The TB vaccine clinical trial centre directory: An inventory of clinical trial centres in Sub-Saharan Africa.

BACKGROUND: There are over ten vaccine candidates for tuberculosis (TB) in the clinical pipeline that require testing in TB-prevalent populations. To accelerate the clinical development of TB vaccines, a directory of clinical trial centres was established in sub-Saharan Africa (SSA) to assess capacity for conducting late-stage TB vaccine trials. METHODS: TB vaccine-related parameters were identified, and trial centres in SSA were identified and prioritized based on whether they had experience with TB or non-TB vaccine trials. A survey was sent to identified centres, and the resulting directory presents their capacity for TB vaccine trials. Centres that identified as eligible for TB vaccine trials also had the opportunity to participate to the survey. This article provides an overview of the TB vaccine clinical trial centre directory, including the number and distribution of centres, their general characteristics, and their experience with prior TB vaccine trials. It includes information on the capacity of the centres, such as laboratory biosafety level, patient support, and community engagement. It also includes a case study to demonstrate how the directory can be used to identify trial centres with specific capabilities needed for a particular TB vaccine trial. RESULTS: Of the 134 identified centres, 56 provided information. Of these centres, 51 (91%) had phase 3 clinical trial experience and previous TB trials were conducted at 38 centres. Regarding TB vaccine trials, 19 centres conducted prevention of disease trials, 14 conducted prevention of infection trials, and 27 had no experience with TB vaccine clinical trials. From the respondents, 29 centers in South Africa were identified that could potentially conduct TB vaccine trials, followed by Tanzania (5), Kenya (5), Nigeria (3), and Uganda and Ethiopia (2 each). Trial sites in other countries were underrepresented, based on this survey. CONCLUSION: The establishment of a clinical trial centre directory can provide a basis for decision-making by various stakeholders. Despite some limitations in survey methodology, the findings suggest opportunities for expanding the evaluation of clinical trial capacity in other disease-prevalent countries and continents. Such data would be valuable in further enriching the Clinical Trial Community which a resource that geographically highlights clinical trial investments and capacities in African research ecosystem. SUMMARY POINTS: New TB vaccine candidates need to be assessed in clinical trials in countries with high rates of TB in the coming years.An open-access directory of TB vaccine clinical trial centres in sub-Saharan Africa was established, providing an overview of the capacity to conduct clinical trials for TB vaccine candidates (http://www.edctp.org/our-work/coordination-tb-vaccine-funded-research/directory-tb-vaccine-clinical-trial-sites-sub-saharan-africa/).The directory is intended for clinical triallists, funders, policymakers, and researchers to accelerate the clinical development of novel TB vaccines by providing useful information.Regular updates are necessary to ensure the directory remains relevant for vaccine development and feeds into the continental Clinical Trials Community (https://ctc.africa/).

Perspectives on development and advancement of new tuberculosis vaccines.

Tuberculosis (TB) remains a leading cause of death worldwide and is estimated to have caused 1.3 million deaths worldwide in 2022. Approximately one quarter of the world's population are infected with Mycobacterium tuberculosis, of whom up to 10% will progress to developing active TB disease. Achieving the World Health Organization End TB Strategy targets of a 95% reduction in TB mortality and a 90% reduction in TB incidence worldwide by 2035 remains a daunting task. The continuing spread of multidrug-resistant TB adds another obstacle to achieving global TB control. Larger funding pledges coupled with technological advances have recently enabled the enhancement of TB vaccine development efforts. These are yielding a pipeline of over 17 products currently in different stages of clinical trials. Emerging promising phase I and II trial results and advancement to phase III trials have necessitated "vaccine preparedness" in parallel so that a smooth transition from any positive clinical trial result to phase IV evaluation and implementation into policy and practice can follow. Promotion of a human rights-based approach, which recognizes and upholds the fundamental rights of all affected by the disease, is essential to ensure universal access to quality TB vaccines, regardless of their background or personal circumstances.

Health trends, inequalities and opportunities in South Africa's provinces, 1990-2019: findings from the Global Burden of Disease 2019 Study.

BACKGROUND: Over the last 30 years, South Africa has experienced four 'colliding epidemics' of HIV and tuberculosis, chronic illness and mental health, injury and violence, and maternal, neonatal, and child mortality, which have had substantial effects on health and well-being. Using data from the 2019 Global Burden of Diseases, Injuries and Risk Factors Study (GBD 2019), we evaluated national and provincial health trends and progress towards important Sustainable Development Goal targets from 1990 to 2019. METHODS: We analysed GBD 2019 estimates of mortality, non-fatal health loss, summary health measures and risk factor burden, comparing trends over 1990-2007 and 2007-2019. Additionally, we decomposed changes in life expectancy by cause of death and assessed healthcare system performance. RESULTS: Across the nine provinces, inequalities in mortality and life expectancy increased over 1990-2007, largely due to differences in HIV/AIDS, then decreased over 2007-2019. Demographic change and increases in non-communicable diseases nearly doubled the number of years lived with disability between 1990 and 2019. From 1990 to 2019, risk factor burdens generally shifted from communicable and nutritional disease risks to non-communicable disease and injury risks; unsafe sex remained the top risk factor. Despite widespread improvements in healthcare system performance, the greatest gains were generally in economically advantaged provinces. CONCLUSIONS: Reductions in HIV/AIDS and related conditions have led to improved health since 2007, though most provinces still lag in key areas. To achieve health targets, provincial governments should enhance health investments and exchange of knowledge, resources and best practices alongside populations that have been left behind, especially following the COVID-19 pandemic.

Strengthening capacity for clinical research in sub-Saharan Africa: partnerships and networks.

Global research collaboration, through partnerships and networks, is an effective way to deliver highly impactful and sustainable research that is collectively owned and promoted for the global good. Many models exist for effective North-South collaborations that are built on trust and balanced benefits. The European & Developing Countries Clinical Trials Partnership (EDCTP) model emphasises capacity development in clinical trials and product-focused implementation research. To ensure effectiveness and sustainability, capacity development requires a long-term perspective, an integrated system-wide approach, and local ownership and leadership from countries experiencing high disease burdens. Guided by these principles, the EDCTP2 programme, established in 2014, has developed and strengthened human capital and institutional capacities in 39 countries in sub-Saharan Africa to undertake high-quality clinical research guided by good clinical and regulatory practices. Projects in these countries have involved 238 African and 163 European institutions. To date, EDCTP has supported 171 Fellows and 232 postgraduate trainees. EDCTP-short-term training activities have equipped 9628 researchers and medical personnel. The EDCTP capacity-building described here includes its Regional Networks of Excellence and its Consortia for public health emergencies which provide the foundation for sustained efforts against emerging and re-emerging global health threats.

Strengthening national health research systems in the WHO African Region - progress towards universal health coverage.

BACKGROUND: Health challenges and health systems set-ups differ, warranting contextualised healthcare interventions to move towards universal health coverage. As such, there is emphasis on generation of contextualized evidence to solve local challenges. However, weak research capacity and inadequate resources remain an impendiment to quality research in the African region. WHO African Region (WHO AFR) facilitated the adoption of a regional strategy for strengthening national health research systems (NHRS) in 2015. We assessed the progress in strengthening NHRS among the 47 member states of the WHO AFR. METHODS: We employed a cross sectional survey design using a semi structured questionnaire. All the 47member states of WHO AFR were surveyed. We assessed performance against indicators of the regional research strategy, explored facilitating factors and barriers to strengthening NHRS. Using the research barometer, which is a metric developed for the WHO AFR we assessed the strength of NHRS of member states. Data were analysed in Excel Software to calculate barometer scores for NHRS function and sub-function. Thematic content was employed in analysing the qualitative data. Data for 2014 were compared to 2018 to assess progress. RESULTS: WHO AFR member states have made significant progress in strengthening their NHRS. Some of the indicators have either attained or exceeded the 2025 targets. The average regional barometer score improved from 43% in 2014 to 61% in 2018. Significant improvements were registered in the governance of research for health (R4H); developing and sustaining research resources and producing and using research. Financing R4H improved only modestly. Among the constraints are the lengthy ethical clearance processes, weak research coordination mechanisms, weak enforcement of research laws and regulation, inadequate research infrastructure, limited resource mobilisation skills and donor dependence. CONCLUSION: There has been significant improvement in the NHRS of member states of the WHO AFRO since the last assessment in 2014. Improvement across the different objectives of the regional research strategy is however varied which compromises overall performance. The survey highlighted the areas with slow improvement that require a concerted effort. Furthermore, the study provides an opportunity for countries to share best practice in areas of excellence.

Strengthening health research capacity in sub-Saharan Africa: mapping the 2012-2017 landscape of externally funded international postgraduate training at institutions in the region.

BACKGROUND: The objective was to guide key stakeholders on future directions of external funding of international postgraduate training (Master's and PhD) of health research students at institutions in sub-Saharan Africa by mapping the numbers and characteristics of students, the location of institutions, and sources of external support. A cross-sectional survey of eligible external funding organizations and programmes was conducted in 2017. Information was gathered from funders' websites or through the assistance of institutional contacts. The information requested included the number of Master's and PhD grantees supported from January 2012 to June 2017, as well as each grantee's institution of study, gender, country of origin and research area. RESULTS: Of 72 organizations contacted, there were 44 responses. Of the 44, 30 funders reported programmes within the inclusion criteria, and 19 funders provided data on relevant programmes. The Wellcome Trust, the International Development Research Centre and the Norwegian Agency for Development Cooperation supported the greatest number of grantees. There was concentrated support for grantees in eastern and southern Africa, countries with developed research capacity, and highly-developed research and training centres. More support was provided for PhD than Master's degree programmes and for research areas more upstream along the research spectrum. Challenges were identified in recognizing relevant funding organizations and obtaining responses. Information was presented inconsistently across organizations, which were often unable to provide relevant and complete data within the survey timeframe. CONCLUSIONS: External funders should collect, analyse and report data at regular intervals on their support for strengthening postgraduate health research capacity in sub-Saharan Africa. Standardization of this process and development of an online database would not only help to avoid overlap between programmes and promote synergy between funders, but also inform dialogue between external funders and key stakeholders on strategic issues. These issues include how external funders can a) optimise their support for research capacity strengthening to maximise the benefits of research for health and development on an equitable basis, and b) optimise the distribution of support for researchers at different career stages and for research on different parts of the research spectrum to maximise the health benefits of research.

Towards host-directed therapies for tuberculosis.

The treatment of tuberculosis is based on combinations of drugs that directly target Mycobacterium tuberculosis. A new global initiative is now focusing on a complementary approach of developing adjunct host-directed therapies.

Tuberculosis treatment and management--an update on treatment regimens, trials, new drugs, and adjunct therapies.

WHO estimates that 9 million people developed active tuberculosis in 2013 and 1·5 million people died from it. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis continue to spread worldwide with an estimated 480,000 new cases in 2013. Treatment success rates of MDR and XDR tuberculosis are still low and development of new, more effective tuberculosis drugs and adjunct therapies to improve treatment outcomes are urgently needed. Although standard therapy for drug-sensitive tuberculosis is highly effective, shorter, more effective treatment regimens are needed to reduce the burden of infectious cases. We review the latest WHO guidelines and global recommendations for treatment and management of drug-sensitive and drug-resistant tuberculosis, and provide an update on new drug development, results of several phase 2 and phase 3 tuberculosis treatment trials, and other emerging adjunct therapeutic options for MDR and XDR tuberculosis. The use of fluoroquinolone-containing (moxifloxacin and gatifloxacin) regimens have failed to shorten duration of therapy, and the new tuberculosis drug pipeline is sparse. Scale-up of existing interventions with increased investments into tuberculosis health services, development of new antituberculosis drugs, adjunct therapies and vaccines, coupled with visionary political leadership, are still our best chance to change the unacceptable status quo of the tuberculosis situation worldwide and the growing problem of drug-resistant tuberculosis.

Tackling the tuberculosis epidemic in sub-Saharan Africa--unique opportunities arising from the second European Developing Countries Clinical Trials Partnership (EDCTP) programme 2015-2024.

Tuberculosis (TB) today remains a global emergency affecting 9.0 million people globally. The African Region bears the highest global TB/HIV burden and over 50% of TB cases in SSA are co-infected with HIV. An estimated 1.5 million died from the TB globally in 2013. A large majority of the 360,000 HIV-positive TB cases who died were from sub-Saharan Africa. Research and development is an important pillar of the WHO post-2015 global TB strategy. Advances in development of diagnostics, drugs, host-directed therapies, and vaccines will require evaluation under field conditions through multi-centre clinical trials at different geographical locations. Thus it is critically important that these evaluations are fully supported by all African governments and the capacity, trained staff and infrastructure required to perform the research and evaluations is built and made available. This viewpoint article reviews the opportunities provided by recently launched second programme (2015-2024) of the European & Developing Countries Clinical Trials Partnership (EDCTP2) for tackling the TB epidemic in Africa through its magnanimous portfolio. The unique opportunities provided by EDCTP2 for leadership of scientific research in TB and other diseases fully devolving to Africa are also covered.

Why healthcare workers are sick of TB.

Dr Thato Mosidi never expected to be diagnosed with tuberculosis (TB), despite widely prevalent exposure and very limited infection control measures. The life-threatening diagnosis of primary extensively drug-resistant TB (XDR-TB) came as an even greater shock. The inconvenient truth is that, rather than being protected, Dr Mosidi and thousands of her healthcare colleagues are at an increased risk of TB and especially drug-resistant TB. In this viewpoint paper we debunk the widely held false belief that healthcare workers are somehow immune to TB disease (TB-proof) and explore some of the key factors contributing to the pervasive stigmatization and subsequent non-disclosure of occupational TB. Our front-line workers are some of the first to suffer the consequences of a progressively more resistant and fatal TB epidemic, and urgent interventions are needed to ensure the safety and continued availability of these precious healthcare resources. These include the rapid development and scale-up of improved diagnostic and treatment options, strengthened infection control measures, and focused interventions to tackle stigma and discrimination in all its forms. We call our colleagues to action to protect themselves and those they care for.

Initiating and developing clinical services, training and research in a low resource setting: the Malawi ENT experience.

BACKGROUND: Sub-Saharan Africa countries like Malawi have a paucity of ear, nose and throat (ENT) data, services and training opportunities. OBJECTIVE: To reflect on new Malawian ENT experience and to propose guidelines to poorly resourced countries. DESIGN: Analysis of data predating and following establishment of ENT services in Malawi. RESULTS: In 2008 the first and only Malawian ENT specialist established ENT services with external funding. Fifteen clinical officers have been trained and a nurse placed at each outreach hospital. In 2012, 15,284 consultations were recorded: 543 (3.6%) from outreach clinics. Forty-nine percent needed medical treatment, while 45% needed medical advice. Surgery was performed on 2.7% of patients; 21% for foreign bodies in the nose and throat and 18% for foreign bodies and biopsies of ears. CONCLUSIONS: To establish accessible and sustainable specialist ENT services in a poor country requires building on an established local health delivery system, careful planning and investment in personnel, infrastructure, training and data collection.

Consensus standards for introductory e-learning courses in human participants research ethics.

This paper reports the results of a workshop held in January 2013 to begin the process of establishing standards for e-learning programmes in the ethics of research involving human participants that could serve as the basis of their evaluation by individuals and groups who want to use, recommend or accredit such programmes. The standards that were drafted at the workshop cover the following topics: designer/provider qualifications, learning goals, learning objectives, content, methods, assessment of participants and assessment of the course. The authors invite comments on the draft standards and eventual endorsement of a final version by all stakeholders.

European and Developing Countries Clinical Trials Partnership (EDCTP): the path towards a true partnership.

BACKGROUND: European and Developing Countries Clinical Trials Partnership (EDCTP) was founded in 2003 by the European Parliament and Council. It is a partnership of 14 European Union (EU) member states, Norway, Switzerland, and Developing Countries, formed to fund acceleration of new clinical trial interventions to fight the human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS), malaria and tuberculosis (TB) in the sub-Saharan African region. EDCTP seeks to be synergistic with other funding bodies supporting research on these diseases. METHODS: EDCTP promotes collaborative research supported by multiple funding agencies and harnesses networking expertise across different African and European countries. EDCTP is different from other similar initiatives. The organisation of EDCTP blends important aspects of partnership that includes ownership, sustainability and responds to demand-driven research. The Developing Countries Coordinating Committee (DCCC); a team of independent scientists and representatives of regional health bodies from sub-Saharan Africa provides advice to the partnership. Thus EDCTP reflects a true partnership and the active involvement and contribution of these African scientists ensures joint ownership of the EDCTP programme with European counterparts. RESULTS: The following have been the major achievements of the EDCTP initiative since its formation in 2003; i) increase in the number of participating African countries from two to 26 in 2008 ii) the cumulative amount of funds spent on EDCTP projects has reached 150 m euros, iii) the cumulative number of clinical trials approved has reached 40 and iv) there has been a significant increase number and diversity in capacity building activities. CONCLUSION: While we recognise that EDCTP faced enormous challenges in its first few years of existence, the strong involvement of African scientists and its new initiatives such as unconditional funding to regional networks of excellence in sub-Saharan Africa is envisaged to lead to a sustainable programme. Current data shows that the number of projects supported by EDCTP is increasing. DCCC proposes that this success story of true partnership should be used as model by partners involved in the fight against other infectious diseases of public health importance in the region.