Includes abstract. / Includes bibliographical references. / Croup is a common respiratory illness that has been recognized for many years. Despite recent advances in the utilization of steroids to treat the condition, it remains a significant cause of morbidity in children. In the developing world it may also remain a significant cause of mortality. Despite comprehensive descriptions of the disease process, its aetiological agents and clinical course, there are very few descriptions of the mechanics of breathing in croup. In addition there are very few methods described of measuring the severity of airway obstruction in patients with croup.

Background: Infections cause significant morbidity and mortality in children with cancer, which may be related to the cancer or treatment received. There is paucity of data on the epidemiology of bloodstream infection (BSI) in sub-Saharan Africa. To address this knowledge gap, the present study was conducted at Red Cross War Memorial Children's Hospital (RCWMCH) in Cape Town, South Africa. Methods: Structured literature review: From 1 April 2016 to 31 May 2016 a PubMed search was undertaken on BSI in Paediatric Oncology. The search string used was (bacteraemia OR blood stream infection) AND (paediatric OR pediatric) AND (oncology). Studies that did not describe infection patterns, risk factors for infection, morbidity/mortality, articles not in English and those exclusively describing neonatal or ICU patients were excluded from full review. Retrospective cohort study: A retrospective cohort study was conducted at the haematology-oncology unit of RCWMCH. All positive blood cultures from RCWMCH oncology patients taken between 1 January 2012 and 31 December 2014 were retrieved to identify patients who had BSI. Results: Structured literature review: 508 abstracts / articles were initially retrieved and screened. 478 studies were excluded as per the literature review exclusion criteria. Thus, 30 articles were included in full analysis, 17 retrospective studies, 4 prospective multicentre studies, 6 prospective single centre studies, 2 systematic reviews and 1 case report. All were observational studies. This literature review showed that BSI is a frequent and important cause of morbidity and mortality in paediatric oncology. Gram-positive bacteria was noted to be the leading type of pathogen causing BSI. Increased risk of BSI may be from the cancer itself, chemotherapy, hospitalisation, central venous catheter insertion, and oncology patients were at risk of multi-drug resistant infection. Research gaps noted included paucity of studies from Sub-Saharan Africa, limited analysis of the antimicrobial susceptibility of causative microorganisms and limited description of fungal BSI in oncology patients. Retrospective cohort study: From 436 positive blood culture results, 150 BSI episodes were identified amongst 89 patients; 49.1% of the culture isolates were Gram-positive bacteria, 41.6 were Gram-negative bacteria and 9.3% were fungal. Coagulase Negative Staphylococcus and Viridans Group Streptococcus were the most common Gram-positive isolates, and Escherichia coli and Klebsiella species the commonest Gram-negative isolates. The majority of BSI episodes occurred in patients with haematological malignancies (74%), in the presence of severe neutropaenia (76.4%) and whilst on or following chemotherapy (88%). Complications occurred in 14% of the BSI episodes. Fungal infections had the highest prevalence of complications (21.4%). Three children died during BSI as a result of multidrug resistant isolates, giving a case-fatality rate of 2%. Conclusion: The findings of our cohort study show that BSI are mainly caused by Gram-positive bacteria and associated with a low case-fatality rate. The results of this study are consistent with worldwide experience of BSI in paediatric oncology patients. This study provides an understanding of the spectrum of organisms causing BSI and the outcome of BSI in a sub-Saharan African context.

BACKGROUND: Asthma prevalence in African children is high and increasing, with more severe disease than that in high income countries. Specific factors driving the rising prevalence or disease severity are poorly understood. The aim of this study was to investigate environmental factors associated with asthma and severity in African children using data obtained from International Study of Asthma and Allergies in Childhood, (ISAAC) III. METHODS: A population based cross-sectional study of children aged 13-14 years from 10 African centres who participated in ISAAC III from randomly selected schools. The prevalence of asthma or severe asthma was calculated for each centre. Self-reported environmental exposures included engaging in physical exercise, television watching, biomass and ETS exposure, consumption of paracetamol, large family sizes and having pets in the home. Univariable and multivariable analyses were done adjusting for centre variations. Odds ratio and respective 95% confidence intervals (CI) were calculated. RESULTS: Amongst 28490 adolescents from 232 schools in 10 African centres (4 middle income and 6 low income), the prevalence of asthma was 12.8% (CI 12.4-13.2), while prevalence of severe disease was 8.7% (CI 8.4-8.0). Factors most strongly associated with asthma were maternal smoking (OR= 1.41; 95% CI: 1.23 - 1.64), exposure to open fire heating (OR=1.28; 95% CI: 1.08 - 1.51) and electric heating (OR=1.13; 95% CI: 1.01 - 1.28), engaging in strenuous exercise (OR= 1.29; 95% CI: 1.11 - 1.50 and monthly use of paracetamol (OR 1.23; 95% CI 1.13 - 1.33, while having an elder sibling was protective for asthma (OR=0.87; 95% CI 0.77 – 0.98). Factors strongly associated with severe asthma were maternal smoking (OR=1.61; 95% CI: 1.38 - 1.89), having a cat pet at home (OR=1.14; 95% CI: 1.04 - 1.25), engaging in≥3 weekly physical exercise (OR=1.42; 95% CI: 1.23 - 1.64) and monthly consumption of paracetamol (OR=1.20; 95% CI: 1.07 - 1.34). CONCLUSION: There was a high prevalence of severe asthma in African children. Several environmental exposures were associated with asthma or with severe disease. Strategies to reduce harmful environmental exposures must be strengthened to reduce the burden of childhood asthma in Africa.

Objectives: To describe a rational basis for the definition of a long-stay patient (LSP) in a South African paediatric intensive care unit (PICU); to review the characteristics and outcomes of the patients who comply with the LSP definition; to assess the proportion of resources allocated to the LSP cohort; and to determine if the results of this study could be used as a predictive tool for future admissions. Methods: A retrospective descriptive study of routine data collected over one calendar year (2009) from a 20-bedded multidisciplinary PICU was conducted. The definition of a LSP in this setting was established using various models. The characteristics and outcomes of the long- and short- stay groups were compared using nonparametric Mann-Whitney U and Chi2 tests, with significant results entered into a stepwise multiple regression model. The proportion of ICU days consumed by LSP was calculated. Human Research Ethics Committee approval was obtained (Ref/Rec 105/2011).

Three hundred and seventeen patients meeting the diagnostic criteria for immune thrombocytopenia presented to Red Cross War Memorial Children's Hospital between 1991 and 2011. We retrospectively reviewed these patients in order to describe patient demography, the natural history of the disease, and different approaches to diagnosis and management. There were 162 males and 155 female patients. The median age of onset was 3.48 years old (IQR 1.66-6.36). In the 4 weeks preceding presentation, 98 (31%) patients had a viral illness. The median presenting platelet count was 7 x 109/L (IQR 3-14.5). Petechiae were the most common clinical sign at presentation (58%; 184/317). None of the patients presented with intracranial haemorrhages. The majority of patients in the study were admitted (234/317; 74%) with a median stay of 4 days (IQR 0-6). Bone marrow aspirates (BMA) were performed in 188 patients (59%). There was a reduction in BMA from 1991-2000 to 2001-2011 (p<0.001). There was an increase in the percentage of patients treated from 1991-2000 (77/170; 44%) to 2001-2011 (99/147, 67% p< 0.001). Resolution occurred in 75% of patients with a median time to resolution of 31 days (IQR 11-73 days). When we analysed the "survival estimate" from the 2 decades, despite differing rates of BMA, treatment rates and regimens, there was no statistical difference in resolution.

Includes bibliographical references (leaves 49-57). / Pelvi-ureteric junction obstruction is an important cause of congenital renal and urinary tract abnormality. It is the commonest cause of antenatally detected hydronephrosis. The increasing use of antenatal ultrasound as a screening tool for congenital abnormalities in the developing foetus has resulted in a more frequent rate of detection of foetal hydronephrosis with the likely consequence of significant anxiety among parents. This is because most of these infants with antenatally detected hydronephrosis will be subjected to frequent radiological and other investigations and there will also be concern about outcome. Knowing what postnatal investigations are necessary for any child with this condition and when to do it becomes a priority. This is because it is known that a significant percentage of children with antero-posterior (AP) diameter of 12mm or less experienced complete and spontaneous resolution of the hydronephrosis in early life. This study is a retrospective folder review of one hundred children with PUJ obstruction managed at Red Cross Children’s Hospital over a six-year period from Jan 2002 to Dec 2007.

Bibliography: leaves 170-173. / In recent years it has become fairly commonplace to make comparisons between the Holocaust and Apartheid. This dissertation explores similarities and differences. It acknowledges that both systems were rooted in ideas of race, but while the tools used by the Nazis in Germany and the apartheid government in South Africa are superficially similar, their very different objectives brought about radically different outcomes once their policies were enforced. The dissertation opens with a discussion of the methods used by each of the different systems to define the victim races, and justify their inferior status. In Germany the reasons given were the desire to preserve the pure Aryan volk and protect the volkisch culture. In South Africa the stated premise was that each 'ethnic' group would best realise its full potential if it was encouraged to preserve its integrity and promote its own culture. In both countries separation was followed by deprivation of citizenship. Under German rule Jews were rendered stateless and expelled as far as possible from the Reich. In South Africa 'blacks' were made citizens of 'ethnic homelands'. Unlike the German Jews, South African 'blacks' had at least some kind of nominal right to equality in their designated 'homelands'. Freedom of movement was restricted and residential segregation enforced in both countries. Jews, previously prominent in the cultural, academic and economic life of Germany, were impoverished and dehumanized. 'Blacks' in South Africa were locked into their role of unskilled, manual labourers, a position that they had occupied since the beginning of 'white' settlement in the Cape. Initially Jews were confined to ghettos, eventually to labour and death camps. In South Africa people of colour were forcibly removed to rural 'homelands'. However the demand for cheap labour eventually necessitated their admission to the urban industrial areas, and although they were restricted to living in 'townships' their exclusion was never total and their physical destruction was never contemplated. In both countries government controlled local authorities kept tight rein on the administration of the residential areas that were demarcated for the disadvantaged. In Nazi Germany the SS appointed Judenrate (Jewish Councils) to administer the ghettos. These councils were used to secure the peaceful acquiescence of Jews en route to the death camps. Eventually the councillors were killed together with the people they were supposed to govern. In South Africa town councils were established for local government in the townships, but these councils were unsuccessful because they were government controlled and illegitimate. Their purpose was to administer the separate development areas, not to pave the way for eventual extermination of their inhabitants. In neither Germany nor South Africa did churches play an active role in preventing discrimination and injustice. In Germany this was simply a continuation of the traditional attitude of anti-Judaism nurtured by the refusal of Jews to convert to Christianity. In South Africa missionaries worked hard to convert 'blacks' to Christianity, but Dutch Reformed Church ministers believed that it was God's will that 'black' and 'white' should be kept separate, church services were strictly segregated, and this was in keeping with the apartheid ideal. With regard to the media, both Nazi Germany and the apartheid regime backed those sectors of the media that promoted negative images of Jews and 'blacks', while censoring those that were more liberally inclined. The fundamental differences between the Holocaust and apartheid became most apparent in their terminal stages. Whereas Nazism led to genocide, the leitmotif of apartheid was cheap labour, not planned extermination. The Nazis created death camps and designed advanced technology especially for the purpose of speeding up mass murder and body disposal. Apartheid killings in South Africa were carried out by traditional means on an individual basis and not by large-scale extermination techniques. The killings in South Africa were directed only at opponents of the regime and not for the purpose of exterminating a specific ethnic group. This dissertation presents two case studies of racist ideology which promoted discrimination and the elevation of a 'superior' race at the expense of the disadvantaged. In Germany this resulted in a programme of genocide whereas the apartheid system in South Africa, though intended to service the material interests of the ruling group, nevertheless proved dysfunctional and sowed the seeds of its own demise.

Objective: To document the demographics, the pattern of clinical and laboratory characteristics at the time of diagnoses for all the newly diagnosed diabetics younger than 14 years reviewed at the Diabetic clinic at the Red Cross War Memorial Children's Hospital (RCWMH) during 2005-2009. Method: A retrospective folder review was done of all the newly diagnosed diabetics younger than 14 years old at the age of diagnosis. 225 patients were included for analysis. Patients were grouped according to age into a young group (1 month to < 5 years old), a middle group (5years - < 9 years) and an older group (9years - <14 years). Neonates were excluded as well as children who became diabetic secondary to another condition. Results: 58% of the patients were female and most of the patients were diagnosed with type 1 diabetes (96%). The median age at diagnosis was 8.5 years with a mean HbA1c of 11, 3%. 68% of the patients were in the normal weight category while 8, 4% of the patients were obese. 148 (65%) of the 225 patients presented in diabetic ketoacidosis (DKA). Only one of the patients classified with type 2 diabetes presented in DKA. 51 (22,67%) of the patients were less than 4 years old at the time of diagnosis. 53% of the Caucasian children were less than 4 years old at diagnosis while most of the children in the black and coloured group were diagnosed after 10 years of age. A seasonal variation was seen especially in the young age group with 66% presenting in autumn or winter months. Conclusions: Almost a quarter of diabetic children presented before the age of 4 years. A large proportion of patients presented in diabetic ketoacidosis which can be life threatening. Due to lack of information at diagnosis, this could be under reported significantly and calls for increase awareness amongst physicians and parents to recognise symptoms earlier. Prospective studies on childhood diabetes in South Africa are needed as well as a registry for childhood diabetes.

Background: Asthma and allergic disease are the result of a complex interaction between genetic predisposition and environmental exposure. It is likely that multiple genes are involved in the progression from allergen exposure to the development of signs and symptoms of allergic disease. Although advances in genetic research have progressed exponentially in the past twenty years, and a growing body of evidence from the developed world has yielded several promising candidate polymorphisms, the precise nature of the genetic basis for allergic disease remains to be elucidated. In addition, there is a paucity of literature in this field from the developing world, and for people of African origin in particular. Several studies suggest that the prevalence of asthma and allergic disease in South Africa has increased significantly over the past forty years, at a rate that is too rapid to be explained by genetic modification. A likely explanation for this trend is that an increasing number of genetically susceptible individuals are being exposed to environmental stimuli that are critical to the formation of allergic disease. It is possible, although unproven, that evolutionary adaptation of inflammatory immune responses may increase the genetic predisposition to allergic disease amongst people of Black African origin. This thesis represents the first analysis of several single nucleotide polymorphisms (SNPs) with regards to their prevalence in the Xhosa population, as well as the correlation between these SNPs and clinical and laboratory markers of allergic disease in this population. Methods: A cross-sectional sample of about 300 unrelated Xhosa school children was obtained from a local high school. Phenotypic data was collected in the form of a symptom questionnaire, blood samples for total IgE as well as IgE to Ascaris lumbricoides, skin prick tests to common local food and aeroallergens, as well as a modified methacholine challenge to establish the prevalence of bronchial hyper-reactivity. In addition, genotyping was performed to investigate the prevalence of twenty-seven SNPs in this population. We aimed to establish a baseline of the prevalence of potential pro-inflammatory alleles (PIAs), as well as to investigate the relationship between these PIAs and clinical and laboratory markers of asthma and allergic disease. Results: We found several significant associations between several SNPs and allergic disease, specifically in genes relating to the development of immune tolerance (IL-10), genes relating to TH1 inflammation (IL-12 and IFNGR1) and genes relating to TH2 inflammation (IL-4, IL- 4R, IL-13). Unfortunately, the generalizability of our findings is limited by, amongst others, the selection of pupils from a single school and the use of self-reported end points as markers of clinical phenotypes rather than physician diagnosed allergic illnesses. Conclusion: This is the first trial of its kind in the Xhosa population. Despite the limitations described above, we feel that this study has provided valuable baseline prevalence data, and unearthed some interesting associations between PIAs and allergic disease. We would welcome further research in this population to confirm or refute our findings.

Juvenile idiopathic arthritis (JIA) is defined as arthritis of unknown aetiology that begins before the 16th birthday and persists for at least 6 weeks, other conditions being excluded. As JIA is a disease with serious functional implications, a descriptive study would not be complete without reviewing both the functional and clinical parameters of the disease. There has been very little African data on this subject. The objective of this study is to describe the functional disability and clinical disease characteristics in a sample of children diagnosed with JIA in Cape Town, South Africa.