Background: The large scale-up of paediatric HIV care necessitated down-referral of many children receiving antiretroviral therapy (ART) from Red Cross War Memorial Children's Hospital (RCWMCH). No published data exists on the outcomes of these children. Objectives: To assess clinical, immunological and virological outcomes of children receiving ART in the first 12 months after down-referral to primary health care (PHC) clinics, and identify determinants of successful down-referral. Methods: We conducted a retrospective cohort study of children <15 years of age who commenced ART at RCWMCH and were subsequently down-referred to one of two PHC clinics between January 2006 and December 2012. Baseline characteristics of patients and caregivers as well as CD4 counts, viral loads and weights were collected at 6 and 12 months post-down-referral. Outcomes included retention in care and viral suppression. Results: One hundred and sixteen children down-referred to Heideveld and Gugulethu were included. After down-referral 13.8% of the cohort never arrived at the designated clinic and 10% took longer than 8 weeks, therefore probably experiencing treatment interruption. At 12 months post down-referral only 68.2% remained in care at the designated clinics. No factors were associated with retention in care. For those children who remained in care at the PHC clinics, the clinical and immunological gains achieved prior to down-referral were sustained through 12 months of follow up, and 54.7% of the retained cohort had documented viral suppression at 12 months. Conclusion: Down-referral of children on ART is a vulnerable process with risk of loss to follow-up and treatment interruption.

Includes bibliographical references / Background: Pneumonia is an important cause of morbidity and mortality in children. Viruses have emerged as important aetiological agents in childhood pneumonia. The aim of this study was to document the clinical presentation, severity and outcome of adenoviral-associated pneumonia (AVP) in children and identify risk factors associated with poor outcome. Methods: A retrospective study of laboratory-confirmed AVP cases was conducted between 1 January and 31 December 2011. The medical records of adenovirus PCR positive respiratory tract samples identified through the National Health Laboratory Service (NHLS) database were retrieved. Demographic, clinical and outcomes data of children with AVP were extracted and analysed. Outcome measures were death and development of chronic lung disease (CLD). Results: 1910 respiratory samples were submitted to the NHLS from which 206/1910 (11%) AVP cases were identified. The median age was 12 months (IQR 6-24), 70 (34%) children were malnourished and 14 (7%) HIV-infected. Fever was the commonest presenting symptom occurring in 159 (77%) of cases. Seventy six (37%) required intensive care unit (ICU) admission. There was a high prevalence of co-morbid conditions with 98 (47%) having at least one; cardiac disease was the most common (48 (23%). Twenty nine (14%) developed CLD which was associated with hypoxia at presentation (26/29, 90%, p = 0.01) and admission to ICU (18/29, 62%, p < 0.01). Eighteen (9%) children died. Admission to ICU (OR 8.3, 95% CI 2.3-29.0) and blood stream infection (OR 11.2; 95% CI 2.3-54.1) were independent risk factors for mortality. Conclusion: Adenoviral-associated pneumonia is an important cause of pneumonia and CLD in young children in South Africa. Admission to ICU and blood stream infection were associated with poor outcome

Background: Acute and chronic malnutrition continue to impede child health and well-being in South Africa. This study aims to assess the nutritional outcomes of children under five years of age referred for underweight or growth faltering who were treated at Philani clinics in Khayelitsha, Crossroads and Browns Farm. Children were assessed by a medical doctor, and received nutritional supplementation according to the Nutrition Therapeutic Programme guidelines. Methods: We conducted a retrospective cohort study of children under 5 years who attended a Philani clinic between 2008 and 2018. Participants were included if they attended a Philani clinic for a minimum of three months. The primary outcome was rehabilitation of weight-for-age (WAZ) above -2 Standard deviations (SD), according to the World Health Organisation child growth standards. Results: Of 1803 folders screened, 933 met inclusion criteria, from which 592 were randomly selected. There were 326 (55.1%) girls, and the median age of the children at study entry was 7.9 (interquartile range [IQR] 3.5; 14.9) months. The median follow-up period was 9.9 (IQR 6.7; 15.7) months, and the total follow-up period was 621.6 child years. There were high levels of poverty with 401 (67.7%) children living in an informal dwelling and 267 (46.6%) children experiencing a lack of food in their household. Background vulnerability to undernutrition was common, including HIV exposure (n=277, 46.8%), HIV infection (n=45, 7.6%), low birth weight (n=324, 54.7%) and foetal alcohol spectrum disorders (n=36, 6.1%). At study entry, 392 (66.2%) children were assessed as moderately to severely underweight for age. The median WAZ at study entry was -2.6 (IQR -3.4; -1.6) standard deviations (SD) and at exit was -1.7 (IQR -2.5; -0.7) SD; p< 0.001. Of the 392 children underweight at the start, 243 (62.0%; 95% confidence interval (CI) 57.0 – 66.8%) showed improvement. Of these children, 173 (71.2%; 95% CI 65.1 – 76.8%) were rehabilitated to a normal weight, and 70 (28.8%), although not rehabilitated, improved from severely to moderately underweight for age. The median change in WAZ from study entry to exit was 0.2 (IQR -0.3; 0.8) SD for children whose weight was normal at the start; 0.5 (IQR 0.0; 1.2) SD for children who were moderately underweight at the start; and 1.4 (IQR 0.6; 2.6) SD for children who were severely underweight at the start; p=0.0001. Seven children (1.2%) died, all but one without rehabilitation. In total, 164 (27.7%) children were lost to follow-up. Conclusion: Children attending Philani's nutrition clinics come from poor socio-economic conditions, with high rates of poverty and infectious diseases. The intervention delivered by Philani's nutrition clinics was able to improve the nutritional status of over 62% of underweight children. In over 71% of the improved children, the change was to normal weight for age. Children who were severely malnourished at entry to the clinics achieved that largest change in weight-for-age z-scores (WAZ). Philani's structured nutrition intervention provides a model that could be replicated in other vulnerable communities to improve the wellbeing of South Africa's children.

Complications of respiratory infections include pleural effusion (PE), associated with a high morbidity. Differentiating between PE caused by bacterial infections and Mycobacterium tuberculosis (TB) in endemic areas is difficult in children, impacting treatment. We investigated the aetiology of PE and features distinguishing TB from bacterial PE in children. Methods In this prospective study, children with PE admitted to a tertiary hospital in Cape Town from December 2016 to December 2019 were enrolled. Clinical information and routine laboratory investigations were compared between children with bacterial, TB or unclassified PE, categorised according to study definitions. Results A total of 91 patients were included; their median age was 31 months (IQR 11.8–102.1). Aetiology was bacterial in 37 (40%), TB in 36 (39%) and unclassified in 18 (20%) patients. Staphylococcus aureus was the most common bacterial isolate, confirmed in 24/37 (65%) patients; and Streptococcus pneumoniae confirmed in only 3/37 patients (8%). TB was microbiologically confirmed in 12/36 (33%) patients. Patients with TB were older (median age 91.6 vs 11.8 months, p< 0.001), with more weight loss (28/36 (77.8%) vs 12/37 (32%) patients, p< 0.001), and longer cough duration (10 vs 4 days, p< 0.001) than those with bacterial PE. In contrast, the latter had significantly higher median values: serum C-reactive protein (250 vs 122 mg/L, p< 0.001), procalcitonin (11 vs 0.5 mg/L, p< 0.001) pleural fluid lactate dehydrogenase (7280 vs 544 U/L, p< 0.001), and adenosine deaminase levels (162 vs 48 U/L, p< 0.001) and lower glucose levels (1.3 vs 4 mmol/L, p< 0.001). Conclusion Post-PCV, S. aureus is the dominant cause of PE in children using traditional culture methods, while TB remains a common cause of PE in our setting. Useful clinical and laboratory differences between TB and bacterial PE were identified, but the cause of PE in 20% of children was underdetermined. Molecular testing of pleural fluid for respiratory pathogens may be useful in such children.

of children perinatally infected with HIV, with an increasing number surviving into adolescence, accompanied by the development of chronic comorbidities. However, there is limited knowledge on the spectrum of comorbidities, determinants, and risk factors among youth living with perinatally acquired HIV (YLPHIV) especially in sub-Saharan Africa, with most data from high-income countries. There is a critical need for data on health and chronic comorbidities among YLPHIV from countries with a high HIV prevalence. Aim: To investigate the spectrum and determinants of HIV-associated comorbidities among YLPHIV on ART in Cape Town, South Africa. Specific objectives were to investigate cardiovascular, musculoskeletal, mental health and metabolic outcomes in YLPHIV compared to HIV-uninfected adolescents. Method: In a prospective study YLPHIV on ART were enrolled in the Cape Town Adolescent Antiretroviral Cohort (CTAAC) from seven health-care sites in Cape Town, South Africa, between July 2013 – April 2015. Eligibility criteria were adolescents, 9-14 years old, with perinatally acquired HIV, been on ART for at least six months, and who were aware of their HIV status. A control group of HIVuninfected adolescents' frequency-matched by age and sex was also enrolled. The cohort was longitudinally followed for development or progression of comorbidities with clinical and laboratory measurements. Comorbidities assessed included: (1) cardiovascular health: echocardiography was used to investigate cardiac structure and endothelial peripheral arterial tonometry technique (EndoPAT) was used for endothelial function. The pathobiological determinants of atherosclerosis in youth (PDAY) risk score was used to assess long-term cardiovascular risk for atherosclerotic disease at the coronary artery (CA) and abdominal aorta (AA). A PDAY score ≥1 was regarded as elevated; (2) bone health: quantitative ultrasound was used to evaluate calcaneal stiffness index (SI); (3) mental health: the Child Behavior Checklist (CBCL) and BECK youth inventories were utilised. The association of mental health with metabolic abnormalities was investigated. Statistical analyses included descriptive data and regression modelling analysis, using the software, Stata® 14.2 to 16 (Stata Corp LP. College Station, Texas, USA). Results: Overall, 515 YLPHIV and 110 HIV-uninfected participants with median age 12.0 years (IQR 11.9, 10.7) and 11.8 years (IQR 11.7, 10.0) were enrolled; YLPHIV with median duration of ART of 7.6 years (IQR: 4.6–9.2), also had a median CD4 cell count of 713 cells/mm3 (IQR: 561.0–957.5), and 387 (75%) had a viral load (VL) of 500 cell/mm3 (RR 1.04, p=0.76), VL (RR 1.01, p=0.78) or current ART class (protease inhibitor-based vs non-nucleoside inhibitor-based, RR 0.90, p=0.186) were not associated with ED after adjustment. At 48 months of follow-up, among YLPHIV, 8% (n=17) had sustained viraemia, and 54% (n=118) had transient viraemia through this period. The median duration on ART was 12 years (IQR 8-14); 57% (n=124) were on a non-nucleoside reverse transcriptase inhibitor-based ART, while the rest received protease inhibitor-based ART. Few YLPHIV met the criteria for hypertension (2%, n=4) or hyperglycaemia (0.5%, n=1). None of the HIV-uninfected youth had hypertension or hyperglycaemia. Fewer YLPHIV smoked compared to the uninfected youth (15.6% vs 11.5%, p=0.50. Elevated PDAY scores for CA (30.3% [n=66] vs 31.3% [n=10], p=0.74) and AA (18.4% [n=40] vs 21.9% [n=7], p=0.20), respectively among YLPHIV and HIV-uninfected adolescents differed slightly but did not reach statistical significance. Among YLPHIV, sustained viraemia [adjusted odds ratio (aOR)=18.4, p50 copies/ml (OR=2.06, p=0.023) were associated with an increased risk of low SI, while the use of efavirenz (OR=0.41, p=0.009) was associated with a decreased risk of low SI. YLPHIV had more impairment in mental health in several domains: functional competence (40% vs 25%, p=0.02), self-concept (23% vs 9%, p=0.03), higher depression (6% vs 2%, p< 0.01), anger (6% vs 2%, p=0.04), and disruptive behaviour (4% vs 0%, p p<0.01). Among YLPHIV, higher levels of anger were associated with increased total cholesterol and low-density lipoprotein (LDL) levels (ß=0.010, p=0.041 and ß=0.012, p=0.048, respectively), higher disruptive behaviour with increased LDL levels (ß=0.010, p=0.043), and severer CBCL-internalizing problems with low albumin levels (ß=-0.067, p=0.052) after adjusting for age, sex, and BMI z-score. Conclusion: YLPHIV are at higher risk of having subclinical cardiac structural abnormality and ED compared to uninfected adolescents. Both groups had a substantial proportion with high PDAY scores reflecting increased aggregate atherosclerotic risk. Bone health was worse among YLPHIV. HIV-related factors such as ART initiation at an older age, advanced clinical disease, and specific ARTs were significant risk factors for these conditions. Mental health impairment was common and associated with increased lipid concentration in YLPHIV. These data highlight a high prevalence of chronic comorbidities in YLPHIV, specific risk factors associated with these and provide information for strengthened strategies to prevent or monitor HIV-associated illnesses.

Background Child pneumonia is a substantial cause of childhood mortality and morbidity; it is the largest single cause of under-5 mortality outside the neonatal period. Incidence of child pneumonia, and pneumonia mortality, have decreased substantially due to improved socio-economic attainment, improved HIV programs, coverage of new conjugate vaccines against Streptococcus pneumoniae (PCV) and Haemophilus influenzae type B (Hib), access to early antibiotic therapy, and changing prevalence of pneumonia risk factors. Measurement of community-based pneumonia incidence is difficult; risk factors for pneumonia incidence and factors associated with pneumonia mortality are poorly described in low- and middle-income countries. Careful measurement of pneumonia incidence, and prospective analysis of risk factors is necessary to appreciate the evolving complexities of pneumonia causality and mortality. The aim of this work was to describe the incidence and severity of pneumonia in a birth cohort of children in the first 2 years life; and identify risk factors for pneumonia and for severe outcomes. Methods A prospective birth cohort, the Drakenstein Child Health Study, enrolled mother-infant pairs in two communities outside Cape Town, South Africa. Pregnant women were recruited and followed through pregnancy, labour and delivery, and the first 2 years of the child's life. Comprehensive data collection of risk factors was done through the first 2 years of life. A community pneumonia surveillance system was established; active case finding was used for birth cohort participants over 4 respiratory seasons. Children were examined at scheduled visits and at the time of pneumonia events. Pneumonia or severe pneumonia was diagnosed according to revised World Health Organisation (WHO) guidelines. Chest x-rays were classified according to WHO guidelines. Predictors of ambulatory and hospitalized pneumonia were explored with Poisson regression using generalized estimating equations clustered on mother-infant pairs. Factors associated with death or admission to intensive care unit were analysed with prevalence ratios from modified Poisson regression with robust variance estimation. Findings From March 2012 to March 2015, 1137 pregnant women were enrolled, delivering 1143 live-born infants. Household environmental tobacco smoke exposure was common: 82% of children were exposed in the first 6 months of life. Maternal HIV infection was common: 249 (22%) of 1143 children were HIV-exposed, but only 2 children became HIV-infected. Coverage of primary series of hexavalent vaccine, PCV and Hib was excellent (92%). During the study period (2012 to 2017), there were 795 pneumonia episodes (621 (78%) ambulatory, 274 (22%) hospitalised) in the first 2 years of life. Pneumonia incidence was higher in the first year of life (0.51 episodes per child year (e/cy)) and decreased to 0.25 e/cy in the second year. Active case finding in the birth cohort was more accurate than passive surveillance performed at the community clinics; pneumonia incidence measured by passive surveillance was significantly lower (incidence rate ratio 0.72, 95% CI 0.58 – 0.89) compared to active surveillance. Pneumonia mortality was low: 1.7% of hospitalised cases, and 0.35% of all clinical cases. There was marked variability in pneumonia incidence from year to year during the study. Many risk factors for pneumonia did not have fixed effects, but had different impacts at different ages, and variable effect on ambulatory and hospitalised pneumonia. In multivariable regression, adjusted incidence rate ratios were calculated for 5 risk factors (age< 6 months, male sex, low birth weight (<2500g), maternal smoking, delayed vaccines), which were associated with consistent effects on ambulatory and hospitalised pneumonia. Risk factors for serious outcomes of pneumonia (death or admission to intensive care unit) were identified: age under 2 months, low birth weight and hypoxia. Conclusion In this birth cohort, with low socio-economic status but high vaccination coverage, we demonstrated higher-than expected incidence of pneumonia, but very low mortality, with specific risk factors identified. Active surveillance was important for accurate detection of pneumonia. Children born at low birth weight are at increased risk for pneumonia and for serious outcomes. Pulse oximetry to detect hypoxia, and access to oxygen for children with hypoxic pneumonia, should be included in guidelines. These data will have global applicability for estimation of child pneumonia incidence in regions where direct measurement is impossible. These data can be applied to epidemiology and disease-modelling for child health; they will contribute to long-term morbidity follow-up studies; and they will contribute to understanding the constantly-evolving epidemiology of child pneumonia.

Background: Urinary tract infections (UTI) are one of the most common bacterial infections in childhood, with the potential to cause acute and long-term complications. Diagnosing UTI in children is often challenging due to non-specific symptoms, difficulty in collecting sterile specimens, and culture results only becoming available after 24-48 hours, necessitating initiation of empiric antibiotic therapy. Recent data on the epidemiology and antibiotic susceptibility profile of community-acquired bacterial UTI in children in Cape Town is lacking. Objectives: To describe the clinical profile and organisms including antibiotic susceptibility testing (AST) results in children <10 years of age with community-acquired, culture-confirmed bacterial UTI attending Victoria Hospital, Cape Town. To compare the AST findings with the current South African (SA) Hospital Level Paediatric Standard Treatment Guidelines (STG) which recommend oral or parenteral amoxicillin/clavulanic acid as first-line empiric treatment for children with UTI, with ceftriaxone included as an alternative for neonates or acutely ill infants. Methods: A retrospective review of medical records and laboratory results of children <10 years of age who had a urine specimen submitted for culture and AST to the National Health Laboratory Service from Victoria Hospital between 1 February 2016 – 31 July 2019 was performed. The study definition of a culture-confirmed bacterial UTI is modified from the SA STG guidelines: (1) any culture from a suprapubic aspirate, (2) culture of >104 colony forming units (CFU)/mL of a single organism from a catheter urine specimen, (3) culture of >105 CFU/mL of a single organism from a mid-stream clean catch specimen or if the urine sampling technique was not indicated in the laboratory or medical records. Descriptive statistics were used to analyse the data. Results: From 528 urine specimens submitted, 89 specimens met the study definition of bacterial UTI and were included in the microbiological analysis. Seventy-eight children with available medical records were included in the demographic and clinical analysis. Median (interquartile range) age was 25 (0;117) months and 58% were female. One or more nonspecific features of systemic illness were reported in 65% of children, and 51% had at least one symptom specific to the urinary system. Enterobacterales accounted for 99% of the organisms cultured (85% were Escherichia coli) and their susceptibility was amoxicillin/clavulanic acid (58%), cefuroxime (84%), third and fourth generation cephalosporins (88%), ciprofloxacin (94%), gentamicin (86%) and nitrofurantoin (90%). Eleven (12%) isolates were extended spectrum beta lactamase-producing organisms but no carbapenem-resistant organisms were isolated. Conclusion: Although this study did not evaluate clinical outcomes of children, the AST finding that only 58% of Enterobacterales isolates were susceptible to the recommended empiric treatment with amoxicillin/clavulanic acid raises the concern that children may not be receiving appropriate treatment for UTI. Further research is needed on the antibiotic susceptibility profile and clinical outcome of children treated for UTI in order to inform appropriate empiric antibiotic treatment recommendations.

Deficiencies of vitamin A, iron, and iodine continue to be prevalent in developing countries worldwide and can, in addition to the classic consequences such as nutritional anaemia, goitre, cretinism, xerophthalmia and blindness caused by severe deficiencies, also affect the growth, development and immunity of young children. The various internationally acknowledged strategies for combating micronutrient deficiencies include high-dose supplementation, food fortification, dietary diversification and nutrition education. The aim of this research was to evaluate a micronutrient-fortified biscuit as a strategy to address micronutrient deficiencies in primary school children from a poor rural community. The research comprised three phases. During the first phase the effect of a biscuit fortified with iron, iodine, and B-carotene on the vitamin A, iron and iodine status of 115 children was evaluated and compared with 113 controls, in a randomised placebo-controlled trial. To enhance the absorption of iron a vitamin C-fortified cold drink was given together with the biscuit. Anthropometric status, cognitive function and morbidity were assessed as secondary outcomes. The 12-month intervention resulted in a significant improvement in serum retinol, serum ferritin, transferrin saturation, haemoglobin and urinary iodine excretion. Morbidity and cognitive function, particularly the cognitive function in the children presenting with low iron status and with goitre! at baseline, were also favourably affected. Linear growth was positively affected only in the children with marginal iron stores at baseline. During the second phase of this study the long-term effectiveness of the biscuit programme, in terms of elimination of micronutrient deficiencies, compliance, acceptability and sustainability, was evaluated in a longitudinal study over a period of 30 months. In addition, cross-sectional data on vitamin A and iron status from subsequent studies conducted in the same school at 33, 42 and 45 months after the start of the original biscuit intervention, during which time the fortified biscuit continued to be distributed at the school, are reported. Although micronutrient status improved significantly during the 12 months of the first study, all variables (except urinary iodine) returned to pre-intervention levels when the schools reopened after the summer holiday. Serum retinol increased again during the next nine months, but was significantly lower in a subsequent survey, carried out directly after the summer holiday; this pattern was repeated in two further cross-sectional surveys. Iron status showed no recovery during a subsequent intervention period when the vitamin C-fortified cold drink was supplied on a less frequent basis, or during the period that ferrous bisglycinate was used as iron fortificant. Because of the compulsory iodisation of salt, that came into effect halfway through the first phase of the study, improved iodine status, as measured by urinary iodine excretion, was maintained. In the third phase of the research, red palm oil, a rich natural source of B-carotene, was examined as an alternative vitamin A fortificant in the biscuit. This study contained elements of both a randomised placebo-controlled trial and an equivalence trial. The biscuit with a red palm oil-based shortening was shown to be as effective as the biscuit with fl-carotene from a synthetic source in improving the vitamin A status of these children. In conclusion, the results of the studies described in this thesis showed that a micronutient-fortified biscuit is a feasible, practical and effective way of improving the micronutrient status of primary school children from a poor rural community. Long-term evaluation of this programme, however, showed that improved micronutrient status is not sustained during the long summer school holidays, and it is suggested that the biscuit programme is supplemented with other strategies, such as local food production programmes and nutrition education. Red palm oil, with all of its additional qualities (i.e. no trans fatty acids; rich source of antioxidants), appears to be an attractive alternative for use as a vitamin A fortificant. The choice of the iron compound to be used in the biscuit, however, needs further investigation.

No description available.

Objective: This study examines the use of a clinical pathway in the management of infants hospitalised with bronchiolitis. Study Design: A clinical pathway for the care of infants with bronchiolitis was developed from pathways used in tertiary paediatric institutions in Australia. 229 infants admitted to hospital with acute viral bronchiolitis and prospectively managed using a pathway protocol were compared with a retrospective analysis of 207 infants managed without a pathway in three regional and one tertiary hospital. Results: There were no differences between groups in demographic factors or clinical severity. The pathway had no effect on length of stay or time in oxygen. Readmission to hospital was significantly lower in the pathway group (P = 0.001). Administration of supplemental fluids (P = 0.001) and use of steroids was lower (P = 0.005) in the pathway group. Identification of parental smoking status was higher in the pathway group (P = 0.029). Data from the pathway demonstrated that boys were three times more likely to return to oxygen after weaning to air (OR = 3.30; 95%CI 1.39 - 7.81) after adjusting for admission oxygen saturation. Documentation of variances from the pathway was misunderstood by staff. Conclusions: A clinical pathway specifying local practice guidelines and discharge criteria can reduce the risk of readmission to hospital, the use of inappropriate therapies, and help with assessment of readiness for discharge.