Includes bibliographical references ( leaves 69-74). / [Introduction] This study formed part of an existing prospective cohort study describing the outcomes of treatment of patients accessing ART in Khayelitsha. Despite the reported favorable outcomes in terms of immunologic responses, the actual variations in patterns of and associations with immunologic response over time among adult patients accessing the community based antiretroviral treatment programme in Khayelitsha are largely unknown. [The aim of the study] The aim of this study focused on describing the patterns of and associations with immunologic response, together with some of their subsequent outcomes among adult patients accessing community based antiretroviral treatment programme in Khayelitsha. [Study design and population] The analysis of this study formed part of an existing prospective cohort study describing the outcomes of antiretroviral treatment of patients in Khayelitsha. The study population included patients accessing ART in Khayelitsha, Cape Town, South Africa. A sample size of 400 HIV positive ART naïve patients was sufficiently powered for the analysis. The socio-demographic and clinical information required for the an alysis was already captured, validated and entered in a database. Summary measures, logistic regressions, survival analysis, simple linear regression and population average models were used to make the analysis and report the findings.

The HIV epidemic in sub-Saharan Africa is understood to be primarily 'sexually transmitted'. The majority of HIV prevention efforts in the region have focused on 'heterosexual sex' as the key transmission vector, without defining what 'heterosexual sex' refers to. Penile-anal intercourse (PAI) has the highest per act risk of HIV acquisition sexually and potentially accounts for a large proportion of HIV infection. Inclusion of PAI in HIV programming has typically only been in reference to men who have sex with men. Despite evidence suggesting that heterosexual PAI is common practice in sub-Saharan Africa, and is likely to be a significant contributor to HIV transmission, it has been largely excluded from HIV interventions. Greater understanding of sexual decision-making and risk-taking related to heterosexual PAI would enable evidence-based HIV intervention. This thesis presents data on conceptualisations and perceptions of heterosexual PAI and associated practices in sub-Saharan Africa, language and discourse pertaining to PAI, as well as challenges in conducting research on it. Qualitative data were gathered in five sub-Saharan African countries between 2010 and 2014. These findings demonstrate that heterosexual PAI is practiced in sub-Saharan Africa for a variety of reasons, some of which have implications for HIV transmission. Many of the factors that influence sexual decision-making and risk-taking related to heterosexual PAI are specific to this sexual behaviour. In addition, the relationship contexts in which heterosexual PAI takes place, gendered power dynamics, sexual agency and 'sexual scripts' framing PAI behaviour, are distinct from those for penile/vaginal intercourse. HIV transmission risks associated with PAI are exacerbated by taboos, social stigmatisation and sexual communication norms, impeding effective communication and safe sex negotiation, limiting individuals' ability to make informed decisions, and impacting on the reporting of PAI in research and clinical settings. Drawing on socio-behavioural theories to guide the data analysis, I developed theoretical models to explain and understand heterosexual PAI practice. The findings presented in this thesis make a unique contribution to the field, being the first in-depth description and analysis of heterosexual PAI behaviour and related practices in sub-Saharan Africa. This research highlights the importance of paying careful attention to the role of heterosexual PAI in HIV transmission in Africa.

Includes bibliographical references (leaves 98-111). / South Africa has very high levels of HIV prevalence, with some provinces having among the highest levels in the world. Within this context it is imperative to have a clear understanding of how the epidemic is affecting infants and children in the population and to what extent interventions are affecting mortality. However, establishing accurate estimates of infant and child mortality levels is very difficult in South Africa because the data available is nearly a decade out of date. Demographic modelling techniques and extrapolations from out of date data provide the closest estimates but are less than ideal in the middle of an HIV epidemic. What is needed is a surveillance method that can provide rapid, up to date information on infant and child mortality, within an environment of high HIV prevalence that can inform health policy for South Africa's youngest citizens. This study utilized routinely collected national vital events data to describe trends in infant and child mortality from 1990 to 2006. Mortality was examined by age of death in months, a finer age resolution than has been previously published. Data used in this study consisted of unpublished mortality statistics collected by Statistics South Africa from 1990 to 2002, and data extracted from the Population Register database maintained by the Department of Home Affairs for the years 1998 to 2006. The Population Register database was investigated for use as a potential mortality surveillance tool to measure current trends in infant and child mortality and to measure any effects by HIV/IAIDS interventions at a population level. Several new and unique findings were revealed in this study. First, a new and increasing all-cause peak in mortality was discovered centring at 3 months of age - a new, previously unpublished, demographic phenomenon. Second, a coding error was found in causes of death of infants under 1 year of age in the data recorded by Statistics South Africa (Stats SA) resulting in the incorrect coding of the majority of deaths in this age group. Despite the problems with coding of cause of death, the peak in mortality at 3 months was shown to be due to HIV/AIDS mortality and was the third finding in this study. The fourth finding was that the Population Register data could further be used with the 3 month peak in mortality as a rapid surveillance tool to measure trends in infant mortality. By utilizing the up to date data from the Population Register database and monitoring the peak in mortality at 3 months, this study was able to show that HIV/AIDS interventions such as the ARV rollout and PMTCT programs are beginning to have a positive effect at a population level. This method of surveillance was able to examine changes in mortality at 3 -months at both a national and provincial level.

To achieve the WHO targets of 95–95–95 by 2030, whereby 95% of all people living with HIV (PLHIV) know their status, 95 % of all people with an HIV diagnosis receive sustained antiretroviral therapy (ART), and 95 % of all people receiving ART achieve viral suppression, it is imperative to introduce novel community–based testing approaches such as HIV self-testing (HIVST). HIV self–testing has been shown to empower non– testers in both developed and underdeveloped countries, to be aware of their HIV status. However, no studies on the uptake of HIVST have been conducted on hard to reach populations in Northern Tanzania. The hard to reach populations for this thesis were female bar workers (FBWs) and mountain climbing porters (MCPS) in Northern Tanzania, who exhibit high-risk behaviours for HIV infection and low rates of HIV testing and / or repeat testing. It is important to find ways to increase the uptake of HIV testing in these populations and HIVST is proposed as a means of improving HIV testing coverage in hard-to-reach populations in the context of a long-standing HIV testing program. Existing implementation science literature suggests that behaviour change interventions (BCIs) guided by behaviour change theories and using planning and evaluation frameworks (i.e. PRECEDE-PROCEED model) can be effective in increasing HIV-related behaviour change. However, the current evidence on the effectiveness of HIV-related BCI is from studies conducted in high-income countries. To address the low HIV testing rates and/or repeat testing, it was important to undertake a project of research to develop and evaluate a theory-based behaviour change intervention (BCI) to increase HIVST uptake and linkage to HIV prevention, care and treatment among FBWs and MCPs in Northern Tanzania. This thesis aimed to develop and evaluate a multi-component theory-based BCI to increase HVST uptake and linkage to HIV prevention, care and treatment among female bar workers and mountain climbing porters in Northern Tanzania.

Includes bibliographical references (leaves 213-234). / [Objectives] Currently, HIV prevention strategies focus on promoting the modification of those individual behaviours that lead to an increase in susceptibility to and transmission of HIV infection. The focus on individuals in HIV voluntary counselling and testing frequently overlooks the fact that communication and collaboration between the sexual partners is required to effect any behavioural change within an intimate partnership. Developing HIV prevention strategies targeting couples is therefore noted to be increasingly relevant for improving HIV/STI risk reduction uptake. Couple HIV counselling and testing (CHCT) is a strategy that aims to bridge this gap by providing a safe environment for partners to be tested and counselled together. In this way, the burden of disclosing one's HIV status to one's partner is eliminated, and the difficulties experienced by the tested individual in negotiating risk reduction uptake are significantly reduced. There is a paucity of data regarding couples' experiences in and perceptions of CHCT within the South African setting. This study explores couples' experiences before, during and after CHCT; determines the socio-behavioural risk factors for HIV status in couples; explores the impact of couple HIV status on fertility desires, and lastly examines the reliability of inter-partner reports on sexual and other behaviours. [Methods] This was a cross-sectional study with baseline and follow-up components; in addition to a qualitative study component. Structured interviewer-administered questionnaires were applied to each member of the couple separately at baseline prior to CHCT (n=600 couples), immediately post CHCT, and at least 1 month post the CHCT process (n= 258 couples). In addition, in-depth qualitative interviews were done with each member of 27 couples at least one month post CHCT. [Results] Overall, the HIV prevalence in the study sample was 30% (24% in male and 35% in the female participants). Of the 600 couples tested for HIV, 354 (59%) were HIV concordant negative, 136 (23%) were HIV serodiscordant and 110 (18%) were HIV concordant positive. Of the HIV serodiscordant, 101(74%) were couples in which the female was the HIV positive partner and 35 (26%) had HIV positive males. Contextual factors such as community perceptions and levels of HIV-related stigma significantly influenced the couples' decision to test for HIV. Couples reported improved risk reduction uptake and improved communication as well as general improvements in other aspects of their lives at follow-up post the CHCT process. Factors such as community and family expectations as well as financial stability seemed to play a more influential role as determinants of fertility desire, compared to the couple HIV status. Comparison of couples' responses to some questions regarding sexual and other behaviours revealed that there was low inter-partner agreement particularly with respect to questions regarding communication behaviours. Key findings indicate that CHCT was acceptable to the couples who attended this process, and yet, making the decision to test was difficult for most couples. Partners devised various strategies to initiate the discussion on the need to test for HIV. However, after CHCT attendance, the process was highly rated, regardless of gender or resultant HIV status. [Conclusion] In order to increase the usefulness and effectiveness of CHCT, the process must be able to address pertinent uncertainties and concerns that couples might have with regard to HIV risk-reduction uptake and fertility desires.

Background Noma, also known as cancrum oris, is a gangrenous infection of the oral cavity, which causes widespread orofacial destruction. If untreated, noma has a reported 90% mortality rate within weeks after the onset of first symptoms. Noma progresses through distinct stages defined by the World Health Organisation (WHO); Stage 0: simple gingivitis; Stage 1: acute necrotizing gingivitis; Stage 2: oedema; Stage 3: gangrene; Stage 4: scarring. Stage 5: sequelae. It is unclear how many patients with the early stages of noma will progress to the later stages of disease. Treatment in the early reversible stages with antibiotics, wound debridement and nutritional support greatly reduces morbidity and mortality. Acute noma is most often reported in children aged between two and five years. Many patients who survive the acute stages of the disease suffer into adulthood with disfigurement and disability of varying degrees. Noma is thought to be most prevalent in developing countries in Africa and Asia. Estimates for noma prevalence and incidence vary. In 1998, the WHO estimated an annual incidence of 140,000 cases of acute noma and 770,000 noma survivors living with sequelae. Two Nigerian studies estimated the burden of disease ranged from seven cases per 1,000 children aged between one and 16 years (2003) to 6.4 per 1,000 children (2003). A study from 2019 estimated the period prevalence of noma from 2010 to 2018 was 1.6 per 100,000 population at risk in Nigeria. These estimates are based on expert opinion, number of hospital admissions and retrospectively collected hospital-based data and it is unclear which stages of noma were included. Risk factors for the disease include poor oral hygiene, malnutrition, comorbidities and low socioeconomic status. Despite its ancient history (reported by Hippocrates (460 - 370 BC)), noma-related literature remains mainly confined to case reports and case series. By employing both qualitative and quantitative methods, we sought to examine the biopsychosocial features of noma, its epidemiology and treatment in northwest Nigeria in order to inform advocacy and prevention efforts. The three overarching objectives to fulfil this aim were to assess the distribution of noma among children in northwest Nigeria; identify factors associated with noma (including factors influencing health-seeking behaviour and risk factors for the development of noma) and gain an understanding of the biomedical and non-biomedical care provided to noma patients in this setting. The knowledge gained through this thesis will support the assessment of the need for advocacy around noma, effective resource allocation and the planning of intervention strategies. Methods We conducted a scoping literature review, three quantitative studies (risk factors, outcomes, prevalence) and two qualitative studies (language and beliefs and traditional healing practices) in northwest Nigeria. Data were collected from patient caretakers at the Noma Children's Hospital, hospital staff, children and traditional healers in villages within Sokoto and Kebbi States. Data collection methods included quantitative surveys, oral screenings, anthropometric measurements, quality of life questionnaires, qualitative in-depth interviews and focus group discussions. Consenting adult respondents answered questionnaires and participated in interviews, and where applicable, data was collected from assenting children. Quantitative analyses included descriptive statistics as well as univariable and multivariable risk factor analyses. Qualitative data was manually coded and analysed thematically. Findings We included 74 cases (noma patients presenting at the hospital in the year preceding data collection) and 222 controls (both median age of five years (inter-quartile range 3, 15 years)) in the risk factor study. Vaccination coverage for polio and measles was below 7% in both cases and controls. The multivariable analysis identified the child being fed pap every day (adjusted odds ratio (aOR) 9.8; 95% confidence interval (CI 1.5, 62.7) as a risk factor. The mother being the primary caretaker (aOR 0.08; CI 0.01, 0.5) and the caretaker being married (aOR 0.006; CI 0.0006, 0.5) were protective factors. Of the 37 patients with noma sequelae included in the outcomes study, 21 (56.8%) were male and 22 (62.9%) were aged six years or older. Fifteen patients (40.5%) had two to three surgeries. The most frequently used surgical procedure was a deltopectoral flap (n=16 patients; 43.2%). Trismus was released in 12 patients (32.4%), of these; none had a normal mouth opening at the follow-up visit. Despite this finding, all respondents reported that the surgery had improved their quality of life. In the cross-sectional study assessing the prevalence of all stages of noma, we included 3,499 households and 7,122 children aged <15 years; 4,239 (59.8%) were aged 0 to 5 years. Simple gingivitis was identified in 3.1% (n=181; CI 2.6-3.8), acute necrotizing gingivitis in 0.1% (n=10; CI 0.1-0.3), and oedema in 0.05% (n=3; CI 0.02-0.2). No cases of late-stage noma were detected. Naming of the disease differed between caretakers and healthcare workers in the language and beliefs study. Beliefs about the causes of noma were varied (spirits, animals, insects, previous infections). Noma patient caretakers spoke of the mental health strain due to stigmatization as a key issue. Difficulty in accessing care was evident. A lack of trust in the health system was mentioned as a barrier to care. Traditional healers offered specialised forms of care for specific conditions and referral guidance. They viewed the stages of noma as different conditions with individualised remedies and were willing to refer noma patients. Caretakers trusted traditional healers. Conclusion Social conditions and childhood feeding practices are associated with the occurrence of noma in northwest Nigeria. This thesis has shown that following their last surgical intervention, noma patients do experience some improvements in their quality of life, but continue to face functional challenges that inhibit their daily life. We found many, widely distributed, early-stage noma cases in northwest Nigeria indicating a large population at risk of progressing to the later stages of disease. Caretaker and practitioner perspectives may enlighten efforts to improve case finding, and to understand barriers to accessing health care. Differences in disease naming illustrated the difference in beliefs about the disease. Traditional healers could play a crucial role in the early detection of noma and the health-seeking decision-making process of patients. Intervention programmes should include traditional healers through training and referral partnerships. In conclusion, this thesis provides a unique view of the biopsychosocial features, epidemiology and treatment options for noma in northwest Nigeria. Noma is a disease, which is indicative of a weak health system and socio-economic environments of extreme deprivation. Intervention programmes should include widespread health system improvements that could address a host of risk factors for noma, and simultaneously other childhood diseases. These include increasing access to quality health care (including vaccinations), ensuring effective referral mechanisms, predominantly in rural areas, and the creation of a robust surveillance network. Health financing initiatives would need to be paired with these improvements. Nutritional programs aimed at caretakers of young children and community-based oral health initiatives could be effective mechanisms to curb the number of noma cases. Awareness-building initiatives targeting healthcare workers and community members are necessary to improve the detection and timely management of noma in endemic settings. The combined findings of this thesis highlight the neglected nature of noma and make a strong case for placing noma on the WHO neglected tropical diseases list. This initiative could foster awareness among policy-makers and governments and direct much needed funding to facilitate further research, surveillance and targeted health interventions that would contribute to the eradication of noma.

Includes abstract. / Includes bibliographical references. / Background: Baker's asthma is the most serious manifestation of occupational allergy among bakery workers. It is caused by IgE-mediated sensitisation and subsequent allergic reaction in the airways to specific occupational airborne allergens in flour or baking ingredients. Major aims of this study were to: characterise asthma phenotypes and environmental exposure to flour allergens among bakers and modifying factors; study associations between phenotype and environmental exposure and identify potential modifying factors of this association; determine the effectiveness of specific interventions in reducing exposure and the risk of sensitisation or allergic respiratory disease. Methods: A cross-sectional study was conducted among 517 bakery workers employed in 31 supermarkets. Health outcomes were assessed using a standardized questionnaire, immunological tests (sIgE, sIgG), methacholine challenge test and fractional exhaled nitric oxide (FeNO). Exposure assessment conducted pre- and post-intervention entailed determination of inhalable concentration of particulate mass and specific allergen levels. The intervention employed a group-randomised design to evaluate dust control measures. Results: Prevalence of probable occupational asthma (POA, 13%) was higher than atopic (AA, 6%), non-atopic (NAA, 6%) and work-aggravated asthma (WAA, 3%). Sensitisation to flour allergens was a major determinant of elevated FeNO among bakers. Bread bakers had the highest dust particulate (mean = 1.33 mg/m3) and allergen exposures. Exposure response relationships followed a bell-shaped curve, with the prevalence of IgE- sensitisation, allergic symptoms and POA, increasing up to 10-15 μg/m3 of airborne wheat allergen concentrations before declining. The association for IgE sensitization was not modified by IgG4 to wheat. The overall effect of the intervention revealed a 50% decrease in mean flour dust, wheat allergen and rye exposures in bakeries. Conclusion: Occupational asthma is the most common phenotype among supermarket bakery workers, with sensitisation to cereal flour allergens being the main determinant of allergic airway inflammation. The bell-shaped exposure response relationship is not modified by the presence of blocking antibodies and is probably due to a healthy worker effect. The multi-pronged intervention strategy was effective in reducing airborne flour dust and allergen levels. It is recommended that further studies investigate the long term health impact of these interventions in reducing the disease burden.

This thesis examines the challenges to and opportunities for comprehensive (primary and secondary) prevention of cervical cancer in South Africa (SA), a middle-income country.

Includes bibliographical references. / This thesis describes the conceptualisation, development and implementation of a mortuary-based system for the routine collection of information about homicide. It traces the evolution of the system from its conceptualisation in 1994, through various iterations as a city-level research tool, to a national sentinel system pilot, as a multicity all-injury surveillance system, and finally its institutionalisation as a provincial injury mortality surveillance system in the Western Cape. In so doing, it demonstrates that the data arising from medico-legal post-mortem investigations described in this thesis were an important source of descriptive epidemiological information on homicide. The 37,037 homicide records described in the thesis were drawn from Cape Town, Durban, Johannesburg, Port Elizabeth and Pretoria, for which the surveillance system maintained full coverage from 2001 to 2005. The aim was to apply more complex statistical analysis and modelling than had been applied previously.

Lack of coordination and integration between routine electronic databases can limit effective data production and utilisation to support health management decision-making. There is currently a need to strengthen data support structures through the harmonisation of multiple databases across different types of health services and organisations. Data harmonisation (DH) is an innovative process of copying existing electronic data captured in various databases into a centralised data repository where the data is integrated and then transformed into useable formats for data users. However, there is limited evidence about the wide range of factors (especially social factors) that impact on DH innovations, such as historical factors, stakeholder relationships and institutional terrain. This doctoral research aimed to identify and explore the factors affecting a DH initiative currently underway in the Western Cape Province of South Africa. The research was conducted using three methodological approaches, namely a historical analysis and synthesis, a scoping review and an ethnographic case study. For the historical analysis, relevant articles were identified through literature searches and data were collected through document reviews and interviews with two key informants. Data were first organised chronologically according to key events that took place in the health information system (HIS). Text from websites, journal articles, internal documents, standard operating procedures and interview notes were then synthesised according to key themes related to HIS interventions. For the scoping review, systematic literature searches were conducted to identify studies that met the eligibility criteria of the review. Two review authors (one being the doctoral student) screened titles, abstracts and full-texts and then sampled studies based on the range, variation and similarities or differences in definitions and concepts and intervention descriptions. Manual coding and the filter option in Excel were used to provide (a) numerical analysis of the characteristics of included studies; (b) narrative synthesis of the different DH definitions, components and processes, as well as intentions, suggestions and/or explanations of how DH may lead to improved health management decision-making. For the ethnographic case study, data were collected using participant observation (including conversations, meeting attendance and telephone and email communication), document reviews and in-depth interviews. Participants included data clerks, facility managers, health information staff and managers, DH innovators, researchers, public health specialists and database managers. Raw data were collected in the form of meeting minutes, field notes, interview notes and document extracts. Data analysis was conducted using thematic data analysis. The doctoral student manually coded data by highlighting recurring themes and evidence, and by extracting prominent themes from the various sources of data. As a strategy for testing the validity of emerging themes, the doctoral student used triangulation of different data sources; including looking for consistencies or inconsistencies between data sources. Five main findings emerged from the doctoral research. The first finding affirms that DH is a multi-faceted intervention. In the literature, it is defined and described using different terms for similar aims and activities (such as record linkage, data warehousing, health information exchange). Key characteristics emerging from a synthesis of DH studies include: a process of multiple steps to integrate electronic data; different types of databases, institutions and technical activities; integrating data involves using unique patient identifiers; and framing interventions or activities around a specific scope or purpose (such as geographic area, disease surveillance and treatment management). DH interventions contributed to three levels of health management decision-making, namely clinical support, operational and strategic management, and populationlevel disease surveillance. The second finding relates to the concept of ‘cultivation’. Cultivation is an ongoing and iterative social process to deal with problems between people, institutions and technology as they engage with each other in the context of an emerging innovation. The third finding is about striking a balance between the role of champions in designing and piloting innovations and the role of institutions in operationalising innovations and incorporating them into the broader health system for acceptance amongst implementers and users and for sustainability in the future. The fourth finding is about the motivations and opportunities that contributed to the emergence of a DH initiative in the Western Cape Province of South Africa. Opportunities for the new DH initiative include well-developed individual electronic databases, a government-university collaboration, and the positive attitude of frontline health workers towards DH projects. The new initiative faced design and operational challenges such as difficulty to access data from different health authorities and the incompleteness of electronic data. However, new data access and transfer procedures and existing social relationships were important for dealing with the changes that occurred as DH projects were being operationalised. The last finding highlights tensions that emerged between DH innovators and other health information technology (HIT) stakeholders because of institutional and conceptual differences (such as different approaches to data access and governance, differences in conceptualisations of the value of data, and misunderstandings about the purpose of formal data procedures). DH innovators were able to navigate conflicts emerging from institutional and conceptual differences because of their strong leadership and team setup, institutional positioning and stakeholder engagement activities, to become institutionalised within the health system. These findings provide health system, information technology and research stakeholders with a broader understanding of the range of social factors that impact on DH innovations. This research promotes a more comprehensive approach in designing, implementing and evaluating DH innovations to limit poor outcomes of innovations and wasted resources.