Joint models for nonlinear longitudinal profiles in the presence of informative censoring

Malaria is the parasitic disease which affects the most humans, with Plasmodium falciparum malaria being responsible for the majority of severe malaria and malaria related deaths. The asexual form of the parasite causes the signs and symptoms associated with malaria infection. The sexual form of the parasite, also known as a gametocyte, is the stage responsible for infectivity of the human host (patient) to the mosquito vector, and thus ongoing transmission of malaria and the spread of antimalarial drug resistance. Historically malaria therapeutic efficacy studies have focused mainly on the clearance of asexual parasites. However, malaria in a community can only be truly combated if a treatment program is implemented which is able to clear both asexual and sexual parasites effectively. In this thesis focus will be on the modeling of the key features of gametocytemia. Particular emphasis will be on the modeling of the time to gametocyte emergence, the density of gametocytes and the duration of gametocytemia. It is also of interest to investigate the impact of the administered treatment on the aforementioned features. Gametocyte data has several interesting features. Firstly, the distribution of gametocyte data is zero-inflated with a long tail to the right. The observed longitudinal gametocyte profile also has a nonlinear relationship with time. In addition, since most malaria intervention studies are not designed to optimally measure the evolution of the longitudinal gametocyte profile, there are very few observation points in the time period where the gametocyte profile is expected to peak. Gametocyte data collected from malaria intervention studies are also affected by informative censoring, which leads to incomplete gametocyte profiles. An example of informative censoring is when a patient who experiences treatment failure is “rescued", and withdrawn, from the study in order to receive alternative treatment. This patient can be considered to be in worse health as compared to the patients who remain in this study. There are also competing risks of exit from the study, as a patient can either experience treatment failure or be lost to follow-up. The above mentioned features of gametocyte data make it a statistically appealing dataset to analyze. In literature there are several modeling techniques which can be used to analyze individual features of the data. These techniques include standard survival models for modeling the time to gametocyte emergence and the duration of gametocytemia. The longitudinal nonlinear gametocyte profile would typically be modeled using nonlinear mixed effect models. These nonlinear models could then subsequently be extended to accommodate the zero-inflation in the data, by changing the underlying assumption around the distribution of the response variable. However, it is important to note that these standard techniques do not account for informative censoring. Failure to account for informative censoring leads to bias in parameter estimates. Joint modeling techniques can be used to account for informative censoring. The joint models applied in this thesis combined the longitudinal nonlinear gametocyte densities and the time to censoring due to either lost to follow up or treatment failure. The data analyzed in this thesis were collected from a series of clinical trials conducted be- tween 2002 and 2004 in Mozambique and the Mpumulanga province of South Africa. These trials were a part of the South East African Combination Antimalarial Therapy (SEACAT) evaluation of the phased introduction of combination anti-malarial therapy, nested in the Lubombo Spatial Development Initiative. The aim of these studies was primarily to measure the efficacy of sulfadoxine-pyrimethamine (SP) and a combination of artesunate and sulfadoxine-pyrimethamine (ACT), in eliminating asexual parasites in patients. The patients enrolled in the study had uncomplicated malaria, at a time of increasing resistance to sulfadoxine-pyrimethamine (SP) treatment. Blood samples were taken from patients during the course of 6 weeks on days 0, 1, 2, 3, 7, 14, 21, 28 and 42. Analysis of these blood samples provided longitudinal measurements for asexual 1 parasite densities, gametocyte densities, sulfadoxine drug concentrations and pyrimethamine drug concentrations. The gametocyte data collected in this study was initially analyzed using standard survival modeling techniques. Non-parametric Cox regression models and parametric survival models were applied to the data as part of this initial investigation. These models were used to investigate the factors which affected the time to gametocyte emergence. Subsequently, using the subset of the population which experienced gametocytemia, accelerated failure time models were applied to investigate the factors which affected the duration of gametocytemia. It is evident that the findings from the aforementioned duration investigation would only be able to provide valid duration estimates for patients who were detected to have gametocytemia. This work was extended to allow for population level duration estimates by incorporating the prevalence of gametocytemia into the estimation of duration, for generic patients with specific covariate patterns. The prevalence of gametocytemia was modeled using an underlying binomial distribution. The delta method was subsequently used to derive confidence intervals for the population level duration estimates which were associated with specific covariate patterns. An investigation into the factors affecting the early withdrawal of patients from the study was also conducted. Early exit from the study arose either through loss to follow-up (LTFU) or through treatment failure. The longitudinal gametocyte profile was modeled using joint modeling techniques. The resulting joint model used shared random effects to combine a Weibull survival model, describing the cause- specific hazards of patient exit from the study, with a nonlinear zero-adjusted gamma mixed effect model for the longitudinal gametocyte profile. This model was used to impute the incomplete gametocyte profiles, after adjusting for informative censoring. These imputed profiles were then used to estimate the duration of gametocytemia. It was found, in this thesis, that treatment had a very strong effect on the hazard of gametocyte emergence, density of gametocytes and the duration of gametocytemia. Patients who received a combination of sulfadoxine-pyrimethamine and artesunate were found to have significantly lower hazards of gametocyte emergence, lower predicted durations of gametocytemia and lower predicted longitudinal gametocyte densities as compared to patients who received sulfadoxine-pyrimethamine treatment only

Disasters and development nexus : theory and practice - a case of Zimbabwe

This study is premised on the notion that disasters and development have a nexus, both theoretically and practically although the two fields have been traditionally viewed as antagonistic at face value. The principal objective was to analyze the existing theoretical and practical gaps between disasters and development in Zimbabwe. Furthermore, factors that affect achievement of disaster mitigation and development linkages in Zimbabwe were critically examined. The study conceptualizes disasters and development from multiple angles. The nested relationship between disasters and development are reinforced with the use of multiple disaster risk reduction strategies to mitigate vulnerability in both rural and urban areas. Hence, this study opted for the mixed methods approach from conceptualization throughout the research process so as to capitalize on the strengths entrenched in both qualitative and quantitative approaches. Drawing on a mixed methodology approach, this study approached the variables from multiple dimensions since disasters and development are intertwined. Evidently, the study demonstrates that disasters and development have a strong nexus, theoretically and practically. This confirms the study hypothesis that disasters and development are correlated, as disasters can both destroy development initiatives and create development opportunities, and that development schemes can both increase and decrease vulnerability. The study also found that policy practice in Zimbabwe is heavily fragmented, thereby leading to incoherent policy implementation. This results in increased vulnerability and huge disaster impacts that erode development gains therefore compromising achievement of sustainable development goals. Hence, the study recommended for the adoption of a Disaster Risk Reduction theoretical framework in cementing the disasters and development linkages theoretically and pragmatically. DRR enhances community’s resilience capacity in curtailing the progression of vulnerability and mitigate the accelerated incubation of disasters that impact on development strides

An analysis of the impact of nationalism on the rights of dual citizens in Zambia: an equality approach

ThesisZambia’s Constitution (Amendment) Act, No. 2 of 2016 provides rights and places duties upon the status of citizenship. Equality and non- discrimination are recognized as national values used to interpret the Constitution and in the enactment of laws. Nevertheless, the Constitution seemingly discriminates against citizens with ‘Dual Citizenship’, from eligibility to serve in public office such as the President, Vice President, National Assembly Speaker, and service under the Defense and National Security agencies. This demonstrates conflict of policy objectives underlying national values and the prohibitive clauses. For liberalists, this derogates from citizenship rights, because despite recognizing equality and non- discrimination, ‘Dual Citizenship’ is a status viewed as challenging to communitarian notions of nationalism. Underpinned by a doctrinal approach carried out through desk research and thematic analysis of the sources of the material, this study ascertains how nationalism impacts on dual citizen’s rights, and whether justifications exist, in light of principles of equality and nondiscrimination, among citizens. This study also interrogates the consequences of the said impact on the state and citizen, and what lessons could be learnt from other jurisdictions. The study revealed that notions of nationalism limit citizenship rights relating to political participation and equality of opportunity. The loyalty justification for the restrictions remains questionable, because reviewed studies do not reveal consensus that loyalty to a specific political state is the precondition for office holders. Furthermore, legislative provision for the limitations does not make them justifiable in a democratic society, as discriminatory practices are challengeable, even when legal. For differential treatment to be discriminatory, it should lack reasonable justification. A difference in enjoyment of citizenship rights was established despite the Constitution not distinguishing in its definition of ‘citizen’. The study argues that the absence of conclusive data from studies on ‘divided allegiances’ makes the restrictions unreasonably justifiable treatment as the discrimination proves unfair, due to its impact on the victims. Adverse economic, social and political consequences of this for the state and the citizen are numerous. Conversely, the United Kingdom places no distinction in the nature of British citizenship that qualifies for office of Prime Minister. The United Kingdom extends its liberal approach to non-British citizens, particularly, Irish and Commonwealth citizens, including eligibility to join British armed forces. Nigeria is also progressive as ‘Dual Citizenship’ is no disqualification for high level public office for citizens by birth. This study recommends legislative reforms to eliminate citizenship inequality by narrowing restrictions premised on perceived divided loyalties. These include: requiring dual citizens in public office to declare conflict of interest in specific situations, executing bilateral or multilateral agreements confining dual citizens’ military service to countries of habitual residence and enlisting army personnel on professional basis than imputing loyalty associated with citizenship. The impact of the findings and recommendations on the study is that they provide a basis upon which the study can inform the need for reform both in policy and the law. Keywords: Citizenship, ‘Dual Citizenship’, Nationalism, Equality and Non-discriminatio

Disasters and development nexus : theory and practice - a case of Zimbabwe

This study is premised on the notion that disasters and development have a nexus, both theoretically and practically although the two fields have been traditionally viewed as antagonistic at face value. The principal objective was to analyze the existing theoretical and practical gaps between disasters and development in Zimbabwe. Furthermore, factors that affect achievement of disaster mitigation and development linkages in Zimbabwe were critically examined. The study conceptualizes disasters and development from multiple angles. The nested relationship between disasters and development are reinforced with the use of multiple disaster risk reduction strategies to mitigate vulnerability in both rural and urban areas. Hence, this study opted for the mixed methods approach from conceptualization throughout the research process so as to capitalize on the strengths entrenched in both qualitative and quantitative approaches. Drawing on a mixed methodology approach, this study approached the variables from multiple dimensions since disasters and development are intertwined. Evidently, the study demonstrates that disasters and development have a strong nexus, theoretically and practically. This confirms the study hypothesis that disasters and development are correlated, as disasters can both destroy development initiatives and create development opportunities, and that development schemes can both increase and decrease vulnerability. The study also found that policy practice in Zimbabwe is heavily fragmented, thereby leading to incoherent policy implementation. This results in increased vulnerability and huge disaster impacts that erode development gains therefore compromising achievement of sustainable development goals. Hence, the study recommended for the adoption of a Disaster Risk Reduction theoretical framework in cementing the disasters and development linkages theoretically and pragmatically. DRR enhances community’s resilience capacity in curtailing the progression of vulnerability and mitigate the accelerated incubation of disasters that impact on development strides

Social relationships and identity online and offline: a study of the interplay between offline social relationships and facebook usage by Rhodes University students from socially disadvantaged backgrounds

Based on in-depth focus group and individual interviews, this thesis examines how Rhodes University students from socially disadvantaged backgrounds experience campus social life and how they subsequently use Facebook to perform, represent and negotiate their social identities. The study discusses utopian and dystopian positions and interrogates these theoretical perspectives in relation to the students‟ Facebook usage. The popularity and uptake of Facebook by students from disadvantaged backgrounds, such as those here at Rhodes University, is a growing phenomenon, provoking questions about the relationship between social experiences, social identity and social networks. Rhodes University‟s social space has been identified by previous studies as modern, liberal, “elite” and divided along race and class lines. The ways in which students experience this campus social space relates to their subject positions and identities. The study employs different perspectives of identity construction to interrogate the students‟ subject experiences in home and school contexts before coming to Rhodes University. The students‟ subjective positions are primarily embedded in tradition and their subject positions are sometimes in tension or come in conflict with the modern and liberal elements permitted by the Rhodes University context. The students also experience and adopt modern and liberal elements in their lifestyles which are permitted within the Rhodes University social space. The thesis found that Facebook offers a platform which facilitates a social connectivity that influences how students perform their identities in relation to their offline social identities and lived social experiences. This study concludes that the mediated symbolic materials for the construction and negotiation of identity provided by Facebook are sometimes in tension with the demands of traditional subjectivities experienced by these students at Rhodes University. Facebook allows the students to reinforce and affirm the validity of their traditional identities in this modern and liberal space. However, it also emerged that Facebook facilitates and allows students who experience and incorporate the modern and liberal elements permitted at Rhodes University to represent and negotiate their subjective positions online. The findings of the study indicate that participants primarily communicate with their friends, families, relatives and acquaintances - people they know personally offline, in line with the theoretical position which argues that online relationships are primarily shaped by offline relationships

Extensive cerebrovascular disease and stroke with prolonged prodromal symptoms as first presentation of perinatally-acquired human immunodeficiency virus infection in a young adult.

A 26-year-old black African woman presented with an acute onset of hemiparesis and visual symptoms. This had been preceded several months by symptoms which were apparently psychiatric in nature. She had no apparent risk for cerebrovascular disease. Neurological evaluation revealed a striking burden of cerebrovascular disease for her age, including the rare stroke syndrome of basilar artery occlusion. Human immunodeficiency virus (HIV) infection was identified during clinical assessment. This was judged to be perinatally acquired, as there was no history of sexual debut or blood transfusion; her mother was taking antiretroviral therapy and she had facial planar warts and underlying bronchiectasis. Therefore, it has been concluded that presentation of stroke should prompt HIV testing in young people and perinatally-acquired infection can present in adulthood

HIV/AIDS Workplace Policy Implementation in Selected Private Sector Workplaces in Lusaka District: Implementer's Perspective

MASTER IN PUBLIC HEALTHIntroduction: Adult HIV prevalence in Zambia has declined from 16 % (2001-2002) to 13% (2013-2014) but still remains high. The UNAIDS call on eradicating HIV/AIDS by 2030 challenges strengthening multi–sectral response to HIV/AIDS. To understand factors affecting implementation of HIV/AIDS workplace policies, especially in the private sector, it is important to know the extent to which policies exist and experiences on implementation. Methods: A mixed method analysis of availability and implementation of policy using the health policy initiative implementer’s tool was conducted. Data from 128 member companies of the Zambia Federation of Employers was randomly collected through purposively sampled policy implementers. Categorized variables on implementation were analysed using Stata version 12.0: Fishers’ exact test and logistics regression were applied to implementation factors. Concurrently, 28 in-depth interviews on purposively sampled implementers were done. Thematic analysis was used and qualitative results integrated with quantitative findings. Results: Policies were available in 47/128 (36.72%) workplaces. The private sector accounted for 34/47 (72.34%) of all workplaces with policy. Programs were available in 56/128 (43.75%) workplaces. Both policy and programs were found in 46/47 (97.87 %) workplaces. Availability of policy was 2.7 times more likely with the increase in the size of a workplace, P Value=0.0001, (P<0.05). Top management support and having a specific budget for HIV programs were strongly associated with implementation. Management support was 0.253 times more likely in workplaces with policy, P value=0.013, (P<0.05).A specific budget for programs was 0.23 times more likely with policy (P<0.05). Implementation was hindered by reduced funding, lack of time, lack of sensitisation, ill-defined indicators and lack of Monitoring/Evaluation systems. Experiences with implementation, found HIV/AIDS/Stigma and awareness were the most addressed HIV epidemic drivers in workplace programs. Commercial sex workers, GBV, Mother to Child Transmission and Males having sex with males were the least addressed. Onsite VCT and provision of MC, ART were provided through health insurance, government clinics, and subcontracted providers. Conclusion: HIV/AIDS Workplace policies exist in the private sector at a very low proportion but policy translation into programs among workplaces with policies was very high suggesting that workplaces with policies are more likely to translate their policy into a program. Recommendation: Structures for addressing health and safety of employees exist and should be strengthened through sensitisation to include response to HIV/AIDS towards eradicating HIV/AIDS by 2030. The extent to which workplace programs address HIV/AIDS epidemic drivers in Zambia should focus on marginalised populations, gender integration and a wellness approach. Key Words: HIV/AIDS, workplace, policy, programs, implementation

Determinants of health insurance ownership among South African women

BACKGROUND: Studies conducted in developed countries using economic models show that individual- and household- level variables are important determinants of health insurance ownership. There is however a dearth of such studies in sub-Saharan Africa. The objective of this study was to examine the relationship between health insurance ownership and the demographic, economic and educational characteristics of South African women. METHODS: The analysis was based on data from a cross-sectional national household sample derived from the South African Health Inequalities Survey (SANHIS). The study subjects consisted of 3,489 women, aged between 16 and 64 years. It was a non-interventional, qualitative response econometric study. The outcome measure was the probability of a respondent's ownership of a health insurance policy. RESULTS: The χ(2 )test for goodness of fit indicated satisfactory prediction of the estimated logit model. The coefficients of the covariates for area of residence, income, education, environment rating, age, smoking and marital status were positive, and all statistically significant at p ≤ 0.05. Women who had standard 10 education and above (secondary), high incomes and lived in affluent provinces and permanent accommodations, had a higher likelihood of being insured. CONCLUSION: Poverty reduction programmes aimed at increasing women's incomes in poor provinces; improving living environment (e.g. potable water supplies, sanitation, electricity and housing) for women in urban informal settlements; enhancing women's access to education; reducing unemployment among women; and increasing effective coverage of family planning services, will empower South African women to reach a higher standard of living and in doing so increase their economic access to health insurance policies and the associated health services

Unpacking early infant male circumcision decision-making using qualitative findings from Zimbabwe.

BACKGROUND Early infant male circumcision (EIMC) has been identified as a key HIV prevention intervention. Exploring the decision-making process for adoption of EIMC for HIV prevention among parents and other key stakeholders is critical for designing effective demand creation interventions to maximize uptake, roll out and impact in preventing HIV. This paper describes key players, decisions and actions involved in the EIMC decision-making process. METHODS Two complementary qualitative studies explored hypothetical and actual acceptability of EIMC in Zimbabwe. The first study (conducted 2010) explored hypothetical acceptability of EIMC among parents and wider family through focus group discussions (FGDs, n = 24). The follow-up study (conducted 2013) explored actual acceptability of EIMC among parents through twelve in-depth interviews (IDIs), four FGDs and short telephone interviews with additional parents (n = 95). Short statements from the telephone interviews were handwritten. FGDs and IDIs were audio-recorded, transcribed and translated into English. All data were thematically coded. RESULTS Study findings suggested that EIMC decision-making involved a discussion between the infant's parents. Male and female participants of all age groups acknowledged that the father had the final say. However, discussions around EIMC uptake suggested that the infant's mother could sometimes covertly influence the father's decision in the direction she favoured. Discussions also suggested that fathers who had undergone voluntary medical male circumcision were more likely to adopt EIMC for their sons, compared to their uncircumcised counterparts. Mothers-in-law/grandparents were reported to have considerable influence. Based on study findings, we describe key EIMC decision makers and attempt to illustrate alternative outcomes of their key actions and decisions around EIMC within the Zimbabwean context. CONCLUSIONS These complementary studies identified critical players, decisions and actions involved in the EIMC decision-making process. Findings on who influences decisions regarding EIMC in the Zimbabwean context highlighted the need for EIMC demand generation interventions to target fathers, mothers, grandmothers, other family members and the wider community