Introduction: Several studies in developed countries such as the USA have reported low serum or plasma vitamin A levels in adults with HIV disease. Limited data suggests that HIV-infected adults from developing countries show even lower vitamin A levels. Factors that contribute to a low vitamin A status include a poor intake, malabsorption and repeated episodes of infections resulting in a decreased hepatic mobilisation of vitamin A during the acute phase response, an accelerated utilisation of vitamin A or increased urinary losses of vitamin A. Aim: To determine the vitamin A status of HIV-infected adults without major active opportunistic infections with WHO clinical stages 1 to 4 HIV-infection. Methods: One hundred and thirty-two HIV-positive patients were included in a cross-sectional study at the outpatient clinic at Groote Schuur Hospital. Exclusion criteria included current use of multivitamin or vitamin A supplements, pregnancy, pyrexia (> 38 °C) and patients who had received TB treatment for less than 12 weeks. We obtained data on demographic characteristics, weight and height, CD4 lymphocyte levels, CD4:CD8 ratio, full blood count and plasma levels of retinal, retinal-binding protein, zinc and CRP. Results: The sample consisted of 51, 48 and 33 patients with WHO Stage 1/2, 3 and 4 HIV-infection, respectively. The proportion of patients with borderline vitamin A levels (< 30 μg/dl) for male and female subjects increased linearly across clinical stage categories. Thirty nine percent (20/51) of patients with early disease, 48% (23/48) with Stage 3 HIV-disease and 79% (26/33) of patients with AIDS showed a borderline vitamin A status (p < 0.001). Plasma retinal status was associated with CD4 lymphocyte levels (r=0.27; 95% Cl: 0.1-0.43) and the CD4:CD8 ratio (r=0.33; 95% Cl: 0.1 ;0.42). Only one subject demonstrated CRP levels > 100 mg/l. Seventy seven percent (39/51) of patients with early disease had CRP levels < 10 mg/l, compared to 52% (25/48) and 58% (19/33) of patients with stage 3 and 4 HIV disease. CRP levels were divided according to 3 categories: < 10 mg/l, 10-40 mg/l and > 40 mg/l. The median retinal level of patients with CRP levels> 40 mg/l (n=7) was 16.8 μg/l versus 27.3 μg/l and 30.2 μg/l in the other two categories (p < 0.05). A similar relationship between CRP and plasma zinc levels was observed, although not significant (p < 0.1). Multivariate analysis revealed that a borderline retinal status was independently associated with a 3-fold increase (95%CI: 2-5.6) in the risk of having stage 4 disease or AIDS after adjusting for CD4 lymphocyte count or the CD4:CD8 ratio, haemoglobin, plasma zinc and body weight. Conclusions: Patients with advanced disease are more likely to have a borderline vitamin A status in the absence of opportunistic infections. The majority of patients with symptomatic disease had mildly raised CRP levels, possibly reflecting HIV-viral activity. CRP levels were associated with low retinal levels only in a small number of subjects, possibly indicating the presence of underlying infection, despite the clinical review of our data. Although our data indicates an independent relationship between retinal levels and advanced disease, the cross-sectional design precludes causal inferences about this association.

Background: Our previous epidemiological study have investigated the effect of pesticides on growth of boys in the Western Cape rural area, in this cross-sectional study, we extend those initial observation into a more detailed exploration of t he growth pattern in anthropometric variables and hormonal indicators, and its relation to pubertal stage. Reference data in relation to pubertal stage are presented, and compared with other international findings. Objective: To investigate the anthrop ometric growth and reproductive hormones alternation of Western Cape Rural boys who are potentially exposed to agricultural pesticides. Methods: A cross-sectional study of 269 boys was conducted in the rural Western Cape in South Africa. Tests included serum gonadotrophin releasing hormone (GnRH), lutenizing hormone (LH), follicle stimulating hormone (FSH), testosterone, sex hormone binding globulin (SHBG) and estradiol (E2); a physical examination of height, weight and BMI measurements; sexual matura tional assessment and a questionnaire (demographics and general medical history). Median of anthropometric variables and hormone levels by pubertal stage were compared with international references. Results: Median age of pubertal onset is 11.6 years old, later than African American boys and Urban South African boys. Western Cape rural boys were apparently shorter and lighter compared with the CDC and the WHO growth standards in the prepubertal and early pubertal stage, and then catch-up evidently in the mid and late puberty. Compared with previous pubertal hormonal studies, our boys were low in serum levels of testosterone were low and high in oestradiol levels throughout entire pubertal stages and the classic endocrine Negative Feedback Loops in hy pothalamic pituitary gonadal axis were established earlier. Conclusion: The results provide further evidence for the effects potentially from agricultural pesticides exposure in the pattern of growth in height and weight, and hormonal fluctuations dur ing the development of puberty.

Background: Despite technological and programmatic advances in the prevention of vertical transmission of HIV and early infant diagnosis (EID), paediatric HIV continues to have a significant impact on infant and child survival in low- and middle-income countries. Many EID programmes follow the WHO recommendation of initial infant HIV testing with a nucleic acid assay at 4-6 weeks old. In general this strategy has been poorly implemented with substantial attrition after birth such that, according to UNAIDS, only 51% of HIV-exposed infants received a virological test in the first two months of life in 2015. In addition, there is concern about the sensitivity of the nucleic acid assays at six weeks in the context of exposure to prolonged multidrug antiretroviral therapy as infant post-exposure prophylaxis, and in breast milk. HIV-PCR testing at birth has been promoted as a means of maximizing the number of infants who receive an HIV test as well as identifying in utero-infected infants in whom HIV infection may follow an aggressive course. Evidence from pilot studies and modelling data was sufficiently compelling for the WHO to include a conditional recommendation for the addition of a birth HIV-PCR (either routine or targeted at high risk groups) to its EID algorithms in 2015. The Western Cape introduced targeted birth HIV testing for high risk infants in August 2014 and expanded this in line with the South African National Prevention of Mother-to-Child Transmission Guidelines, to include all HIV-exposed infants in December 2015. Methods: Between 2013 and 2016 we conducted an implementation science project to iteratively assess the implementation and effectiveness of the vertical transmission prevention of HIV in a chain of referral facilities in Cape Town (i.e. from primary to tertiary care). The e-register provided a single longitudinal record for each woman (linked to her infant after birth) and enabled assessment of HIV testing and treatment from first antenatal visit through delivery to infant HIV testing. Using a cohort of HIV-exposed live infants from this database, a protocol was designed (Section A: Protocol) to assess the implementation and outcome of effectively three different EID policy periods in the facility chain. i.e. an initial period of birth HIV-PCR at the clinician’s discretion if evidence of HIV infection; a period of targeted birth testing of high risk infants and lastly, of routine birth HIV-PCR for all HIV-exposed infants. A critical review of the literature appraised published assessments of birth HIV testing programmes in low- and middle-income countries (Section B: Literature Review) with the aim of assessing in utero transmission rates, follow-up testing and transmission rates and the resources required for implementation. Studies that modelled the impact of birth HIV testing were specifically reviewed. The manuscript (Section C: Manuscript) presented an analysis of the HIV-infected/exposed mother/infant dyads from the e-register of the Closing the Gaps study. Using this database adherence to guidelines in each period was assessed as well as the outcome of HIV-PCR at four delivery sites and the impact of the policies on return for follow-up EID. Results: South Africa is the first country in sub-Saharan Africa to implement birth HIV testing and most of the studies in support of this strategy were generated here. There was limited literature which highlighted the need for further investigation into the implementation and effectiveness of such programmes. No prospective data addressed targeted birth testing and those reporting on more routine birth HIV-PCR demonstrated success in timeous diagnosis and treatment although significant additional project resources were required. The retrospective laboratory data indicated that receipt of a birth HIV-PCR reduced the likelihood for follow-up at later testing time-points. This is important as the modelling studies suggested that the clinical and financial benefits of adding birth testing to existing algorithms would be lost if follow-up was poor. In the cohort of 2012 HIV-exposed infants in the study presented in the manuscript, the proportion who received birth testing increased with the progression of the EID policies but guideline implementation was poor, especially in primary care, with only 60% of infants being tested as recommended. The proportion of infants with positive HIV-PCR decreased as the pool of HIV-exposed infants undergoing testing expanded, being highest during the periods of targeted birth testing. In concurrence with the South African literature, receipt of a birth HIV-PCR decreased the likelihood of follow-up testing at 6-10 weeks. Among infants tested at 6-10 weeks old, the proportion who were positive for the first time at this time- point increased with the introduction of routine birth testing for all HIV-exposed infants, emphasizing the importance of the follow-up EID time-points. Conclusion: Virological testing at birth effectively increased the number of HIV-exposed infants who received an HIV test and was effective in identifying in utero infection in high risk infants (who could start treatment early with the attendant benefits.) The Western Cape EID policies were incompletely implemented in the study facilities over this time with many infants not being tested as indicated. Birth HIV-PCR decreased follow-up testing, an unintended consequence of serious concern. Adherence to the provincial and national guidelines needs to be re-enforced at delivery sites and at the primary care facilities where follow-up EID occurs.

Includes bibliographical references. / For this study we collected demographic information on women with oesophageal cancer being treated at Groote Schuur Hospital in Cape Twon, South Africa. The data formed part of a general cancer database in shich cases of cancer confirmed by histopathology were collected. The majority of patients originated from Eastern Cape province of South Africa and lived in rural areas.

Due to the epidemiological transition, diabetes prevalence in South Africa is increasing, while HIV prevalence remains high. Diabetes, along with HIV, has been found to be a significant risk factor for the development of tuberculosis. Early detection and treatment of tuberculosis is essential to prevent unwarranted morbidity and mortality. This hinges on efficient diagnostic methods and tools. The chest radiograph remains a cornerstone in pulmonary tuberculosis diagnosis, especially in those where microbiological evidence of disease is lacking. A study was conducted to investigate the chest radiographic presentation of pulmonary tuberculosis in patients with diabetes, as well as to analyse the effect of HIV comorbidity on this association. The study was conducted in Khayelitsha, Cape Town, an area with a high tuberculosis, HIV and diabetes burden. A literature review was conducted to identify the key features of pulmonary tuberculosis on chest radiograph for patients with diabetes and HIV. We found that patients with diabetes were more likely to have lower lung field infiltrates and increased cavitation, with glycaemic control affecting the presence of these findings. Patients with HIV presented more often with features of primary tuberculosis on chest radiograph, namely hilar and/or mediastinal adenopathy, diffuse reticulonodular infiltrate, and lower lung field (LLF) infiltrates and cavities. These features were influenced by degree of immunosuppression. This review also found that there was no literature describing the influence of HIV on the chest radiographic features of tuberculosis in patients with diabetes. This study was conducted between June 2013 - October 2015, where 377 patients with pulmonary tuberculosis, from Ubuntu and Site B primary care clinics in Khayelitsha, underwent posterior-anterior chest radiography. Chest radiographs were read using a CRRS tool. Participants with diabetes and tuberculosis (TBDM) had a higher proportion of lower lung field opacification (76,2%: 95% CI: 56,3 – 96,1) and were 3,92 times more likely to have LLF cavitations than patients with TB only. TBDM participants with HbA1c levels over 10% had more frequent LLF involvement overall (90,9% vs 61,9% p=0,052) and isolated LLF involvement (27,3% vs 3,6%; p= 0,019) than TB only participants. Both TBDM and TBDM participants with HIV (TBDMHIV) had higher proportions of isolated LLF lesions as compared to TB only participants (14,3% vs 3,6%; p=0,093 and 15,2% vs 3,6%; p = 0,039, respectively). As CD4 counts increased, there was an upward trend towards an increase in the proportion of cavitations for TBDMHIV participants, but this was not evident in participants with TB and HIV (TBHIV). This study confirms the atypical nature of chest radiograph in persons with TBDM, TBHIV and TBDMHIV, with diabetes driving the presence of lower lung field involvement. These findings can be used in bi-directional screening algorithms for patients with diabetes, with or without HIV and highlights the important role of radiographic examination in pulmonary tuberculosis.

includes bibliographic references. / TB incidence in South Africa remains high, despite high rates of successful treatment suggesting ongoing transmission and a large reservoir of latently infected persons. Isoniazid preventive therapy (IPT) is recommended as preventive therapy in HIV-infected persons. However, implementation has been slow, impeded by barriers and challenges including the fear of non-adherence. A protocol was therefore written to conduct a study to measure IPT completion rates and evaluate predictors of non-completion of a six-month IPT course in Khayelitsha, an informal township in Cape Town. Prior to data analysis, a structured literature review was conducted to assess available evidence particularly from high-burden settings on IPT completion rates and factors associated with loss to follow up.

HealthKick is a primary school-based nutrition and physical activity intervention programme aimed at promoting the adoption of healthy lifestyle behaviour to reduce diabetes risk factors in disadvantaged communities in South Africa. HealthKick aims to promote and increase learners', teachers' and parents' consumption of healthy food and their participation in health enhancing physical activity. This dissertation sub-study forms part of the evaluation of the greater HealthKick project. The primary objective of the study was to compare the dietary adequacy of learners at intervention and control schools after 18 months of intervention. The subsidiary objective was to identify the determinants of dietary adequacy.

The aim of this study is to investigate the linkage of newly-diagnosed HIV positive clients from a mobile testing unit (Tutu Tester) to HIV care at public healthcare facilities as well as to investigate the reasons for not linking to care.

Includes bibliographical references. / Since the successful use of antiretroviral therapy for the prevention of mother-to-child transmission of human immunodeficiency virus (HIV), there has been a steady increase in the number of infants born to HIV-infected mothers who remain uninfected. The characteristics of these HIV-exposed uninfected infants are not well known, including growth and other health outcomes. The International Epidemiologic Databases to Evaluate AIDS Southern Africa (IeDEA-SA) research strategy 2011-2016 includes specific studies in pregnant women, infants, children and adolescents. This study addresses one of the IeDEA-SA objectives, namely to establish and describe a sub-cohort of HIV-infected pregnant women and their exposed infants. Part A, the protocol, includes background information on sites contributing to this cohort of HIV-exposed uninfected (HEU) infants. It also details the aims, objectives and methodology of this study. Part B, the literature review, discusses what is known about HIV-exposed uninfected infants to date. It includes maternal disease factors, the use of antiretroviral therapy and the association between feeding modality and growth, focussing on studies conducted on the African continent. Part C, the manuscript, details the methodology, results and their interpretation of longitudinal analysis of growth among HEU infants in the IeDEA-SA collaboration. This cohort of HEU infants included 2621 infants from two South African sites. The median birth WAZ was -0.65 (IQR -1.46; 0.0), 51% were male and there was a median of 2 visits per infant. The feeding modalities practised were as follows: 0.5% exclusive breastfeeding, 7.9% unknown breastfeeding exclusivity, 78.6% mixed breastfeeding and 10.6% formula feeding. Mothers with a CD4 <200 cells/&#956;l delivered infants with a lower birth WAZ (adjusted ß -0.253 [95% CI -0.043; -0.072], p = 0.006) compared to mothers with a CD4 &#8805;500 cells/&#8807;l. Similarly, iv mothers who did not receive antiretroviral (ARVs) drugs delivered infants with a lower birth WAZ (adjusted ß -0.49 [95% CI -0.78; -0.20], p = 0.001) compared to mothers who received antenatal ARVs. Antenatal maternal ARVs and CD4 cell count did not have an effect on postnatal growth. Mixed effects models using maximum likelihood estimation for the longitudinal analysis of growth showed that exposure to breast milk positively influenced growth, albeit the effect was small. Infants with a birth weight <2 500g (ß 0.069 [95% CI 0.061; 0.078], p <0.0001) experienced faster growth within the first 28 weeks of life compared to infants with a birth weight &#8805;2 500g. In this cohort of South African HEU infants, less severe maternal disease and the use of ARVs positively impacted birth weight. Mixed feeding was common, and any breastfeeding may have a positive effect on longitudinal growth.

Pneumonia remains a global health priority in children. It is the leading cause of death in children outside the neonatal period, over 90% of which occur in low-resource settings, and a major cause of morbidity, accounting for over 100 million episodes globally each year. Early, correct diagnosis is a modifiable factor which can potentially improve pneumonia outcomes. Current guidelines recommend the use of clinical signs and symptoms alone to make a diagnosis of pneumonia in low risk, ambulatory cases with clinically mild disease. However, clinical diagnosis lacks specificity and may lead to antibiotic overuse and drive antibiotic resistance. Addition of chest X-ray (CXR) to diagnostic algorithms improves specificity, but CXR use is limited by radiation exposure and relatively high costs, limiting access in low-resource settings. Current guidelines therefore reserve CXR for moderate to severe disease and hospitalised cases, even in well-resourced settings. Lung ultrasound (LUS) is a promising imaging modality which uses no radiation, is less costly than CXR and can improve the time to results when used as a point-of-care tool by clinicians outside the radiology department. These characteristics make LUS, at least theoretically, a potential option either as add-on screening test aimed at decreasing unnecessary antibiotic prescription or as a lower risk, lower cost definitive diagnostic test capable of replacing CXR, or both. The objective of this study was to understand the role of LUS as a diagnostic test for pneumonia in children by performing a structured literature review and metaanalysis summarizing the current evidence comparing diagnostic performance of LUS and CXR, and by reporting previously unpublished data from the Drakenstein Child Health Study comparing diagnostic performance of LUS and CXR for pneumonia in children in a resource-constrained, African setting.