Pneumonia is the greatest cause of childhood mortality outside the neonatal period, yet the pathogen-specific aetiology of childhood pneumonia remains poorly defined. Vaccine probe studies estimate that approximately one third of children <5 years of age with radiographic endpoint consolidation have pneumococcal pneumonia in settings prior to the introduction of pneumococcal conjugate vaccination (PCV), such as much of South Asia. 10-valent PCV was introduced to the Nepali infant immunisation schedule in August 2015. I investigated childhood pneumococcal pneumonia in Nepal. I aimed to describe the prevalence of pneumococcal infection in children with suspected invasive bacterial disease admitted to Patan Hospital, Kathmandu, Nepal; to assess the impact of 10- valent PCV on pneumococcal pneumonia; and to assess two potential diagnostic tests for pneumococcal pneumonia based on the childhood response to pneumococci - assay of antibodies from lymphocyte supernatant (ALS) and analysis of differential gene expression (transcriptomics) - in children with pneumonia at Patan Hospital. Pneumococci were the second-most most prevalent pathogen isolated from the blood of children between 2005 and 2016. Interrupted time series analyses of data from children admitted with pneumonia from March 2014 - December 2016, showed a small increase (approximately 4%) in the odds of admission with pneumonia in comparison to non-pneumonia admis- sions temporally associated with 10-valent PCV introduction. However, it was not possible to adjust these time series analyses for extreme events including earthquakes (April 2015) and clean fuel shortages/increased air pollution (winter 2015/2016). In contrast, the indirect cohort method (a case-control approach in vaccinated vs unvaccinated children) showed vaccine effectiveness of 84% on the odds of nasopharyngeal carriage of vaccine-type pneumococci, but no effectiveness on pneumonia in these early data. Assay of IgG ALS pneumococcal capsular polysaccharides was complicated by what appear to be non-specific binding to capsular polysaccharides (of both S. pneumoniae, particularly serotype 3, and H. influenzae). Assay of IgG ALS to the best-performing of five pneumococcal proteins assessed had a sensitivity of 88% and specificity of 71% for the discrimination of pneumococcal pneumonia from other bacterial pneumonia. A transcriptomic signature discriminated between pneumococcal pneumonia and other bacterial pneumonia with a sensitivity of 91% and specificity of 100%. This thesis therefore contributes to knowledge of the clinical epidemiology of pneumococcal disease in South Asia. These data may also contribute to public health policy-making in the region. In addition, the development of two diagnostic tests for the aetiology of childhood pneumonia may be useful for future studies of childhood pneumonia aetiology.

Background: Children with congenital heart disease (CHD) often face barriers unique to their diagnoses, making participation in community physical activity programs difficult. This pilot, feasibility study evaluated the appropriateness (i.e. feasibility and enjoyment ) of the Sportball program among a group of children with CHD. This study also sought to observe any changes in physical literacy outcomes and to explore physical activity perceptions of participants, in order to better inform the future use of community-based interventions for this population. Methods: This study employed a mixed-methods evaluation of a 10-week community-based intervention. Data from two focus groups (baseline and post-intervention) and field notes after each intervention session were collected. Physical literacy outcomes were determined using the Canadian Assessment of Physical Literacy. Results: Participants with CHD (n=9) successfully participated in Sportball, as demonstrated by the ability of all participants to complete program activities, participants’ overall enjoyment of the program and fair attendance (approximately 80% of intervention sessions). Improvements in motor skill and torso strength were observed, with a statistically significant difference (p < 0.01) in motor skill classification. Participation in Sportball facilitated positive social interactions during sport and was influenced by personal, social and environmental factors. Conclusion: Overall, participation in Sportball is appropriate for children with CHD who may have motor development delays and/or activity restrictions.

The psychology service programme was implemented at the Kalafong Paediatric HIV Clinic. The students from the Department of Psychology from the University of Pretoria were involved. The aim of the study was to explore, explain and describe the experiences of the personnel at the Clinic during the implementation of the programme in terms of an interpretive narrative framework. A qualitative research design was used. The primary source of data collection was through interviews. Interpreting experience took place at Reissman’s five levels of representation and Labov’s six elements for data reduction and interpretation were used. The emerged interpretive categories were presented as questions. The study found that the multidisciplinary team identified the need for psychological intervention, more so during the time when some of the adolescent patients had discovered that they were HIV positive. The patients were struggling to cope with the reality of accepting the diagnosis. The study noted the challenges that were experienced during the implementation, as well as the highlights. Availability of the psychology students seemed to be the greatest challenge as well as the issue of arranging psychological consultations to coincide with the same date for other consultations among other challenges. This study exhibited a mutual feeling that the implementation of the psychology service programme was a good initiative and ought to be continued at the Clinic. / Dissertation (MA)--University of Pretoria, 2013. / gm2014 / Psychology / unrestricted

It is well established that engaging in a physically active lifestyle benefits the long-term development and well-being of all children and youth. For children living with chronic medical conditions (CMCs), the benefits of participating in physical activity are critically important for achieving positive health outcomes and mitigating the risk of secondary chronic disease and more significant morbidity. Unfortunately, most children with CMCs are insufficiently active to achieve its associated benefits, often citing disease-related barriers to participation. To better understand how children with CMCs navigate their participation in physical activity, the concept of physical literacy can be applied as a helpful lens. In brief, physical literacy describes one’s physical, cognitive, and affective capacities to engage in an active lifestyle. Despite facing unique risks and barriers in active contexts, some evidence suggests that children with CMCs can still achieve or excel in their physical literacy. This suggests that those who are struggling to navigate their participation in an active lifestyle would benefit from potential support in their physical literacy development. However, efforts to intervene could be misplaced or misguided without adequate contextual knowledge about how the lived experiences of children with CMCs inform their physical literacy development. The overall purpose of this research was to comprehensively examine how physical literacy is developed among children with CMCs. Collectively, this is accomplished throughout the dissertation by contextualising, describing, and reflecting on how children with CMCs develop physical literacy. Margaret Whitehead’s conceptualisation of physical literacy was the guiding framework for this work, built on a philosophical foundation combining monism, existentialism, and phenomenology. A pragmatic approach was applied to guide the research process, employing mixed and multiple methods. This research was conducted with school-aged children, 8 to 12 years old, living with CMCs and recruited from outpatient Cardiology, Endocrinology, Hematology, Cystic Fibrosis/Respirology, and Neurology clinics at a local children’s hospital in Ottawa, Ontario. Where applicable, physical literacy was measured using the second edition of the Canadian Assessment of Physical Literacy. Qualitative methods were strategically applied and combined throughout the research program, including interviews, focus groups, open-ended questionnaires and field notes. This research was conducted during the COVID-19 pandemic, which dramatically influenced physical activity behaviours worldwide. Thus, the physical literacy development of children with CMCs could only be understood by first acknowledging the relative impact of the pandemic. The purpose of Article 1 was to evaluate and understand how the COVID-19 pandemic influenced the physical literacy development of children with CMCs during the first two years (2020-22). Compared to pre-pandemic matched pairs, the overall physical literacy levels of children with CMCs were significantly diminished during the pandemic, driven primarily by decreases in physical competence and daily behaviour. It was challenging for children with CMCs to play active games in the context of the pandemic, where they had to learn how to navigate additional constraints to prevent the spread of COVID-19. These precautions also constrained how children with CMCs developed social connections, which was cited as a reason that participants felt less motivated to engage in physical activities during the pandemic. Children with CMCs also spoke hesitantly about returning to pre-pandemic activities, as they perceived changes in their physical competence and the participation contexts would make it difficult to be engaged (i.e., mask-wearing requirements, uncertain safety rules, potentially sudden closures). Nonetheless, participants with CMCs maintained high levels of measured intrinsic motivation and confidence in physical activity. Once the pandemic context was better understood, the purpose of Article 2 was to describe the overall physical literacy development of children with CMCs by examining measured outcomes and comparing the experiences and perspectives of those with high and low levels of physical literacy. Most children with CMCs (~80%) were beginning (< 17th percentile) or progressing (<65th percentile) in their physical literacy journey when compared to normative classifications. Total physical literacy seemingly contributed to a sense of self and how participants with CMCs approached new experiences. In the affective domain, attitudes towards physical activity were generally informed by prior experiences, and the meaningfulness of physical activity was more salient than enjoyment. In their physical competence, participants with CMCs found it particularly difficult to navigate bodily self-regulation alongside complex movement patterns and understood the implications of practice for sustained participation in physical activity. Cognitively, it is promising that children with CMCs adopted general definitions of physical activity, recognising the benefits of an active lifestyle for their health, and understood the relative importance of evaluating risks in active contexts. Participants with higher scores spoke more about physical activity experiences where the affective, cognitive, physical, and behavioural domains seemingly overlapped (i.e., curiosity in active settings, valuing practice experiences, performing complex movement patterns in game contexts, etc.). Overall, findings identified multiple areas where children with CMCs may be supported in their physical literacy development, including opportunities to practice bodily self-regulation strategies and develop confidence in risk evaluation. Finally, the purpose of Article 3 was to reflect upon the acquired knowledge of physical literacy among children with CMCs by observing how it may be applied within a community-based setting. The “I Can Play Anything” multi-sport program was developed for the RA Centre, a community-based recreational facility in Ottawa, Ontario. The program was designed based on the concept of physical literacy and teaching principles drawn from various behaviour change theories, including self-determination theory. Descriptive, reflective and reflexive data were collected using a combination of interviews, focus groups, field notes and open-ended questionnaires. The developed themes represent the combined expectations, applications, and potential implications of the program for children with CMCs, which are: 1) Learning to play, 2) Inclusion supported by individualised variations, and 3) Understanding one’s need for rest. Reported perceptions and experiences within the community-based multi-sport program reflect how children with CMCs may be effectively supported in similar, active contexts. The final chapter of this dissertation integrates the results from all three articles, emphasising areas of physical literacy development which are particularly relevant to the lived experiences of children with CMCs. Salient ideas discussed throughout this dissertation were recognising and valuing skill progressions developed through practice, the influence of meaningful experiences on active behaviours, self-regulating activity intensities in active contexts, and applying a general definition of embodied participation to physical literacy. My research contributes valuable knowledge to the methodological, theoretical, and practical advancement of physical literacy research, particularly among children with CMCs. This dissertation emphasises and encourages the unique potential for collaboration between the health and recreation sectors to facilitate the ongoing physical literacy development of children living with CMCs.

Background Procedural sedation and analgesia (PSA) is considered a core competency in emergency medicine as patients present to the Emergency Centre (EC) on an unscheduled basis, often complex complaints that necessitate emergent management (1). Previous evidence has consistently shown that procedural sedation and analgesia(PSA) in the EC in the paediatric population, even the very young, is safe if appropriate monitoring is performed and appropriate medications are used (2–5). The aim of the study was to describe the indications for PSA in the paediatric EC population, the fasting status of paediatric patients undergoing PSA, and the complications observed during PSA in a single Western Cape emergency centre. Methods A retrospective, descriptive study was conducted at Mitchells Plain Hospital, a district-level hospital situated in Mitchells Plain, Cape Town. All paediatric patients younger than 13 years of age who presented to the EC and received PSA during the study period (December 2020 – April 2021) were included in the study. Data was extracted from a standardised PSA form and simple descriptive statistics were used. Results A total of 116 patients (70,7% male) were included: 13 infants (<1 year of age) 48 young children (1-5 years of age) and 55 older children (5-13 years of age). There were only 2 (1,7%) complications documented, both of which were vomiting and did not require admission. The most of patients received ketamine (93,1%). The standardised PSA form was completed in 49,1% of cases. Indications for PSA included burns debridement (11,2%), suturing (17,2%), fracture reduction (23,3%), lumbar punctures (31,9%) and others (27,6%). The indications for PSA varied between the different age groups. Conclusion The study findings are in accordance with previous international literature. Emergency Centre PSA in the paediatric populations did not show an increase in interventions or complications, despite the fasting status (6). Safe, timely PSA with minimal pain and unnecessary suffering can become the norm in Emergency Medicine practice in South Africa.

Background: Seasonal fluctuations in outdoor temperature have been shown to affect blood pressure in adults. We have asked whether or not there is either a seasonal variation or an influence of outdoor temperature on blood pressure measurements in children and adolescents in middle Europe. Methods: Blood pressure was routinely measured in healthy and sick children and adolescents in outpatient clinics and during hospitalisation in a total of 6714 subjects (3,497 boys/3,237 girls), age 3 to 21 years, with a median of 10.6 years. Results: Cross-sectional analysis showed a significant seasonal variation in blood pressure measurements. The mean increase of systolic and diastolic blood pressure was 4.45/2.42 mmHg during winter. A significant correlation between average outdoor temperatures and systolic blood pressure was found (ρ=-0.074 p<0.001). However, the effect was only detectable at an average temperature below 0° C/32° F and above 10° C/50° F. For each degree Celsius increase in average outdoor temperature, the systolic blood pressure fell by 0.12 mmHg. Conclusion: Blood pressure measurements in children and adolescents, even in a temperate climate, are influenced by temperature and seasonal variation. Considering seasonal variations in blood pressure could be of clinical interest. / Background: High blood pressure is a major risk factor for cardiovascular disease. Blood pressure tracking could help to identify individuals with potential hypertension. Therefore, we have asked whether or not tracking was of predictive value for the development of hypertension in early life. Methods: Blood pressure was routinely measured in 13,261children and adolescents in outpatient clinics as well as during hospitalization. In a sub-analysis 568 individuals with normotensive and elevated blood pressure were compared after three follow-up periods (two, four and six years) and 2,157 normotensive individuals were compared in a paired t-test. Results: The follow-up analysis showed a significant tracking effect. However, the Pearson correlation coefficients of the systolic and diastolic blood pressure SDS decreased over time. Upon the follow-up after six years 35.6% of the children and adolescents with elevated blood pressure values remained in the elevated range group. Of the children within the normotensive blood pressure range 80.4% remained normotensive after six years. Children with normotensive blood pressure showed a stronger tracking than those who had had one hypertensive blood pressure reading. Children with high body weight gain left their SDS track to higher blood pressure values. Conclusion: Blood pressure tracking in children and adolescents is moderate. We conclude that the predictive power of a single hypertensive blood pressure measurement during a single visit is rather small, and thus repetitive measurements across several consecutive visits are necessary.

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This research was motivated by the urgent need for global health institutions like the World Health Organization and UNITAID to adopt an informed, market based approach to engaging with the research and development pipeline for drugs that treat children infected with the HIV virus. As the market size for these products declines over the next decade, the usual incentives for pharmaceutical and biotech companies to invest in the development of new drugs and new formulations of existing drugs is likely to dwindle. Innovated solutions are needed if a business case is to be made that addresses this important public health need. The objectives of the research include firstly, describing the public health need for research and development into paediatric Antiretroviral drugs; secondly describing the various stakeholders and their interests; and finally exploring and indentifying potential collaborative / partnership opportunities that can be employed to address the existing public health need while satisfying the various stakeholder interests at play.

Background: Persistent cough following an acute respiratory tract infection is a challenging and frequently encountered problem in primary care. Mycoplasma pneumoniae (M. pneumoniae) and Bordetella pertussis (pertussis) particularly predispose patients to persistent cough. Whilst the incidence of M. pneumoniae is highest in children, pertussis may also occur in adults. Method: Four studies were conducted for this thesis. First, a systematic review to assess the diagnostic accuracy of symptoms and signs in the clinical recognition of M. pneumoniae. Second, a retrospective analysis of a cohort of children with persistent cough to assess the prognostic value of diagnosing M. pneumoniae. Third, a prospective cohort study to estimate the prevalence of M. pneumoniae and pertussis in children with persistent cough following recent changes in vaccination policy. Fourth, a double-blind randomised placebo-controlled trial to determine the effectiveness of montelukast in the treatment of persistent cough and pertussis-induced cough in adults. Results: M. pneumoniae and pertussis can each be found in one-sixth of children who present in primary care with persistent cough. Although coverage with the preschool pertussis booster vaccine is high, its efficacy wanes rapidly, with the likelihood of pertussis increasing by 30% per year after vaccination. Montelukast is not an effective treatment for persistent cough, but may be an effective treatment for pertussis-induced cough. Median duration of cough in children with M. pneumoniae is only one-third of that in children with pertussis (39 days versus 118 days). However, the diagnostic accuracy of symptoms and signs in the clinical recognition of M. pneumoniae is limited. Since M. pneumoniae occurs in cyclical epidemics, clinicians should consider current prevalence of M. pneumoniae when making a clinical diagnosis. Conclusions: Diagnosing M. pneumoniae and pertussis can help clinicians give patients an explanation for their cough and inform them about its likely prognosis. At the moment, clinicians should adopt a conservative approach to managing postinfectious persistent cough. A further trial is needed to assess the efficacy of montelukast for the treatment of pertussis-induced cough.