Ongoing mpox outbreak in Kamituga, South Kivu province, associated with monkeypox virus of a novel Clade I sub-lineage, Democratic Republic of the Congo, 2024.

Since the beginning of 2023, the number of people with suspected monkeypox virus (MPXV) infection have sharply increased in the Democratic Republic of the Congo (DRC). We report near-to-complete MPXV genome sequences derived from six cases from the South Kivu province. Phylogenetic analyses reveal that the MPXV affecting the cases belongs to a novel Clade I sub-lineage. The outbreak strain genome lacks the target sequence of the probe and primers of a commonly used Clade I-specific real-time PCR.

Strengthening research ethics governance and regulatory oversight in Central America and the Dominican Republic in response to the COVID-19 pandemic: a qualitative study.

BACKGROUND: Good governance and regulatory supervision are required to conduct research in an international public health emergency context and to ensure compliance with ethical standards. The "Strengthening research ethics governance and regulatory oversight in Central America and the Dominican Republic in response to the COVID-19 pandemic" study is a regional effort in which research ethics stakeholders participated in addressing research ethics governance and preparedness response challenges to the COVID-19 pandemic in Central America and the Dominican Republic. METHODS: A qualitative action research study was conducted following a participatory approach. Research ethics stakeholders in Central America and the Dominican Republic were mapped; a regional webinar and three virtual workshops were conducted discussing research ethics governance, ethics review and collaborative research practice during the pandemic. A roundtable session presented results and obtained feedback on a draft of a policy to strengthen regional research ethics governance. RESULTS: Countries across Central America and the Dominican Republic are at different stages in their development of research ethics systems. Countries with more established systems before COVID-19 were better organized and prepared to respond. This finding argues against improvisation and supports further work on strengthening governance of research ethics systems. Community engagement in research ethics public policy-making is practically absent in the region. Research and research ethics collaboration schemes are lacking amongst the countries; however, there are incipient initiatives in the region, such as the Central America and Caribbean Network of Research Ethics Committees. A policy brief with recommendations on how to advance towards strengthening the governance of research ethics systems was prepared and submitted to the Central American Integration System for analysis and possible approval. CONCLUSION: National research ethics systems in Central America and the Dominican Republic were unprepared to respond to the COVID-19 pandemic with respect to research oversight and effective collaboration. In most cases, national research ethics systems were found to be weak, and regional research collaboration was practically absent. To promote collaboration, a joint strategy needs to be developed with a regional vision towards sharing knowledge and best practices.

Experimental Treatment of Ebola Virus Disease with TKM-130803: A Single-Arm Phase 2 Clinical Trial.

BACKGROUND: TKM-130803, a small interfering RNA lipid nanoparticle product, has been developed for the treatment of Ebola virus disease (EVD), but its efficacy and safety in humans has not been evaluated. METHODS AND FINDINGS: In this single-arm phase 2 trial, adults with laboratory-confirmed EVD received 0.3 mg/kg of TKM-130803 by intravenous infusion once daily for up to 7 d. On days when trial enrolment capacity was reached, patients were enrolled into a concurrent observational cohort. The primary outcome was survival to day 14 after admission, excluding patients who died within 48 h of admission. After 14 adults with EVD had received TKM-130803, the pre-specified futility boundary was reached, indicating a probability of survival to day 14 of ≤0.55, and enrolment was stopped. Pre-treatment geometric mean Ebola virus load in the 14 TKM-130803 recipients was 2.24 × 109 RNA copies/ml plasma (95% CI 7.52 × 108, 6.66 × 109). Two of the TKM-130803 recipients died within 48 h of admission and were therefore excluded from the primary outcome analysis. Of the remaining 12 TKM-130803 recipients, nine died and three survived. The probability that a TKM-130803 recipient who survived for 48 h will subsequently survive to day 14 was estimated to be 0.27 (95% CI 0.06, 0.58). TKM-130803 infusions were well tolerated, with 56 doses administered and only one possible infusion-related reaction observed. Three patients were enrolled in the observational cohort, of whom two died. CONCLUSIONS: Administration of TKM-130803 at a dose of 0.3 mg/kg/d by intravenous infusion to adult patients with severe EVD was not shown to improve survival when compared to historic controls. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201501000997429.

Trial design for evaluating novel treatments during an outbreak of an infectious disease.

Tragically, the outbreak of Ebola that started in West Africa in 2014 has been far more extensive and damaging than any previous outbreaks. The duration of the outbreak has, for the first time, allowed the clinical evaluation of Ebola treatments. This article discusses the designs used for two such clinical trials which have recruited patients in Liberia and Sierra Leone. General principles are outlined for trial designs intended to be deployed quickly, adapt flexibly and provide results soon enough to influence the course of the current epidemic rather than just providing evidence for use should Ebola break out again. Lessons are drawn for the conduct of clinical research in future outbreaks of infectious diseases, where the sequence of events may or may not be similar to the West African Ebola epidemic.

Evaluating clinical trial designs for investigational treatments of Ebola virus disease.

BACKGROUND: Experimental treatments for Ebola virus disease (EVD) might reduce EVD mortality. There is uncertainty about the ability of different clinical trial designs to identify effective treatments, and about the feasibility of implementing individually randomised controlled trials during an Ebola epidemic. METHODS AND FINDINGS: A treatment evaluation programme for use in EVD was devised using a multi-stage approach (MSA) with two or three stages, including both non-randomised and randomised elements. The probabilities of rightly or wrongly recommending the experimental treatment, the required sample size, and the consequences for epidemic outcomes over 100 d under two epidemic scenarios were compared for the MSA, a sequential randomised controlled trial (SRCT) with up to 20 interim analyses, and, as a reference case, a conventional randomised controlled trial (RCT) without interim analyses. Assuming 50% 14-d survival in the population treated with the current standard of supportive care, all designs had similar probabilities of identifying effective treatments correctly, while the MSA was less likely to recommend treatments that were ineffective. The MSA led to a smaller number of cases receiving ineffective treatments and faster roll-out of highly effective treatments. For less effective treatments, the MSA had a high probability of including an RCT component, leading to a somewhat longer time to roll-out or rejection. Assuming 100 new EVD cases per day, the MSA led to between 6% and 15% greater reductions in epidemic mortality over the first 100 d for highly effective treatments compared to the SRCT. Both the MSA and SRCT led to substantially fewer deaths than a conventional RCT if the tested interventions were either highly effective or harmful. In the proposed MSA, the major threat to the validity of the results of the non-randomised components is that referral patterns, standard of care, or the virus itself may change during the study period in ways that affect mortality. Adverse events are also harder to quantify without a concurrent control group. CONCLUSIONS: The MSA discards ineffective treatments quickly, while reliably providing evidence concerning effective treatments. The MSA is appropriate for the clinical evaluation of EVD treatments.

Mortality after fluid bolus in African children with severe infection.

BACKGROUND: The role of fluid resuscitation in the treatment of children with shock and life-threatening infections who live in resource-limited settings is not established. METHODS: We randomly assigned children with severe febrile illness and impaired perfusion to receive boluses of 20 to 40 ml of 5% albumin solution (albumin-bolus group) or 0.9% saline solution (saline-bolus group) per kilogram of body weight or no bolus (control group) at the time of admission to a hospital in Uganda, Kenya, or Tanzania (stratum A); children with severe hypotension were randomly assigned to one of the bolus groups only (stratum B). All children received appropriate antimicrobial treatment, intravenous maintenance fluids, and supportive care, according to guidelines. Children with malnutrition or gastroenteritis were excluded. The primary end point was 48-hour mortality; secondary end points included pulmonary edema, increased intracranial pressure, and mortality or neurologic sequelae at 4 weeks. RESULTS: The data and safety monitoring committee recommended halting recruitment after 3141 of the projected 3600 children in stratum A were enrolled. Malaria status (57% overall) and clinical severity were similar across groups. The 48-hour mortality was 10.6% (111 of 1050 children), 10.5% (110 of 1047 children), and 7.3% (76 of 1044 children) in the albumin-bolus, saline-bolus, and control groups, respectively (relative risk for saline bolus vs. control, 1.44; 95% confidence interval [CI], 1.09 to 1.90; P=0.01; relative risk for albumin bolus vs. saline bolus, 1.01; 95% CI, 0.78 to 1.29; P=0.96; and relative risk for any bolus vs. control, 1.45; 95% CI, 1.13 to 1.86; P=0.003). The 4-week mortality was 12.2%, 12.0%, and 8.7% in the three groups, respectively (P=0.004 for the comparison of bolus with control). Neurologic sequelae occurred in 2.2%, 1.9%, and 2.0% of the children in the respective groups (P=0.92), and pulmonary edema or increased intracranial pressure occurred in 2.6%, 2.2%, and 1.7% (P=0.17), respectively. In stratum B, 69% of the children (9 of 13) in the albumin-bolus group and 56% (9 of 16) in the saline-bolus group died (P=0.45). The results were consistent across centers and across subgroups according to the severity of shock and status with respect to malaria, coma, sepsis, acidosis, and severe anemia. CONCLUSIONS: Fluid boluses significantly increased 48-hour mortality in critically ill children with impaired perfusion in these resource-limited settings in Africa. (Funded by the Medical Research Council, United Kingdom; FEAST Current Controlled Trials number, ISRCTN69856593.).

Investigating the Secondary Use of Clinical Research Data: Protocol for a Mixed Methods Study.

BACKGROUND: The increasing emphasis to share patient data from clinical research has resulted in substantial investments in data repositories and infrastructure. However, it is unclear how shared data are used and whether anticipated benefits are being realized. OBJECTIVE: The purpose of our study is to examine the current utilization of shared clinical research data sets and assess the effects on both scientific research and public health outcomes. Additionally, the study seeks to identify the factors that hinder or facilitate the ethical and efficient use of existing data based on the perspectives of data users. METHODS: The study will utilize a mixed methods design, incorporating a cross-sectional survey and in-depth interviews. The survey will involve at least 400 clinical researchers, while the in-depth interviews will include 20 to 40 participants who have utilized data from repositories or institutional data access committees. The survey will target a global sample, while the in-depth interviews will focus on individuals who have used data collected from low- and middle-income countries. Quantitative data will be summarized by using descriptive statistics, while multivariable analyses will be used to assess the relationships between variables. Qualitative data will be analyzed through thematic analysis, and the findings will be reported in accordance with the COREQ (Consolidated Criteria for Reporting Qualitative Research) guidelines. The study received ethical approval from the Oxford Tropical Research Ethics Committee in 2020 (reference number: 568-20). RESULTS: The results of the analysis, including both quantitative data and qualitative data, will be available in 2023. CONCLUSIONS: The outcomes of our study will offer crucial understanding into the current status of data reuse in clinical research, serving as a basis for guiding future endeavors to enhance the utilization of shared data for the betterment of public health outcomes and for scientific progress. TRIAL REGISTRATION: Thai Clinical Trials Registry TCTR20210301006; https://tinyurl.com/2p9atzhr. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/44875.

Enabling evidence to tackle everyday diseases to mitigate another pandemic.

The next emergent novel pathogen is likely to occur where the ability to undertake health research and collect life-saving data is lacking. Without embedded and ongoing research activities in place spotting and stopping a new threat is not possible, thereby enabling undetected infection and unchecked transmission within a community. Without local existing capabilities to collect such data delay is catastrophic. Fundamental goals in pandemic preparedness should be to stop an outbreak before it becomes a pandemic. This requires immediate action from teams already in place with the right skills, this could be readily achieved if we shift our thinking and enable research capabilities to be present in every healthcare setting. Addressing fundamental gaps in health research capacity and equity could tackle this and then we would be better prepared, globally.

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.

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.

Efficacy of RTS,S/AS01E vaccine against malaria in children 5 to 17 months of age.

BACKGROUND: Plasmodium falciparum malaria is a pressing global health problem. A previous study of the malaria vaccine RTS,S (which targets the circumsporozoite protein), given with an adjuvant system (AS02A), showed a 30% rate of protection against clinical malaria in children 1 to 4 years of age. We evaluated the efficacy of RTS,S given with a more immunogenic adjuvant system (AS01E) in children 5 to 17 months of age, a target population for vaccine licensure. METHODS: We conducted a double-blind, randomized trial of RTS,S/AS01E vaccine as compared with rabies vaccine in children in Kilifi, Kenya, and Korogwe, Tanzania. The primary end point was fever with a falciparum parasitemia density of more than 2500 parasites per microliter, and the mean duration of follow-up was 7.9 months (range, 4.5 to 10.5). RESULTS: A total of 894 children were randomly assigned to receive the RTS,S/AS01E vaccine or the control (rabies) vaccine. Among the 809 children who completed the study procedures according to the protocol, the cumulative number in whom clinical malaria developed was 32 of 402 assigned to receive RTS,S/AS01E and 66 of 407 assigned to receive the rabies vaccine; the adjusted efficacy rate for RTS,S/AS01E was 53% (95% confidence interval [CI], 28 to 69; P<0.001) on the basis of Cox regression. Overall, there were 38 episodes of clinical malaria among recipients of RTS,S/AS01E, as compared with 86 episodes among recipients of the rabies vaccine, with an adjusted rate of efficacy against all malarial episodes of 56% (95% CI, 31 to 72; P<0.001). All 894 children were included in the intention-to-treat analysis, which showed an unadjusted efficacy rate of 49% (95% CI, 26 to 65; P<0.001). There were fewer serious adverse events among recipients of RTS,S/AS01E, and this reduction was not only due to a difference in the number of admissions directly attributable to malaria. CONCLUSIONS: RTS,S/AS01E shows promise as a candidate malaria vaccine. (ClinicalTrials.gov number, NCT00380393.)

A phase I trial to evaluate the safety and pharmacokinetics of low-dose methotrexate as an anti-malarial drug in Kenyan adult healthy volunteers.

BACKGROUND: Previous investigations indicate that methotrexate, an old anticancer drug, could be used at low doses to treat malaria. A phase I evaluation was conducted to assess the safety and pharmacokinetic profile of this drug in healthy adult male Kenyan volunteers. METHODS: Twenty five healthy adult volunteers were recruited and admitted to receive a 5 mg dose of methotrexate/day/5 days. Pharmacokinetics blood sampling was carried out at 2, 4, 6, 12 and 24 hours following each dose. Nausea, vomiting, oral ulcers and other adverse events were solicited during follow up of 42 days. RESULTS: The mean age of participants was 23.9 ± 3.3 years. Adherence to protocol was 100%. No grade 3 solicited adverse events were observed. However, one case of transiently elevated liver enzymes, and one serious adverse event (not related to the product) were reported. The maximum concentration (C(max)) was 160-200 nM and after 6 hours, the effective concentration (C(eff)) was <150 nM. CONCLUSION: Low-dose methotraxate had an acceptable safety profile. However, methotrexate blood levels did not reach the desirable C(eff) of 250-400-nM required to clear malaria infection in vivo. Further dose finding and safety studies are necessary to confirm suitability of this drug as an anti-malarial agent.

Measuring research capacity development in healthcare workers: a systematic review.

OBJECTIVES: A key barrier in supporting health research capacity development (HRCD) is the lack of empirical measurement of competencies to assess skills and identify gaps in research activities. An effective tool to measure HRCD in healthcare workers would help inform teams to undertake more locally led research. The objective of this systematic review is to identify tools measuring healthcare workers' individual capacities to conduct research. DESIGN: Systematic review and narrative synthesis using Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist for reporting systematic reviews and narrative synthesis and the Critical Appraisals Skills Programme (CASP) checklist for qualitative studies. DATA SOURCES: 11 databases were searched from inception to 16 January 2020. The first 10 pages of Google Scholar results were also screened. ELIGIBILITY CRITERIA: We included papers describing the use of tools/to measure/assess HRCD at an individual level among healthcare workers involved in research. Qualitative, mixed and quantitative methods were all eligible. Search was limited to English language only. DATA EXTRACTION AND SYNTHESIS: Two authors independently screened and reviewed studies using Covidence software, and performed quality assessments using the extraction log validated against the CASP qualitative checklist. The content method was used to define a narrative synthesis. RESULTS: The titles and abstracts for 7474 unique records were screened and the full texts of 178 references were reviewed. 16 papers were selected: 7 quantitative studies; 1 qualitative study; 5 mixed methods studies; and 3 studies describing the creation of a tool. Tools with different levels of accuracy in measuring HRCD in healthcare workers at the individual level were described. The Research Capacity and Culture tool and the 'Research Spider' tool were the most commonly defined. Other tools designed for ad hoc interventions with good generalisability potential were identified. Three papers described health research core competency frameworks. All tools measured HRCD in healthcare workers at an individual level with the majority adding a measurement at the team/organisational level, or data about perceived barriers and motivators for conducting health research. CONCLUSIONS: Capacity building is commonly identified with pre/postintervention evaluations without using a specific tool. This shows the need for a clear distinction between measuring the outcomes of training activities in a team/organisation, and effective actions promoting HRCD. This review highlights the lack of globally applicable comprehensive tools to provide comparable, standardised and consistent measurements of research competencies. PROSPERO REGISTRATION NUMBER: CRD42019122310.

Setting up a pragmatic clinical trial in a low-resource setting: A qualitative assessment of GoLBeT, a trial of podoconiosis management in Northern Ethiopia.

BACKGROUND: Clinical trials are often perceived as being expensive, difficult and beyond the capacity of healthcare workers in low-resource settings. However, in order to improve healthcare coverage, the World Health Organization (WHO) World Health Report 2013 stated that all countries need to become generators as well as recipients of data. This study is a methodological examination of the steps and processes involved in setting up the Gojjam Lymphoedema Best Practice Trial (GoLBeT; ISRCTN67805210), a highly pragmatic clinical trial conducted in northern Ethiopia. Challenges to the trial and strategies used to deal with them were explored, together with the reasons for delays. METHODOLOGY AND PRINCIPAL FINDINGS: Qualitative research methods were used to analyse emails and reports from the period between trial inception and recruitment. This analysis was complemented by interviews with key informants from the trial operational team. The Global Health Research Process Map was used as a framework against which to compare the steps involved in setting up the trial. A mini-group discussion was conducted with the trial operational team after study completion for reflection and further recommendations. This study showed that the key areas of difficulty in setting up and planning this trial were: the study design, that is, deciding on the study endpoint, where and how best to measure it, and assuring statistical power; recruitment and appropriate training of staff; planning for data quality; and gaining regulatory approvals. Collaboration, for example with statisticians, the trial steering committee, the study monitors, and members of the local community was essential to successfully setting up the trial. CONCLUSIONS AND SIGNIFICANCE: Lessons learnt from this trial might guide others planning pragmatic trials in settings where research is not common, allowing them to anticipate possible challenges and address them through trial design, planning and operational delivery. We also hope that this example might encourage similar pragmatic studies to be undertaken. Such studies are rarely undertaken or locally led, but are an accessible and efficient way to drive improved outcomes in public health.

Engaging local health research communities to enhance long-term capacity building in Brazil.

The '2019 Research Capacity Network (REDe) workshop series' was an initiative led by Brazil-based REDe coordinators and The Global Health Network (TGHN) in partnership with Brazilian researchers interested in arboviruses. This workshop initiative has provided crucial training to the local research community offering transferable skills to effectively respond to health emergencies, with an impact beyond arboviral diseases, as evidenced by further activities undertaken during the COVID-19 pandemic. The success of this approach resulted from several factors, especially the workshops' local leadership and the combination of in-person training with online sharing of the resources generated in the local language. Analytics data from REDe online platform evidenced the wider reach of the shared resources to a larger audience than the workshop attendees. Importantly, the impact of this approach extends beyond the workshop series per se, with workshop participants afforded access to wider training, career development and collaborative opportunities through REDe and TGHN platforms. In addition, this initiative design resulted in the development of new collaborations between the workshop leaders and other local researchers, who have been jointly writing research projects and applying for grants. As a result, REDe has become a highly dynamic community of practice for health researchers in the region, strengthening the research culture and improving connectivity. Here, we describe the design and implementation of this initiative and demonstrate the value of integrating local expertise, and a practical workshop series format with digital dissemination of research resources and training materials to generate a vibrant and robust community of practice.

The legacy of ZikaPLAN: a transnational research consortium addressing Zika.

Global health research partnerships with institutions from high-income countries and low- and middle-income countries are one of the European Commission's flagship programmes. Here, we report on the ZikaPLAN research consortium funded by the European Commission with the primary goal of addressing the urgent knowledge gaps related to the Zika epidemic and the secondary goal of building up research capacity and establishing a Latin American-European research network for emerging vector-borne diseases. Five years of collaborative research effort have led to a better understanding of the full clinical spectrum of congenital Zika syndrome in children and the neurological complications of Zika virus infections in adults and helped explore the origins and trajectory of Zika virus transmission. Individual-level data from ZikaPLAN`s cohort studies were shared for joint analyses as part of the Zika Brazilian Cohorts Consortium, the European Commission-funded Zika Cohorts Vertical Transmission Study Group, and the World Health Organization-led Zika Virus Individual Participant Data Consortium. Furthermore, the legacy of ZikaPLAN includes new tools for birth defect surveillance and a Latin American birth defect surveillance network, an enhanced Guillain-Barre Syndrome research collaboration, a de-centralized evaluation platform for diagnostic assays, a global vector control hub, and the REDe network with freely available training resources to enhance global research capacity in vector-borne diseases.

Excess mortality among people with podoconiosis: secondary analysis of two Ethiopian cohorts.

BACKGROUND: While morbidity attributable to podoconiosis is relatively well studied, its pattern of mortality has not been established. METHODS: We compared the age-standardised mortality ratios (SMRs) of two datasets from northern Ethiopia: podoconiosis patients enrolled in a 1-y trial and a Health and Demographic Surveillance System cohort. RESULTS: The annual crude mortality rate per 1000 population for podoconiosis patients was 28.7 (95% confidence interval [CI] 17.3 to 44.8; n=663) while that of the general population was 2.8 (95% CI 2.3 to 3.4; n=44 095). The overall SMR for the study period was 6.0 (95% CI 3.6 to 9.4). CONCLUSIONS: Podoconiosis patients experience elevated mortality compared with the general population and further research is required to understand the reasons.

The remaining unknowns: a mixed methods study of the current and global health research priorities for COVID-19.

INTRODUCTION: In March 2020, the WHO released a Global Research Roadmap in an effort to coordinate and accelerate the global research response to combat COVID-19 based on deliberations of 400 experts across the world. Three months on, the disease and our understanding have both evolved significantly. As we now tackle a pandemic in very different contexts and with increased knowledge, we sought to build on the work of the WHO to gain a more current and global perspective on these initial priorities. METHODS: We undertook a mixed methods study seeking the views of the global research community to (1) assess which of the early WHO roadmap priorities are still most pressing; (2) understand whether they are still valid in different settings, regions or countries; and (3) identify any new emerging priorities. RESULTS: Thematic analysis of the significant body of combined data shows the WHO roadmap is globally relevant; however, new important priorities have emerged, in particular, pertinent to low and lower middle-income countries (less resourced countries), where health systems are under significant competing pressures. We also found a shift from prioritising vaccine and therapeutic development towards a focus on assessing the effectiveness, risks, benefits and trust in the variety of public health interventions and measures. Our findings also provide insight into temporal nature of these research priorities, highlighting the urgency of research that can only be undertaken within the period of virus transmission, as well as other important research questions but which can be answered outside the transmission period. Both types of studies are key to help combat this pandemic but also importantly to ensure we are better prepared for the future. CONCLUSION: We hope these findings will help guide decision-making across the broad research system including the multilateral partners, research funders, public health practitioners, clinicians and civil society.