PhD, Faculty of Health Sciences, University of the Witwatersrand / Background: In low- to middle-income countries, rising levels of overweight and obesity are a result of multiple transitions, in particular, a nutrition transition. Consequently, in these countries, metabolic diseases are contributing increasingly to disease burden, despite the persisting burden of undernutrition and infectious diseases. Understanding the patterns and factors associated with persistent undernutrition and emerging obesity in children and adolescents, and concomitant risk for metabolic disease, is therefore of criticial importance. This should contribute to public health policy on interventions to prevent adult disease. Aims: To better understand the double burden of malnutrition in a poor, high HIV prevalent, transitional society in a middle-income country; In so doing, to inform policies and interventions to address the double burden of malnutrition. Methods: A cross-sectional growth survey was conducted in 2007 targeting 4000 children and adolescents 1-20 years of age living in rural South Africa. The survey was nested within the ongoing Agincourt Health and Socio-demographic Surveillance System, which acted as the sampling frame and also provided data for explanatory variables. Anthropometric measurements were performed on all participants using standard procedures. In addition, HIV testing was done on children aged 1 to 5 years and Tanner pubertal assessment was conducted among adolescents 9-20 years. A one-year follow-up of HIV positive children included a matched control group of HIV negative counterparts. Data collection involved both quantitative and qualitative methods. Growth z-scores were used to determine stunting, underweight and wasting and were generated using the 2006 WHO growth standards for children up to five years and the 1977 NCHS/WHO reference for older children. Overweight and obesity were determined using the International Obesity Task Force cut-offs for BMI for children aged up to 17 years and adult cut offs of BMI =25 and =30 kg/m2 for overweight and obesity respectively for adolescents 18 to 20 years. Waist circumference cut-offs of =94cm for males and =80cm for females, and waist-to-height ratio of 0.5 for both sexes, were used to determine central obesity and hence metabolic disease risk in ix adolescents. Descriptive analysis described patterns of nutritional status by age, sex, pubertal stage and HIV status. Linear and logistic regression was done to determine predictors of nutrional outcomes. A p-value of <0.05 was considered statistically significant. Results: Prevalence of undernutrition, particularly stunting, was substantial: 18% among children aged 1-4 years, with a peak of 32% in children at one year of age. Stunting and underweight were also substantial in adolescent boys, with underweight reaching a peak of 19% at 14 years of age. Concurrently, the prevalence of combined overweight and obesity, almost non-existent in boys, was prominent among adolescent girls, increasing with age, and reaching a peak of 25% at 18 years. Risk for metabolic disease using waist circumference cut-offs was substantial among adolescents, particularly girls, increasing with sexual maturation, and reaching a peak of 35% at Tanner stage 5. Prevalence of HIV in children aged 1-4 years was 4.4%. HIV positive children had poorer nutritional outcomes than that of HIV negative children in 2007. The impact of paediatric HIV on nutritional status at community level was, however, not significant. Significant predictors of undernutrition in children aged 1-4 years, documented at child, maternal, household and community levels, included child’s HIV status, age and birth weight; maternal age; age of household head; and area of residence. Significant predictors of overweight/obesity and risk for metabolic disease in adolescents aged 10-20 years, documented at individual/child and household levels included child’s age, sex and pubertal development; and household-level food security, socio-economic status, and household head’s highest education level. There was a high acceptance rate for the HIV test (95%). One year following the test, almost all caregivers had accepted and valued knowing their child’s HIV status, indicating that it enhanced their competency in caregiving. Additionally, nutritional status of HIV positive children had improved significantly within a year of follow-up. Conclusions: The study describes co-existing child stunting and adolescent overweight/obesity and risk for metabolic disease in a society undergoing nutrition transition. While likely that this profile reflects changes in nutrition and diet, variation in infectious disease burden, physical activity patterns, and social influences need to be investigated. The findings are critical in the wake of the rising public health importance of metabolic diseases in low- to middle-income countries, despite the unfinished agenda of undernutrition and infectious diseases. Clearly, policies and interventions to address malnutrition in this and other transitional societies need to be double-pronged. In addition, gender-biased nutritional patterns call for gender-sensitive policies and interventions. The study further documents a significant role of paediatric HIV on nutritional status, and the potential for community-based paediatic HIV testing to ameliorate this. Targeted early paediatric HIV testing of exposed or at risk children, followed by appropriate health care for infected children, may improve their nutritional status and survival.

abstract: Over the past several decades, there has been a growing interest in the use of fluorescent probes in low-cost diagnostic devices for resource-limited environments. This dissertation details the design, development, and deployment of an inexpensive, multiplexed, and quantitative, fluorescence-based lateral flow immunoassay platform, in light of the specific constraints associated with resource-limited settings. This effort grew out of the need to develop a highly sensitive, field-deployable platform to be used as a primary screening and early detection tool for serologic biomarkers for the high-risk human papillomavirus (hrHPV) infection. A hrHPV infection is a precursor for developing high-grade cervical intraepithelial neoplasia (CIN 2/3+). Early detection requires high sensitivity and a low limit-of-detection (LOD). To this end, the developed platform (DxArray) takes advantage of the specificity of immunoassays and the selectivity of fluorescence for early disease detection. The long term goal is to improve the quality of life for several hundred million women globally, at risk of being infected with hrHPV. The developed platform uses fluorescent labels over the gold-standard colorimetric labels in a compact, high-sensitivity lateral flow assay configuration. It is also compatible with POC settings as it substitutes expensive and bulky light sources for LEDs, low-light CMOS cameras, and photomultiplier tubes for photodiodes, in a transillumination architecture, and eliminates the need for expensive focusing/transfer optics. The platform uses high-quality interference filters at less than $1 each, enabling a rugged and robust design suitable for field use. The limit of detection (LOD) of the developed platform is within an order of magnitude of centralized laboratory diagnostic instruments. It enhances the LOD of absorbance or reflectometric and visual readout lateral flow assays by 2 - 3 orders of magnitude. This system could be applied toward any chemical or bioanalytical procedure that requires a high performance at low-cost. The knowledge and techniques developed in this effort is relevant to the community of researchers and industry developers looking to deploy inexpensive, quantitative, and highly sensitive diagnostic devices to resource-limited settings. / Dissertation/Thesis / Doctoral Dissertation Electrical Engineering 2018

Neglected tropical diseases (NTD) in low- and middle-income countries are still not on target per the World Health Organization's (WHO) elimination goal of 2020. Mass drug administration (MDA) is one of the effective strategies supported by the WHO for the control and subsequent elimination of NTD. This quantitative study explored how supply chain logistic capacity may be hampering MDA coverage in countries in which the diseases are endemic. The study examined secondary data from WHO data bank for MDA coverage, to quantify the relationship between supply chain logistics capacity, as measured by the World Bank's logistics performance index (LPIs), and the control of NTD using MDA. The ecological theory of health behavior was the theoretical framework for this study. The research questions explored whether a low- and/or middle-income country's supply chain infrastructure, logistics services, customs and border procedures, and supply chain reliability, predict the coverage of MDA in controlling NTD. A multiple regression model determined the linear relations between each predictor: supply chain infrastructure (H1), logistics services (H2), custom and border procedures (H3), and supply chain reliability (H4) and the control of neglected diseases as determine by MDA. Results indicated that supply chain capacity, custom and border processes, and supply chain reliability are statistically significant in predictors of MDA coverage in the control of NTD in developing countries. This study may enhance social change by improving supply chain capacity for more effective distribution of PCT drugs, thus helping with the elimination of NTDs and improved health outcomes in low- and middle-income countries.

La Couverture Santé Universelle (CSU) vise permettre à chaque individu d’utiliser les services de santé dont il a besoin sans risque de ruine financière ou d’appauvrissement. Bien que le concept de CSU offre un cadre directeur important pour une nation, tous les pays, quel que soit leur niveau de revenu, sont aux prises avec la réalisation ou le maintien de la couverture universelle. Dans ce contexte, générer des preuves sur les expériences des pays et partager les leçons sur les principales contraintes et les choix stratégiques utilisés pour surmonter les barrières techniques serait susceptible de permettre aux pays à revenus faibles ou intermédiaires d’aller de l'avant et de progresser plus rapidement vers la CSU. La thèse propose une analyse comparative de plusieurs instruments politiques, utilisés par cinq cas pays (Niger, Vietnam, Bangladesh, Gabon, France), pour étendre la couverture sanitaire et la protection financière. L’analyse montre que les interventions simples, comme la suppression des frais des utilisateurs (Niger) ou de l'assurance santé à base communautaire (Bangladesh), peuvent accroître l'utilisation des services pour les groupes les plus défavorisés, mais font face à de fortes limitations dans l’atteinte de plus grandes ambitions. Des réformes plus articulées ont démontré des gains importants dans le développement de la couverture santé, mais font également face à des défis pour trouver l'espace budgétaire suffisant (Gabon) et améliorer l’efficience et l'équité du système (Vietnam). Enfin, la thèse analyse les effets de différentes réformes utilisées pour maintenir les gains de la CSU dans des systèmes de santé mûrs, tel que la France. Dans l'ensemble, la thèse a démontré que le menu des réformes vers la couverture universelle est vaste, complexe et perpétuel mais que certains chemins peuvent conduire au succès. / Universal Health Coverage (UHC) is to ensure that everyone can use the health services they need without risk of financial ruin or impoverishment. While the UHC concept offers a powerful framework for a nation, all countries, irrespective of their income level, are struggling with achieving or sustaining universal coverage. In this context, generating evidence about countries’ experiences and sharing lessons on key constraints and strategic choices used to overcome technical barriers would likely enable low-and-middle countries to move forward and make faster progress toward UHC. The thesis provides a comparative analysis of policy instruments used by five selected country cases (Niger, Vietnam,Bangladesh, Gabon and France), to expand health coverage and financial coverage. Analysis shows that single interventions, like user fee removal (Niger) or community-based insurance (Bangladesh), can increase service utilization for the most disadvantaged groups but face strong limitations toward greater ambitions. More articulated reforms have demonstrated significant gains in expanding health coverage but also face challenges in finding the adequate fiscal space (Gabon) and in strengthening system’s efficiency and equity (Vietnam). Finally, the thesis analyzed the effects of different reforms used to sustain gains of UHC in mature health systems, like France. Overall, the thesis demonstrated that the reform agenda for universal coverage is large, complex and perpetual but that certain pathways can ensure success.

Introduction: The burden of road traffic injuries (RTI) is worsening globally, particularly in low- and middle-income countries (LMIC) and among the young and economically productive populations. A major barrier to improving road safety in India and other LMIC is that existing RTI data sources are severely limited by poor population coverage and data quality. This dissertation explores the reliability and feasibility of using a novel data source with verbal autopsy (VA) methods for the purposes of RTI surveillance in India. Methods: The reliability of the VA methods was assessed using physician agreement on the specific categories of injury death as the metric. Next, a nationally representative household mortality survey with VA methods was used to directly estimate the age- and gender-specific RTI death rates and to identify context-specific RTI risk factors in India. Finally, a national spatial database was constructed to quantify potential access to trauma care in relation to the spatial distribution of RTI deaths in India. Results: Across a broad array of application settings in India, the level of physician agreement was high indicating that the VA methods were reliable in distinguishing RTI deaths among other specific categories of injury deaths. The estimated 183,600 RTI deaths in 2005 from the mortality survey were over 50% more than the national police statistics. Of these RTI deaths, 65% were males between ages 15-59 years, 68% were pedestrians and other vulnerable road users, and over 55% occurred at the scene of collision, within minutes of collision, and/or involved a head injury. The existing community health centres and district hospitals in the Indian public health system had inadequate trauma care capacity but were suitably located to allow broad spatial access to timely trauma care for the majority of RTI deaths in India, which were most problematic in the northern states of Punjab, Haryana, Himachal Pradesh and in Tamil Nadu. Conclusions: Properly designed VA studies can provide accurate and reliable RTI surveillance data and assist in identifying context-specific road safety interventions.

The purpose of this study is to examine how the health care system in Babati meets the increasing need for control, treatment and prevention of diabetes and hypertension. By defining what kind of specific problems and obstacles that exists in this area, the result of the research can contribute to creation and adoption of improved policies and interventions. Field studies were conducted in Babati, Tanzania for three weeks in February and March 2014. This is a qualitative study with data collected through semi-structured interviews with informants from different levels of the health system, based on the pyramidal structure of Tanzania's health care system. The theoretical framework for the study is based on aspects that corresponding to critical functions of health systems. The type of problem being treated affects the adoption and diffusion of new health interventions and the extent to which they are integrated into critical health systems functions. The study shows that diabetes and hypertension is an increasing problem in Babati. In relation to the burden, resources are lacking at all investigated levels. Therefore it is difficult to meet the increasing needs for diabetes and hypertension. To meet the future challenges, a number of cost effective strategies with focus to improve the prevention, control and reduce modifiable risk factors is suggested. / Syftet med studien är att undersöka hur hälso-och sjukvården i Babati möter det ökande behovet för kontroll, behandling och förebyggande åtgärder för diabetes och högt blodtryck. Genom att definiera vilka typer av specifika problem och hinder som finns, kan resultat från studien bidra till att skapandet och antagandet av förbättrade strategier och åtgärder. Fältstudier genomföres i Babati, Tanzania under tre veckor i februari och mars 2014. Detta är en kvalitativ studie med data insamlat genom semistrukturerade intervjuer med informanter från olika nivåer inom sjukvårdsystemet baserat på den pyramidala struktur Tanzanias sjukvårdssystem bygger på. Det teoretiska ramverket för studien baseras på aspekter som motsvarar kritiska funktioner för sjukvårdssystem. Antagandet och spridning av nya hälsointerventioner och i vilken mån de är integrerade i kritiska hälso- systemfunktioner påverkas av den typ av problem som behandlas. Studien visar att diabetes och högt blodtryck är ett ökande problem i Babati. I relation till hur sjukdomsbördan ser ut, saknas det resurser på samtliga undersökta nivåer. Därför är det svårt att möta de ökande behov som finns för att hantera diabetes och högt blodtryck. För att möta de framtida utmaningarna i Babati har ett antal kostnadseffektiva strategier med fokus att förbättra förebyggande, kontroll och minska påverkbara riskfaktorer föreslagits.

Introduction: The burden of road traffic injuries (RTI) is worsening globally, particularly in low- and middle-income countries (LMIC) and among the young and economically productive populations. A major barrier to improving road safety in India and other LMIC is that existing RTI data sources are severely limited by poor population coverage and data quality. This dissertation explores the reliability and feasibility of using a novel data source with verbal autopsy (VA) methods for the purposes of RTI surveillance in India. Methods: The reliability of the VA methods was assessed using physician agreement on the specific categories of injury death as the metric. Next, a nationally representative household mortality survey with VA methods was used to directly estimate the age- and gender-specific RTI death rates and to identify context-specific RTI risk factors in India. Finally, a national spatial database was constructed to quantify potential access to trauma care in relation to the spatial distribution of RTI deaths in India. Results: Across a broad array of application settings in India, the level of physician agreement was high indicating that the VA methods were reliable in distinguishing RTI deaths among other specific categories of injury deaths. The estimated 183,600 RTI deaths in 2005 from the mortality survey were over 50% more than the national police statistics. Of these RTI deaths, 65% were males between ages 15-59 years, 68% were pedestrians and other vulnerable road users, and over 55% occurred at the scene of collision, within minutes of collision, and/or involved a head injury. The existing community health centres and district hospitals in the Indian public health system had inadequate trauma care capacity but were suitably located to allow broad spatial access to timely trauma care for the majority of RTI deaths in India, which were most problematic in the northern states of Punjab, Haryana, Himachal Pradesh and in Tamil Nadu. Conclusions: Properly designed VA studies can provide accurate and reliable RTI surveillance data and assist in identifying context-specific road safety interventions.

Submitted by Rey Buckman (rey.buckman@gmail.com) on 2016-01-10T15:01:59Z No. of bitstreams: 1 2015-Dec_MSc-Thesis_mHealth-Entrepreneurship-LMICs_Buckman.pdf: 5201516 bytes, checksum: 5c371c945ff66496fee5110423bd8cb8 (MD5) / Rejected by Ana Luiza Holme (ana.holme@fgv.br), reason: Dear Reymound, In the first page your name should appear before the title of your thesis. The number of the pages should appear in the introdution, they should count form the first page but only appear in the thesis in the introdution. and it can'T be as you put in the thesis ex: i of 149 pages You can't have a page in blank in your thesis. Ana Luiza Holme 3799-3492 on 2016-01-11T11:29:28Z (GMT) / Submitted by Rey Buckman (rey.buckman@gmail.com) on 2016-01-12T23:30:25Z No. of bitstreams: 1 2015-Dec_MSc-Thesis_mHealth-Entrepreneurship-LMICs_Buckman.pdf: 5038358 bytes, checksum: 4f2b04bebf79c72c1aa4664114581fb6 (MD5) / Approved for entry into archive by Ana Luiza Holme (ana.holme@fgv.br) on 2016-01-13T11:07:34Z (GMT) No. of bitstreams: 1 2015-Dec_MSc-Thesis_mHealth-Entrepreneurship-LMICs_Buckman.pdf: 5038358 bytes, checksum: 4f2b04bebf79c72c1aa4664114581fb6 (MD5) / Made available in DSpace on 2016-01-13T12:13:06Z (GMT). No. of bitstreams: 1 2015-Dec_MSc-Thesis_mHealth-Entrepreneurship-LMICs_Buckman.pdf: 5038358 bytes, checksum: 4f2b04bebf79c72c1aa4664114581fb6 (MD5) Previous issue date: 2015-12-14 / Tecnologias móveis na saúde (mHealth) representam há alguns anos a força de transformação para melhorar problemas de saúde em países de baixa e média renda (LMIC). Embora vários estudos tenham identificado evidências inconsistentes e novos quadros de avaliação tenham sido propostos, poucos trabalhos exploraram o papel do empreendedorismo para criar mudança disruptiva em um setor tradicionalmente conservador. Defendo que a melhoria da eficácia dos empresários mHealth pode aumentar a adoção de soluções mHealth. Assim, este estudo tem como objetivo propor um modelo de gestão para a análise de soluções mHealth do ponto de vista empresarial no contexto de LMIC. Identifiquei o ‘Khoja-Durrani-Scott (KDS) framework’ como base teórica para o modelo de gestão, devido ao seu foco explícito no contexto de LMICs. Na pesquisa exploratória introduzida a seguir utilizei entrevistas semi-estruturadas com cinco especialistas em mHealth, os sistemas de saúde locais e de investimento para identificar as necessárias adaptações ao modelo. Os resultados das entrevistas propuseram que especialmente a questão econômica deveria ser clarificada, assim como a questão empresarial deveria ser adicionada. Além disso, foi proposto um questionário de avaliação. Na segunda fase, apliquei o questionário a cinco start-ups, que operam no Brasil e na Tanzânia. Realizei entrevistas semi-estruturadas com os empresários para obter insights práticos para o desenvolvimento teórico. Três dos cinco empresários perceberam que os resultados correlacionavam com as expectativas dos pontos fortes e fracos das start-ups. As principais deficiências do modelo foram relacionadas com a ambigüidade de algumas questões. Além dos resultados para o modelo, os resultados das pontuações foram analisados. A análise sugeriu que entre os start-ups que participaram os resultados ‘comportamentais e sócio-técnicos’ foram os mais fortes e os resultados ‘política’ foram os mais fracos. O modelo de gestão integra várias perspectivas, estruturadas em torno do empresário. A fim de validar o modelo, a pesquisa futura pode vincular o desenvolvimento de uma start-up com a evolução das pontuações em estudos de caso longitudinais ou testes em grande escala. / Since some years, mobile technologies in healthcare (mHealth) stand for the transformational force to improve health issues in low- and middle-income countries (LMICs). Although several studies have identified the prevailing issue of inconsistent evidence and new evaluation frameworks have been proposed, few have explored the role of entrepreneurship to create disruptive change in a traditionally conservative sector. I argue that improving the effectiveness of mHealth entrepreneurs might increase the adoption of mHealth solutions. Thus, this study aims at proposing a managerial model for the analysis of mHealth solutions from the entrepreneurial perspective in the context of LMICs. I identified the Khoja–Durrani–Scott (KDS) framework as theoretical basis for the managerial model, due to its explicit focus on the context of LMICs. In the subsequent exploratory research I, first, used semi-structured interviews with five specialists in mHealth, local healthcare systems and investment to identify necessary adaptations to the model. The findings of the interviews proposed that especially the economic theme had to be clarified and an additional entrepreneurial theme was necessary. Additionally, an evaluation questionnaire was proposed. In the second phase, I applied the questionnaire to five start-ups, operating in Brazil and Tanzania, and conducted semi-structured interviews with the entrepreneurs to gain practical insights for the theoretical development. Three of five entrepreneurs perceived that the results correlated with the entrepreneurs' expectations of the strengths and weaknesses of the start-ups. Main shortcomings of the model related to the ambiguity of some questions. In addition to the findings for the model, the results of the scores were analyzed. The analysis suggested that across the participating mHealth start-ups the ‘behavioral and socio-technical’ outcomes were the strongest and the ‘policy’ outcomes were the weakest themes. The managerial model integrates several perspectives, structured around the entrepreneur. In order to validate the model, future research may link the development of a start-up with the evolution of the scores in longitudinal case studies or large-scale tests.

Smokefree environment created by smokefree policies is associated with smoking reduction; however, there is paucity of literature on the relationship between smokefree home rules and smoking intensity in low-and-middle income countries (LMICs), and how smokefree policy affects smoking behavior of smokers at different stages of smoking cessation. This study examined the relationship between smokefree home rules and average number of cigarettes smoked per day (CPD) among daily smokers at different stages of the transtheoretical model (TTM) of change. Data from 18,718 current daily cigarette smokers from the Global Adult Tobacco Survey (GATS) conducted from 2011 to 2017 in 20 LMICs were analyzed. Weighted multivariable linear regression analyses were conducted using the log of CPD as the outcome variable with smokefree home rules as the exposure variable, controlling for selected covariates. Approximately 15% of the participants were in precontemplation, 5% were in preparation, 15% lived in partial smokefree homes, and 30% lived in complete smokefree homes. The average number of CPD was 12.3, 12.0, and 10.6 among participants living in homes where smoking was allowed, partial smokefree homes, and complete smokefree homes, respectively. Compared to living in homes where smoking was allowed, living in complete smokefree homes were associated with 22.5% (95%CI = 18.4%–26.5%), 17.9% (95%CI = 8.4%–27.3%), and 29.3% (95% CI = 17.1%–41.5%) fewer CPD among participants in precontemplation, contemplation, and preparation stages, respectively. These findings suggest that complete smokefree home policy will benefit smokers in LMICs irrespective of their intention to quit smoking in addition to protecting non-smokers from secondhand smoke exposure.

Treatment outcomes of young patients with invasive breast cancer treated radically at Groote Schuur Hospital from 2013 to 2017: A single centre study Background: Breast cancer is the leading cause of cancer- related deaths globally, and the commonest cancer in women under 40 years. There is currently a lack of data relating to treatment outcomes of young women with breast cancer particularly in low-and middle-income countries. Aim: This study aims to evaluate the treatment outcomes of young patients (under 40 years) treated radically for invasive breast cancer in a low-and middle-income setting. Settings: Groote Schuur Hospital, Cape Town, South Africa Methods: A retrospective review of 101 women under 40 years, with invasive breast cancer treated radically, between 2013 and 2017 was conducted. Patient characteristics, tumour characteristics, disease stage, treatment, and follow-up were recorded. Primary objectives included evaluating overall and disease free survival, and analysing recurrence patterns and clinicopathological features. Results: The five-year overall and disease free survival for the entire cohort was 77% and 51%, respectively. Five-year overall survival by molecular subtype showed that Luminal A had the best survival, while triple negative breast cancer had the worst overall survival. Conclusion: Young women with breast cancer have poor survival outcomes despite early presentation. There is limited data regarding breast cancer treatment outcomes in patients under forty years.