SAM even after they are released from the hospital and identifies high-risk populations that require focused interventions to enhance outcomes