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Therapeutic innovation to address sickle cell disease (SCD) is at a historical apex, characterized by a drug discovery, development, and commercialization landscape that includes potentially curative gene therapies. Given the wide geographic distribution of SCD, with a major presence in Africa, it is imperative that new medicines are designed to meet the specific needs of persons with SCD everywhere. Target product profiles (TPPs) detail the desired attributes of new medicines and serve as a guide for drug developers. To support research efforts for curative treatments for SCD, we mobilized a large multi-disciplinary expert group to generate consensus-driven TPPs for ex vivo and in vivo SCD gene therapies, utilizing a modified Delphi methodology supplemented with virtual workshops. The main findings are TPPs that describe 20 minimal and optimal criteria for novel gene therapy products in categories of scope (3 criteria), performance/safety (11 criteria), manufacturing (4 criteria), and administration (2 criteria). TPPs for ex vivo and in vivo products differed in some performance/safety criteria and all criteria pertaining to manufacturing and administration. These outputs will ideally support development of durable treatments that are safe, efficacious, and practical for persons with SCD in global settings.

Abstract Background Sickle cell disease (SCD) is an inherited blood disorder that predominantly affects individuals in sub-Saharan Africa. However, research that elucidates links between SCD pathophysiology and nutritional status in African patients is lacking. This systematic review aimed to assess the landscape of studies in sub-Saharan Africa that focused on nutritional aspects of SCD, and highlights gaps in knowledge that could inform priority-setting for future research. Methods The study was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Inclusion criteria comprised original, peer-reviewed research published between January 1995 and November 2020 involving individuals in Africa with any phenotypic variant of SCD and at least one nutritional status outcome. Nutritional status outcomes were defined as those that assessed dietary intakes, growth/anthropometry, or nutritional biomarkers. Databases used were Ovid Embase, Medline, Biosis and Web of Science. Results The search returned 526 articles, of which 76 were included in the final analyses. Most investigations (67%) were conducted in Nigeria. Studies were categorized into one of three main categories: descriptive studies of anthropometric characteristics (49%), descriptive studies of macro- or micronutrient status (41%), and interventional studies (11%). Findings consistently included growth impairment, especially among children and adolescents from sub-Saharan Africa. Studies assessing macro- and micronutrients generally had small sample sizes and were exploratory in nature. Only four randomized trials were identified, which measured the impact of lime juice, long-chain fatty acids supplementation, ready-to-use supplementary food (RUSF), and oral arginine on health outcomes. Conclusions The findings reveal a moderate number of descriptive studies, most with small sample sizes, that focused on various aspects of nutrition and SCD in African patients. There was a stark dearth of interventional studies that could be used to inform evidence-based changes in clinical practice. Findings from the investigations were generally consistent with data from other regional settings, describing a significant risk of growth faltering and malnutrition among individuals with SCD. There is an unmet need for clinical research to better understand the potential benefits of nutrition-related interventions for patients with SCD in sub-Saharan Africa to promote optimal growth and improve health outcomes.

Objectives Given the fundamental role of newborn bloodspot screening (NBS) to enable prompt diagnosis and optimal clinical management of individuals with sickle cell disease (SCD), we sought to systematically assess enablers and barriers to implementation of NBS programmes for SCD in Africa using established qualitative research methods.Setting Childbirth centres and NBS laboratories from six countries in East, West and Southern Africa.Participants Eight programme leaders involved with establishing and operating NBS programmes for SCD in Angola, Democratic Republic of Congo, Ghana, Liberia, Nigeria and Tanzania.Primary and secondary outcome measures Data obtained through a structured, phased interview approach were analysed using a combination of inductive and deductive codes and used to determine primary themes related to the implementation and sustainability of SCD NBS programmes.Results Four primary themes emerged from the analysis relating to governance (eg, pragmatic considerations when deploying overcommitted clinical staff to perform NBS), technical (eg, design and execution of operational processes), cultural (eg, variability of knowledge and perceptions of community-based staff) and financial (eg, issues that can arise when external funding may effectively preclude government inputs) aspects. Key learnings included perceived factors that contribute to long-term NBS programme sustainability.Conclusions The establishment of enduring NBS programmes is a proven approach to improving the health of populations with SCD. Organising such programmes in Africa is feasible, but initial implementation does not assure sustainability. Our analysis suggests that future programmes should prioritise government partner participation and funding from the earliest stages of programme development.

Information and communication technologies (ICTs) have been provided by higher education authorities to ensure that teachers use ICT to enhance their teaching, learning, and research outcomes. However, ICT has been found to be underutilized, especially by teachers. To investigate this issue, the technology adoption and gratification (TAG) model was validated and used to examine Malaysian university teachers' adoption and gratification of ICT for teaching and research purposes and then used to investigate the moderating effect of universities in different regions. The 397 teachers from the west and east Malaysian universities were surveyed using a stratified random sampling technique. The research data were analyzed using the three-stage structural equation modeling. There were focused use factors: 1) academic purpose; 2) research purpose; and 3) teaching purpose. The TAG model was useful in explaining differences in ICT uses. West Malaysian teachers' perceived usefulness and ease of use mediated the relationships between computer self-efficacy, gratification, and intention to use ICT, respectively. However, for east Malaysian teachers, only perceived ease of use did not mediate the relationship between computer self-efficacy and gratification. Finally, west and east Malaysian teachers' intentions to use ICT mediated the relationships between actual use, perceived usefulness, and ease of use. This paper confirms the utility of the TAG model for comparing teachers' adoption and gratification of ICT. In addition, this paper provides a basis for the targeted professional development of teachers in the east and west Malaysian universities which were selected based on the known differences.

Abstract Background Scientific and professional development opportunities for early career scientists in low- and middle- income countries (LMICs) are limited and not consistent. There is a disproportionately low number of biomedical and clinical researchers in LMIC’s relative to their high burden of disease, a disparity that is aggravated by emigration of up to 70% of scientists from their countries of birth for education and employment elsewhere. To help address this need, a novel University-accredited, immersive fellowship program was established by a large public-academic-private network. We sought to describe the program and summarize progress and lessons learned over its first 7-years. Methods Hallmarks of the program are a structured learning curriculum and bespoke research activities tailored to the needs of each fellow. Research projects expose the scientists to state-of-the-art methodologies and leading experts in their fields while also ensuring that learnings are implementable within their home infrastructure. Fellows run seminars on drug discovery and development that reinforce themes of scientific leadership and teamwork together with practical modules on addressing healthcare challenges within their local systems. Industry mentors achieve mutual learning to better understand healthcare needs in traditionally underserved settings. We evaluated the impact of the program through an online survey of participants and by assessing research output. Results More than 140 scientists and clinicians from 25 countries participated over the 7-year period. Evaluation revealed strong evidence of knowledge and skills transfer, and beneficial self-reported impact on fellow’s research output and career trajectories. Examples of program impact included completion of post-graduate qualifications; establishment and implementation of good laboratory- and clinical- practice mechanisms; and becoming lead investigators in local programs. There was a high retention of fellows in their home countries (> 75%) and an enduring professional network among the fellows and their mentors. Conclusions Our experience demonstrates an example for how multi-sectoral partners can contribute to scientific and professional development of researchers in LMICs and supports the idea that capacity-building efforts should be tailored to the specific needs of beneficiaries to be maximally effective. Lessons learned may be applied to the design and conduct of other programs to strengthen science ecosystems in LMICs.

Abstract Background The large global burden of rheumatic heart disease (RHD) has come to light in recent years following robust epidemiologic studies. As an operational research component of a broad program aimed at primary and secondary prevention of RHD, we sought to determine the current prevalence of RHD in the country’s capital, Lusaka, using a modern imaging-based screening methodology. In addition, we wished to evaluate the practicality of training local radiographers in echocardiography screening methods. Methods Echocardiography was conducted on a random sample of students in 15 schools utilizing a previously validated, abbreviated screening protocol. Through a task-shifting scheme, and in the spirit of capacity-building to enhance local diagnostic and research skills, general radiographers based at Lusaka University Teaching Hospital (UTH) were newly trained to use portable echocardiography devices. Students deemed as screen-positive were referred for comprehensive echocardiography and clinical examination at UTH. Cardiac abnormalities were classified according to standard World Heart Federation criteria. Results Of 1102 students that were consented and screened, 53 students were referred for confirmatory echocardiography. Three students had definite RHD, 10 had borderline RHD, 29 were normal, and 11 students were lost to follow-up. The rates of definite, borderline, and total RHD were 2.7 per 1000, 9.1 per 1000, and 11.8 per 1000, respectively. Anterior mitral valve leaflet thickening and chordal thickening were the most common morphological defects. The pairwise kappa test showed fair agreement between the local radiographers and an echocardiographer quality assurance specialist. Conclusion The prevalence of asymptomatic RHD in urban communities in Zambia is within the range of results reported in other sub-Saharan African countries using the WHF criteria. Task-shifting local radiographers to conduct echocardiography was feasible. The results of this study will be used to inform ongoing efforts in Zambia to control and eventually eliminate RHD. Trial registration The study was registered on clinicaltrials.gov (#NCT02661763).