The impact of dual HIV and HPV vaccine strategies among adolescents in a resource constrained setting

A thesis completed by published work, Submitted to the School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, in fulfilment of the requirements for the degree of Doctor of Philosophy Johannesburg, South Africa December 2016.Introduction With the largest epidemic in the world, the consequences of human immunodeficiency virus (HIV) in South Africa extend far beyond its disease burden. In fact, patterns of HIV-related infection and mortality in South Africa still reflect social cleavages and inequalities. Similarly, poverty-related issues such as poor education, unemployment and subsequent low socio-economic status, rural residence and inadequate access to health care are all implicated in human papillomavirus (HPV) associated cervical cancer-related mortality (of which South Africa also has the highest globally). Despite the knowledge of reproductive functions and sexuality being poor among adolescents in South Africa, the majority commence their sexual activity early with an estimated national average of 15 years for girls and 14 years for boys. Further, many South African adolescents engage in sexual risk-taking behaviours including concurrent partners and unprotected sexual acts that considerably increase their vulnerability to sexually transmitted infections including HIV and HPV. In recognising the unique health needs of adolescents in South Africa, the national government has already pin-pointed school health services as a strategic arm of primary health care re-engineering. The aim of this body of work is to elaborate on restructuring of adolescent health care by introducing the HIV and HPV vaccine concomitantly in South Africa via a school-based sexual and reproductive health service. Methodology Data from four studies were analysed and are presented in three published and two unpublished papers. The first study evaluated the synergism between HIV and HPV in the South African context and formed the basis of the literature review. The second study considered HIV vaccine implementation alone. The third study assessed dual HIV and HPV vaccine strategies among females and the final study compared the dual vaccination strategy against recognised biomedical HIV prevention interventions. The studies evaluated the implementation of a hypothetical HIV vaccine and the bivalent HPV vaccine both individually and in combination when administered to school-going adolescents in South Africa. The health outcomes and the cost-effectiveness of these strategies were assessed. Assumptions were made regarding the hypothetical HIV vaccine (based on HIV vaccine studies conducted to date) including a coverage rate of 60% (uncertainty range: 30-70%), vaccine efficacy of 50% (uncertainty range: 30-70%) and vaccine price per dose of US$12 (uncertainty range: US$ 3-24). The uncertainty ranges were tested in the sensitivity analysis. Mortality statistics, disease transition parameters (for the individual diseases and the models representing joint disease) and HPV vaccine characteristics were drawn from the South African literature. The joint effectiveness of the dual vaccine strategy was considered multiplicative. Nine year old adolescents attending South African schools in 2012 were eligible for the intervention (vaccination) that was introduced opportunistically as part of the national health initiative introducing school-based sexual and reproductive health services. The learners were targeted prior to their reported sexual debut. The HIV vaccine was considered against the comparator of HIV counselling and testing (HCT) and the national roll-out of antiretroviral therapy (ART) that constituted the standard of care in South Africa. The HPV vaccine was modelled as prevention against HPV-related cervical cancer and pre-cancerous HPV-related cervical states. The health service provider (provider) perspective was adopted and the cohort was modelled through a lifetime horizon of 70 years with annual cycles. The economic costs and health outcomes were discounted at 3% with an uncertainty range between 0% and 6% assessed. Cost valuations were for 2012 and costs were adjusted to this common year. The quality-adjusted life year (QALY) was used as the outcome measure of health related quality of life and was used to calculate the incremental cost-effectiveness ratio (ICER) of the comparator against the vaccination interventions. The core model was a semi-Markov simulation with annual cycles. The study population entered the model HIV and HPV disease free and were exposed to the risk of acquiring each disease annually. The model structure was parameterised drawing from South African data available in the literature. One-way sensitivity analyses evaluated the impact of single assumptions on cost and outcomes. Probabilistic sensitivity analysis (PSA) with a bootstrapping technique explored the uncertainty in the model and evaluated the robustness of the results. The PSA data generated determined if the intervention fell below the willingness-to-pay (WTP) threshold. As South Africa does not have a pre-defined WTP threshold, the Gross Domestic Product (GDP) per capita (for 2012) was used as a proxy in accordance with the World Health Organization’s Guide to Cost-Effective Analysis. Additionally, benchmark interventions were used in the final comparison study as a measure of cost-effectiveness. Ethical approval for the study was obtained from the Human Research Ethics Committee (Medical) of the University of the Witwatersrand. Findings The second study explored the implementation of the HIV vaccine on an individual and national, programmatic level. The simultaneous implementation of HIV vaccination services with current HIV management programmes would be cost-effective, even at relatively higher vaccine cost. At base vaccine cost of US$12, the ICER was US$ 43 per QALY gained, with improved ICER values yielded at lower vaccine costs. The ICER was sensitive to the duration of vaccine-mediated protection and to variations in the vaccine efficacy. Data from this work demonstrate that vaccines offering longer duration of protection and at lower cost would result in improved ICER values. Assessing this HIV vaccine model on a national programmatic level, yielded an ICER of US$5 per life-year gained (LYG) (95$ 3-12) compared with the comparator. This fell considerably below the national WTP threshold of cost-effectiveness. This also translated to an 11% increase in per capita costs from US$80 to US$ 89. National implementation of this intervention could potentially result in an estimated cumulative gain of 24 million years of life (95% CI 8–34 million years) among those adolescents aged between 10-19 years that were vaccinated. The 10 year absolute risk reduction projected by HIV vaccine implementation was 0.42% for HIV incidence and 0.41% for HIV mortality. The ICER was sensitive to the HIV vaccine efficacy, coverage and vaccine pricing in the sensitivity analysis. The third study assessed the impact of dual HIV and HPV implementation strategies. Programmes that involved the dual vaccine strategy were assessed as cost-saving. ICER values were sensitive to the HIV vaccine cost. The dual vaccine strategy resulted in 10 year absolute risk reductions in HIV incidence (5.24%), dual mortality (1.21%) and a reduction in HPV incidence (0.39%) compared with no vaccination. Importantly, the reduction in HIV incidence rate and dual mortality rate in the dual vaccine strategy exceeded the reductions noted with the use of the HIV vaccine alone. All scenarios assessed with the dual vaccine strategy were cost-effective. Lower vaccine prices and reduced discount rates were associated with improved ICER outcomes. The final study compared the biomedical interventions of oral pre-exposure prophylaxis (PrEP), voluntary medical male circumcision (VMMC) and the scaling-up of ART coverage against the vaccine strategies. When compared with other biomedical HIV prevention interventions, the dual vaccination intervention was the most cost-effective strategy (US$7 per QALY gained) and averted 29$ 30 per QALY gained) proved more cost-effective than HIV vaccination alone (US$ 93 per QALY gained), though VMMC averted 6% more new infections than the HIV vaccine. PrEP interventions were the least cost-effective. Combined dual vaccination and VMMC strategies represent the only dominant intervention. Strategies involving oral PrEP were the least cost-effective. Conclusion The findings of this thesis have implications for school-based adolescent health care and HIV- and HPV-related disease prevention among adolescents, a highly susceptible population. The cost-effectiveness of the dual HIV and HPV vaccine strategy was demonstrated, and the improved health outcomes associated with the interventions quantified. Proposals were suggested regarding possible combinations of HIV prevention interventions that could yield the favourable health outcomes with the most efficient use of financial resources. Several important areas for future research were identified to shed light on improving adolescent health care and for optimising HIV prevention strategies. These include integrating HIV and HPV services as part of the re-engineering of primary health care in South Africa, and then formulating economic evaluations of HIV/HPV prevention strategies targeting adolescents specifically. Further, more effective methods of collecting data on socially marginalised populations such as young people need to be explored. Another vital research area is the discussion and implementation of existing school health documents with the ideals embodied in the school health programme envisaged under the National Health Insurance restructuring. Once these are integrated, the cost implication of the combined programmes need to be assessed.MT201

Cardio-metabolic disease and associated risk factors in the Johannesburg Health District

Introduction: The global burden of non-communicable diseases (NCDs) has long been neglected, with the omission of NCDs from the Millennium Development Goals (MDGs) bearing testament to this. The growing prevalence of chronic cardio-metabolic diseases in South Africa places huge demands on the health system. This study sought to determine the community prevalence of these cardio-metabolic diseases and associated risk factors in Chiawelo, Soweto – a township undergoing rapid urbanization in the Johannesburg Health District. Methods: The study comprised 337 participants: 124 male and 213 female. This was a community based cross sectional survey using questionnaires, anthropometric and biochemical measurement of HbA1c. Cluster sampling techniques identified eligible adult participants. Regression models were performed to identify factors associated with disease. Ethical approval to conduct the study was obtained from the University of the Witwatersrand and written informed consent was obtained from the participants. Results: The study population was black with middle to higher socio-economic status and education levels below Grade 12 mostly. The prevalence of diabetes mellitus (DM) in this study population was 14%, with many undiagnosed and those with disease poorly controlled. More than half the study population had hypertension (HPT) (58%) and most were poorly controlled. This was a markedly obese population (39%) with 54% of women having a body mass index (BMI) categorised as obese (BMI ≥ 30 kg/m2). Conclusions: The burden of chronic cardio-metabolic diseases in the Johannesburg Health District has been grossly underestimated. The prevalence of HPT and DM was high and both diseases were poorly controlled with obesity reaching epidemic proportions. Countering the burden of disease involves targeting females as a high risk priority group, engaging the community in health promotion and developing a NCD surveillance system. Clinically, it is the findings of this study to support the screening of cardio-metabolic diseases from as early as 30 years of age in males and 40 years of age in females

Identification of barriers, enablers and interventions to inform deimplementation of low-value care in emergency medicine practice: A protocol for a mixed methods scoping review informed by the Theoretical Domains Framework

INTRODUCTION: Low-value care can lead to patient harm, misdirected clinician time and wastage of finite healthcare resources. Despite worldwide endeavours, deimplementing low-value care has proved challenging. Multifaceted, context and barrier-specific interventions are essential for successful deimplementation. The aim of this literature review is to summarise the evidence about barriers to, enablers of and interventions for deimplementation of low-value care in emergency medicine practice. METHODS AND ANALYSIS: A mixed methods scoping review using the Arksey and O’Malley framework will be conducted. MEDLINE, CINAHL, EMBASE, EMCare, Scopus and grey literature will be searched from inception. Primary studies will be included. Barriers, enablers and interventions will be mapped to the domains of the Theoretical Domains Framework. Study selection, data collection and quality assessment will be performed by two independent reviewers. NVivo software will be used for qualitative data analysis. Mixed Methods Appraisal Tool will be used for quality assessment. Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews framework will be used to present results. ETHICS AND DISSEMINATION: Ethics approval is not required for this scoping review. This review will generate an evidence summary regarding barriers to, enablers of and interventions for deimplementation of low-value care in emergency medicine practice. This review will facilitate discussions about deimplementation with relevant stakeholders including healthcare providers, consumers and managers. These discussions are expected to inform the design and conduct of planned future projects to identify context-specific barriers and enablers then codesign, implement and evaluate barrier-specific interventions

Health service delivery and workforce in northern Australia: a scoping review

Introduction: Delivering health services and improving health outcomes of the 1.3 million people residing in northern Australia, a region spanning 3 million km2 across the three jurisdictions of Western Australia, Northern Territory and Queensland, presents specific challenges. This review addresses a need for systems level analysis of the issues influencing the coverage, quality and responsiveness of health services across this region by examining the available published literature and identifying key policy-relevant gaps. Methods: A scoping review design was adopted with searches incorporating both peer-reviewed and grey literature (eg strategy documents, annual reports and budgets). Grey literature was predominantly sourced from websites of key organisations in the three northern jurisdictions, with peer-reviewed literature sourced from electronic database searches and reference lists. Key articles and documents were also contributed by health sector experts. Findings were synthesised and reported narratively using the WHO health system ‘building blocks’ to categorise the data. Results: From the total of 324 documents and data sources included in the review following screening and eligibility assessment, 197 were peer-reviewed journal articles and 127 were grey literature. Numerous health sector actors across the north – comprising planning bodies, universities and training organisations, peak bodies and providers – deliver primary, secondary and tertiary healthcare and workforce education and training in highly diverse contexts of care. Despite many exemplar health service and workforce models in the north, this synthesis describes a highly fragmented sector with many and disjointed stakeholders and funding sources. While the many strengths of the northern health system include expertise in training and supporting a fit-for-purpose health workforce, health systems in the north are struggling to meet the health needs of highly distributed populations with poorly targeted resources and ill-suited funding models. Ageing of the population and rising rates of chronic disease and mental health issues, underpinned by complex social, cultural and environmental determinants of health, continue to compound these challenges. Conclusion: Policy goals about developing northern Australia economically need to build from a foundation of a healthy and productive population. Improving health outcomes in the north requires political commitment, local leadership and targeted investment to improve health service delivery, workforce stability and evidence-based strengthening of community-led comprehensive primary health care. This requires intersectoral collaboration across many organisations and the three jurisdictions, drawing from previous collaborative experiences. Further evaluative research, linking structure to process and outcomes, and responding to changes in the healthcare landscape such as the rapid emergence of digital technologies, is needed across a range of policy areas to support these efforts

Democratising data to address health system inequities in Australia

Understanding the health status of a population or community is crucial to equitable service planning. Among other uses, data on health status can help local and national planners and policy makers understand patterns and trends in current or emerging health and well-being, especially how disparities relating to geography, ethnicity, language and living with disability influence access to services. In this practice paper we draw attention to the nature of Australia’s health data challenges and call for greater ‘democratisation’ of health data to address health system inequities. Democratisation implies the need for greater quality and representativeness of health data as well as improved access and usability that enable health planners and researchers to respond to health and health service disparities efficiently and cost-effectively. We draw on learnings from two practice examples, marred by inaccessibility, reduced interoperability and limited representativeness. We call for renewed and urgent attention to, and investment in, improved data quality and usability for all levels of health, disability and related service delivery in Australia

Projected economic evaluation of the national implementation of a hypothetical HIV vaccination program among adolescents in South Africa, 2012

Abstract Background Adolescents in South Africa are at high risk of acquiring HIV. The HIV vaccination of adolescents could reduce HIV incidence and mortality. The potential impact and cost-effectiveness of a national school-based HIV vaccination program among adolescents was determined. Method The national HIV disease and cost burden was compared with (intervention) and without HIV vaccination (comparator) given to school-going adolescents using a semi-Markov model. Life table analysis was conducted to determine the impact of the intervention on life expectancy. Model inputs included measures of disease and cost burden and hypothetical assumptions of vaccine characteristics. The base-case HIV vaccine modelled cost at US$12 per dose; vaccine efficacy of 50$ 5 per LYG (95 % CI ZAR 2.77–11.61) compared with the comparator, which is considerably less than the national willingness-to-pay threshold of cost-effectiveness. This translated to an 11 % increase in per capita costs from US$80 to US$ 89. National implementation of this intervention could potentially result in an estimated cumulative gain of 23.6 million years of life (95 % CI 8.48–34.3 million years) among adolescents age 10–19 years that were vaccinated. The 10 year absolute risk reduction projected by vaccine implementation was 0.42 % for HIV incidence and 0.41 % for HIV mortality, with an increase in life expectancy noted across all age groups. The ICER was sensitive to the vaccine efficacy, coverage and vaccine pricing in the sensitivity analysis. Conclusions A national HIV vaccination program would be cost-effective and would avert new HIV infections and decrease the mortality and morbidity associated with HIV disease. Decision makers would have to discern how these findings, derived from local data and reflective of the South African epidemic, can be integrated into the national long term health planning should a HIV vaccine become available

Digital Chest Radiography Enhances Screening Efficiency for Pulmonary Tuberculosis in Primary Health Clinics in South Africa

Background: Optimized tuberculosis (TB) screening in high burden settings is essential for case finding. We evaluated digital chest X-ray with computer-aided detection (CAD) software (d-CXR) for identifying undiagnosed TB in three primary health clinics in South Africa. Methods: The cross-sectional study consented adults who were sequentially screened for TB using the World Health Organization (WHO) 4 symptom questionnaire and d-CXR. Participants reporting ≥1 TB symptom and/or CAD score ≥60 (suggestive of TB) provided 2 spot sputum for Xpert MTB/RIF Ultra (Xpert Ultra) and liquid culture testing, respectively. TB yield (proportion of screened tested positive) and number needed to test (NNT; no of tests to identify one TB patient) were calculated. Risk factors for microbiologically confirmed or presumed (on radiological grounds) were determined. Results: Among 3041 participants, 45% (1356 of 3041) screened positive on either d-CXR or symptoms. TB yield was 2.3% (71 of 3041) using Xpert Ultra and 2.7% (82 of 3041) using Xpert Ultra plus culture. Modelled TB yield (identified by Xpert Ultra) by screening approach was: 1.9% (59 of 3041) for d-CXR alone, 2.0% (62 of 3041) for symptoms alone and 2.3% (71 of 3041) for both. The NNT was 9.7 for d-CXR, 17.8 for symptoms and 19.1 for d-CXR and/or symptom. Males, those with previous TB, untreated HIV or unknown HIV status, and acute illness were at higher risk of developing TB. Conclusion: d-CXR screening identified a similar yield of undiagnosed TB compared to symptom-based screening, however required fewer diagnostic tests. Due to its objective nature, d-CXR screening may improve case detection in clinics

Use and impact of breast cancer survivorship care plans: a systematic review

Background: Survivorship care plan (SCP) comprising a treatment summary and plan for follow-up care is recommended by various organizations to address long-term needs of an increasing number of breast cancer survivors. Although there have been previous systematic reviews of SCPs in cancer, none has focused on breast cancer exclusively. This systematic review evaluates the use and impact of SCP in breast cancer survivors. Methods: Randomized (RCTs) and non-randomized (non-RCT) studies evaluating health care and patient-related outcomes after implementation of SCPs for survivors were identified by searching databases (MEDLINE, EMBASE, CINHAL, and Scopus). Data were extracted, quality assessed, and summarized on the basis of qualitative synthesis. Results: Ten non-RCTs and 14 RCTs met the inclusion criteria. Although the overall quality of RCTs was superior to non-RCTs with mean quality score of 81.5% vs 64.3%, two mixed-methods non-RCTs which were individualized and included both provider and patient perspectives had comparable scores like RCTs. Several models of SCP were evaluated (paper based/online, oncologist/nurse/primary-care physician-delivered, and different templates). Descriptive information from non-RCTs suggests improvement in survivorship knowledge, satisfaction with care, and improved communication with providers. Findings from RCTs were variable. Potential gaps existed in content of SCP including unclear recommendation on frequency and ownership of follow-up. Levels of survivor satisfaction with, and self-reported understanding of, their SCP were high. Distal outcomes like health care delivery measures including costs and efficiency were mostly mixed, but heterogeneous study designs make interpretation difficult. Conclusions: Existing research provides positive impact of SCPs on more proximal outcomes of patient experience and care delivery but mixed results for health outcomes in breast cancer survivors. Future research should focus on better defining SCP content and ensuring follow-up recommendations are acted upon, and provider feedback is included and use of novel tools to empower stakeholders

What works for and what hinders deimplementation of low-value care in emergency medicine practice? A scoping review

Objectives Low-value care can harm patients and healthcare systems. Despite a decade of global endeavours, low value care has persisted. Identification of barriers and enablers is essential for effective deimplementation of low-value care. This scoping review is an evidence summary of barriers, enablers and features of effective interventions for deimplementation of low-value care in emergency medicine practice worldwide.Design A mixed-methods scoping review was conducted using the Arksey and O’Malley framework.Data sources Medline, CINAHL, Embase, EMCare, Scopus and grey literature were searched from inception to 5 December 2022.Eligibility criteria Primary studies which employed qualitative, quantitative or mixed-methods approaches to explore deimplementation of low-value care in an EM setting and reported barriers, enablers or interventions were included. Reviews, protocols, perspectives, comments, opinions, editorials, letters to editors, news articles, books, chapters, policies, guidelines and animal studies were excluded. No language limits were applied.Data extraction and synthesis Study selection, data collection and quality assessment were performed by two independent reviewers. Barriers, enablers and interventions were mapped to the domains of the Theoretical Domains Framework. The Mixed Methods Appraisal Tool was used for quality assessment.Results The search yielded 167 studies. A majority were quantitative studies (90%, 150/167) that evaluated interventions (86%, 143/167). Limited provider abilities, diagnostic uncertainty, lack of provider insight, time constraints, fear of litigation, and patient expectations were the key barriers. Enablers included leadership commitment, provider engagement, provider training, performance feedback to providers and shared decision-making with patients. Interventions included one or more of the following facets: education, stakeholder engagement, audit and feedback, clinical decision support, nudge, clinical champions and training. Multifaceted interventions were more likely to be effective than single-faceted interventions. Effectiveness of multifaceted interventions was influenced by fidelity of the intervention facets. Use of behavioural change theories such as the Theoretical Domains Framework in the published studies appeared to enhance the effectiveness of interventions to deimplement low-value care.Conclusion High-fidelity, multifaceted interventions that incorporated education, stakeholder engagement, audit/feedback and clinical decision support, were administered daily and lasted longer than 1 year were most effective in achieving deimplementation of low-value care in emergency departments. This review contributes the best available evidence to date, but further rigorous, theory-informed, qualitative and mixed-methods studies are needed to supplement the growing body of evidence to effectively deimplement low-value care in emergency medicine practice