Includes bibliographical references (leaves 96-98). / This thesis examines the associations between self-reported hypertension diagnosis and Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) defined a) anxiety disorders b) depressive disorders and c) comorbid anxiety-depression, both lifetime and 12-month, adjusting for potential confounding variables.

Background: The management of hypertension according to the patient' s absolute risk of cardiovascular disease. rather than their blood pressure in isolation from other risk factors, is now widely advocated because it targets treatment at those with most to gain. In South Africa blood pressure is traditionally managed according to the patient's level of blood pressure. Main Objective: To identify the proportion of traditionally treated hypertensive patients who may benefit from cessation or intensification of treatment as judged by a risk-based approach to their management. Design: A cross sectional descriptive survey of patients and their medical records with assessment of absolute risk of cardiovascular disease using Framingham risk equations. Setting: Eight Clothing Industry Health Benefit Fund clinics in Cape Town, South Africa. Participants: 382 women and men, predominantly coloured, attending for the treatment of hypertension Main outcome measure: The proportions of patients in whom the predicted risk of a cardiovascular event within 5 years is less than 10% and those in whom the risk within five years is greater than 20%. Results: 65% of participants (CI 60 - 70%) were at less than 10% risk of a cardiovascular event in the next 5 years and 19% (Cl 15-23%) were at more than 20% risk of a cardiovascular event despite current treatment. 5% (CI 3.2-7.9%) were at greater than 20% risk of a cardiovascular event in the next 5 years having no previous history of a cardiovascular event. 14% (CI 10-17%) were at greater than 20% risk of a cardiovascular event in the next 5 years because of a previous history of a cardiovascular event. 1.3% (CI 0.4-3%) were at less than 10% risk of a cardiovascular event within the next 5 years, despite having a systolic blood pressure over 170mmHg. Conclusion: Assessment of the cardiovascular risk of patients treated for hypertension identifies those patients at most and least risk. Resources could therefore be targeted at those with the most to gain from treatment and the unwanted side effects of antihypertensive medication avoided in those at low risk. Almost two thirds of patients currently being treated for hypertension were at less than 10% risk of developing a cardiovascular event within the next 5 years. A trial of medication reduction or cessation in this group is justified and the resources could be redirected at those 5% whose risk remains very high despite current levels of treatment.

BACKGROUND: Long-term exposure to organophosphates (OPs) can cause chronic neurotoxic effects which may be modulated by genetic polymorphisms of xenobiotic metabolising enzymes (XMEs). No previous study investigated XME modulation of neurotoxicity outcomes. OBJECTIVES: To investigate whether XMEs polymorphisms modulate OP neurotoxicity among emerging farmers. METHODS: A cross-sectional study of 301 emerging farmers was conducted in the rural Western Cape of South Africa. Neurotoxicity testing included the World Health Organisation Core Test Battery (digit span forward and backward) and vibration sensitivity testing. Questionnaire items included demographic data, potential confounders and work history of pesticide exposures. Blood samples were analysed for genetic polymorphisms of the following XMEs; glutathione S-transferases (GST), N-acetyltransferases (NAT) and Paraoxonase (PON1). RESULTS: Median age was 39 (30-48) and most had 9 years of education or less (65.5%). 54% of the participants were OP pesticide applicators. There was a low prevalence of the GST null genotype (GSTT-1% and GSTM-16%) and the GA and GG genotype for NAT (10%). Modulation of OP exposure and neurotoxic outcome relationships by NAT, PON1 at position 192 and GST was indicated in multivariate analysis. The strongest evidence of modification was by NAT on the relationship between pesticide poisoning and impaired vibration sense. Poisoned individuals with the GG genotype were more likely to suffer from impaired vibration sense compared to GA and AA genotypes. CONCLUSION: Genetic polymorphisms of NAT, PON1 (at position 192) and GSTM may modify the relationship between OP exposure and neurotoxicity. Larger longitudinal studies are required to determine whether preventive strategies can be developed to improve health amongst the identified vulnerable groups.

A large proportion of chlamydial and gonococcal infections are asymptomatic. In lower- and middle-income countries like South Africa, where syndromic management is practiced, it is likely that a large proportion of curable STIs go untreated, as screening for asymptomatic STIs is rarely conducted. Due to the lack of empirical data on the efficacy of STI screening programs, dynamic mathematical modelling has been used to assess the impact of screening, but most previous modelling studies have focused on high-income settings. Here we utilize dynamic mathematical modelling to evaluate the potential impact of opportunistic STI screening programs on the incidence and prevalence of Chlamydia trachomatis and Neisseria gonorrhea in South Africa. We extended an existing agent-based model of heterosexual HIV and STI transmission in South Africa to investigate the impact of targeted screening strategies directed at high risk groups including youth, female sex workers, pregnant women and patients in HIV care. All four screening strategies resulted in reductions in general and key population STI transmission. Opportunistic STI screening of youth and ART patients were shown to be most effective and represent viable interventions for reducing STI transmission in the South African population. Additionally, we compared the modelled impact of a standardized screening program to results obtained from other published mathematical models of chlamydia screening. Differences between models could be attributed to differences in the modelled heterogeneity in sexual behaviour as well as differences in assumptions about immunity following chlamydia recovery.

This study is an extension of a prospective epidemiological study of TB disease and infection in adolescents in the Worcester and surrounding areas in the Western Cape carried out from 2005 to 2009, in which 6363 participants were enrolled from local public schools. In this follow-on study, a subset of adolescents who were identified to have converted their QFT status during the original study will be followed up and observed for the occurrence of active TB disease over a period of two years. A similar sized, random sample of participants identified to have a QFT status that remained negative throughout the original study will be used as the control group.

Background In 2019, 1 million in utero-HIV-exposed but -uninfected children (CHEU) were born in sub-Saharan Africa. In the absence of breastfeeding and maternal antiretroviral therapy (ART), HIV-exposed uninfected children (CHEU) have higher risks of mortality, growth faltering, infectious morbidity, and developmental delay than the general population, but data are limited on these outcomes among breastfed CHEU born to women who received universal (not restricted by disease severity) ART in pregnancy. This thesis addresses these knowledge gaps by comparing health outcomes of breastfed CHEU to breastfed CHU in the first year of life. Methods This research incorporates data from two prospective, linked cohort studies of pregnant women living with HIV (Maternal Child Health Antiretroviral, MCH-ART study, 2013-2016) and without HIV (HIV-unexposed uninfected, HU2 study; 2014-2017) in Gugulethu, Cape Town, South Africa. Enrolled at first antenatal visit at a primary care clinic, women were followed-up during pregnancy and postpartum with their breastfed infants, through 12 months with ~3-monthly study visits. Study staff administered questionnaires addressing maternal and child health, infant feeding, psycho-social and behavioural factors; and measured maternal-infant anthropometry [expressed as Z-scores for age: weight-for-age, WAZ; length-for-age, LAZ; head circumference-for-age, HCAZ]; WLHIV provided blood for repeated HIV viral load. At 12 months, the Bayley Scales of Infant Development, 3rd edition (BSID-III) was used to assess neurodevelopment. Findings WLHIV (100% antenatal ART) reported worse living conditions and higher risks of alcohol use and intimate partner violence than HIV-negative women. Similar proportions of CHEU and CHU were born preterm (11%) or small-for-gestational-age (10%). Exclusive breastfeeding was more common among CHEU than CHU, but overall duration of breastfeeding was shorter among CHEU. However, unless otherwise reported, adjustment for confounders did not change inferences below. In analysis of child growth, weight and head circumference trajectories were similar for CHEU and CHU from 6 weeks to 12 months. Both groups exhibited rapid weight gain with increasing WAZ over time; by 12 months, almost one-fifth of all children were overweight. Length trajectories for CHEU and CHU diverged after 6 months, with onset of linear growth faltering occurring earlier and more rapidly among the CHEU; by 12 months, stunting risk was doubled among CHEU vs CHU. Stratified by birth size, differences in LAZ between CHEU and CHU were magnified for those born small-forgestational age and absent for those born appropriate-for-gestational age. Infectious morbidity analyses revealed greater risks among CHEU than CHU in the first 6 months with not thereafter. Between 7 days and 3 months of life, CHEU (vs CHU) experienced three times more infection-related hospitalisations; rates for CHEU with healthier mothers (lower viral load, higher CD4 count, ART started early in pregnancy) approximated those of CHU, while CHEU of mothers with late ART initiation and advanced disease had four-fold more infectious-cause hospitalization. Breastfeeding and complete vaccinations were protective. At 12 months, mean composite cognitive, motor and language scores were within normal range and similar for both groups. Overall, risks of any developmental delays were low but slightly higher among CHEU than CHU in cognitive and motor domains. Compared to term HU, term HEU children had similar odds of motor delay, preterm HU children had 5-fold increased odds of delay and preterm HEU children, 16-fold. In CHEU, cumulative maternal viremia was associated with lower average scores and increased risk of moderate delays in motor and language domains. Conclusion Subtle health outcome differences persisted between CHEU and CHU despite breastfeeding and universal maternal ART in pregnancy. Reassuringly, the magnitudes of differences were small and predominantly associated with preventable factors including late ART initiation, advanced maternal disease stage, lack of breastfeeding, and incomplete vaccination. CHEU born too soon or too small were at highest risk of adverse outcomes, suggesting fetal origins of disease in the context of maternal HIV.

Background: Adherence to the recommended age-specific immunisation schedules is critical in ensuring vaccine effectiveness against vaccine preventable diseases (VPDs). Delays in the uptake of routine childhood immunisations lead to an increase in children susceptible to VPDs. Catch-up vaccination campaigns are strategies aimed at minimising the time at risk of VPDs and alleviating missed immunisation opportunities. However, there is limited data on immunisation timeliness in the Western Cape to contribute to developing effective catch-up vaccination campaigns. Therefore, this study sought to assess the timeliness of age-specific routine childhood immunisation within the Western Cape province of South Africa. Methods: We reviewed 709 participant records from a prospective health-facility based study conducted between 2012 and 2016 in Cape Town, South Africa. The primary outcome of interest was receiving age-specific immunisations ≥ 4 weeks (28 days) of that recommended for age as per the South African Expanded Programme on Immunisation (EPI) schedule. Using secondary data, the prevalence of delayed uptake of immunisations and time-at-risk for each vaccine was determined using proportions and medians and interquartile range (IQR). Multivariable logistic regression (p< 0.05) was used to determine the association between potential socio-economic risk factors and delayed uptake of routine childhood immunisations. Results: A total of 652/709 (91.9%) participants with a median age of 11 [IQR 4.5 – 28.0] months were eligible for analysis in this study. A trend of decreasing immunisation coverage with increasing age was observed among study participants. Notably, a trend of increasing delay in the uptake of routine vaccines and an increasing median time-at-risk of VPDs in age-specific immunisations was observed with increasing age. The highest delay in the uptake of vaccine doses was observed among the 3rd dose of the DTP3 vaccine 163 (34.6%), while the lowest was seen among the birth doses [(BCG – 40 (6.5%) and OPV – 43 (7%)]. The longest median time-at-risk of VPDs, was with the 2nd dose of the measles vaccine dose [12.9 (IQRs 6.7-38.6) weeks] and the lowest was OPV birth dose [6.3 (5.3-9.1) weeks]. Multivariable logistic regression analysis showed that participants who attended pre-school or creche compared to those who did not, were protected against delaying uptake of the 3 rd dose of the Hepatitis B vaccine and 2nd dose of the measles vaccine. While those who had adult caregivers compared to those who had adolescent caregivers, were protected against delaying the uptake of the 1 st rotavirus vaccine dose. Participants from households of low and upper-middle socio-economic IQR compared to high socio-economic status (SES) based on SES scores calculated from household data (i.e., availability and sources of amenities such as water, fuel, toilets, and level of maternal education) were more likely to delay uptake of the 3 rd does of the Pneumococcal Conjugate Vaccine and the 1 st dose of the measles vaccine, respectively. Conclusion: Using DTP3 coverage as proxy for national immunisation coverage, immunisation coverage in this population fell below the recommended 95% immunisation coverage rate. Additional population delays in the uptake of vaccine doses increases the time during which infants and children are susceptible to potential fatal VPDs. The observed increase in delayed immunisation and increased time-at-risk of VPDs, calls for an urgent need to address timing of vaccination particularly in late infancy and in the second year of life. There is an urgent need to develop strategies aimed at mitigating factors associated with delay in uptake of routine childhood vaccines in the Western Cape Province. Since creche attendance conferred protection against the delay in uptake of vaccines, mitigation strategies implemented upstream by the department of basic education, as well as health and immunisation service providers should strengthen collaborations to ensure that timely vaccine uptake among creche attendees is regularly monitored. Where delays are identified, catch-up strategies can be implemented at educational facilities or referrals to immunization clinics. It is important that this strategy is coupled with caregiver and healthcare worker vaccine education on the importance of timely immunisation uptake. Education about timely vaccine uptake will aid in the provision of informed council from healthcare providers to – not only adult caregivers - but adolescent caregivers as well, with the aim to reduce delayed uptake of vaccine amongst those raised by adolescent caregiver. The health system and the Expanded Programme of Immunisation on South Africa (EPISA) should couple these interventions with effective mobile reminder systems. These reminder systems will particularly serve the purpose to remind those caregivers whose delay uptake of vaccines as a result of a busy schedule. This could improve adherence to the recommended childhood immunisation schedule. Generally, for such interventions to work, effective monitoring and surveillance of immunisation services and vaccines is critical in achieving a high immunisation coverage and timely uptake of vaccines. Future studies should continuously monitor immunisation coverage and timeliness data in the Western Cape Province and South Africa as a whole to support evidence-based strengthening of provincial and national immunisation services.

No description available.

No description available.

No description available.