Health systems in a context of HIV/AIDS : an analysis of impact, health policy and health care reform in KwaZulu-Natal and South Africa.

Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2007.The development of health systems in sub-Saharan Africa has been seriously challenged in the last two decades by the rise of HIV/AIDS. In this thesis I argue that the interface between health policy and HIV/AIDS in South Africa is poorly understood and that this has been to the detriment of fairly radical health care reforms as well as more general health systems development. The research problem outlined above is two-fold, requiring different types of enquiry and analysis. Firstly, there is a gap in our understanding of the impact of HIV/AIDS on health systems. Empirical evidence is presented from research on health facilities and health management structures in Ugu district, KwaZulu-Natal to address this concern. Secondly, it is asserted that our limited understanding of the impact of HIV/AIDS and the nature of the epidemic have prevented a true appreciation of its significance for health policy. This dimension of the problem is addressed through an analysis of South African health policy from 1994 through to the present, as well as a more theoretical look at the potential future influence of the antiretroviral therapy programme on the health system. Both quantitative and qualitative methodologies are employed in this research to acquire empirical insights. Health service utilisation trends are assessed retrospectively by quantitative analysis of key indicators from district and provincial information systems. Meanwhile, the prospective component of the quantitative research can best be described as repeat cross-sectional surveys of a selection of health facilities in Ugu district. These surveys capture data on the profile of patients seeking care and the resource requirements for managing these patients. Qualitative methodologies (predominantly semi-structured interviews) are used at facility level to gain insight into human resource issues and at the management level to better understand health system functioning in relation to HIV/AIDS. One would expect the increasing HIV prevalence and burden of AIDS illness in South Africa to translate into a higher demand for health care. However, this has not occurred in Ugu district, largely because of difficulties with access to care. Despite this, at lower level health services, namely clinics and district hospitals, HIV-related service provision has outpaced an increase in resources. Specifically, the introduction of the antiretroviral therapy programme and the decentralisation of a range of HIV/AIDS services are causing new strains on the system. In essence, the epidemic has created a need to address barriers to accessing care and to expand support for district health services. HIV/AIDS not only increases the demand for health care, but on the supply side erodes the capacity of the health system to deliver care. My research demonstrates that health care workers in KwaZulu-Natal are being severely impacted by the epidemic, with the nature of their work contributing to both their susceptibly and vulnerability. Not only is HIV/AIDS increasing absenteeism and attrition through escalating morbidity and mortality, but it is also working in more subtle ways to contribute to a range of 'push' factors driving health workers from the public health sector. None of these issues have been addressed because of the narrow definition of 'human resource management', despite the obviously heightened need to monitor attrition trends and develop creative retention strategies. My research looks not only at the impact of HIV/AIDS impact on health services in Ugu district, but also at the impact of the epidemic on higher levels of the health system which constitute management structures. At these levels, the health system is challenged by an urgency to deliver HIV/AIDS services, as well as an increasing involvement of donors and partners such as civil society organisations or faith based organisations. This has resulted in trends towards more centralised control of planning and management and, in some instances, a deflection of resources towards HIV/AIDS issues and programmes. This context has called for a strong focus on capacity development and means to ensure the integration of health programmes. Many of the trends in Ugu district demonstrate the insidious nature of HIV/AIDS impact and give some insight into why these trends have not been adequately addressed by South African health policies. My analysis suggests that despite the appropriateness of the overarching direction of health reforms, some concerns arising from the HIV/AIDS epidemic have received little attention. These include a need to: 1) manage human resource impacts, 2) develop home community based care and establish a continuum of care, and 3) lead and direct the involvement of donors and partners in the health sector. On the other hand, there have been some beneficial policy developments, such as the elimination of user fees for certain services and the attention paid to the way in which a focus on HIV/AIDS care can potentially weaken the health system. Unfortunately, in many instances HIV/AIDS has also widened the gap between policy and implementation and opportunities have been missed to develop the health system in an appropriate manner. The South African antiretroviral therapy programme, launched in 2003, is a source of uncertainty regarding the future development of health policy in the country. My analysis makes use of scenarios to explore the potential future impact of the programme. I consider the ways in which the programme is steering us away from our post-apartheid vision of an equitable and well functioning national health system and towards 'AIDS exceptionalism'. I look to Botswana, the first country in southern Africa to provide antiretroviral therapy in the public health sector, for early lessons as to what we might expect. My case study of this programme suggests that HIV/AIDS care can be integrated with time, so limiting damage to the development of fragile health systems. Only through ongoing reassessment of the South African situation will it become apparent whether such lessons are transferable. Nonetheless, forward thinking should allow us to move from a crisis-orientated response to one that is more strategic. This thesis concludes with four key messages (or recommendations) emerging from both the empirical research and the health policy analysis. Firstly, there is a clear need to establish systems that can provide comprehensive and timely information concerning the impact of HIV/AIDS on public health services. Secondly, trusting relationships have to be built between academics/researchers and health policy makers so that research informs policy. Thirdly, there is a need to (re)establish a shared vision of the national health system and maintain a focus on achieving this vision. Finally, priority programmes and resources allocated to these must be used to strengthen our national health system in creative ways

Unplanned antiretroviral treatment interruptions in southern Africa: how should we be managing these?

Adherence to antiretroviral therapy is essential for maximising individual treatment outcomes and preventing the development of drug resistance. It is, however, frequently compromised due to predictable, but adverse, scenarios in the countries most severely affected by HIV/AIDS. This paper looks at lessons from three specific crises in southern Africa: the 2008 floods in Mozambique, the ongoing political and economic crisis in Zimbabwe, and the 2007 public sector strike in South Africa. It considers how these crises impacted on the delivery of antiretroviral therapy and looks at some of the strategies employed to mitigate any adverse effects. Based on this it makes recommendations for keeping patients on treatment and limiting the development of drug resistance where treatment interruptions are inevitable

The evolving impact of HIV/AIDS on outpatient health services in KwaZulu-Natal, South Africa

Background and Objective The high HIV prevalence in KwaZulu Natal (KZN) places immense pressure on the health system. The burden of HIV/AIDS on health services is evolving as the epidemic progresses and as Antiretroviral Treatment becomes more widely available. For health policy makers and managers, timely and appropriate information is needed to facilitate adaptive management of health services. Through longitudinal research covering outpatient health services in KZN we examined the dynamics of the evolving HIV/AIDS burden and the resource implications of this burden, necessary for resource allocation decisions. Methods Data was collected between 2004 and 2005 in outpatient services across six health facilities in the province. The burden of HIV/AIDS was measured by assessing the proportion of outpatients presenting as HIV positive, determined by a clinical diagnosis (and test result where available). The burden was also measured by looking at the type of diseases presenting at outpatient facilities. Moreover, the paper assessed the burden experienced by health care workers and financial implications for health facilities. Results and Conclusions The study demonstrates that the burden on outpatient services is significant but has not been increasing over time, suggesting that people aren’t accessing care if and when they need it. However, in terms of resources, this burden has been increasing and shifting from tertiary services to more primary services. Thus, in order to accommodate the demands of HIV/AIDS, our focus needs to turn towards outpatient services and in particular at the primary care level

Comparative health systems research in a context of HIV/AIDS: lessons from a multi-country study in South Africa, Tanzania and Zambia

Comparative, multi-country research has been underutilised as a means to inform health system development. South-south collaboration has been particularly poor, even though there have been clearly identified benefits of such endeavours. This commentary argues that in a context of HIV/AIDS, the need for regional learning has become even greater. This is because of the regional nature of the problem and the unique challenges that it creates for health systems. We draw on the experience of doing comparative research in South Africa, Tanzania and Zambia, to demonstrate that it can be useful for determining preconditions for the success of health care reforms, for affirming common issues faced by countries in the region, and for developing research capacity. Furthermore, these benefits can be derived by all countries participating in such research, irrespective of differences in capacity or socio-economic development

Spatiotemporal regulation of clonogenicity in colorectal cancer xenografts

Cancer evolution is predominantly studied by focusing on differences in the genetic characteristics of malignant cells within tumors. However, the spatiotemporal dynamics of clonal outgrowth that underlie evolutionary trajectories remain largely unresolved. Here, we sought to unravel the clonal dynamics of colorectal cancer (CRC) expansion in space and time by using a color-based clonal tracing method. This method involves lentiviral red-green-blue (RGB) marking of cell populations, which enabled us to track individual cells and their clonal outgrowth during tumor initiation and growth in a xenograft model. We found that clonal expansion largely depends on the location of a clone, as small clones reside in the center and large clones mostly drive tumor growth at the border. These dynamics are recapitulated in a computational model, which confirms that the clone position within a tumor rather than cell-intrinsic features, is crucial for clonal outgrowth. We also found that no significant clonal loss occurs during tumor growth and clonal dispersal is limited in most models. Our results imply that, in addition to molecular features of clones such as (epi-)genetic differences between cells, clone location and the geometry of tumor growth are crucial for clonal expansion. Our findings suggest that either microenvironmental signals on the tumor border or differences in physical properties within the tumor, are major contributors to explain heterogeneous clonal expansion. Thus, this study provides further insights into the dynamics of solid tumor growth and progression, as well as the origins of tumor cell heterogeneity in a relevant model system

Differential Expressed Genes Identified Between African American and European American Keloid Fibroblasts

Keloids are benign fibroproliferative tumors due to dysregulation of collagen remodeling and abnormal wound healing. Although worldwide, there is a higher incidence of keloid disease (KD) in skin of color, little is known about this predisposition. In this study, we used one tissue micro array slide comprised of six AA and 6 EA punch biopsies of primary untreated keloid tissue from the head and neck area was created, following the NanoString® DSP Technology Access Program protocol. The GeoMx Human Whole Transcriptome Atlas Assay was performed, using morphology marker FAP. Polygonal region of interests selection strategy for Fibroblast Activation Protein (FAP) positive cells was conducted. Univariate analysis was performed, using linear regression models to identify differentially expressed genes (DEG) at a false discovery rate (FDR) of 0.05. Ingenuity pathway analysis (IPA) software was used to determine DEG pathway enrichment. 1,450 DEG were identified (p-va

Neuroimaging of decoding and language comprehension in young very low birth weight (VLBW) adolescents : Indications for compensatory mechanisms

In preterm children with very low birth weight (VLBW amp;lt;= 1500 g), reading problems are often observed. Reading comprehension is dependent on word decoding and language comprehension. We investigated neural activation-within brain regions important for reading-related to components of reading comprehension in young VLBW adolescents in direct comparison to normal birth weight (NBW) term-born peers, with the use of functional magnetic resonance imaging (fMRI). We hypothesized that the decoding mechanisms will be affected by VLBW, and expect to see increased neural activity for VLBW which may be modulated by task performance and cognitive ability. The study investigated 13 (11 included in fMRI) young adolescents (ages 12 to 14 years) born preterm with VLBW and in 13 NBW controls (ages 12-14 years) for performance on the Block Design and Vocabulary subtests of the Wechsler Intelligence Scale for Children; and for semantic, orthographic, and phonological processing during an fMRI paradigm. The VLBW group showed increased phonological activation in left inferior frontal gyrus, decreased orthographic activation in right supramarginal gyrus, and decreased semantic activation in left inferior frontal gyrus. Block Design was related to altered right-hemispheric activation, and VLBW showed lower WISC Block Design scores. Left angular gyrus showed activation increase specific for VLBW with high accuracy on the semantic test. Young VLBW adolescents showed no accuracy and reaction time performance differences on our fMRI language tasks, but they did exhibit altered neural activation during these tasks. This altered activation for VLBW was observed as increased activation during phonological decoding, and as mainly decreased activation during orthographic and semantic processing. Correlations of neural activation with accuracy on the semantic fMRI task and with decreased WISC Block Design performance were specific for the VLBW group. Together, results suggest compensatory mechanisms by recruiting additional brain regions upon altered neural development of decoding for VLBW.Funding Agencies|FORSS-the Medical Research Council of Southeast Sweden [FORSS-159881]</p