Epidemiology and Biostatistics

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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.
The association between taking HAART and hypertension
(Stellenbosch : Stellenbosch University, 2017-12) Mangunda, Tichatonga John; Machekano, Rhoderick; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.
ENGLISH SUMMARY: Prevalence of hypertension in patients on HAART compared to pre-ART patients at Sithobela Hospital. Background: The use of Highly Active Anti-retroviral Therapy (HAART) has improved the quality of life among people with HIV/AIDS, but there are concerns about its effect on hypertension and other cardiovascular diseases. Objectives: In this study we sought to find out if HAART is associated with hypertension and to describe lifestyle and socio-demographic factors among people on pre-ART and HAART. Methods: We conducted a cross sectional study of HIV infected patients initiated on HAART and pre-ART at Sithobela health centre. Results: We enrolled a total of 410 participants, 205 in the ART group and 205 in the pre-ART group. The estimated prevalence of hypertension among those on ART was 14.2% [95% CI: 9.3-18.9] and 19%[95% CI: 13.6-24.4] among pre-ART patients. There was no significant difference in the prevalence of hypertension between the two groups (p=0.185). However, after adjusting for age, marital status, level of education, stage of disease, smoking history, waist to hip ratio, occupation, income level, history of smoking and alcohol use, HAART was significantly associated with hypertension (AOR= 0.43 [95% CI: 0.23-0.83]). Patients who reported drinking alcohol were likely to be hypertensive (AOR 10.96 [95% CI: 2.36-50.92]). Smokers were 3 times more likely to be hypertensive compared to non-smokers but this association was found not to be statistically significant on multivariate analysis. Conclusion: our study demonstrated a potential beneficial effect of HAART in reducing hypertension among HIV infected people in Sithobela, Swaziland.
Association of home hygienic practice and diarrhoeal presence in low-cost housing in Cape Town, South Africa
(Stellenbosch : Stellenbosch University, 2017-12) Brand, Amanda; Esterhuizen, Tonya; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.
ENGLISH SUMMARY: Background: Good home hygiene in key high-risk areas shows potential to be a simple and cost-effective intervention for preventing infectious disease transmission in low income homes. Knowledge of good home hygiene does not, however, always translate to practice due to complex factors which hinder translation. The objective of the study was to investigate whether an association between cleanliness and diarrhoeal disease exists, and to understand the factors which impede knowledge translation. Method: This cross-sectional study in low-income areas in Cape Town, South Africa took the format of an administered questionnaire focusing on health, and hygienic behaviour. Interviewer-assessed cleanliness was also recorded for each home. Results: Gastrointestinal symptoms were significantly associated with unclean kitchens and toilets (odds ratio (OR)=5.93 (1.98 – 19.78) and OR=17.67 (5.20 – 63.90), respectively). The presence of diarrhoea was significantly associated with dirty toilet areas (OR=8.94 (2.34 – 40.96)), despite its relatively low prevalence (17% (11 – 25%)). While knowledge of home hygiene and health was high, a lack of association between knowledge and observed cleanliness indicated a gap in the translation of knowledge to practice. Proposed emotional drivers of this process could not be substantiated, but evidence suggested that lack of understanding of underlying reasons plays an important role, but it may be effectively overcome by education. Conclusions: Good home hygiene shows potential for preventing infectious disease risk in low-income areas, but knowledge does not translate to effective practice. This is likely attributable to a lack of understanding of underlying principles, specifically among persons with low levels of formal schooling.
Barriers and facilitators to linkage, adherence and retention in care among HIV positive patients : an overview of qualitative systematic reviews using mega-aggregation framework synthesis
(Stellenbosch : Stellenbosch University, 2019-04) Hendricks, Lynn Avril; Rohwer, Anke; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.
ENGLISH SUMMARY : Background: People living with Human Immunodeficiency Virus (PLHIV) continue to struggle with the complexities related to having a chronic disease and integrating antiretroviral treatment (ART) and care into their daily lives. This overview aimed to assess existing evidence related to self-reported barriers and facilitators to linkage to ART, adherence to ART and retention in care for PLHIV and to identify gaps in the evidence. Methods: The novel pragmatic approach of mega-aggregation framework synthesis was developed, described and applied in this overview using Kaufman’s interpretation of the socio-ecological framework. We included qualitative systematic reviews, up to July 2018, and used a systematic and rigorous approach to select reviews and extract data. We assessed methodological quality using an amended version of the Joanna Briggs Institute Critical Appraisal Checklist for Systematic Reviews. Results: We included 33 systematic reviews, from low, middle and high income countries and included 1 111 964 HIV positive children and adults. Methodological quality varied considerably across reviews. Using the mega-aggregative framework approach, we found 544 unique third order concepts, from the included systematic reviews, and reclassified the third order concepts into 45 fourth order themes within the individual, interpersonal, community, institutional and structural levels of the Kaufman HIV Behaviour Change model. Our overview found that the main barriers and facilitators to linkage, adherence and retention such as psychosocial personal characteristics of perceptions of ART, desires, fears, experiences of HIV and ART, coping strategies and mental health, were interwoven with other factors on the interpersonal, community, institutional and structural level. Conclusions: High quality qualitative review level evidence on self-reported barriers and facilitators of linkage, adherence and retention in care is lacking for adults and even more so for children. Overviews are useful in the identification of evidence gaps to inform new review questions and researchers are encouraged to build on the method of mega-aggregative framework synthesis as the place of overviews become more prominent with the growing body of qualitative reviews. Systematic review registration: The protocol of this overview was registered on PROSPERO (CRD42017078155) on 17 December 2017.
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.
Combining sexual behavioural survey data, phylodynamics and agent-based models towards a unified framework for HIV prevention research
(Stellenbosch : Stellenbosch University, 2021-12) Niyukuri, David; Nyasulu, Peter Suwirakwenda; Delva, Wim; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.
ENGLISH SUMMARY: Background: Sub-Saharan African countries carry a disproportionate burden of the Human Immunodeficiency Virus (HIV) infection. Thus, beyond estimation tools which are used to produce HIV epidemic estimates, there is a need for simulation tools to understand the structure and the dynamics of sexual networks, and HIV transmission underlying factors. This can help to design and implement effective interventions. These simulation tools should be able to take advantage of existing multi-source data. Furthermore, with such multi-data generation tools, we can be able to assess new methodologies and the accuracy of different inferences made from available real-world data. Methods: We developed a unified simulation framework which combines in one model world the simulation of sexual dynamic network, HIV transmission, and between-host viral evolution for infected individuals. We used that simulation framework to run a benchmark study to infer age-mixing patterns in HIV transmission in different sequence missingness scenarios. We used transmission clusters from phylogenetic trees and compute proportions of pairings between men and women who were phylogenetically linked across different age groups. We assessed the usability of our simulation framework through a calibration study. We focused on fitting the simulation framework to summary features from multiple data sources to increase the accuracy of estimates. The case study was the estimation of determinants of HIV transmission network, namely age-mixing patterns in sexual partnerships, distribution of onward transmission, and temporal trend of HIV incidence. We also used simulated polymerase and protease viral data on same transmission network with Simpact Cyan to check in the phylogenetic results, mainly root-to-tip regression, and transmission clusters. Results: The proof of concept of the appropriateness of the modelling framework was determined by the ability to capture HIV transmission dynamics, and the temporal trends of branching times of a phylogenetic tree built from simulated viral sequence data. For age-mixing patterns in HIV transmission, the results of the simulation suggested that proportions of men/women linked to women/men across different age groups, together with the mean and standard deviation of age difference can unveil age-mixing patterns in HIV transmission networks. For the calibration study, the results showed that the relative errors between true benchmark values and post calibration values of the determinants of HIV transmission network were relatively close in the three calibration scenarios. In post-calibration simulation age-mixing patterns and the distribution of onward HIV transmission had relatively small error values, but the age-gender strata temporal trend of incidence was poorly captured. The root-to-tip regression of phylogenetic trees from protease and polymerase data simulated on the same HIV transmission network showed that the dispersion of the genetic distance with branching and sampling times was explained at 95% and 49% for polymerase and protease data, respectively. For transmission clusters, we could still get at least 90% of individuals within big the size clusters if we use polymerase or protease viral sequence data. This showed that even with the short sequences we could still get useful epidemiological data. Conclusion: The unified framework could be used as a data generation method for benchmark studies. This is so despite the simplistic assumption for HIV viral evolutionary dynamic through consideration of host evolution only. These methods could also help to investigate the effect of sexual dynamic network on HIV transmission and estimate age related individual-level features affecting the HIV transmission dynamic. Furthermore, this simulation framework could i) contribute to the advancement of phylogenetic-based inference methodology; and ii) advance epidemiological methods focusing on combining epidemiological data, sexual behaviour data, viral phylodynamics, and agent-based simulation models.
Comparative, cross-sectional study describing agreement and accuracy of emergency centre triage using either a mobile application or manual triage
(Stellenbosch : Stellenbosch University, 2016-03) Khan, Yaseen; Govender, Thashlin; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.
ENGLISH SUMMARY: Background and Purpose: Unacceptable patient waiting times and misidentification of critically ill patients are significant problems within Emergency Centres (ECs). Triage, when performed correctly, is acritical process to address this. The South African Triage Scale (SATS) is widely used. Manually performed triage may be prone to inaccuracies and prolonged triage time. A mobile tablet application to facilitate use of the SATS by automating triage calculation and guiding nurses has been developed. Methods: This is a comparative cross-sectional study to observe the accuracy of triage using the mobile tablet application compared with triage performed manually. Under classroom examination conditions, nurses calculated triage scores on written case scenarios of typical EC presentations. A total of 59 nurses across five hospitals in the Western Cape Province, South Africa were randomized into an ‘app group’ and a ‘manual group’. Results: The app group scored a 23% higher level of agreement with the expert-validated results than the manual group. Kappa of 0.735 (0.719 - 0.770) and 0.597 (0.545 - 0.656) were found respectively. One in five patients are triaged more correctly using the app. Sensitivity for emergency cases was 65.5% and 53% respectively, with and without the app. Conclusions: Nurses triaging written scenarios with the aid of the app were observed to have a higher agreement with the expert-validated results than nurses performing traditional manual triage. The effect size is considerable and of practical relevance. The app could have significant benefit in busy Emergency Centres of public sector hospitals. A larger study involving real patients is recommended.
Completeness of HIV intervention trial protocols : a systematic survey
(Stellenbosch : Stellenbosch University, 2019-04) Samupindi, Shingirayi Irene; Dzikiti, Moleen; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.
ENGLISH SUMMARY : Introduction: The Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT1) 2013 guideline provides guidance to improve the quality of protocols. The aim of this study was to determine the completeness of randomised controlled trial protocols evaluating the efficacy or effectiveness of HIV prevention, treatment and care strategies using the SPIRIT 2013 checklist, and to identify factors associated with completeness of trial protocols. Methods: We searched MEDLINE, EMBASE, LILACS, Africa-wide information (EBSCOhost), Web of Science, Clinicaltrials.gov and CENTRAL (Wiley Cochrane Library) for randomized controlled trial protocols in May and June 2018. We included protocols for interventions in the HIV prevention, treatment and care fields published between 2008 and 2018. Two individuals independently screened the titles and abstracts. The adapted SPIRIT checklist was pilot tested independently in duplicate on the first 4 (5%) protocols. The rest of the data was collected by a single individual and verified by second reviewer. Disagreements were resolved by consensus. We summarized categorical data using count (percent) and continuous variables using mean (standard deviation). Generalised estimation equations assuming a Poisson distribution were used to assess association of protocol factors with number of checklist items reported. Results: Seventy-nine protocols met the eligibility criteria and were included in the analysis. A mean of 32 (SD= 5) of the possible 51 SPIRIT checklist items were reported in the protocols. Detailed methodological aspects relating to intervention allocation, blinding, data management, study monitoring and dissemination policy information were often missing in the protocols. Intervention category, period of publication (before or after SPIRIT 2013 publication) and study setting were not significantly associated with protocol completeness. Conclusion: There is need for improvement in the reporting of recommended SPIRIT 2013 checklist items in HIV intervention protocols. We recommend active implementation strategies of the SPIRIT guideline from publishing journals and HIV trialists to ensure more improvement in protocol quality.
The effects of longitudinal HIV viral load exposure on immune outcomes, mortality, and opportunistic infections in people on ART in sub-Saharan Africa
(Stellenbosch : Stellenbosch University, 2017-12) Sempa, Joseph Bukulu; Nieuwoudt, Martin; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.
ENGLISH SUMMARY : Introduction: Longitudinal viral load monitoring is used as a cross-sectional marker for treatment failure in HIV infected people receiving antiretroviral therapy. Cumulative viral load, as quantified by area under the viral load curve during combination antiretroviral therapy, has been correlated with treatment outcomes in studies outside, but not within, sub-Saharan Africa. We investigate the effects of exposure to longitudinal viral load on, the incidence of opportunistic infections, mortality and immune recovery in local, previously combination antiretroviral therapy naïve, cohorts. Further, we systematically review statistically derived immune response models and use this to define priors for Bayesian models for application on a previously undescribed treatment cohort. Methods: We analyze data from the Infectious Diseases Institute (IDI) cohort, Kampala-Uganda, and the Antiretroviral Clinic at Tshwane District Hospital in Gauteng-South Africa. For the systematic review, we use ‘Preferred Reporting Items for Systematic Review and Meta- Analyses’ guidelines. We also compare cumulative viral load as numerically estimated using two methods: area under the viral load curve, which is then log-transformed, named, ‘untransformed cumulative viral load’; and area under the log-transformed viral load curve, above the kit-based detection limit of 400 copies/mL, named, ‘transformed cumulative viral load’. We use Cox Proportional Hazards and Bayesian Generalized Mixed Effects to define treatment outcome models. Results: In the IDI cohort most recent viral load, not cumulative viral load, is associated with a 1.34-fold (95% confidence interval: 1.12, 1.61) increase in the risk of opportunistic infections. Transformed, not untransformed, cumulative viral load is associated with mortality and immune response. Each log10 copy-yr/mL increase corresponds to a 1.63-fold (95% confidence interval: 1.02, 2.60) increase in risk of mortality. Systematic review of immune response statistical models also reveals many differences in the number and type of variables adjusted-for, variable transformations and scales and scant details regarding the modelling methods employed. In the Tshwane cohort, using Bayesian methods, for the slope of longitudinal CD4 counts, each log10 copy-yr/mL increase cumulative viral load corresponds to a mean annual CD4 count decrease of -19.5 cells/μL (95% credible interval: -28.34, -10.72). Further, in the asymptote model, each log10 copy-yr/mL increase reduced the odds of having a CD4 count ≥500 cells/μL to 0.42 (95% credible interval: 0.242, 0.724). Modelling inherently variable absolute CD4 count using a Student’s t-distribution produced better fits than assuming a Gaussian normal distribution. Discussion: Transformed cumulative viral load is associated with both mortality and long-term immune response, while most recent viral load is associated with incidence of opportunistic infections. This thesis emphasizes the need for the review of existing literature prior to any statistical analyses, so that more comparable and robust statistical models than have been available to date will be constructed. In particular, comparing immunological outcomes (CD4 counts), statistical models for sub-Saharan African cohorts would benefit from the application of more uniform modelling techniques. Adjusting for transformed cumulative viral load and the use of appropriate distributional assumptions, improves the modelling of immune response to antiretroviral therapy. Future statistical immune response models would benefit from the use of Bayesian methods owing to their flexibility in the selection of prior distributions and hierarchical model designs.
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.
Evaluation of the Mean Duration of Recent Infection (MDRI) and the False Recent Rate (FRR) for the Limiting Antigen Avidity Enzyme Immune Assay (LAg) and Bio-Rad HIV ½ Plus O Avidity Incidence Assay (BRAI)
(Stellenbosch : Stellenbosch University, 2017-12) Gonese, Elizabeth; Hargrove, John; Nachega, Jean; Van Zyl, Gert; Kilmarx, Peter H.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.
ENGLISH SUMMARY : Background: The evaluation of laboratory assays in estimating HIV incidence has become a priority because of the complexity of HIV epidemics and the need to measure the impact of public health interventions targeting reduction of HIV incidence. Biomarkers should have test properties that allow the lowest possible False Recent Rate (FRR, or probability of diagnosing a long-term infection as recently infected) over the longest possible period (Mean Duration of Recent Infection or MDRI) during which the case is considered as a recent infection. Methods: We compared the BED Capture Enzyme Immunoassay (BED), Sedia Limiting Antigen (LAg) and Bio-Rad HIV ½ Plus O Avidity Incidence Assay (BRAI) using samples from a prospective cohort trial, the Zimbabwe Vitamin A for Mothers and Babies Project (ZVITAMBO) 1997–2000. We determined MDRI using 591 samples from 184 seroconverting women, and determined FRR by testing 2825 cases known to be HIV- positive for >12 months. We used these results to estimate HIV incidence over the first 12 months postpartum, and during the period prior to childbirth. Results: At recommended cut-offs MDRI values were: BRAI, 135 days (120 – 151) at Avidity Index (AI) 30%; LAg, 104 days (98 - 110) at ODn cut-off 1.5; BED, 188 days (180 -196) at ODn cut-off 0.8. All error bounds in this thesis signify 95% confidence intervals. The coefficients of variation (CV) of the MDRI estimates for BRAI, LAg and BED were 5.9%, 2.9% and 2.1%, respectively. Corresponding FRRs were 1.1% (0.7-1.5) for BRAI, 0.6% (0.3-0.9) for LAg and 4.8% (4.1-5.7) for BED. MDRI and FRR estimates, all derived using postpartum women, were lower than in other published studies. Using original ZVITAMBO HIV diagnoses, adjusted HIV incidence over the first 12 months postpartum was estimated as; BRAI, 2.7% (1.8-3.7); LAg, 3.7% (2.7-4.8); BED, 3.6% (2.4 -4.9). Follow-up incidence was 3.4% (3.0-3.8). When cases with viral load <1000 copies/ml were defined as long-term infections, regardless of serological biomarker level, FRRs were; BRAI, 1.0% (0.7-1.5); LAg, 0.2% (0.2 -0.7); BED 3.8% (3.1-4.6). MDRIs were; BRAI, 133 days (113-154); LAg, 101 days (87-115); BED, 177 days (155 - 199). Corresponding incidences, unadjusted for FRR, were: BRAI, 3.9% (2.9-4.9); LAg, 3.1% (2.1-4.0); BED, 6.2 % (5.0-7.3). Adjusted estimates were 2.7% (1.5-4.0), 2.5% (1.6-3.5) and 2.6% (1.6-3.7) respectively. At baseline, with no follow-up estimate for comparison, adjusted incidence for serological biomarkers used alone were; BRAI, 8.1% (6.6-9.7); LAg, 6.9% (5.7-8.1); BED 6.7% (5.5-7.9). When viral load was also used, the adjusted and unadjusted incidence estimates were; BRAI, 7.3% (5.7-8.8) and 8.4% (6.8-10.0); LAg, 5.1% (3.9-6.3) and 5.7% (4.5-6.9); BED, 5.4% (4.1-6.7) and 8.6% (7.3-10.0). Conclusion: At recommended cut-offs; BRAI FRR was 1.9 times higher than that of LAg. BRAI MDRIs were also 1.3 times higher, but with a relative standard error 2.4 times as high. Postpartum BRAI incidence estimates were consistently lower than follow-up estimates. Adjusted biomarker estimates under-estimated follow-up incidence when we used viral load in combination with either serological test.
HIV continuum of care outcomes among female sex workers in Kampala Uganda
(Stellenbosch : Stellenbosch University, 2022-12) Atuhaire, Lydia; Nyasulu, Peter; Shumba, Constance; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.
ENGLISH SUMMARY: Background: Female sex workers (FSWs) account for 11% of all HIV infections globally and are twenty-six times at a greater risk of acquiring HIV than their female counterparts in the general population. In Uganda, HIV prevalence among FSWs is estimated at 31% - 37%, six times higher than the HIV prevalence of 5.4% in the general population. FSWs, not only are confronted by heightened risk to HIV infection, but they are also more vulnerable to social and economic inequalities that hinder access to HIV services throughout the HIV care continuum. Moreover, the few HIV positive FSWs who eventually access HIV care, experience unique barriers that hinder their continuity on life-long Antiretroviral therapy (ART) and thus drop out of care along the various stages of HIV continuum of care. Consequently, FSWs continue to widen the gap to attaining the global HIV treatment targets of 95-95-95 by 2025 and ending the AIDS epidemic by 2030. Notably, there has been an increased focuson improving HIV care continuum. However, data are sparse regarding the service uptake across the HIV care cascade for FSWs. Absence of recent data for FSWs impedes monitoring of HIV service provision and identifying missed opportunities important in guiding program strategies, optimal for improved and equal access to HIV services among FSWs. The aim of this research project was to understand service delivery approaches along the HIV continuum of care for FSWs in a routine care setting in Kampala, Uganda. Methods: The research project used multiple approaches to respond to the objectives as described as follows: In objective one, we conducted a systematic review on the implementation of community interventions for any of the HIV care cascade stage. We conducted a systematic search of randomized controlled trials, cohort and cross-sectional studies done in sub-Saharan African countries and published from 2004 to 2020. The study outcomes were HIV testing and diagnosis, linkage to care, receipt of ART and achievement of viral suppression. The data were analysed using random effects meta-analysis, where possible and for the rest of the studies, data were synthesized using summary statistics. For objective two, we conducted a cross-sectional survey and used simple random sampling method to select 200 participants from 12 sex work hotspots in Kampala. Participants were allocated proportionally in each hotspot. Frequencies were used to describe categorical characteristics of FSWs, and a multivariable logistic regression model was used to determine the factors associated with adherence to the HIV testing guidelines. In the third objective, we performed a retrospective cross-sectional study of routine patient management data for FSWs diagnosed with HIV and enrolled in care from January 2018 to December 2020 at the government primary health care facilities in Kampala. Two outcome variables were assessed and these which included i) Lost-to-follow-up from HIV care; and ii) Virological non-suppression. We used cluster sampling methods to select initial clusters and purposively selected a cluster of six health facilities and data was collected from 275 medical records. Both univariable and multivariable logistic regression models were performed on study outcomes. Data were analysed using Stata 15.1 software (Stata Statistical Software: Release 14. College Station, TX: Stata Corp LP). Finally, the fourth objective applied a qualitative descriptive design through use of in-depth interviews among FSWs, who were accessing HIV services through differentiated service delivery models in primary health facilities and drop-in centres in Kampala. We purposively sampled 2 health facilities and 2 drop-in centres and following the principle of data saturation, 24 FSWs were interviewed. Data analysis was conducted manually using framework analysis, and we applied an inductive approach which involved systematically reviewing the code framework, reduction, and interpretation of the data. Results: From the systematic review, the results showed variations in the effectiveness of community-based interventions along the various stages of HIV care cascade. The level of effectiveness was more pronounced in HIV testing and ART use; with average effectiveness observed in HIV diagnosis, than it is for linkage to care and viral load suppression. In addition, the interventions tended to be more impactful if they were provided in a combination of various strategies unique for each HIV care cascade stage. Among the sample of two hundred study participants from the adherence to HIV testing guidelines study, 88% of the study participants reported their HIV testing status; of these, 56% adhered to the HIV testing guidelines, having tested three or more times in the 12 months preceding the survey. Attaining a secondary education was associated with adherence to HIV testing guidelines [odds ratio (OR) 1.86, 95% confidence interval (CI) 1.01 – 3.44; P = 0.047]. Testing for sexually transmitted infection in the preceding 3 months (OR: 2.13, 95% CI: 0.95 – 4.74, P = 0.065) and accessing HIV testing at a drop-in centre (OR: 5.90, 95% CI: 0.71 – 49.1; P = 0.101) were associated with higher odds of adherence to the HIV testing guidelines, although the association was not significant. Results from the study on retention and non-viral suppression showed retention of 85.1% (n = 234) at six months, corresponding to LTFU of 14.9% (n = 41) within the same period. Retention decreased with duration of being in care to 73.5% (n = 202) at 24 months, translating to LTFU of 26.5% (n = 73). Viral load testing coverage was 62% (n = 132) and of these, 90.9% (n = 120) were virally suppressed. Factors associated with LTFU at <0.2 significance level in univariable logistic regression model were age, marital status, education level, having treatment supporter, having a telephone contact, WHO stage at baseline, and having been diagnosed with TB during the study period. In multivariable logistic regression model, age (OR: 0.56, 95% CI: 0.031 - 1.00, p = 0.049), marital status (OR: 0.46, 95% CI: 0.23 - 0.89, p = 0.021), having telephone contact (OR: 0.22, 95% CI: 0.07 - 0.70, p = 0.010) and WHO stage at baseline (OR: 0.11, 95% CI: 0.01 - 0.97, p = 0.046), were significantly associated with LTFU at 0.05 significance level after adjusting for other factors. Factors associated with viral load suppression in univariable logistic regression models included age, having telephone contact, lost to follow up, and reason for lost-to-follow-up at <0.2 level of significancy. Age at enrolment remained statistically significant in multivariable logistic regression model (OR: 0.09, 95% CI: 0.01 – 0.82 P = 0.033) at 0.05 level of significance. Findings from the qualitative phase of the research study showed that HIV services provided through community based Differentiated Service Delivery (DSD) models were perceived to be of low quality, with a non-comprehensive package of HIV services for FSWs which did not match FSWs’ needs, preferences, and health risks. In addition, services were provided irregularly with compromised privacy and being provided by health workers who were perceived to have less than adequate specialised skills. Further, the process of deciding on how and what services should be provided through community DSD models targeting FSWs, the latter were not part of the process. Consequently, FSWs preferred facility-based models even though community DSD models were considered to be as a more convenient and a less costly option for access to HIV services and were thought to be a good complementary option if the quality of services provided in the community would be improved. Conclusion: Evidence brought forward in this research project shows that the effect of community-based interventions varies across the various stages of HIV care cascade. Therefore, it is critical to consistently monitor, review, and evaluate strategies under implementation to identify and realign those that have long term impact in improving HIV services access along the care continuum for FSWs. In addition, the suboptimal retention and viral load testing coverage underscores the need to improve the quality of services provided under differentiated care models, by ensuring that services are tailored to FSWs individual preferences, needs, and contexts.
Identifying gaps using the EPICOT+ framework and exploring the association between funding sources and author conclusions in primary nutrition research addressing non-communicable diseases from Cochrane nutrition reviews : a descriptive-analytical cross-sectional study
(Stellenbosch : Stellenbosch University, 2021-03) Ruzive, Sheena; Naude, Celeste E.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.
ENGLISH SUMMARY : Background: With the rise in non-communicable diseases (NCDs) globally, we aimed to summarise the research gaps and describe the adequacy of the reporting of future research recommendations in Cochrane reviews of nutrition interventions addressing NCDs. We also aimed to explore the influence of funding sources and author- sponsor financial ties on author conclusions in a subset of primary studies included in these reviews. Methods: Two researchers independently screened a Cochrane nutrition reviews database (n=470, July 2015) to identify reviews addressing four NCDs (cardiovascular diseases, cancer, chronic respiratory diseases and diabetes). The “implications for research” section of eligible reviews was analysed using the evidence, population, intervention, comparison, outcome, timeframe, study design and burden of disease (EPICOT+) framework to describe the extent of reporting of research recommendations and to summarise gaps. A purposive sample of English full-text studies included in reviews addressing alternative nutrition supplements were analysed to assess reporting of conflict of interest (COI), funding sources and author-sponsor financial ties, and to explore influences of funding sources and author-sponsor financial ties on author conclusions. Results: Ninety-eight eligible reviews were analysed. The EPICOT+ reporting was as follows: evidence 34/98 (33.7%), population 68/98 (69.4%), intervention 90/98 (91.8%), comparison 26/98 (26.5%), outcomes 78/98 (79.6%), study design 85/98 (86.7%), time frame 52/98 (53.1%), and burden of disease 7/98 (7.1%). Studies requiring better quality, different interventions, and outcomes in low- and middle-income countries (LMICs) were highlighted. Seven reviews addressed alternative nutrition supplements, including 51 eligible primary studies. Conflicts of interest were disclosed in 10/51 (19.2%); funding in 27/51 (51.9%), of which, 11/27 (40.7%) were industry and 16/27 (59.3%) were non-industry sponsors; and author-sponsor financial ties in 9/51 (13.4%), of which 1/9 (11.1%) was industry and 8/9 (88.9%) were non-industry. There was no association between authors making favourable conclusions and having industry sponsors and author-sponsor financial ties (8/12) compared with non-industry sponsors and no author-sponsor financial ties (10/24), (Fisher exact p =0.289). Conclusions: EPICOT+ items were not well reported in most reviews. Future studies of better quality, different interventions, outcomes or populations in LMICs are needed. Authors should disclose all COI, funding sources and author-sponsor financial ties. Possible influences of funding sources and author-sponsor financial ties on author conclusions needs further investigation.
The impact of caring for a school-going visually impaired child in Cape Town, Western Cape on the home caregiver and the rest of the family – the health, socio-economic and psychological health burdens
(Stellenbosch : Stellenbosch University, 2021-03) St. Jerry, Marlyse; Barnes, J. M. (Johanna Maria); Nyasule, Peter S; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.
ENGLISH SUMMARY : Background: Visually impaired (VI) children need additional care for daily tasks due to their diminished independent living skills (ILS). In learners in Special Educational Needs (LSEN) schools and specially-adapted mainstream schools, occupational therapy and trained assistants help to bridge the gap that diminished ILS pose to their education. However, in impoverished areas of the Cape Metropole, many families cannot afford trained caregivers in their homes. Typically a maternal figure fulfils the responsibilities of caring for the VI child as well as for the rest of the household; such a person then becomes the VI child’s primary home caregiver. Aims and Objectives: The main focus of the study was to determine the caregiving load and its impact on the caregiver's physical, mental and emotional well-being. Methods: The cross-sectional study used a questionnaire consisting of a self-designed questionnaire based on issues from literature on the subject and the validated Caregiver Strain Questionnaire – Short Form (CGSQ-SF). The CGSQ-SF provides qualitative data on the noticeable, emotional, and overall impact of caregiving. During prescheduled home interview sessions, the caregivers completed the questionnaires. The mixed research method used measurable data such as financial status and qualitative data, such as the emotional experiences associated with caring for a VI child. The University of Stellenbosch ethics committee (S13/03/049) and the Western Cape Education Department (20130704-13796) approved the study. Professor M. Kidd of the Centre for Statistical Services at the University of Stellenbosch carried out the statistical analyses, Mann-Whitney U tests and Kruskal-Wallis tests analysed the relationship of variables with CGSQ-SF scores. Results: Of the population of 320 VI learners from the only school for the VI in the Cape Metropole, 150 learners resided at home during the school term. According to the inclusion criteria, only 95 of the 150 home caregivers were eligible. The study obtained consent from 73 caregivers. The CGSQ-SF scoring showed that the majority of the 73 caregivers experienced moderate strain in terms of overall (55/73; 75.3%), objective (57/73; 78.1%) and subjective internalised caregiver strain (55/73; 75.3%). Elevated caregiver strain frequently occurred with these factors: financial difficulty; diminished ILS; and reluctance to spend time away from the VI child. Conclusion: All the caregivers experienced a considerable caregiving load and subsequently substantial caregiver strain level. All the participating households experienced both poverty and caring for a VI child. This bias in the design made it difficult to attribute what strainload was due to either of these variables. It was not possible to determine whether having a VI child increased the household’s strain compared to those who did not have a VI child. The confounding nature of the design made it challenging to unravel the relationship between poverty and caregiver strain due to the presence of a VI child. Qualitative information from the caregivers suggested that they did not view their child’s special needs as the only cause for the financial struggles they face and that their biggest concern was their child’s future as a disabled adult.
The impact of missing data on estimating HIV/AIDS prevalence and incidence in demographic sentinel survey studies
(Stellenbosch : Stellenbosch University, 2022-04) Mosha, Neema Ramadhani; Machekano, Rhoderick; Young, Taryn; Todd, Jim; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.
ENGLISH SUMMARY: Background: Missing data is a challenge in most research, especially with observational population data such as demographic surveys. These studies often account for survey designs and clustering when estimating disease prevalence or incidence, but do not account for missing data. In other circumstances they do not explicitly state how they dealt with missing data during analysis or inappropriately handles them in practice. There are many challenges in conceptualising the pattern of missingness, its occurrence mechanism and complexity of methods for handling the problem of missing data. Ignoring the missingness of survey data can cause biased estimates and invalid conclusions. The primary aim of this PhD was to evaluate the impact of missing data on estimating HIV/AIDS prevalence in demographic sentinel surveillance studies. Methods: A systematic review of HIV studies to identify and describe methods used to analyse studies with missing data was done. A series of simulation studies to explore the precision and efficiency of the prevalence estimates using complete case analysis (CCA), multiple imputation (MI), inverse probability weighting (IPW) and double robust estimator (DR), when data are missing at random (MAR) in survey studies was done. A descriptive statistics and a complete case analysis to determine the incidence and population prevalence estimates ignoring the missingness on four different survey rounds of Magu Health Demographic Sentinel Surveillance (HDSS) was done.The surveys were conducted between 2006 and 2016, they included adults aged 15 years and above and about 50% of the population was tested for HIV in each survey. This was followed by data exploration assessing the missingness occurrence and association between missingness and other study characteristics. Finally, application of the statistical methods used in the simulations study was performed to re-estimate the prevalence of the surveys data taking into account the missingness. Results: The systematic review found 24 eligible articles from population, demographic and cross-sectional surveys that acknowledged the presence of missing data. In these studies, complete case analysis was the standard method of choice (100%) followed by multiple imputations (46%) and Heckman’s selection models (38%). A simulation study generated a hypothetical HIV survey with 32 different scenarios exploring data when an outcome is missing 20% and 55%. This simulation showed that when data are MAR, complete case analysis produces biased and inefficient estimates. Results showed that the three methods (MI, IPW and DR) were valid and efficient if the missingness or imputation models are correctly specified, but if either of the MI or IPW models are mis-specified, then the DR estimator can still be valid. Regarding to performance of the methods, provided that correct models are used, MI is more unbiased even when there is 55% of the data missing. However with 55% missingness all estimators are less reliable. In the complete case analysis, the overall population prevalence estimates for HIV decreased from 7.2% in 2006 to 6.6% in 2016. Cox models were used to determine HIV incidence rates and risk factor analysis by sex. The incidence rate was 5.5 per 1000 person - years in women compared to 4.6 per 1000 person-years in men. Residence, marital status, mobile individuals, and individuals with two or more partners were associated with the increase in incidence of HIV in bivariate analysis. The missingness OF HIV was as high as 60.3% (in the 2016 survey) and in all surveys(Sero 5 to 8) it was associated with age, sex, residence, and marital status. Further analysis using MI, IPW and DR assuming the outcome was MAR showed that the overall HIV prevalence was not significantly different from the complete case analysis in all four of the surveys. However, there were significant differences in the HIV estimates when stratified by the covariates. Looking at the confidence intervals width multiple imputations outperformed IPW and DR by producing more narrower estimates. Conclusion: Overall, this dissertation showed that despite the availability of methods to adjust for missing data, many surveys still ignore the missingness. The reporting among articles adjusted for missingness was below guideline standards. Understanding the mechanism of missingness enhances the proper application of advanced methods to account for the missingness. With data missing at random, IPW, MI, and DR can account for the missingness and produce unbiased and efficient estimates in HIV survey studies. Also, more simplified information and awareness are still needed to allow researchers to make informed choices, specifically on which method to apply and in which situation it works best for the estimates to be more reliable and representative.
Influence of previous tuberculosis treatment on time to culture conversion for patients receiving a bedaquiline-containing regimen at Sizwe Tropical Disease Hospital, South Africa
(Stellenbosch : Stellenbosch University, 2021-03) Saimen, Amashnee; Esterhuizen, Tonya; Padanilam, Xavier; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.
ENGLISH SUMMARY : Tuberculosis remains one of the leading causes of death worldwide. There is a growing crisis concerning the number of drug resistant TB cases. New drug regimens were urgently needed to improve mortality and morbidity among drug resistant TB patients. Bedaqualine is a newly developed diarylquinoline with a unique mechanism of action. . Studies have reported varying time to culture conversion regarding RR/MDR-TB patients with history of previous TB treatment. The Rv0678 mutation found in patients with prior Rifampicin exposure has demonstrated a more than four-fold increase in the minimum inhibitory concentrations of Bedaquiline. Previously treated TB patients may be more likely to have higher bacterial load due to extensive parenchymal damage. This study will provide information on effective Bedaquiline treatment duration for those previously exposed to TB treatment. Aim: To determine whether previous exposure to TB treatment influences the time to culture conversion as compared to no previous TB treatment exposure in patients receiving a DR- TB regimen containing Bedaquiline. Primary Objective: To compare the time to culture conversion for previously treated and new DR-TB patients receiving the Bedaquiline containing regimen. Secondary Objectives: 1.To evaluate treatment regimens at time of culture conversion for previously treated andnew DR-TB patients 2.To compare the rate of relapse in previously treated and new DR-TB patients receivingthe Bedaquiline containing regimen. 3.To compare the duration of Bedaquiline therapy in previously treated and new DR-TBpatients 4.To establish the severity of disease of previously treated and new DR-TB patients. Setting and Study Population: The study will be conducted at Sizwe Tropical Disease Hospital in Gauteng Province. Sizwe Tropical Disease Hospital serves as a referral centre for complicated MDR/XDR-TB cases in Gauteng. Study Design: A retrospective cohort study will be undertaken for confirmed DR-TB patients who were initiated on DR-TB regimen containing Bedaquiline from April 2016 to March 2019. Inclusion Criteria: Bacteriologically confirmed DR-TB All patients receiving DR-TB Regimens containing Bedaquiline including new DR-TB with no previous history of TB treatment Documented culture conversion Variables: Culture Conversion; Time to culture conversion; Duration of Bedaquiline treatment Sampling Technique: The group sample sizes were determined to be 76 (Previous treatment group) and 304 (New treatment group), power of 80% with a level of significance of α 0.05. Time Frame: The study will be conducted from June 2020 to November2020.
Knowledge of male partner HIV status as a risk factor for HIV indicators in women using prevention of mother-to-child transmission of HIV services in WHO priority countries : a systematic review and meta-analysis
(Stellenbosch : Stellenbosch University, 2022-12) Mmotsa, Tshiamo Moshading; Ngandu, Nobubelo K.; Adetokunboh, Olatunchi O.; Nyasulu, Peter; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.
ENGLISH SUMMARY: Elimination of new maternal and infant Human Immunodeficiency Virus (HIV) cases has been a top global priority and various targets have been introduced to end HIV in pregnant, postpartum women and their infants. To achieve these targets, it is important to understand factors related to unfavourable outcomes in the prevention of mother-to-child transmission of HIV (PMTCT, MTCT) programme cascade. The role of a male partner, especially HIV status non-disclosure is one of several important factors. Our study aimed to determine whether not knowing a male partner’s HIV status was a significant risk factor for HIV indicators, including poor HIV clinical outcomes, among pregnant, postpartum women and their infants in the 21 World Health Organization (WHO) priority countries for eliminating MTCT. We conducted a systematic review and meta-analysis of literature through four electronic databases in April 2022 for eligible studies from the 21 WHO priority countries. We included observational studies examining male partner HIV status non-disclosure as a risk factor for HIV indicators in pregnant, postpartum women and their infants conducted after the implementation of the Option B+ treatment policy (i.e., lifelong antiretroviral therapy (ART) regardless of clinical disease status) were included. We conducted a meta-analysis for studies without heterogeneity and assessed the certainty of the evidence assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) for each outcome. Forty-six full-text articles were screened and only three articles were included. The included studies were cross-sectional and retrospective cohort studies, conducted in Malawi, South Africa, and Uganda, with a total of 5248 participants. Sub-optimal ART adherence was significantly greater among women who did not know their male partner’s HIV status compared to those who knew the partner’s HIV status (2 studies; n= 3263: Odds ratio (OR) 1.85; 95% confidence interval (CI) 1.49–2.29; P <0.01) with no significant heterogeneity (P = 0.72; I2 = 0%). Complete ART adherence was significantly less among women who did not know their male partner’s HIV status compared to those with knowledge of the partner’s HIV status (1 study; n= 465: OR 0.47; 95% CI 0.32 – 0.69). MTCT was not significantly associated with male partner HIV status non-disclosure (1 study; n= 2881: OR 1.35; 95% CI 0.84 – 2.15). The certainty of evidence from all the studies was low for all outcomes. We found that there was limited evidence to fully understand the role a male partner’s HIV status disclosure plays in the PMTCT cascade. The available studies showed that the likelihood of ART non-adherence was increased by not knowing a male partner’s HIV status, therefore, highlighting the importance of knowing a male partner’s HIV status in the PMTCT cascade. We could not explore the other HIV indicators i.e., MTCT and other clinical outcomes due to the limited and non-availability of primary studies. More and appropriately designed studies within the WHO priority countries are needed urgently to inform policies and interventions for improving male partner involvement. These studies should also include a clear definition of male partner involvement which also highlights HIV testing and male partner disclosure.
Knowledge, attitudes and practices regarding the prevention of type 2 Diabetes Mellitus among overweight and obese adults in Manzini, Eswatini : a cross-sectional study
(Stellenbosch : Stellenbosch University, 2020-12) Chideme-Chinovhiringa, Karen; Chivese, Tawanda; Dudley, Lilian; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.
ENGLISH SUMMARY : Introduction: Being overweight or obese is one of the strongest risk factors for type 2 diabetes. Eswatini has a high prevalence of undiagnosed type 2 diabetes and half of its adults are either overweight or obese. However, there is a paucity of data on knowledge, attitudes and practices towards the prevention of type 2 diabetes in people at risk in Eswatini. This study aims to assess knowledge, attitudes and practices towards the prevention of type 2 diabetes mellitus among overweight and obese adults presenting at an urban outpatient clinic in Manzini, Eswatini. Methods: A cross-sectional study of adults who were either overweight or obese attending the clinic was carried out. Knowledge, attitudes and practices towards the prevention of type 2 diabetes mellitus were assessed using a validated researcher administered questionnaire. Knowledge, attitudes and practices were compared between overweight and obese participants. In addition, the correlation between knowledge, attitudes and practices was evaluated using a correlation matrix. Results: A total of 105 participants, with a mean age of 35.2 (SD 10.7) years participated in the study. Of these, 55 (52.4%) and 50 (47.6%) were overweight and obese, respectively. The majority of the participants showed acceptable knowledge levels, with 61% of the participants having good knowledge and 30% excellent knowledge. Participants showed positive attitudes towards diabetes prevention, 69.5% of participants had satisfactory attitudes, 21.0% had excellent attitudes and 9.5% had neutral attitudes towards the prevention of type two diabetes mellitus. Practices were generally poor with only 33.3% meeting the World Health Organisation recommended 150 minutes of physical activity per week. Just over half (53.0%) of participants who met the criteria for screening had screened for diabetes. Dietary practices were poor with just over a third (36.2%) of participants meeting the World Health Organisation recommended daily vegetable and/or fruit intake of five servings a day and 85.7% exceeding the World Health Organisation daily recommended limit of sugar intake. There were no significant differences between participants who were overweight and those who were obese in their knowledge, attitudes and practices towards preventing type 2 diabetes mellitus. There was a significant, positive correlation between total knowledge scores and total attitude scores (r= 0.42, p<0.01). Conclusion: Overweight and obese adults visiting the outpatient clinic had satisfactory knowledge and attitude levels towards the prevention of type 2 diabetes. Practices towards prevention were generally poor with few participants meeting the World Health Organisation recommendations for physical activity and fruit and/or vegetable daily intake. Just over half of the eligible participants had screened for diabetes prior to the study. In addition to information, interventions are needed to motivate patients at high risk to adopt healthier dietary and physical activity practices.
Mechanical debridement with antibiotics in the treatment of chronic periodontitis : effect on systemic biomarkers : a systematic review
(Stellenbosch : Stellenbosch University, 2019-04) Munasur, Sudhir L.; Chikte, Usuf M. E.; Turawa, Eunice B.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.
ENGLISH SUMMARY : Background: Chronic periodontitis is an inflammatory oral disease which leads to the destruction of the supporting tissues of the teeth, leading to bone resorption and tooth loss. Destruction of the periodontal attachment apparatus can result in gingival recession and root furcation exposure in advanced stages resulting in tooth mobility and tooth loss. Mechanical debridement is the most frequent treatment for chronic periodontitis, in severe cases systemic antibiotics in conjunction with mechanical debridement have been used. The efficacy and the beneficial effect of this combination on the inflammatory biomarkers require further investigation. Objectives: The aim of this systematic review was to assess the effectiveness of adjunctive antibiotics in the improvement of inflammatory systemic biomarkers in the treatment chronic periodontitis. Search methods: We searched the following electronic databases: Cochrane Oral Health Group Trials Register (30th June 2018). The Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2018 – current issue), MEDLINE (1966 to present), EMBASE (1982 to present), CINAHL via EBSCO (1990 -present), Google scholar (1990 - present). Web of Knowledge (1990 to May 2018), The meta-Register of Controlled Trials (www.controlled-trials.com), The US National Institutes of Health On-going Trials Register (www.clinicaltrials.gov). The World Health Organization International Clinical Trials Registry platform (www.who.int/trialsearch) was searched to identify relevant trials for inclusion in the review. Conference proceedings, on-going trials registers (02/06/2018) and reference list of included articles were assessed for relevant trials. No language or date of publication restrictions applied. Selection criteria: We searched for randomised controlled trials (RCTs that evaluated the effectiveness of adjunct antibiotic therapy on the systemic biomarkers in the treatment of chronic periodontitis. All trials that compared adjunctive systemic antibiotics with mechanical debridement or mechanical debridement alone, or scaling and root planning, oral hygiene and prophylaxis or placebo were included in the study. Data collection and analysis: Two reviewers independently examined the titles and abstracts retrieved by the search to identify relevant trials for inclusion in the review. All included trials were assessed for risk of bias and data were extracted for further analysis. The primary outcomes assessed include: changes in serum/blood levels of inflammatory biomarkers such as Matrix Metalloproteinases (MMPs), Tissue Inhibitors of MMPs(TIMs), Cytokines, C-Reactive Protein(CRP) and Glycated haemoglobin(HbA1c). Secondary outcomes include periodontal indices such as bleeding on probing (BOP), gingival index (GI), clinical attachment level (CAL), plaque index (PI) and probing pocket depth (PPD). Main results: Fourteen trials (n=1457 participants) were included in the review. Seven trials reported on MMP-8, with average of 3 months time to event. Five trials reported on IL-1β, three trials on IL-6 and two on IL-8 serum level. Four trials reported on CRP; while eight reported on HbA1c level and one on TIMP-1 level. Trials were assessed for risk of bias and judged as low, high, or unclear of risk of bias. Six studies showed no significant differences in MMP-8 concentration level between the two intervention groups. Significant decrease (60%) in odds of increased MMP-8 levels during 2-year study was reported in one trial (OR 0.40, 95%CI: 0.21 to 0.77, p=0.006). One study reported no significant difference for TIMP-1 (0.96, 95% CI: 0.78 to 1.18, p=0.7), while two studies showed significant reduction in HbA1c (10%) at 3 months. Other studies reported no difference in HbA1c levels (%): (Mean (SD) 7.00 (0.76) versus 7.11 (0.99); p=0.710), (Median (Interquartile Range [IQR]) 6.3 (5.5,7.3) versus 6.7 (6.3, 7.7); p=0.8), (p=0.35, 0.55, 0.33, and 0.62, at baseline, 3 months, 6 months, and after 1 year of treatment respectively. Metaanalysis showed a mean reduction of 0.24mm in the periodontal pockets (PD) at 3 months [MD, -0.25 with 95% CI -0.38 to -0.12]. Two trials revealed no significant difference PD≤3mm at 3 months, [MD, -1, 95% CI -22.54 to 20.53 (p=0.19)]. A decrease in periodontal pockets(PD≥4mm) and a reduction of 3.38mm in favour of SRP+antibiotics after 3 months [MD, -3.38, 95% CI -6.51 to -0.25 (p=0.93, I2=0%)] was observed for probing depth(PD). No significant difference in clinical attachment level (CAL) at 3 months [MD, -0.13, 95% CI -0.34 to 0.07; Chi2=0.98, df=3, p=0.81, I2=0%]. The overall quality of evidence was low largely because of attrition bias (24%; 32%) connoting high risk of bias and wide confidence intervals which suggests imprecision of results. Authors' conclusions: There is limited but low-level of evidence suggesting that systemic antibiotic therapy combined with mechanical debridement improves the systemic biomarker levels during the treatment of chronic periodontitis.
Model-based inference on the impact of early access to antiretroviral therapy to all on HIV incidence among adolescent girls and young women in Eswatini
(Stellenbosch : Stellenbosch University, 2021-04) Chibawara, Trust; Nyasulu, Peter; Kajungu, Dan; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Global Health. Epidemiology and Biostatistics.
ENGLISH SUMMARY: Introduction: The introduction of antiretroviral drugs has enabled people living with HIV (PLHIV) to have a much better prognosis. As such, the use of antiretroviral drugs has resulted in the decline of global HIV incidence over the last decade. Whilst this achievement is important, the role of the widespread use of antiretroviral drugs on the HIV epidemic among adolescent girls and young women is still unknown. This study aimed to evaluate the impact of Early Access for all HIV-positive Adults to Antiretroviral (EAAA) on HIV incidence among adolescent girls and young women in Eswatini. Methods: To accomplish our research objectives, this research provided elaborate mathematical concepts that are multidisciplinary in nature and included evidence based systematic review, statistics, data science and public health approaches. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines was used for the systematic review. Using Simpact, an individual-based, event-driven, stochastic simulation tool, a specially designed HIV transmission model was adopted to simulate the heterosexual transmission of HIV in Eswatini. The application of a simplified model calibration approach combined clinical, biological, and behavioural indicators from the Eswatini implementation study called “Maximizing Antiretroviral Treatment for Better Health and Zero New HIV Infection: Early Access to Antiretroviral Treatment for All (MaxART EAAA)” and Eswatini demographic summary statistics to infer the impact of EAAA on HIV incidence in adolescent girls and young women. Results: The results of the systematic review showed that globally, there was no published or unpublished research found on the impact of the use of ART by HIV positive adults on HIV incidence in adolescent girls and young women. While on the other hand, our model which aimed to evaluate the impact of EAAA on older men aged 18 years and above in Eswatini showed a 45% (95% Confidence interval (CI): 37-55) reduction on HIV incidence among the adolescent girls and young women aged 15-24-years-old as opposed to CD4 cell count threshold for ART eligibility (Standard of care). Furthermore, simulated data showed that early access to ART has a similar impact of 47% (95% CI: 33-59) reduction in HIV incidence among adolescent boys and young men of the same age group. Conclusion: This study has demonstrated the impact of EAAA as a strategy to reduce new HIV infections among adolescent girls and young women aged between 15-24-years-old in the Eswatini population. These findings reinforce the need to adopt provisions for early initiation of ART treatment among HIV infected adults as a catalyst to minimize transmission of HIV to the adolescent population. Data from this study also highlight the need for other countries in the region who are faced with similar challenges of harbouring a high HIV prevalence to adopt EAAA as it has shown to be an effective approach to reduce HIV/AIDS incidence in the population. While these benefits are applaudable, we do recognize that HIV/AIDS treatment on its on is not sufficient; therefore, behavioural changes that guard against age-disparate relationships should be reinforced.

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