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.

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.

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.

Lesotho, like many other developing countries, has a high incidence of maternal deaths. Minimal research has however been undertaken to establish the actual maternal mortality rate. The result has been a very wide gap between the officially quoted figure (282/100,000 live births) and the various estimates that have been made over the years. It was only in 1997 that a survey based on active case finding revealed a maternal mortality rate of738/100,000 live births. The researchers noted that not all cases of maternal deaths that occurred during the survey period might have been traced. The figure was however an eye opener to the magnitude of the problem in Lesotho. One of the main limitations of the 1997 survey was that no attempt was made to establish the causes of the documented maternal deaths. This was the motivation behind the current research.

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.

This study evaluates the input, process and output parameters of the Western Cape Developmental Screening Programme in order to inform policy and practice regarding developmental screening in the province. The study describes the background, development and implementation of the screening programme and examines its current delivery, including the main enabling factors and barriers to implementation. In order to achieve the abovementioned objectives, a combination of predominantly qualitative and some quantitative data was gathered in stages from all levels of the health system (provincial, regional and district levels) using a number of different methods. In addition to documentary and literature reviews, information was gathered via structured interviews with key health managers at a provincial and regional level, a rapid facility survey and facility based assessments. Information gathered from interviews and focus groups was analysed thematically, while rapid facility survey results were analysed via Epilnfo. Despite numerous successes in its development and the overall awareness of the Developmental Screening Programme, developmental screening is not conducted uniformly across the province. Almost a quarter of primary health care facilities do not deliver any aspect of the programme and only one of nine facilities deliver according to protocol. This study concludes that despite the Developmental Screening Programme being a well-conceptualised and highly valued programme, its delivery has failed as a result of constraints within the broader health system. As previous evaluations of child health programmes have demonstrated, the overall transformation of the health system, organisation of service delivery at a primary health care level and gaps in human resource development and information systems impact significantly on the delivery of preventive service delivery for children. As official programmes for developmental screening are not conducted in any other provinces, the study results may also inform policy and practice on a national level.

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.

The purpose of this study was to examine the prevalence of overweight and report mean Body Mass Index (BMI) and percent body fat (%BF) in Black and non-Black children, 7-9 years of age. The study involved 172 students divided as follows: 56 (32.6%) Black females, 45 (26.2%) Black males, 34 (19.7%) non-Black females, and 37 (21.5%) non-Black males. Percent body fat (%BF) was determined by bioelectrical impedance analysis (BIA). Body mass index was calculated as weight (kg)/height (m)². Black females had a statistically greater BMI (19.3 ± 4.8) and %BF (25.7 ± 10.6) than all other groups. Prevalence of at-riskor-overweight and overweight for the entire sample was 20.9 % and 19.2%, respectively. In conclusion, 40.1 % of 7 to 9 year old children assessed in this study were at-riskor-overweight or overweight, and the BMI and %BF for Black females were statistically greater than the other groups.

Molluscum contagiosum (MC) is a common skin condition in children presenting to primary care in the United Kingdom (UK) and is typically diagnosed based on its distinct appearance. There are limited data on the epidemiology of MC in UK children. Little is known about its presenting symptoms, time to resolution, likelihood of transmission and impact on quality of life (QoL), highlighted within a systematic review of the epidemiology of childhood MC presented early in this thesis. This thesis aimed to address this gap in evidence. A retrospective longitudinal cohort of 9,245,847 children registered at primary care centres in the UK extracted routinely collected data from the Clinical Practice Research Datalink (CPRD). The study highlighted decreasing trends in consultation rates for MC by 50% during the 10 year study period 2004-13. Children who were previously diagnosed with atopic eczema were more likely to have a future MC consultation than controls. The ‘Molluscum Contagiosum Diagnostic Tool for Parents’ (MCDTP) was developed to aid parents in diagnosing spots, lumps or bumps on a child’s skin as being MC or not. The MCDTP was assessed in primary care centres to measure its diagnostic accuracy (n=203, sensitivity=92%, specificity=88%), and used to recruit a prospective community cohort of 306 UK children with MC. Results showed that MC lesions were most common on legs and arms, and nearly 70% of children had lesions in more than one site. The average time to resolution was 12 months, however over a quarter still had lesions after 18 months and 12% after 24 months. Nearly half of households reported transmission to one or more children from an index case. Overall MC had a small effect on QoL however, 1 in 10 children experienced a very severe effect on QoL. The findings presented in this thesis can facilitate self-care of MC in the community where parents can self-diagnose their child’s spot, lumps or bumps on the skin as MC or not using the MCDTP. These data can provide parents, and other interested stakeholders, with accurate information of the epidemiology of the condition to aid the management in both clinical and community settings.

This thesis analyses the effects of various structural and organisational characteristics of specialist neonatal units on the clinical and economic outcomes of infants treated within them. Data are utilised from the National Neonatal Research Database (NNRD) which is extracted from the electronic patient records of all infants admitted to the vast majority of neonatal units in England over the period 2006-13 along with national healthcare expenditure and demographic data. Firstly, I examine the effects of neonatal unit volume and designation on infant clinical outcomes. In 2003, neonatal units in England and Wales were re-organised into networks to facilitate access to high level and volume neonatal units for the sickest infants as infants treated in these units had previous been shown to be at less risk of adverse outcomes. No previous studies have examined the effects of neonatal unit volume and designation in such a networked setting. Secondly, I estimate the effect of neonatal healthcare expenditure on the risk of mortality, and in so doing determine the cost-effectiveness of neonatal healthcare. Thirdly, I analyse the effect of nurse to patient ratios in neonatal intensive care on the risk of mortality, recent evidence has demonstrated that neonatal units are often understaffed with respect to clinical guidelines, yet little is known about the consequences of this on infant clinical outcomes. Finally, I explore the effect of local economic conditions at the time of conception on infant health at birth. The number of admissions to neonatal specialist healthcare units has increased in recent years to approximately 10% of all live births. Understanding the mechanisms underlying this increase is important both for healthcare capacity planning and also development of policies aimed at improving infant health at birth. The results in this thesis support policies aimed at increasing the proportion of infants born in hospitals with high volume neonatal units along with an increased provision of resources for neonatal healthcare.