Doctoral Degrees (Epidemiology and Biostatistics)


Recent Submissions

Now showing 1 - 5 of 9
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    Optimisation and benchmarking of analytical approaches to estimation of population level HIV incidence from survey data
    (Stellenbosch : Stellenbosch University, 2022-04) Mhlanga, Laurette; Welte, Alex; Grebe, Eduard; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.
    ENGLISH SUMMARY: Disease prevalence (the proportion of a population with a condition of interest) is conceptually and procedurally much more straightforward to estimate than disease incidence (the rate of occurrence of new cases - for example, infections). For long-lasting conditions, incidence is fundamentally more difficult to estimate than prevalence, but also more interesting, as it sheds light on current epidemiological trends such as the emerging burden on health systems and the impact of recent policy interventions. Progress towards reducing reliance on questionable assumptions in the analysis of large population based surveys (for the estimation of HIV incidence) has been slow. The work of Kassanjee et al and the work of Mahiane et al, in particular, provide rigorous ways of estimating incidence by using 1) markers of ‘recent infection’, 2) the ‘gradient’ of prevalence, and 3) ‘excess mortality’ associated with HIV infection, without the need for simplifying assumptions to the effect that any particular parameters are constant over ranges of time and/or age. To date, the use of these methods has largely ignored 1) the rich details of the age and time structure of survey data, and 2) the opportunities for combining the two methods. The primary objective of this work was to find stable approaches to applying the Mahiane and Kassanjee methods to large age/time structured population survey data sets which include HIV status, and optionally, ‘recent infection’ status. In order to evaluate proposed methods, a sophisticated simulation platform was created to simulate HIV epidemics and generate survey data sets that are structured like real population survey data, with the underlying incidence, prevalence, and mortality explicitly known. The first non-trivial step in the analysis of survey data amounts essentially to performing a smoothing procedure from which the (age/time specific) prevalence of HIV infection, the prevalence of ‘recent infection’, and the gradient of prevalence of infection can be inferred without recourse to ‘epidemiological’ assumptions. The second step involves the correct accounting for uncertainty in a context-specific weighted mean of the Mahiane and Kassanjee estimators. These two steps are approached incrementally, as there are numerous details which have not previously been systematically elucidated. The investigation culminates in a proposed generic ‘once size fits most’ algorithm based on: 1) fitting survey data to generalised linear models defined by simple link functions and high order polynomials in age and time; 2) the use of a ‘moving window’ rule for data inclusion into a separate analysis for each age/time point for which incidence is to be estimated; 3) a ‘variance optimal’ weighting scheme for the combination of the Mahiane and Kassanjee estimators (when both are applicable); 4) flexible use of a delta method expansion or bootstrapping to estimate confidence intervals and p values. We find it is relatively easy to obtain estimates with practically negligible bias, but samplesizes/ sampling-density requirements are always considerable. We also make numerous observations on survey design and the inherent challenges faced by all attempts to estimate HIV incidence using surveys of reasonable size.
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    Assessment of point-of-care testing for prediction of aromatase inhibitor-associated side effects in obese postmenopausal breast cancer patients screened for cardiovascular risk factors
    (Stellenbosch : Stellenbosch University, 2021-12) Milambo, Jean Paul Muambangu; Akudugu, John M.; Nyasulu, Peter S.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.
    ENGLISH SUMMARY : Background: Aromatase inhibitors (AIs) constitute a standard of care for post- and premenopausal patients with estrogen receptor-positive breast cancer (BC). Obesity and mediators of inflammation have been identified as the most important risk and predictive factors in postmenopausal breast cancer survivors (BCS) using AIs. However, data on the feasibility of point-of-care (POC) genotyping using high sensitivity C-reactive protein (hs-CRP) and body mass index (BMI) as predictors of drug toxicity among postmenopausal BCS in African clinical settings are lacking. Aim: The study was conducted to assess the impact of AIs on hs-CRP and BMI, which are used at POC for prediction of therapy-associated side effects among obese postmenopausal breast cancer patients in Africa. Methods: One hundred and twenty-six female BC patients with cancer stages ranging from 0-III were recruited at Tygerberg Hospital (TBH) in the Western Cape Province of South Africa, between August 2014 and February 2017, for the study. A Quasi-experimental study was conducted. Patients were initially subjected to AIs and subsequently followed up at months 4, 12, and 24. Baseline clinical and biomedical assessments were conducted at commencement of study to predict hs-CRP and BMI at months 12 and 24, using a multiple imputation model. A random effects model was used to monitor the changes over the time. Statistical analyses were performed using SPSS 18.0 software (SPSS Inc., Chicago, IL, USA) and STATA version 16. Analyses were two-tailed and a p-value < 0.05 was considered statistically significant. Results: The mean age of the participants was 61 years (SD = 7.11 years; 95% CI: 60-62 years). Linear regression revealed that hs-CRP was associated with waist circumference (OR: 7.5; p= 0. 0116; 95%CI: 1.45 to 39.61) and BMI (OR: 2.15; p=0.034, 95%CI: 1.02 to 4.56). Waist circumference was associated with hypertension (OR: 3, 83; p= 0.003, 95%CI: 1.56 to 9.39), and chemotherapy was associated with waist circumference by (p= 0. 016; 95%CI: 0.11 to 0. 79). hs-CRP levels were significantly correlated with BMI and total body fat (TBF) among postmenopausal using aromatase inhibitors. Random linear effects modelling revealed stronger statistical association between BMI and homocysteine (p=0.021, 95%CI: 0.0083 to 0.1029). Weight and TBF were strongly associated after 24 months of follow-up. In addition, hs-CRP was associated with BMI (p=0.0001) and other inflammatory markers such as calcium (p=0.021, 95%CI: 0.0083 to 0.1029), phosphate (p=0.039, 95%CI: 0.0083 to 0.1029), and ferritin (p=0.002, 95%CI: 0.0199 to 0.084). Multiple imputation modelling indicated that there were statistically significant variations in TBF, weight, homocysteine, ferritin, and calcium between baseline and after 24 months of follow-up. Mathematical modeling Comparison of genotyping from HyBeacon® probe technology to Sanger sequencing showed that yielded sensitivity of 99% (95% CI: 94.55 to 99.97%), specificity of 89.44% (95% CI: 87.25 to 91.38%), PPV of 51% (95%: 43.77 to 58.26%), and NPV of 99.88% (95% CI: 99.31 to 100.00%). Based on the mathematical model, the assumptions revealed that incremental cost-effective ratio (ICER) was R7 044.55. Conclusion: This study revealed that hs-CRP and BMI are predictors of CVD-related adverse events in obese postmenopausal patients. Calcium, phosphate, homocysteine, and ferritin should also be incorporated in POCT. There were statistically significant variations in TBF, weight, hs-CRP, BMI, homocysteine, ferritin, and calcium between baseline and after 24 months of follow-up. HyBeacon® probe technology at POC for AI-associated adverse events maybe cost-effective in Africa while adjunct to standard practice. The appropriate pathways for implementation of POC testing in postmenopausal breast cancer survivors need further investigation in different clinical settings with real data for external validation.
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    Burden of congenital rubella syndrome and potential impact of rubella vaccine introduction in South Africa
    (Stellenbosch : Stellenbosch University, 2021-12) Motaze, Nkengafac Villyen; Wiysonge, Charles S.; Suchard, Melinda S.; Metcalf, C. Jessica E.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.
    ENGLISH SUMMARY : Background: Introduction of rubella vaccines into public vaccination schedules of all countries is necessary if global rubella elimination is to be achieved. Rubella is targeted for elimination in five World Health Organization (WHO) regions and several international organizations, under the stewardship of the WHO, are working towards this goal. Although there is no rubella elimination or control target for the WHO Africa region, there has been accelerated introduction of rubella vaccination on the continent. South African government is planning to introduce rubella vaccination in its Expanded Programme on Immunization (EPI) schedule and several epidemiological studies have been conducted to aid preparation of this public health intervention. In the absence of vaccination, rubella is mainly a mild endemic childhood viral illness that is asymptomatic in up to 50% of cases. The most severe consequences of rubella occur when infection occurs during pregnancy. These include miscarriages, stillbirths, intra-uterine growth restriction and congenital rubella syndrome. Rubella vaccines are therefore intended to prevent rubella and associated complications. In South Africa, rubella vaccines are not part of the EPI schedule and there is limited information on the epidemiology of rubella and its complications. In addition, the South African government has to cover the cost of introducing rubella vaccination. Therefore, the aim of this research project was to characterize the epidemiology of rubella and congenital rubella syndrome in South Africa, to assess the potential impact of introducing rubella vaccination in the EPI schedule. Methods: Four different studies were carried out as part of this PhD project: a cross-sectional descriptive study, a sero-survey, a mathematical modelling study and a systematic review. Results: The findings of a newly established CRS surveillance system to provide data on disease trends in the absence of rubella vaccination are presented in the first research component. We provided baseline data on laboratory-confirmed CRS that will enable planning and monitoring of RCV implementation in the South African EPI program. Ninety-eight percent of mothers of infants with CRS were young women 14 to 30 years old, indicating a potential immunity gap in this age group for consideration during introduction of RCV. In the second research component, we present results of testing on residual samples collected from public health facilities to identify immunity gaps in various age groups and genders. The bulk of individuals susceptible to rubella are children under sixteen years old and about 20% of individuals 16 to 49 years old are susceptible to rubella. In multivariable logistic regression, age and province of residence were found to be associated with rubella susceptibility.Webuilt on a previously published mathematical model adapted to the South African context in the third research component and provide insights into optimal scenarios for RCV introduction into the South African public immunization schedule. We simulated a number of scenarios that combined infant vaccination with vaccination of older individuals. Routine vaccination at 12 months of age coupled with vaccination of nine-year-old children was associated with the lowest RCV cost per CRS case averted for a similar percentage CRS reduction. Interestingly, at 80% RCV coverage, all vaccine introduction scenarios could achieve rubella and CRS elimination in South Africa.In the final research component, we systematically reviewed mathematical modelling studies to identify the most effective approach for countries introducing RCV into their public immunization schedules. There were variations in the manner in which individual studies reported outcomes. However, we found that better outcomes are obtained when rubella vaccination is introduced into public vaccination schedules at coverage figures of 80%, as recommended by WHO, or higher. Conclusion: The results from these different studies support the implementation of a strategy involving infant vaccination in combination with vaccination of older individuals. Further research projects are required to provide more detail on the burden of CRS and the economic impact of RCV introduction into the EPI schedule.
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    An evaluation of the effectiveness of task-shifting health systems approaches, including community-based and pharmaceutical care models, for HIV treatment and prevention programs in South Africa
    (Stellenbosch : Stellenbosch University, 2020-12) Fatti, Geoffrey; Chikte, Usuf M. E.; Nachega, Jean; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.
    ENGLISH SUMMARY : Southern Africa is the epicenter of the human immunodeficiency virus (HIV) pandemic having the highest burden of HIV globally. Although South Africa has made great strides with the roll-out of its antiretroviral treatment (ART) program, ongoing challenges include high attrition of patients from ART care and ongoing elevated HIV incidence. There is also a severe shortage of professional health workers in the region, which impacts HIV program delivery. Task-shifting health systems approaches have been developed in order for the health system to provide large-scale HIV program delivery with limited numbers of professional health workers. This thesis evaluates the effectiveness of task-shifting health systems interventions in HIV prevention and treatment programs in South Africa, including community-based programs utilizing community healthcare workers (CHWs), and pharmaceutical care models. Data were collected in cohort studies conducted between 2004 and 2015/2016 in four provinces of South Africa. The results chapters of the thesis are presented in the form of published papers. The first paper evaluates the effectiveness of a community-based support (CBS) program amongst a large cohort of adults living with HIV receiving ART up to five years after ART initiation. Adults who received CBS had improved ART outcomes, including improved patient retention with lower loss to follow-up and lower mortality, both of which were reduced by one third. The second paper evaluates the effectiveness of a community-based combination HIV prevention intervention delivered by CHWs for pregnant and postpartum women in a high HIV incidence district in KwaZulu-Natal. Maternal HIV incidence amongst participants who received the intervention was considerably lower compared to other studies from the region. The paper further recommends expanded roll-out of home-based couples HIV counselling and testing, and initiating oral pre-exposure prophylaxis for HIV particularly for pregnant women within serodiscordant couples, in order to reduce maternal HIV incidence. The third paper compares the effectiveness and cost of two task-shifting pharmaceutical care models for ART delivery in South Africa, namely the indirectly supervised pharmacist assistant (ISPA) model and the nurse-managed model. The ISPA model was found to have a higher quality of pharmaceutical care, was less costly to implement and was possibly associated with improved patient clinical outcomes. The fourth paper evaluates the effectiveness and cost-effectiveness of CBS for adolescents and youth receiving ART at 47 health facilities in South Africa. CBS was found to substantially reduce patient attrition from ART care in adolescents and youth, and was a low cost intervention with reasonable cost-effectiveness. Lastly, a published scientific letter is included as an appendix, which is a critique of findings from a cluster-randomized trial investigating the effectiveness of two interventions as part of the current South African National Adherence guidelines (AGL). The letter recommends the inclusion of long-term CBS for ART patients utilizing CHWs in a revised version of the AGL. The thesis concludes that task-shifting healthcare models including communitybased and pharmaceutical care models are effective and cost-efficient for HIV program delivery in South Africa, and can aid the greater Southern African regions’ progress toward several of the interrelated UNAIDS Sustainable Development Goals by 2030.
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    Using quality improvement approach to address missed opportunities for vaccination in Kano Metropolis, Nigeria
    (Stellenbosch : Stellenbosch University, 2019-12) Adamu, Abdu Abdullahi; Wiysonge, Charles S.; Uthman, Olalekan A.; Gadanya, Muktar A.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Family and Emergency Medicine. Family Medicine and Primary Care.
    ENGLISH SUMMARY : Background Strategies to reduce missed opportunities for vaccination (MOV) can potentially increase immunization coverage in health facilities and invariably improve immunization coverage at the district and national level. Yet, there is a dearth of synthesized literature on MOV in Africa, despite being the region with the lowest immunization coverage globally. Furthermore, the use of quality improvement (QI) in health facilities to rapidly address health system problems is growing, but evidence of its use in the immunization sub-system to reduce MOV is scarce. Moreover, it is unclear how the QI approach can be applied in a low resource, low immunization coverage setting like Kano, Nigeria. Therefore in this project, empirical evidence on the burden and dynamics of MOV in Africa was generated as well as the extent to which practitioners in healthcare facilities have used QI to address it. This was followed by the implementation and evaluation of a QI programme to reduce MOV in Nassarawa Local Government Area, Kano State, Nigeria. Methodology A combination of methods including systematic review, scoping review, multilevel modelling, qualitative inquiry, time series, and mixed methods were used. Result The first component of the first phase, a systematic review, revealed that MOV is common among children aged 0 – 23 months who made contact with health facilities in Africa, with a pooled prevalence of 27.26%. However, only 20 MOV assessments from 14 African countries were found. The reasons for MOV were multifactorial and complex because they were interrelated and interdependent. The second component of the first phase, a scoping review, revealed that evidence on the use of QI to reduce MOV and improve immunization coverage in health facilities exists. However, the QI interventions that were found were all implemented in the United States. Plan-do-study-act (PDSA) cycles were the most commonly used models. In these QI programmes, practitioners used multiple change ideas simultaneously. The change ideas were client-related, health worker-related, and cross-cutting health system-related change ideas. The second phase was the pre-implementation period of a QI programme in Kano, Nigeria. The first component of the second phase, a cross sectional study, revealed an MOV prevalence of 36.15% among children aged 0 – 23 months who visited PHC facilities in Nassarawa Local Government Area (LGA) of Kano, Nigeria. MOV was more likely to occur among children who were accompanying a caregiver to the health facility and failure to offer vaccination on the day of clinic visit. In the second component of this phase, a qualitative study based on the lived experiences of caregivers, showed that non-screening of immunization history, refusal to offer vaccination, husband’s refusal and fear of side effects were responsible for MOV. In the third phase, locally relevant change ideas were implemented in five PHC facilities in Nassarawa LGA to address the identified factors. In the first component of the third phase, frontline health workers in these facilities systematically selected and implemented change ideas in two plan-do-study-act (PDSA) cycles that were four weeks apart. Using p-charts, reduction in proportion of MOV per day was seen in two facilities at the sixth week following implementation of the PDSA cycles. Then, an evaluation of the implementation context revealed that several facilitators and barriers influenced the implementation of the QI programme. Conclusion This study confirmed that MOV is a common immunization problem in Kano, like other settings in Africa. A bottom-up QI approach to address MOV, that is led by health workers in facilities, is feasible in this setting. However, rapid assessment of implementation context should be built into the QI process.