Browsing by Subject "Paediatrics and Child Health"

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    A descriptive study of vancomycin usage at Red Cross War Memorial Children's Hospital, Cape Town
    (2023) Greybe, Leonore; Nuttall, James; Eley Brian
    Background: Antimicrobial stewardship principles guide the clinical use of vancomycin, but paediatric vancomycin prescribing practices have not been evaluated in South Africa. Objectives: To document the use, prescribing practices and monitoring of intravenous vancomycin and the spectrum of bacteria isolated on microbiological culture in children treated with intravenous vancomycin during a 12-month period at Red Cross War Memorial Children's Hospital (RCWMCH). Methods: A retrospective audit of intravenous vancomycin use in children admitted to RCWMCH during 2019. Results: All 158 vancomycin prescription episodes for 143 children were included. Overall usage of intravenous vancomycin was 63 days of therapy/1000 patient days (IQR 38–72). The median starting dose was 15 mg/kg/dose (IQR 14 ̶ 15) and median daily dose was 45 mg/kg/day (IQR 43–60). Vancomycin was prescribed as empiric (127/158, 80%) and directed (31/158, 20%) treatment. The median duration of treatment for the directed group was longer than the empiric group (p=0.001). Only 65/98 (66%) episodes where vancomycin treatment exceeded three days had vancomycin serum trough concentrations performed, and only 16/65 (25%) of these samples were obtained before the fourth dose. Prolonged antibiotic treatment of 14 days or more was not associated with gram positive bacteria on culture (OR 1.02, 95% CI 0.17 ̶ 4.2). Conclusion: Prolonged empiric treatment and inappropriate vancomycin monitoring were problems associated with vancomycin prescriptions. Contribution: Our study identified multiple opportunities for improved vancomycin prescribing and monitoring. Further research and implementation of improved prescribing practices could contribute to the preservation of vancomycin as an effective antibiotic.
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    A profile of children with traumatic brain injury admitted to the Red Cross War Memorial Children?s Hospital Paediatric Intensive Care Unit in Cape Town, South Africa, between 2015 and 2019
    (2023) Du Plooy, Elri; Salie, Mogamat; Figaji Anthony
    A Profile of Children with Traumatic Brain Injury Admitted to the Red Cross War Memorial Children's Hospital Paediatric Intensive Care Unit in Cape Town, South Africa, between 2015 and 2019 Background: Paediatric traumatic brain injury (TBI) is a public health problem with high morbidity and mortality. Objectives: We aim to highlight risk factors and describe associated morbidity and mortality of children admitted to our Paediatric Intensive Care Unit (PICU) at Red Cross War Memorial Children's Hospital in Cape Town. Methods: We retrospectively documented the hospitalization of all children with TBI admitted into our PICU between 2015 and 2019. Results: Of 272 children identified, 232 were enrolled: 190 (81.9%) had severe TBI (Glasgow Coma Scale [GCS] ≤8), 32 (13.8%) moderate TBI (GCS 9-12) and 10 (4.3%) mild TBI (GCS ≥13). Median age was 6.5 (IQR 3.5-9) years; 144 (62.1%) were male. Motor vehicle accidents accounted for 77% (179) of injuries. Two hundred (86.2%) children were invasively ventilated for a median of 3.5 (IQR 1-7) days; 26 children (13%, n=200) had a failed extubation and 16/200 (8%) required tracheostomies. Ninety-eight children (42.2%) had intracranial pressure monitoring. Almost 30% (67/232) required vasopressor support. Approximately a third (83/232) developed trauma-related seizures; 25 children (10.8%) required a Thiopentone infusion and 9 children (3.9%) a decompressive craniectomy. Common complications were post-extubation stridor (29/200 [14.5%]), hemiparesis (20/232 [8.6%]) and diabetes insipidus (15/232 [6.5%]). Median PICU stay was 3 (IQR 1-8.3) days, and hospitalization 11 (IQR 5-20) days. Eighty- three (35.8%) children were transferred for further rehabilitation; 24 (10.3%) died. Conclusion: Despite marked improvement since the 1990's, children admitted to PICU with TBI had considerable morbidity and mortality. Enhanced primary preventative strategies, especially for motor vehicle accidents, are imperative to prevent TBI in children.
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    A retrospective review of all children admitted with acute severe asthma to the paediatric intensive care unit, Red Cross War Memorial Children's Hospital between 2009-2019.
    (2023) Salie, Moegamad; Salie, Mogamat
    Background and Aim Asthma is one of the commonest chronic conditions of childhood and affects children worldwide. The majority of children who experience an acute exacerbation of asthma do not require admission to a paediatric intensive care unit (PICU). There is limited data on the admission rates, treatment modalities and length of PICU stay, for children who have acute severe asthma (ASA) in a South African context. In this study, we aim to describe the patient profiles and treatment of all children admitted to the PICU with ASA. Method We conducted a retrospective audit of all children admitted with ASA to the paediatric intensive care unit at Red Cross War Memorial Children's Hospital in Cape Town, South Africa between 01 January 2009 - 31 December 2019. Results There were 14592 PICU admissions over the 11-year period, of which 180 admissions (1,2%) were for acute severe asthma. There were 96 male (53,3%) admissions and the median, interquartile range (IQR) age on admission was 67 (37 – 93) months. Nearly all the patients received nebulisations, steroids, and magnesium sulphate before PICU admission. Half of the patients were loaded with IV salbutamol (n=96; 53,3%) and about a third (n=61; 34%) received a salbutamol infusion before admission to PICU. Similar proportions received nebulisations and steroids in PICU, 34 patients (19%) received magnesium sulphate again in PICU and a total of 130 patients (72,2%) received a salbutamol infusion. Most children received non-invasive respiratory support (n=167; 90,3%), and 18 children (9,7%) required mechanical ventilation for a median (IQR) of 3 (2 – 4) days. The median PICU stay was 1 (IQR 1 – 2) days and median hospital stay was 4 (IQR 3 – 6) days. No children died. Conclusion There has been an increasing number of children admitted to PICU with ASA over the 11- year period. There has been increased utilization of non-invasive ventilation (NIV) strategies, mainly HFNC and the duration of PICU support is short.
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    An Assessment of Critically Ill Children admitted to a General High Care Unit in a Regional Hospital in the Western Cape, South Africa
    (2020) Vosloo, Ruan; Salie, Shamiel; Breytenbach, Willem
    Background Many critically ill children in South Africa are cared for in regional hospitals by general Paediatricians. Critically ill adults and children are usually cared for in the same units. There is limited data on the numbers of children admitted and the outcomes of these children. Objective To describe the patient profile and outcomes of children admitted to a general high care unit (HCU) in a regional hospital in the Western Cape, South Africa. Methods This was a retrospective descriptive study of all children admitted to the HCU of George Regional Hospital during a one year period (2016). Demographic data, HIV, anthropometric data, immunisation status, diagnoses, medical interventions, length of stay, death or survival, and referral data to the tertiary paediatric intensive care unit (PICU) were collected. The PIM3 score and Standardized Mortality Ratio (SMR) was calculated. Results Thirty percent (144/468) of the HCU admissions were children. Most (70%) were admitted after hours. Half were under 9 months (range 3 days to 149 months). Sixty-five percent of the children required respiratory support and 45% needed inotropic support. Twenty percent of the children were transferred to the PICU. Twelve children (8,5%) died with most deaths (75%) occurring at regional level. Half of the deaths were due to sepsis with pneumonia (25%) and diarrhoea with shock (25%) accounting for the rest. The cumulative PIM3 score was 9.049 (95%CI 6.430-11.668) with an SMR of 1.326 (95%CI 1.028-1.866) observed. Conclusion Critically ill children accounted for a third of HCU admissions. Most children needed medical interventions. These require specific training and equipment that are often lacking. After hours admissions also put strain on limited staff. Most children were successfully discharged demonstrating a good outcome. This was achievable with good channels of communication and transport to a tertiary PICU.
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    Anaesthetic method and short-term outcomes of preterm infants delivered by caesarean section in a tertiary hospital in South Africa
    (2021) Stander, Raphaella; Horn, Alan; Tooke Lloyd
    Background. There are inconsistent published data describing the influence of anaesthetic type during caesarean section (CS), on outcomes of preterm neonates. Objectives. To describe indications and type of anaesthesia in preterm neonates and to describe short-term outcomes, comparing spinal anaesthesia (SA) to general anaesthesia (GA). Methods. Data were collected retrospectively on preterm babies born at 28 – 35 weeks' gestation by CS, between 1 January and 30 Sep 2014 at Groote Schuur Hospital, Cape Town, South Africa. Babies with missing data were excluded. The largest group of babies with similar indications for delivery were identified from the theatre register. Baseline characteristics and short-term outcomes for this group were extracted from an existing prospective data base, and compared between those delivered under SA and GA. Results. Data were available for 226 deliveries, having excluded 23 with incomplete data. Most babies (75%) were delivered under SA. The most common indication for CS was ‘cardiotocograph abnormalities,' in 139 deliveries. Within this group, SA was more frequent (81.7% vs. 12.9%) while GA was associated with lower Apgar scores (p < 0.001) and more intubation at birth (p = 0.004). There was no difference in mortality when comparing SA with GA. Conclusion. Our data suggest a sedative effect of maternal GA on preterm babies delivered by CS, and the need for staff with advanced resuscitation skills. This study provides novel baseline data in our setting, but these data need to be validated in a prospective study.
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    Aspects of paediatric gastro oesophageal scintigraphy
    (1988) Wynchank, Sinclair; Mann, Michael D
    This work is concerned with the application of scintigraphy in studies of foregut motility in paediatric patients; notably oesophageal transit during swallowing, gastro oesophageal reflux (GOR) and stomach emptying as measured by the gastric contents 30 and 120 minutes after deglutition of liquid. Relevant anatomy, physiology, pathophysiology and non-radioisotopic methods of gastro oesophageal examination are outlined. The extremely important question of dose deposited by ionising radiation in paediatric patients is also considered. Because currently available estimations of absorbed dose after swallowing non- absorbable radionuclides are unsatisfactory and often contradictory, a new model was derived. It is based on more physiological principles than previous models, with a continuously varying exponential passage between four compartments in the gastrointestinal tract. From a review of previous work and our experience, a standard method of examination was developed. There is emphasis on normal physiological manoeuvres. The broad extent of useful information available in the study stems from the positions in which the patient is investigated, the quantity of labelled fluid swallowed, its physiological nature and observations of oesophageal transit, GOR, gastric emptying and pulmonary aspiration after two hours. The wide range of paediatric problems amenable to investigation by this means is described, including those of a life-threatening nature. Also, the importance of using this examination to determine the likelihood of successful surgical intervention in the gastro oesophageal region is explained. By using the observations made during swallows in neonates, the closure of the lower oesophageal sphincter (LOS) was observed during a short series of rapid deglutitions. This extends previous knowledge of the function of the neonatal LOS. These findings were very clearly demonstrated by the condensed image technique. A comparison between the abilities of radiology and scintigraphy to detect GOR in paediatric patients, with and without oesophagitis, gives unequivocal results in favour of scintigraphy. Two independent clear correlations between oesophageal transit time and the severity of GOR and age are demonstrated by variance and correlation analysis. The mean duration of GOR, maximum height of a GOR, gastric contents 30 and 120 min after deglutition, the effect of the nature of liquid swallowed and age are also examined and their relations are described. The application of the method to assess drug response is illustrated by the paediatric use of cisapride, an experimental drug which increases acetylcholinesterase release. The deductions from this work include values of the radiation dose deposited in paediatric patients of various ages, after swallowing non- absorbed Tc-99m compounds. Other contributions are a scintigraphic means to allow recognition of the importance of oesophageal dysmotility in paediatrics, especially in the absence of GOR and its relevance to the efficacy of surgery in cases of apparent GOR. Also, this gastro oesophageal scintigraphic study provided information on the paediatric use of cisapride, the relevance of GOR to repeated respiratory problems and the recognition of a new paediatric syndrome analogous to the diffuse oesophageal spasm syndrome of adulthood. It has been demonstrated that a routine, uncomplicated, paediatric scintigraphic examination, useful for investigating a wide range of problems in both a first and third world setting is possible for a nuclear medicine practitioner with normally available radiopharmaceuticals, equipment and radiographical expertise.
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    An audit of transfers into the PICU at the Red Cross War Memorial Children's Hospital: a follow up study
    (2016) Dimitriades, Konstantinos; Argent, Andrew C; Morrow, Brenda M
    Background: Children are transferred from various facilities into the paediatric intensive care unit (PICU) at the Red Cross War Memorial Children's Hospital for critical care, without a specialised paediatric transfer service. A previous audit in 2003 reported a high incidence of technical, clinical and critical adverse events during transfers. Objective: To conduct a follow -up audit on interfacility transfers into PICU to determine practice and outcome changes. Methodology: Prospective observational study of all patients transferred into PICU between 1 Dec ember 2013 and 30 November 2014 and compared to the 2003 audit by Hatherill et al. Results: Analysis was performed on 204 transfers (median (IQR) age 1.8 (0.2 – 12.6) months and compared to results reported by Hatherill et al (2003). The proportion of medical transfers decreased (49% to 34.3% p=0.003) as well as the referrals from metropolitan hospitals (34.7% to 17.6%, p = 0.0001), whilst the number of referrals from academic hospitals increased from 35.1% to 44.6% (p = 0.05). Staff accompanying transfers and transfer times remained unchanged. The proportion of fixed wing transfers increased from 14.4% to 25.5% (p=0.006) whilst Helicopter transfers decreased from 9.9% to 1% (p <0.0001). 58.4% of patients were in tubated for transfer in 2003 compared to 69.1% in 2014 (p = 0.02). The rate of technical (35.6% to 39.7%, p = 0.4), clinical (26.7% to 31.9%, p = 0.25), and critical (8.9% to 8.8%, p = 0.97) adverse events remained unchanged. PICU Mortality decreased from 16.8% to 9.45% (p=0.03) with a decrease in Standardized Mortality Rate from 1.11 to 0.68. Three children died on arrival to PICU. The communication tool was used in 45.1% of transfers and its use was noted to be associated with significantly less critical adverse events (4.3% vs. 12.5%, p = 0.048). Technical adverse events were positively correlated with the clinical adverse events (Spearman's R = 0.3; p=0.000008) and critical adverse events (Spearman's R = 0.1; p = 0.03). In turn the total number of clinical adverse events were positively correlated with the total number of critical adverse events (Spearman's R = 0.5; p < 0.000001). The multiple regression analysis for PICU mortality found the total number of clinical adverse events to be independently associated with ICU mortality (adjusted OR 95% CI 2.8 (1.7 -4.7); p = 0.0001) Conclusion: The rate and staffing structure of interfacility transfers into PICU have remained unchanged, and associated adverse event rates remain high. Changes are noted in the profile of transferred patients as well as adverse events. Efforts to formalize the paediatric transfer service must be strengthened whilst using interim measures to improve the current standard through education, improved skills and PICU support.
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    Characterisation of the T cell responses induced by BCG in infants over the first year of life
    (2011) Kwong Chung, Cheong Kwet Choy; Hanekom, Willem A
    Mycobacterium bovis Bacille Calmette Guerin (BCG) is the only licensed tuberculosis (TB) vaccine. Despite the immunisation of 3 billion individuals with this vaccine, TB remains a major cause of mortality worldwide. Therefore, there is an urgent need for more effective TB vaccines. BCG is likely to remain central to future TB prevention strategies, which could include a BCG prime at birth, followed by boosts with novel TB vaccines within the first year of life, or at later ages. Therefore, a comprehensive understanding of BCG induced immunity is required for the successful design and implementation of novel TB vaccination strategies. This was addressed in the following two studies.The aim of the first study was to characterise specific T cell immunity following BCG vaccination. These data are critical to determine when to optimally boost BCG induced immunity in infants. We enrolled infants routinely vaccinated with BCG at birth, and determined the frequency of T cells induced by immunisation, at various time points over the first year of life. The T cells were identified by binding of cell surface markers and characterised by cell-specific cytokine production, following 12 hr incubation of infant whole blood with BCG. Multiparameter flow cytometry was used for the analysis. We found that the peak vaccine induced CD4+ T cell response occurred at 10 weeks, followed by a contraction phase. BCG specific CD4+ T cells became more poly functional, and acquired the profile of long-lived T cells (measured by Bcl-2 expression), over the first year of life.
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    Characterization of the genetic defects in patients with Severe Combined Immunodeficiency (SCID)
    (2002) Shaboodien, Gasna
    A specialised clinic for the diagnosis of primary immunodeficiency diseases was established at the Red Cross War Memorial Children's Hospital (RXH) in 1982. The patient load was significant as clinic records indicated that 122 primary immunodeficiency cases were diagnosed on clinical and laboratory data in the period between 1983-1999. More than fifty percent of these conditions were antibody deficiency. Of the rest, nine cases were ascribed to severe combined immunodeficiency (SCID). The aim of the project was to do (1) mutational analysis on the affected families, (2) on the basis of the mutational analysis, offer genetic counselling, (3) do carrier screening tests on the families studied, and (4) to try and find a genotype/phenotype relationship in the gamma chain gene.
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    Cystic fibrosis in South Africa: spectrum of disease, diagnosis, and determinants of outcome
    (2023) Zampoli, Marco; Morrow, Brenda
    Cystic fibrosis (CF) occurs with varying incidence in all populations throughout the world but much less is known about the epidemiology and outcomes of CF in low-or-middle income countries (LMIC) compared with high income settings. Continued improvement in CF-related outcomes and survival witnessed in the past decades is attributed to multiple factors yet sub-optimal quality of CF care, and limited CF diagnosis capacity continue to exist in most LMIC, including South Africa (SA). CF treatment and prognosis have been transformed by the recent introduction of highly effective cystic fibrosis transmembrane conductance regulator modulator drugs (CFTRm). However, access to these transformative drugs for those with eligible genotypes is currently limited to high-income countries. Understanding the clinical spectrum of CF in SA and investigating novel techniques to diagnose CF is important to advocate for improved quality of CF care including CFTRm drugs. The overall aim of this work was to document the spectrum and outcomes of CF in South Africans and to investigate more sensitive measures to diagnose CF and CFTR-related disorders in this population. The studies included in this thesis are divided into two components. This first component comprises observational cohort studies derived from a single-centre CF clinic dataset in Cape Town, SA, and the nation-wide South African CF registry, which was established in 2018 in preparation for this thesis. The CF registry cohort in SA was then compared in a cross-sectional study to a matched Canadian CF registry cohort, and differences in lung function and nutrition outcomes adjusted for known factors. The second component was a prospective study investigating the feasibility and diagnostic utility of the novel β-adrenergic sweat test in a cohort of South Africans with inconclusive CF diagnosis. The chapters of this thesis are presented as published manuscripts, which collectively address the overall aim of this body of work. The SA CF registry in its first year of inception captured a total of 447 people with CF across both private and public health sectors. Summary demographic descriptions of the cohort include median age of 14.7 years with self-identified White race making up 70% of the CF population, followed by Mixed-race ancestry (19%) and Black Africans (10%). Genotype pattern mirrored ancestry with F508del is the most common variant in Whites and people with Mixed-race ancestry, and 3120+1G>A (class I) the most common variant in Black Africans. Overall, 81% of people with CF (pwCF) in SA have at least one copy of F508del and are, thus, eligible for elexacaftor/tezacaftor/ivacaftor. A key finding of the registry-based studies was that lung function and nutrition outcomes in SA were significantly lower across all ages compared with Canada, attributed to differences in the quality of CF care and social determinants of CF health between the two countries. In SA, poor nutrition was the strongest factor independently associated with severe lung disease and was more prevalent in people living in lower 10 socioeconomic conditions, including people who were not White. Another key finding was despite significant improvement in overall CF survival at a single centre in Cape Town over the past 40 years, disparities between race groups still exist in SA with increased risk of mortality observed in young children who were not White. People with Black African ancestry, who form the majority of the SA population, are likely to be underrepresented in the SA CF registry, raising concern that CF is being missed or underdiagnosed in the majority of South Africans. Furthermore, the genotype of Black Africans means that none are eligible for CFTRm, which has serious implications for future treatment. These registry-based studies highlight disparities in CF care and outcomes both within SA and compared with a high-income setting – novel findings because SA is one of only a few LMIC with CF registries. Addressing these disparities affecting people with CF in SA will require interventions such as greater awareness of CF in SA, universal newborn screening for CF, focused attention on improving nutrition and overall improvement in the quality of essential CF care, especially as LMIC have disproportionally more pwCF who are ineligible for CFTRm drugs. The diagnosis of CF using standard approaches may remain inconclusive in a small proportion of individuals, which leads to unnecessary anxiety for families and inappropriate treatment where people do not actually have CF or a CFTR-related disorder. Furthermore, accurate diagnosis of CF is important for research and submission of registry data. The β-adrenergic sweat test was proposed as an easier alternative to other electrophysiological measurements of CFTR function such as nasal potential difference and intestinal current measurements, which are not available in SA. We therefore conducted a study evaluating this hypothesis in adult subject controls, and 32 individuals (mostly children) whose CF diagnosis was inconclusive. Key findings of this study were that the β-adrenergic sweat was superior to sweat chloride test in excluding CF in the majority of subjects and that βadrenergic sweat secretion in children was lower compared to adults. Implications and novelty of this research are that existing reference ranges for this test may not be applicable in children, and confirmation that the β-adrenergic sweat test is a viable alternative for measuring CFTR function. A number of families benefited from this study by reversal of their incorrect CF diagnosis. The overriding finding and impact of this work has been to highlight disparities in diagnosis, treatment, and outcomes of CF within SA and in the global context. The current status of CF care in SA mirrors many other LMIC that share similar challenges and barriers to improving CF care, including access to affordable CFTRm drugs. The findings of this thesis have made valuable contributions to local and global advocacy initiatives to improve CF care and access to CFTR drugs for many thousands of pwCF living in LMIC who are being left behind in this new era of CF treatment.
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    Development of a Duchenne Muscular Dystrophy Registry in South Africa to optimise care
    (2017) Jalloh, Alhaji Alusine; Wilmshurst, Jo M; Wessels, Tina
    Background: The most prevalent, most lethal of the inherited dystrophies is Duchenne Muscular Dystrophy (DMD) and globally, the incidence is 1 in 3500 live male births. Currently, DMD has no cure, the latest care guidelines, especially on corticosteroids, cardiac interventions, and non-invasive ventilation, are all associated with improved muscle function, survival and quality of life. This reflects the fact that the natural history of DMD has been changed by these effective measures. Despite these advances, the progression and disastrous outcome of the disease cannot be modified. Potential therapeutic approaches that target the causative genetic mutations raise hopes of promising treatment for DMD. Many clinical trials of molecular genetic therapies have been planned and conducted for DMD. In South Africa, even though mutational characteristics of South African DMD/BMD patients have been described in several studies, the development of experimental therapies faces many challenges due to the lack of epidemiological data, the natural history of the disease and information about clinical care amongst Africans. Understanding the disease course of the local population can lead to better care approaches, further with the possibility of gene therapy becoming available, patients that would qualify for such treatment need to be identified. Hence the need for a DMD specific disease registry. Objective: This study aims to describe the concept and design of the first DMD disease registry of South Africa using Research Electronic Data Capture (REDCap) Methods: A comprehensive literature review was undertaken to identify the key areas of DMD, which must be recorded to permit comparison across disease expression and intervention variables. The registry was developed using REDCap's web based online designer accessed through the Clinical Research Centre (CRC) in the Faculty of Health Sciences at the University of Cape Town, and the workflow methodology was adopted to manage the registry. Clinical data from DMD patients form the database and consists of seven parts: 1) Enrolment details, 2) Background data, 3) Current disease, 4) Schooling, career prospects, and life style/psychological details, 5) basic activity of living scale, 6) power chart, 7) current motor function/symptoms. Electronic case report forms were created from these clinical data by the use of REDCap and for specific variables serial entries were possible relating to disease progression. We adopted international data standards proposed by TREAT-NMD, a global network of registries on DMD to ensure our data is internationalised and comparable to other registries. Results: Retrospective data entry combined with dynamic prospective recording of data was utilized in this project. Building on an existing basic database, 100 confirmed DMD boys are currently eligible for inclusion into the registry. The registry database consists of 7 forms collecting information on clinical and genetic information, which is subdivided into 100 items making a total of 210 variables. As our registry is an on-going study, sequential analysis of accumulated data will be done going forward to review trends on our DMD patients. Conclusions: This work describes the concept and design of our DMD registry and the steps followed to its establishment with REDCap. The focus is to consolidate clinical and genetic information on South African DMD patients that will translate to clinical research and form the basis for this patient information to be linked nationally and internationally. It is the hope that such an effort can be replicated in the conceptualisation of new disease registries.
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    Development of a process to support stakeholder engaged children's nursing workforce planning for high-need, lower-resourced Primary Health Care systems in Malawi
    (2023) North, Natasha; Coetzee, Minette; Brysiewicz, Petra
    Background: Effective workforce planning requires stakeholders to agree about the desired roles and contributions of advanced and specialist nurses across different tiers of service delivery. Role descriptions can help to reduce role confusion and inform workforce planning if stakeholders use them to establish a shared contextual basis for defining roles within their health service or system. There is a scarcity of rigorously developed role descriptions worldwide, especially role descriptions accurately reflecting the work of advanced and specialist nurses in Africa. Aim: Malawi is one of many African countries investing in establishing a specialist children's nursing workforce as part of globally advocated strategies to improve child health. This study aimed to develop a replicable process to assist stakeholders with specialist nursing workforce planning, informed by understanding the roles and contributions of children's nurses in the context of Malawi's health system. Methods: This study used a multiple methods approach with four phases. Design principles of stakeholder engaged research were incorporated into all research activities, which included: 1) a systematic scoping review to inform stakeholder identification; 2) a situational analysis; and 3) focus groups and interviews with 41 children's nurses in Malawi about their roles. Following qualitative content analysis of interview and focus group data, 4) concept mapping was used to integrate characteristics of the roles of children's nurses in Malawi and published role descriptions of other African specialist and advanced nursing roles with global frameworks for advanced nursing roles. Results: The study generated a framework for systematic identification of nursing HRH stakeholders; a situational analysis; and richly descriptive accounts of the roles of children's nurses in Malawi. The major product of the study was a flexible framework proposing four role domains and associated categories of activity for specialist and advanced practice children's nurses in Malawi, also applicable to other specialisations and other African health systems. Conclusions: The flexible framework is a distinctive response to the needs of African health systems. Advanced and specialist nurses in Africa are establishing their newly introduced roles into health systems in transition, within challenged and challenging practice contexts which demand high levels of adaptability. The framework is positioned to form part of a replicable process for stakeholder engaged nursing workforce planning. It is hoped that it will assist nurses and other stakeholders to manage the development of advanced and specialist roles at the levels of individual nurses, institutions and health systems.
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    Epidemiology of pertussis in children hospitalised with respiratory tract infection
    (2021) Muloiwa, Rudzani; Zar, Heather; Hussey, Gregory
    The availability of an effective vaccine against Bordetella pertussis substantially reduced the morbidity and mortality from pertussis, however, in the last decade there appears to have been a substantial increase in pertussis cases as reported mainly in high income countries. Although it is believed that the greatest burden of pertussis, including deaths, is in low- and middle-income countries (LMICs), there seem to be little data available to back this up. This thesis set out to find data that will give some insight into the burden of pertussis in a low- and middle-income setting in infants and children with severe lower respiratory tract infection (LRTI). Given the paucity of data in LMICs, the thesis started by systematically searching for existing data that will give some indication of the possible extent of the pertussis problem in these countries. Secondly, a prospective study was conducted at a children's hospital. As hospital admission is a marker of severe disease, these children were targeted as the appropriate population in which to meaningfully conduct a primary study on the burden of pertussis. In addition to quantifying the burden by describing the prevalence of confirmed pertussis in this group of children, the study set out to look for potential factors that may be associated with increased risk of pertussis. LRTI are now commonly known to be associated with identification of multiple organisms in respiratory samples, this study aimed to also look at organisms that are detected with Bordetella pertussis; and investigate whether this association was in any way associated with severe disease or negative outcomes. Finally, this study hoped to identify clinical features that could be used to develop a more reliable clinical case definition of pertussis. Chapter 1 gives a background that justifies the undertaking of this study. In chapter 2 a systematic review quantifies, using the best available data, the burden of pertussis in LMICs. Chapter 3 clarifies the methods briefly described in the rest of the manuscript. The burden of pertussis due to the two organisms known to cause the disease, Bordetella pertussis and Bordetella parapertussis, is described in some detail. In both this chapter and the earlier mentioned systematic review (chapter 2), the burden of pertussis is stratified by subgroups to identify potential risk factors. The issue of risk is formally and specifically taken up in the chapter that follows (chapter 5) where potential risk factors are analysed, and the independent impact for some of these factors is established. The last two results chapters (chapters 6 and 7) deal respectively with the conundrum of finding other respiratory organism in the same specimen with Bordetella pertussis and failure to find useful clinical criteria that can help with improved diagnosis of pertussis. While there is no established pattern noted between pertussis and most organisms, a few give signals of being independently associated with Bordetella pertussis even if the clinical relevance is not clear at the moment. In the final chapter of the thesis (chapter 8) I conclude the thesis by making an argument that although there are still knowledge gaps, the thesis gives a clear indication that pertussis remains a serious problem in LMICs especially for some groups that show increased risk of the disease or its severe consequences.
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    Epidemiology of pertussis in children hospitalised with respiratory tract infection
    (2021) Muloiwa, Rudzani; Zar, Heather J; Hussey, Gregory D
    The availability of an effective vaccine against Bordetella pertussis substantially reduced the morbidity and mortality from pertussis, however, in the last decade there appears to have been a substantial increase in pertussis cases as reported mainly in high income countries. Although it is believed that the greatest burden of pertussis, including deaths, is in low- and middle-income countries (LMICs), there seem to be little data available to back this up. This thesis set out to find data that will give some insight into the burden of pertussis in a low- and middle-income setting in infants and children with severe lower respiratory tract infection (LRTI). Given the paucity of data in LMICs, the thesis starts by systematically searching for existing data that will give some indication of the possible extent of the pertussis problem in these countries. Secondly, a prospective study was conducted at a children's hospital. As hospital admission is a marker of severe disease, these children were targeted as the appropriate population in which to meaningfully conduct a primary study on the burden of pertussis. In addition to quantifying the burden by describing the prevalence of confirmed pertussis in this group of children, the study set out to look for potential factors that may be associated with increased risk of pertussis. LRTI are now commonly known to be associated with identification of multiple organisms in respiratory samples, this study aimed to also look at organisms that are detected with Bordetella pertussis; and investigate whether this association was in any way associated with severe disease or negative outcomes. Finally, as data has been emerging that in the context of immunisation, the clinical presentation of pertussis may no longer be following a classical pattern, this study hoped to identify clinical features that could be used to develop a more reliable clinical case definition of pertussis. 2 Chapter 1 gives a background that justifies the undertaking of this study as well as give a summary of the methods used to answer the question of the thesis. The chapter also gives an indication of the structure that the thesis follows. In chapter 2 a systematic review quantifies the burden of pertussis in LMICs using the best available data. In chapter 3 the burden of pertussis due to the two organisms known to cause the disease, Bordetella pertussis and Bordetella parapertussis, is described in some detail. In both this chapter and the earlier mentioned systematic review (chapter 2), the burden of pertussis is stratified by subgroups to identify potential risk factors. The issue of risk is formally and specifically taken up in the chapter that follows (chapter 4) where potential risk factors are analysed, and the independent impact for some of these factors is established. The last two results chapters (chapters 5 and 6) deal respectively with the conundrum of finding other respiratory organism in the same specimen with Bordetella pertussis and failure to find useful clinical criteria that can help with improved diagnosis of pertussis, specifically in children presenting with acute severe lower respiratory tract infection. While there is no established pattern noted between pertussis and most organisms, a few give signals of being independently associated with Bordetella pertussis even if the clinical relevance is not clear at the moment. In the final chapter of the thesis (chapter 7) I conclude the thesis by making an argument that although there are still knowledge gaps, the thesis gives a clear indication that pertussis remains a serious problem in LMICs especially for some groups that show increased risk of the disease or its severe consequences.
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    Evaluating the Psychometric Properties of Neurodevelopmental Assessment Tools in a South African Context
    (2021) Zieff, Michal R; Donald, Kirsten; Hoogenhout, Michelle
    Neurodevelopmental and behavioural tools, used to assess children's cognitive and psychological development, play important supportive roles in clinical decision-making processes. It is therefore important that inferences made based on the information generated by these tools are valid and reliable. Because validity and reliability are inextricably tied to the context in which the tool is administered, it is critical that tools, including established “gold standard” tools, undergo ongoing psychometric evaluation. This is particularly important when tools are used in contexts different to that in which the original tool was developed. The use of poorly performing measures in clinical settings may result in a higher risk of misinterpretation of results or misdiagnosis, carrying serious implications for provision of interventions. This dissertation explored the psychometric properties of two frequently used behavioural tools in a South African context. The first aim of the dissertation was to investigate the use, cultural appropriateness, and psychometric soundness of Achenbach System of Empirically Based Assessment (ASEBA) forms in sub-Saharan Africa. The ASEBA forms are used worldwide to screen children and adolescents for behavioural and emotional problems. To achieve this aim, I conducted a systematic review of the psychometric properties of the ASEBA forms in sub-Saharan Africa. The second aim was to evaluate the structural and construct validity of a commonly used measure of AttentionDeficit/Hyperactivity Disorder (ADHD), the Swanson, Nolan, and Pelham ADHD Rating Scale (SNAP-IV), in a sample of South African children with neurodevelopmental disorders (NDDs), including Autism Spectrum Disorder and Intellectual Disability. The systematic review identified 58 studies with sub-Saharan African participants that reported measurement properties of the ASEBA forms. Most studies came from Southern (n = 29, 50%) or East African (n = 25, 43%) countries. Forty-nine studies (84%) used translated versions of the tool, but details regarding the translation process, if available, were often sparse. Most studies (n = 47, 81%) only reported internal consistency (using coefficient alpha) for one or more subscales. The methodological quality of the psychometric evaluations varied considerably across all measurement properties, except for internal consistency. There is limited good quality psychometric evidence available for the ASEBA forms in sub-Saharan Africa. Recommendations include implementing a standardised procedure for conducting and reporting translation processes and conducting more comprehensive psychometric evaluations of the translated versions of the tools. Parents of 109 children with one or more diagnosed NDDs completed the SNAP-IV. A subset of parents (n = 79) also completed the ASEBA Child Behaviour Checklist (CBCL/6-18). We conducted a confirmatory factor analysis to inspect the two-factor structure of the SNAP-IV (Inattention + Hyperactivity-Impulsivity). We also calculated ordinal coefficient alpha (α) to estimate internal consistency. Finally, we correlated scores of SNAP-IV and CBCL/6-18 subscales to estimate concurrent, convergent (ADHD + externalizing behaviour), and discriminant (ADHD + internalizing behaviour) validity respectively. The two-factor model performed acceptably (χ2 (134) = 249.82, p < 0.001, TLI = 0.868, RMSEA = 0.089, p < 0.001). The model fit improved after removing three problematic items, two of which were dependent on the child's level of spoken language (χ2 (89) = 135.17, p < 0.01, TLI = 0.942, RMSEA = 0.069, p = 0.096). The revised SNAP-IV subscales had acceptable internal consistencies (α = 0.85-0.86). Correlation coefficients between the SNAP-IV and ADHD-related CBCL/6-18 subscales were significant (r = 0.53- 0.62, p < 0.001). Correlations between ADHD and externalizing behaviours (r = 0.45, p < 0.001) and internalizing behaviours (r = 0.38, p < 0.001) respectively were not significantly different (z = 0.97, p = 0.165). The findings tentatively support the use of the SNAP-IV in this group of children. However, there are limitations to its performance in this population likely related to the presence of NDDs. Taken together, the findings of these two studies highlight the need for clinicians and researchers to conduct ongoing psychometric testing of behavioural tools for use with linguistically and culturally diverse sub-Saharan African populations. The data also reveal important insights regarding problems associated with using standard behavioural tools in children with complex clinical presentations.
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    An evaluation of the nutritional status of preschool chldren living in a rural health district : implications for a community based nutrition programme in the Northern Province
    (1999) Saitowitz, Romy; Shung King, Maylene; Hendricks, Michael
    The study aimed to evaluate the nutritional status of pre-school children (0-6 years), and the activities of a local CBNP serving these children, in the Ngwaritsi health district of the Northern Province. The following objectives were identified: o To determine the anthropometric status of children 0-6 years o To determine the dietary intake of children 0-6 years o To evaluate the nutrition services offered to these children by a local CBNP o To make recommendations, based on these findings, for improving existing strategies to address malnutrition in the area.
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    Health status and household survey of the community served by the White Location clinic in the Knysna municipality
    (1996) Stanford, Janet Alice
    The subject of this research is a basic demographic and health status survey. The location of the study is an informal settlement within the Municipality of Knysna, a town on the Southern Cape coast of South Africa with a population of approximately 40 000. Maps in Appendix 1 and 2 show the Western Cape and the study area respectively. The delivery of health services in the area has historically been fragmented, with the private sector and the provincial hospital providing curative services and the Municipality taking responsibility for environmental and personal preventive care such as immunisation and family planning. As a consequence of fragmented health care delivery, health information systems and planning have not been geographically integrated. The philosophy of a cohesive, well planned and equitable service provided to all residents of a district is dependent on adequate information for planning. It is hoped that this study will inform such a planning process.
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    Investigation of Copy Number Variation in South African Patients with Congenital Heart Defects
    (2020) Saacks, Nicole Aimee; Shaboodien, Gasnat; Zühlke, Liesl
    Background: Congenital heart disease (CHD) is the leading non-infectious cause of paediatric morbidity and mortality worldwide and a significant social and healthcare burden. The aetiology of CHD is poorly understood, though heritable genetic factors including copy number variants (CNVs) have been shown to contribute to the risk of CHD in individuals of European ancestry. However, the role of rare CNVs in the development of CHD in African populations including South Africa is unknown. This study aims to identify pathogenic and likely pathogenic CNVs in South African cases of CHD. To our knowledge, this is the first study to investigate the genetic basis of CHD in a South African cohort. Methods: The study cohort included 105 patients presenting to the cardiac clinics at Red Cross War Memorial Children's Hospital and Groote Schuur Hospital with non-syndromic isolated CHD (n = 76), nonsyndromic CHD with additional extra-cardiac anomalies (n = 17), and positive controls with syndromic CHD (n = 12). Genotyping was performed using the Affymetrix CytoScan HD platform. Rare CNVs were filtered using stringent criteria for their size and algorithm-specific quality score and were compared against a gene panel of known CHD-associated genes. Candidate genes were considered based on pLI scores and reported CHD phenotypes in mouse models. The identified CNVs were validated by quantifying the read-coverage of available whole-exome sequencing data of a similar overlapping cohort. Results: Chromosomal microarray analysis was successful for 101 participants (including 89 non-syndromic CHD cases and 12 control cases) and led to the identification of eight CNVs overlapping genes known to be causal for CHD (GATA4, TBX1, FLT4, CRKL, NSD1, and B3GAT3), and four CNVs encompassing candidate genes likely to play a role in the development of CHD (DGCR8, JARID2, KDM2A, and FSTL1). The CNVs were identified in nine unrelated individuals: five of the CNVs were classified as pathogenic or likely pathogenic (5.6% of the cohort) and four were classified as variants of unknown significance (4.6%). CNVs of interest were validated using the available whole-exome sequencing data. Conclusions: In this study, we show that chromosomal microarray analysis is an effective technique for identifying CNVs in patients diagnosed with CHD and that this approach can be performed locally in South Africa, producing results similar to those seen in international CHD studies. The findings of this thesis highlight the wide genetic heterogeneity of CHD and the growing importance of CHD genetic studies for both research and clinical purposes. Advancing our understanding of CHD aetiology will help define disease risk in South Africa and improve the way we care for and assess our cardiac patients.
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    Multimodal neuroimaging and early neurobehavioural and developmental correlates of alcohol and methamphetamine exposed infants in Cape Town
    (2015) Donald, Kirsten Ann Mary; Stein, Dan J; Narr, Katherine L; Riley, Edward P
    Alcohol use and alcohol use disorders contribute a significant proportion of the burden of disease in low, middle, and high-income countries. As a result, fetal alcohol spectrum disorders (FASD) represent one of the most common preventable causes of intellectual disability globally. Understanding the core brain areas of susceptibility to prenatal alcohol as they manifest in early life is key to developing strategies for early focused identification and intervention. This thesis explored the relative impact of prenatal alcohol exposure on the brain in infants as measured by multimodal brain imaging and the relationship of these findings to early neurobehavioral and developmental status. The specific aims the thesis addressed included leveraging structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), proton magnetic resonance spectroscopy (1H-MRS) and resting sate functional MRI (rs-fMRI) scans in approximately 100 infants (50 alcohol exposed and a matched number of control, unexposed babies) at 2-4 weeks of age, to assess group differences in early brain development. Correlations between multimodal neuroimaging measures and neonatal neurobehavioral assessments and associations between early structural imaging findings and later infant developmental, as measured by the Bayley III assessment at 6 months, were further explored in the same group of infants. These studies addressed the hypothesis that maternal alcohol use in pregnancy would result in quantitative MRI abnormalities demonstrable at 2-4weeks of age and that these changes would correlate with early indicators of neurobehavior and development. Chapter 1 presents the rationale and outline of the thesis. The burden of fetal alcohol spectrum disorders (FASD) is described in the context of different resource settings around the world with detailed reference to South Africa. Chapter 2 presents a published systematic literature review of published studies of MRI in children and adolescents with prenatal alcohol exposure. Chapter 3 provides an overall description of the methods and context for this study. Although the results chapters each include a focused methods section, the word restrictions of journal articles did not allow for adequate contextual detail for the project as a whole.
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    Neurocognitive outcome of HIV-infected children on antiretroviral therapy at Red Cross Children's Hospital
    (2004) Smith, Lara; Adnams, Colleen; Eley, Brian
    Central nervous system involvement contributes significantly to the morbidity and mortality of paediatric HIV infection. The spectrum of CNS morbidity varies from minor developmental disabilities to severe, progressive encephalopathy. Therefore regular developmental evaluation should be regarded as an essential component of the overall care of HIV-infected children. Antiretroviral therapy may arrest or even reverse neurocognitive and motor deficits associated with HIV infection.