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.

The characteristics of South Africa’s HIV epidemic mean that approximately 28% of women presenting for antenatal care, are HIV-infected. Maternal HIV-infection can lead to mother-to-child transmission (MTCT) of HIV during pregnancy, labour, delivery or breastfeeding if viral load (VL) is not well controlled by antiretroviral therapy (ART). Globally, 90% of pediatric infections occur via MTCT, though lifelong ART is reducing the rate of new infections. Full benefits of ART can only be realized when ART adherence is high. Evidence from South Africa and elsewhere has shown that ART adherence in pregnant and postpartum women is suboptimal. Potential drivers of suboptimal adherence may include poor or inadequate knowledge of HIV and ART. This thesis investigates how HIV-infected pregnant and postpartum women’s knowledge of HIV and ART-related information may be associated with ART adherence as evaluated by HIV VL measures. Components of this thesis include the research protocol, a literature review of previous studies exploring the relationship between knowledge and HIV-related health outcomes in Sub-Saharan Africa and a manuscript describing the results of an investigation into predictors of HIV and ART-related knowledge and the association of knowledge with maternal vireamia (VL>1000copies/mL). This data for analysis came from a cohort of 376 HIV-infected pregnant women, initiating ART during pregnancy, at a primary care antenatal facility in Gugulethu, South Africa. Participants were followed from their first antenatal visit until twelve months postpartum. Knowledge of HIV and ART-related information were assessed at three time points by two knowledge inventories and items were classified as either relating to general knowledge or prevention of MTCT. HIV VL was measured at delivery and twelve months postpartum. Demographic characteristics were surveyed at the first antenatal visit. Analyses included univariable and multivariable regression models to estimate potential predictors of knowledge among demographic and clinical characteristics, as well as to estimate the association between knowledge and maternal vireamia at delivery and twelve months postpartum. We found that HIV and ART knowledge increased marginally over the repeated study visits. Knowledge relating to general HIV or ART information was typically good while knowledge on PMTCT was lacking. Education (OR=-0.52; 95% CI=-0.83- -0.21; P=0.001), previous HIV diagnoses (OR=-0.36; 95% CI=-0.09- 0.63; P=0.009), and weeks on ART at delivery (OR=-0.03; 95% CI=0.00-0.06; P=0.047) were statistically significant predictors of HIV knowledge in adjusted analyses. The associations between the various knowledge outcomes and vireamia at delivery and twelve months postpartum were mixed and generally not statistically significant. In summary, HIV and ART knowledge both increased with increasing time in care and general knowledge was better than knowledge specific to MTCT. Education, timing of HIV diagnoses and time on ART were identified as potential predictors of HIV-related knowledge. Generally, knowledge of HIV or ART was not meaningfully associated with vireamia at delivery or at twelve months postpartum. There remain significant gaps in the knowledge of HIV-infected women, of childbearing age, around how HIV is transmitted and how to reduce the risk of MTCT.

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.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, in partial fulfilment of the requirements for the degree of Master of Public Health in the field of Hospital Management October, 2014 / Background: The World Health Organization predicts that the deaths related to Non- Communicable Diseases in Africa will rise by 27% over the next decade. As a response to the problem, the National Department of Health in South Africa introduced interventions that focussed on implementing health facility based Non- Communicable Diseases register and a monitoring tool. The Gauteng Department of Health in South Africa started introducing the monitoring tool in public health facilities since April 2011 in a phased manner. This study used a one week data collected in the month of April 2011 in selected health facilities within the Johannesburg Health District. Aim: To describe the socio-demographic and clinical profiles of the study population attending the health facilities in Johannesburg Health District. Methodology: A cross-sectional study design was used for the study. The data was collected from the selected Community Health Centres using the monitoring tool developed by the National Department of Health. The data were collected for a week from randomly selected health facilities in 2011. Results: Nine-hundred and sixty eight study participants were recruited from the five community health centres for the assessment of non-communicable diseases. Among the study participants, the prevalence of hypertension (94.6%) was highest followed by diabetes (39.4%) and hyper-cholesterolaemia (4.6%). A number of study participants had comorbidity associated with all three conditions. The majority of them were 45 years and above (88%), female (53%), and black (98%); There were no significant association between these three conditions and risk factors such as smoking and alcohol drinking. The complications among the study participants include nephropathy, cardiac diseases and retinopathy. Annual screening was done for a number of study participants but it was erratically done so that all study participants were not screened. Twenty-two percent of 968 study participants have blood pressure of more than 140/90mmHg. Twenty percent of study participants have a weight more than 90kg. The sugar level of 22% study participants was more than 7mmol/l. Conclusion: The NCD monitoring tool could be used as an effective tool for management of NCD in PHC setting like Johannesburg Health District.

No description available.

No description available.