The abiding, hidden, and pervasive centrality of the health research workforce.

Research for health and development (R4HD) acknowledges that many of the determinants of health lie outside the boundaries of the health system. The size and quality of the health and care workforce (HCWF) are key drivers towards the future trajectory of many of these factors. We consider researchers for health and development an abiding, pervasive but neglected constituent part of this HCWF. This workforce straddles many professional groups and sectors. The diversity of occupations, lack of standardization in occupational cadres, the complexity and gendered aspects of the labour market, and the variable demographic, epidemiological, socio-economic and health systems' contexts in the global south and the global north, led to a kaleidoscopic perception of the health research workforce that have kept it hidden from public opinion. This led to neglect by science as well as health policymakers and created an orphan sub-set of the HCWF. Understanding the health researchers' labour market will help to identify means to develop, retain and utilize the health research workforce, addressing size, composition, role, skills transferability, careers and social impact through building, enabling or sustaining its research functions, capacity, employment opportunities and career tracks, among other issues. This thematic series of the Human Resources for Health Journal, calls for papers that go beyond narrow conceptual approaches and professional understandings of health care workers and the health research workforce, and requests that contributors examine important workforce issues through the broad lens of R4HD within a sustainable development goals framework.

The European & Developing Countries Clinical Trials Partnership (EDCTP) Knowledge Hub: developing an open platform for facilitating high-quality clinical research.

There is stark global inequity in health research in terms of where studies happen, who leads the research and the ultimate beneficiaries of the results generated. Despite significant efforts made, limited research ideas are conceptualised and implemented in low-resource settings to tackle diseases of poverty, and this is especially true in sub-Saharan Africa. There is strong evidence to show that the barriers to locally led research do not vary largely between disease, study type and location and can be largely solved by addressing these common gaps. The European & Developing Countries Clinical Trials Partnership (EDCTP) was established in 2003 as a European response to the global health crisis caused by the three main poverty-related diseases HIV, tuberculosis and malaria. EDCTP has established a model of long-term sustainable capacity development integrated into clinical trials which addresses this lack of locally led research in sub-Saharan Africa, supporting the development of individual and institutional capacity and research outputs that change the management, prevention and treatment of poverty-related and neglected infectious diseases across Africa. In recognition of emergent data on what the barriers and enablers are to long-term, sustainable capabilities to run studies, EDCTP formed a new collaboration with The Global Health Network (TGHN) in September 2017, with the aim to make a set of cross-cutting tools and resources to support the planning, writing and delivery of high-quality clinical trials available to research staff wherever they are in the world, especially those in low- and middle-income countries (LMICs) via TGHN platform. These new resources developed on the 'EDCTP Knowledge Hub' are those identified in the mixed method study described in this commentary as being key to addressing the gaps that the research community report as the most limiting elements in their ability to design and implement studies. The Knowledge Hub aims to make these tools freely available to any potential health research team in need of support and guidance in designing and running their own studies, particularly in low-resource settings. The purpose is to provide open access to the specific guidance, information and tools these teams cannot otherwise access freely. Ultimately, this will enable them to design and lead their own high-quality studies addressing local priorities with global alignment, generating new data that can change health outcomes in their communities.

Accelerating research and development of new vaccines against tuberculosis: a global roadmap.

To eliminate tuberculosis globally, a new, effective, and affordable vaccine is urgently needed, particularly for use in adults and adolescents in low-income and middle-income countries. We have created a roadmap that lists the actions needed to accelerate tuberculosis vaccine research and development using a participatory process. The vaccine pipeline needs more diverse immunological approaches, antigens, and platforms. Clinical development can be accelerated by validated preclinical models, agreed laboratory correlates of protection, efficient trial designs, and validated endpoints. Determining the public health impact of new tuberculosis vaccines requires understanding of a country's demand for a new tuberculosis vaccine, how to integrate vaccine implementation with ongoing tuberculosis prevention efforts, cost, and national and global demand to stimulate vaccine production. Investments in tuberculosis vaccine research and development need to be increased, with more diversity of funding sources and coordination between these funders. Open science is important to enhance the efficiency of tuberculosis vaccine research and development including early and freely available publication of study findings and effective mechanisms for sharing datasets and specimens. There is a need for increased engagement of industry vaccine developers, for increased political commitment for new tuberculosis vaccines, and to address stigma and vaccine hesitancy. The unprecedented speed by which COVID-19 vaccines have been developed and introduced provides important insight for tuberculosis vaccine research and development.

Creating equity in health research to drive more and better evidence.

Health research is rapidly changing with evidence being gathered through new agile methods. This evolution is critical but must be globally equitable so the poorest nations do not lose out. We must harness this change to better tackle the daily burden of diseases that affect the most impoverished populations and bring research capabilities to every corner of the world so that rapid and fair responses to new pathogen are possible; anywhere they appear. We must seize this opportunity to make research easier, better and more equitable. Currently too many nations are unable to generate the evidence or translate it to directly change health outcomes in their own communities. It is essential to act and harness this emerging change in how research data can be generated and shared, so that all nations sustainably gain from this development. There are positive examples to draw on from COVID-19, but we now need to act. Here we present an initiative to develop a new framework that can guide researchers in the design and execution of their studies. This highly agile system will work by adapting to risk and complexity in any given study, whilst generating quality, safe and ethical data.

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.

Scientific impact increases when researchers publish in open access and international collaboration: A bibliometric analysis on poverty-related disease papers.

BACKGROUND: The European & Developing Countries Clinical Trials Partnership (EDCTP), like many other research funders, requires its grantees to make papers available via open access (OA). This article investigates the effect of publishing in OA journals and international collaboration within and between European and sub-Saharan African countries on citation impact and likelihood of falling into the top 1% and top 10% most cited papers in poverty-related disease (PRD) research. METHODS: Disease-specific research publications were identified in the Web of Science™ and MEDLINE using Medical Subject Heading (MeSH) terms. Data on the open accessibility of scientific literature were derived from 1science oaFindr. Publication data, including relative citation counts, were extracted for 2003-2015. Regression models were applied to quantify the relationship between relative citations and presence in the 1% and top 10% most cited papers versus OA and international collaboration. RESULTS: The results show that since 2003 papers on PRDs have become increasingly available in OA. Among all PRD areas, malaria research is most frequently published in OA and in international collaboration. The adjusted regression analyses show that holding other factors constant, publishing research in OA and in international collaboration has a significant and meaningful citation advantage over non-OA or non-international collaborative research. Publishing papers as part of a European-wide or European- sub-Saharan African collaboration increases research impact. In contrast, such collaboration advantage is not observed for research output involving sub-Saharan Africa only which seems to decrease research impact. CONCLUSIONS: Our results indicate that there is a real, measurable citation advantage for publishing PRD research in OA and international collaboration. However, the international collaboration advantage seems to be region-specific with increased research impact for European-wide and European-sub-Saharan African collaborations but a decrease in research impact of collaborations confined to sub-Saharan African research institutions. Further research is required to further verify this finding and to understand the underlying factors related to this observed decrease in research impact. To target future research capacity building activities in sub-Saharan Africa it is important to assess whether the observed decreased impact reflects the scientific competencies and geographic distribution of individual researchers or institutional-, national- or funder-specific research requirements.

Bibliometric Assessment of European and Sub-Saharan African Research Output on Poverty-Related and Neglected Infectious Diseases from 2003 to 2011.

BACKGROUND: The European & Developing Countries Clinical Trials Partnership (EDCTP) is a partnership of European and sub-Saharan African countries that aims to accelerate the development of medical interventions against poverty-related diseases (PRDs). A bibliometric analysis was conducted to 1) measure research output from European and African researchers on PRDs, 2) describe collaboration patterns, and 3) assess the citation impact of clinical research funded by EDCTP. METHODOLOGY/PRINCIPAL FINDINGS: Disease-specific research publications were identified in Thomson Reuters Web of Science using search terms in titles, abstracts and keywords. Publication data, including citation counts, were extracted for 2003-2011. Analyses including output, share of global papers, normalised citation impact (NCI), and geographical distribution are presented. Data are presented as five-year moving averages. European EDCTP member countries accounted for ~33% of global research output in PRDs and sub-Saharan African countries for ~10% (2007-2011). Both regions contributed more to the global research output in malaria (43.4% and 22.2%, respectively). The overall number of PRD papers from sub-Saharan Africa increased markedly (>47%) since 2003, particularly for HIV/AIDS (102%) and tuberculosis (TB) (81%), and principally involving Southern and East Africa. For 2007-2011, European and sub-Saharan African research collaboration on PRDs was highly cited compared with the world average (NCI in brackets): HIV/AIDS 1.62 (NCI: 1.16), TB 2.11 (NCI: 1.06), malaria 1.81 (NCI: 1.22), and neglected infectious diseases 1.34 (NCI: 0.97). The NCI of EDCTP-funded papers for 2003-2011 was exceptionally high for HIV/AIDS (3.24), TB (4.08) and HIV/TB co-infection (5.10) compared with global research benchmarks (1.14, 1.05 and 1.35, respectively). CONCLUSIONS: The volume and citation impact of papers from sub-Saharan Africa has increased since 2003, as has collaborative research between Europe and sub-Saharan Africa. >90% of publications from EDCTP-funded research were published in high-impact journals and are highly cited. These findings corroborate the benefit of collaborative research on PRDs.

The emerging threat of artemisinin resistance in malaria: focus on artemether-lumefantrine.

The development of artemisinin resistance in the Greater Mekong Subregion poses a significant threat to malaria elimination. Artemisinin-based combination therapies including artemether-lumefantrine (AL) are recommended by WHO as first-line treatment for uncomplicated Plasmodium falciparum malaria. This article provides a comprehensive review of the existing and latest data as a basis for interpretation of observed variability in parasite sensitivity to AL over the last 5 years. Clinical efficacy and preclinical data from a range of endemic countries are summarized, including potential molecular markers of resistance. Overall, AL remains effective in the treatment of uncomplicated P. falciparum malaria in most regions. Establishing validated molecular markers for resistance and strict efficacy monitoring will reinforce timely updates of treatment policies.

A review of the effects of artemether-lumefantrine on gametocyte carriage and disease transmission.

While significant advances have been made in the prevention and treatment of malaria in recent years, these successes continue to fall short of the World Health Organization (WHO) goals for malaria control and elimination. For elimination strategies to be effective, limited disease transmission, achieved through rapid reduction in the infectious parasite reservoir and decreased gametocyte carriage, will be critical. Artemisinin-based combination therapy (ACT) forms the cornerstone of WHO-recommended treatment for uncomplicated Plasmodium falciparum malaria, and in combination with other effective interventions will undoubtedly play a vital role in elimination programmes. The gametocytocidal properties of artemisinins are a bonus attribute; there is epidemiological evidence of reductions in malaria incidence and transmission in African regions since the introduction of these agents. Many studies and analyses have specifically investigated the effects of the ACT, artemether-lumefantrine (AL) on gametocyte carriage. In this systematic review of 62 articles published between 1998 and January 2014, the effects of AL on gametocyte carriage and malaria transmission are compared with other artemisinin-based anti-malarials and non-ACT. The impact of AL treatment of asymptomatic carriers on population gametocyte carriage, and the potential future role of AL in malaria elimination initiatives are also considered. Despite the inherent difficulties in comparing data from a range of different studies that also utilized different diagnostic approaches to assess baseline gametocyte counts, the gametocytocidal effect of AL was proportionately consistent across the studies reviewed, suggesting that AL will continue to play a vital role in the treatment of malaria and contribute to clearing the path towards malaria elimination. However, the specific place of AL is the subject of much ongoing research and will undoubtedly be dependent on different demographic and geographical scenarios. Utilizing ACT, such as AL, within malaria elimination strategies is also associated with a number of other challenges, such as balancing potential increased use of ACT (e g, treatment of asymptomatic carriers and home-based treatment) with rational use and avoidance of drug resistance development.

Efficacy and safety of artemether-lumefantrine in the treatment of acute, uncomplicated Plasmodium falciparum malaria: a pooled analysis.

Randomized trials have confirmed the efficacy and safety of artemether-lumefantrine (AL) for treatment of uncomplicated Plasmodium falciparum malaria. Data from seven studies supported by Novartis (1996-2007), including 647 adults (> 16 years of age, 83.3% completed the study) and 1,332 children (≤ 16 years of age, 89.3% completed the study) with microscopically confirmed uncomplicated P. falciparum malaria and treated with the recommended regimen of AL, were pooled. The 28-day polymerase chain reaction-corrected parasitologic cure rate (primary efficacy endpoint) was 97.1% (495 of 510) in adults and 97.3% (792 of 814) in children (evaluable population). Gametocytemia prevalence after day was 4.2% (23 of 554) in adults and 0.9% (8 of 846) in children. No noteworthy safety signals were observed. Serious adverse events occurred in 1.4% of the adults and 1.3% of the children. This study is the largest data set to date assessing AL therapy for treatment of acute uncomplicated P. falciparum malaria. Artemether-lumefantrine showed high cure rates and rapid resolution of parasitemia, fever, and gametocytemia in adults and children, and showed an excellent safety and tolerability profile.

Community screening and treatment of asymptomatic carriers of Plasmodium falciparum with artemether-lumefantrine to reduce malaria disease burden: a modelling and simulation analysis.

BACKGROUND: Asymptomatic carriers of Plasmodium falciparum serve as a reservoir of parasites for malaria transmission. Identification and treatment of asymptomatic carriers within a region may reduce the parasite reservoir and influence malaria transmission in that area. METHODS: Using computer simulation, this analysis explored the impact of community screening campaigns (CSC) followed by systematic treatment of P. falciparum asymptomatic carriers (AC) with artemether-lumefantrine (AL) on disease transmission. The model created by Okell et al (originally designed to explore the impact of the introduction of treatment with artemisinin-based combination therapy on malaria endemicity) was modified to represent CSC and treatment of AC with AL, with the addition of malaria vector seasonality. The age grouping, relative distribution of age in a region, and degree of heterogeneity in disease transmission were maintained. The number and frequency of CSC and their relative timing were explored in terms of their effect on malaria incidence. A sensitivity analysis was conducted to determine the factors with the greatest impact on the model predictions. RESULTS: The simulation showed that the intervention that had the largest effect was performed in an area with high endemicity (entomological inoculation rate, EIR > 200); however, the rate of infection returned to its normal level in the subsequent year, unless the intervention was repeated. In areas with low disease burden (EIR < 10), the reduction was sustained for over three years after a single intervention. Three CSC scheduled in close succession (monthly intervals) at the start of the dry season had the greatest impact on the success of the intervention. CONCLUSIONS: Community screening and treatment of asymptomatic carriers with AL may reduce malaria transmission significantly. The initial level of disease intensity has the greatest impact on the potential magnitude and duration of malaria reduction. When combined with other interventions (e.g. long-lasting insecticide-treated nets, rapid diagnostic tests, prompt diagnosis and treatment, and, where appropriate, indoor residual spraying) the effect of this intervention can be sustained for many years, and it could become a tool to accelerate the reduction in transmission intensity to pre-elimination levels. Repeated interventions at least every other year may help to prolong the effect. The use of an effective diagnostic tool and a highly effective ACT, such as AL, is also vital. The modelling supports the evaluation of this approach in a prospective clinical trial to reduce the pool of infective vectors for malaria transmission in an area with marked seasonality.