Feeding back of individual genetic results in Botswana: mapping opportunities and challenges.

PURPOSE: We explored the views of Botswana stakeholders involved in developing, implementing and applying ethical standards for return of individual study results from genomic research. This allowed for mapping opportunities and challenges regarding actionability requirements that determine whether individual genomic research results should be fed back. METHODS: Using in-depth interviews, this study explored the views of sixteen (16) stakeholders about the extent, nature and timing of feedback of individual genomic research findings, including incidental findings that arise in the context of African genomics research. Coded data was analyzed through an iterative process of analytic induction to document and interpret themes. RESULTS: Overall, respondents were of the view that feedback of actionable individual genomic results was an important outcome that could benefit participants. However, a number of themes surfaced that pointed to opportunities and challenges that exist in Botswana that could help in planning for feeding back of individual genomic results that were mapped. Some of the opportunities cited by the respondents included the existence of good governance; democracy and humanitarianism; universal healthcare system; national commitment to science; research and innovation to transform Botswana into a knowledge-based economy; and applicable standard of care which could promote actionability. On the other hand, contextual issues like the requirement for validation of genomic research results in accredited laboratories, high cost of validation of genomic results, and linkage to care, as well as lack of experts like genomic scientists and counselors were considered as challenges for return of individual results. CONCLUSION: We propose that decisions whether and which genomic results to return take into consideration contextual opportunities and challenges for actionability for return of results in a research setting. This is likely to avoid or minimize ethical issues of justice, equity and harm regarding actionability decisions.

Addressing exploitation and inequities in open science: A relational perspective.

There are concerns that participation in open science will lead to various forms of exploitation - of researchers and scholars in low-income countries and under-resourced institutions. This article defends a contrary thesis and demonstrates the exact ways the underexplored notions of communal relationships, human dignity and social justice - and the normative principles to which they give rise - grounded in African philosophy can usefully address critical concerns regarding exploitation in the sharing of research resources to facilitate open partnership/collaboration and reuse. Further research is required to study the specific roles different institutions can play in facilitating open practice and contribute towards establishing effective structures that can enhance equity and balance unfavourable power asymmetries.

Competency-based Training Needs Assessment for Research Managers and Administrators in Africa and the United Kingdom to Strengthen Equitable Partnerships.

Background: The need for competent research managers and administrators (RMAs) has increased due to the complexity in managing research projects between disparate and international partners. To facilitate the creation of robust training and professional development programmes it is essential to first understand the status quo. A collaborative project, Sustainable Management and Administration for Research: Training across the project Lifecycle (SMARTLife), made up of RMAs from South Africa, Zimbabwe and the United Kingdom (UK) developed a set of competencies to conduct an RMA competency-based training needs assessment scoping tool. Method: Nine areas were identified: Equitable partnership; Finance Management; Project Management; Monitoring and Evaluation; Reporting and Communications; Equity, Diversity & Inclusion; Training and Capacity Development; Impact a& Sustainability; and Ethical, Social, Legal a& Social Implications.  Tasks for each competency area were identified to develop an scoping tool that had 168 data collection points. The tool was advertised through press releases, mailing lists and social media. Results:  108 responses were obtained:  with 49% from 15 Africa countries/the remainder from the UK. The UK (71%) had more permanent RMA staff members compared to Africa (39%). There were more respondents in Africa with the title of Research Manager/Coordinator(p=0.0132) compared to the UK where most of the RMAs were employed as Finance/Contract officers. 60% of respondents from the UK had more than three years experience while only 35% from Africa had experience. While most RMAs had formal higher education qualifications, their training was not in research management and administration, which requires a diverse range of skills. Confidence in specific tasks varied between the UK and Africa whereas collaborative partnerships challenges and enablers were similar. Conclusion This work highlights differences in RMA training and experience RMA  between Africa and UK, this work could inform much needed competency-based training for RMAs and partnership strategies that aid mutual-learning.

Utilization of Pneumococcal Vaccine and Penicillin Prophylaxis in Sickle Cell Disease in Three African Countries: Assessment among Healthcare Providers in SickleInAfrica.

Sickle cell disease is a genetic disease with a predisposition to infections caused by encapsulated organisms, especially Streptococcus pneumoniae. Pneumococcal vaccines and prophylactic penicillin have reduced the rate of this infection and mortality in sickle cell disease. However, implementation of these interventions is limited in Africa. The objectives of the study were to assess health care providers' behaviors with the implementation of pneumococcal vaccination and penicillin prophylaxis and to identify barriers to their use. A 25-item online questionnaire was administered through SickleinAfrica: a network of researchers, and healthcare providers, in Ghana, Nigeria, and Tanzania, working to improve health outcomes of sickle cell disease in Africa. Data was collected and managed using the Research Electronic Data Capture (REDCap), tools and data analysis was done using STATA version 13 and R statistical software. Eighty-two medical practitioners responded to the questionnaire. Only 54.0 and 48.7% of respondents indicated the availability of published guidelines on sickle cell disease management and pneumococcal vaccine use, respectively, at their facilities. The majority (54.0%) perceived that the vaccines are effective but over 20.0% were uncertain of their usefulness. All respondents from Ghana and Tanzania affirmed the availability of guidelines for penicillin prophylaxis in contrast to 44.1% in Nigeria. Eighty-five percent of respondents affirmed the need for penicillin prophylaxis but 15.0% had a contrary opinion for reasons including the rarity of isolation of Streptococcus pneumoniae in African studies, and therefore, the uncertainty of its benefit. Lack of published guidelines on the management of sickle cell disease and doubts about the necessity of prophylactic measures are potential barriers to the implementation of effective interventions.

Systematic Review of the Economic Evaluation of Returning Incidental Findings in Genomic Research.

Objectives: Discussions regarding who and how incidental findings (IFs) should be returned and the ethics behind returning IFs have increased dramatically over the years. However, information on the cost and benefits of returning IFs to patients remains scanty. Design: This study systematically reviews the economic evaluation of returning IFs in genomic sequencing. We searched for published articles on the cost-effectiveness, cost-benefit, and cost-utility of IFs in Medline, Scopus, PubMed, and Google Scholar. Results: We found six published articles that met the eligibility criteria of this study. Two articles used cost analysis only, one used cost-benefit analysis only, two used both cost analysis and cost-effectiveness, and one used both cost-benefit analysis and cost-utility to describe the cost of returning IFs in genomic sequencing. Conclusion: While individuals value the IF results and are willing to pay for them, the cost of returning IFs depends on the primary health condition of the patient. Although patients were willing to pay, there was no clear evidence that returning IFs might be cost-effective. More rigorous economic evaluation studies of IFs are needed to determine whether or not the cost of returning IFs is beneficial to the patient.

Enhancing Genetic Medicine: Rapid and Cost-Effective Molecular Diagnosis for a GJB2 Founder Mutation for Hearing Impairment in Ghana.

In Ghana, gap-junction protein ß 2 (GJB2) variants account for about 25.9% of familial hearing impairment (HI) cases. The GJB2-p.Arg143Trp (NM_004004.6:c.427C>T/OMIM: 121011.0009/rs80338948) variant remains the most frequent variant associated with congenital HI in Ghana, but has not yet been investigated in clinical practice. We therefore sought to design a rapid and cost-effective test to detect this variant. We sampled 20 hearing-impaired and 10 normal hearing family members from 8 families segregating autosomal recessive non syndromic HI. In addition, a total of 111 unrelated isolated individuals with HI were selected, as well as 50 normal hearing control participants. A restriction fragment length polymorphism (RFLP) test was designed, using the restriction enzyme NciI optimized and validated with Sanger sequencing, for rapid genotyping of the common GJB2-p.Arg143Trp variant. All hearing-impaired participants from 7/8 families were homozygous positive for the GJB2-p.Arg143Trp mutation using the NciI-RFLP test, which was confirmed with Sanger sequencing. The investigation of 111 individuals with isolated non-syndromic HI that were previously Sanger sequenced found that the sensitivity of the GJB2-p.Arg143Trp NciI-RFLP testing was 100%. All the 50 control subjects with normal hearing were found to be negative for the variant. Although the test is extremely valuable, it is not 100% specific because it cannot differentiate between other mutations at the recognition site of the restriction enzyme. The GJB2-p.Arg143Trp NciI-RFLP-based diagnostic test had a high sensitivity for genotyping the most common GJB2 pathogenic and founder variant (p.Arg143Trp) within the Ghanaian populations. We recommend the adoption and implementation of this test for hearing impairment genetic clinical investigations to complement the newborn hearing screening program in Ghana. The present study is a practical case scenario of enhancing genetic medicine in Africa.

Genomic Medicine Without Borders: Which Strategies Should Developing Countries Employ to Invest in Precision Medicine? A New "Fast-Second Winner" Strategy.

Genomic medicine has greatly matured in terms of its technical capabilities, but the diffusion of genomic innovations worldwide faces significant barriers beyond mere access to technology. New global development strategies are sorely needed for biotechnologies such as genomics and their applications toward precision medicine without borders. Moreover, diffusion of genomic medicine globally cannot adhere to a "one-size-fits-all-countries" development strategy, in the same way that drug treatments should be customized. This begs a timely, difficult but crucial question: How should developing countries, and the resource-limited regions of developed countries, invest in genomic medicine? Although a full-scale investment in infrastructure from discovery to the translational implementation of genomic science is ideal, this may not always be feasible in all countries at all times. A simple "transplantation of genomics" from developed to developing countries is unlikely to be feasible. Nor should developing countries be seen as simple recipients and beneficiaries of genomic medicine developed elsewhere because important advances in genomic medicine have materialized in developing countries as well. There are several noteworthy examples of genomic medicine success stories involving resource-limited settings that are contextualized and described in this global genomic medicine innovation analysis. In addition, we outline here a new long-term development strategy for global genomic medicine in a way that recognizes the individual country's pressing public health priorities and disease burdens. We term this approach the "Fast-Second Winner" model of innovation that supports innovation commencing not only "upstream" of discovery science but also "mid-stream," building on emerging highly promising biomarker and diagnostic candidates from the global science discovery pipeline, based on the unique needs of each country. A mid-stream entry into innovation can enhance collective learning from other innovators' mistakes upstream in discovery science and boost the probability of success for translation and implementation when resources are limited. This à la carte model of global innovation and development strategy offers multiple entry points into the global genomics innovation ecosystem for developing countries, whether or not extensive and expensive discovery infrastructures are already in place. Ultimately, broadening our thinking beyond the linear model of innovation will help us to enable the vision and practice of genomics without borders in both developed and resource-limited settings.

Public Health Burden of Hearing Impairment and the Promise of Genomics and Environmental Research: A Case Study in Ghana, Africa.

Hearing impairment (HI) is one of the most disabling conditions of major global health burden that contributes adversely to the social and economic development of a country, if not managed properly. A proper assessment of the nationwide burden and etiology of HI is instrumental in the prevention, treatment, and management of the condition. This article sought to perform an expert review of HI in Ghana to determine the present knowledge of its burden and possible causes of the condition. A literature search was conducted in PubMed using the following keywords: "hearing loss" OR "hearing impairment" OR "deafness" AND "Ghana." The literature was scanned until July 20, 2017, with specific inclusion of targeted landmark and background articles on HI. From the search, 18 of out 5869 articles were selected and considered for the review. The results of the search indicated that there were no extensive studies to determine the national burden of HI in Ghana. However, the few studies assessed suggested that the disease is either acquired or inherited. The burden of acquired HI was higher in adults than children, women than men, and people working in a noisy environment. Regarding the genetic cause, specific founder mutations in GJB2 gene (R143W, L79P, V178A, R184Q, A197S, I203K, and L214P) was the only identified genetic cause of HI in Ghana, but the other HI genes were not investigated. There has been some modest effort to study HI in Ghana, but comprehensive studies on the genetic and environmental etiologies (using the "multi-OMICS" approaches), classification, and burden of HI on Ghana are needed.

Perspectives in Genetics and Sickle Cell Disease Prevention in Africa: Beyond the Preliminary Data from Cameroon.

Management of sickle cell disease (SCD) in Africa needs to be accompanied by various preventive strategies, including early detection via prenatal genetic diagnosis (PND). Contrary to Cameroonian doctors who considered termination of an affected pregnancy (TAP) for SCD in 36.1%, the majority of parents (62.5%) with affected children accepted TAP in principle. In practice, most women opted for TAP (90%), justified by a huge psycho-social burden. The ethical and legal challenges of PND prompted the need to explore the use of genetics for secondary prevention of SCD. In 610 Cameroonian SCD patients, the genomic variations in two principal foetal haemoglobin-promoting loci were significantly associated with foetal haemoglobin levels. In addition, the co-inheritance of a 3.7-kb α-globin gene deletion and SCD was associated with a late disease onset and possibly improved survival: there was a much higher allele frequency of the 3.7-kb α-globin gene deletion in SCD patients (∼ 40%) than in haemoglobin AA controls (∼ 10%). The data indicate the urgent need to develop and implement policy actions in sub-Saharan Africa on at least four levels: (1) the implementation of SCD screening practices and early neonatal follow-up; (2) the development and incorporating of socio-economic support to alleviate the burden of SCD on affected families; (3) the exploration of the appropriateness of the medical abortion laws for SCD, and (4) the development of national plans for genetic medicine, including research on genomic variants that affect the phenotypes of SCD, in order to potentially use them for anticipatory guidance.

Success stories in genomic medicine from resource-limited countries.

In recent years, the translation of genomic discoveries into mainstream medical practice and public health has gained momentum, facilitated by the advent of new technologies. However, there are often major discrepancies in the pace of implementation of genomic medicine between developed and developing/resource-limited countries. The main reason does not only lie in the limitation of resources but also in the slow pace of adoption of the new findings and the poor understanding of the potential that this new discipline offers to rationalize medical diagnosis and treatment. Here, we present and critically discuss examples from the successful implementation of genomic medicine in resource-limited countries, focusing on pharmacogenomics, genome informatics, and public health genomics, emphasizing in the latter case genomic education, stakeholder analysis, and economics in pharmacogenomics. These examples can be considered as model cases and be readily replicated for the wide implementation of pharmacogenomics and genomic medicine in other resource-limited environments.

Translating biotechnology to knowledge-based innovation, peace, and development? Deploy a Science Peace Corps--an open letter to world leaders.

Scholarship knows no geographical boundaries. This science diplomacy and biotechnology journalism article introduces an original concept and policy petition to innovate the global translational science, a Science Peace Corps. Service at the new Corps could entail volunteer work for a minimum of 6 weeks, and up to a maximum of 2 years, for translational research in any region of the world to build capacity manifestly for development and peace, instead of the narrow bench-to-bedside model of life science translation. Topics for translational research are envisioned to include all fields of life sciences and medicine, as long as they are linked to potential or concrete endpoints in development, foreign policy, conflict management, post-crisis capacity building, and/or peace scholarship domains. As a new instrument in the global science and technology governance toolbox, a Science Peace Corps could work effectively, for example, towards elucidating the emerging concept of "one health"--encompassing human, environmental, plant, microbial, ecosystem, and planet health--thus serving as an innovative crosscutting pillar of 21(st) century integrative biology. An interdisciplinary program of this caliber for development would link 21(st) century life sciences to foreign policy and peace, in ways that can benefit many nations despite their ideological differences. We note that a Science Peace Corps is timely. The Intergovernmental Panel on Climate Change (IPCC) of the United Nations released the Fifth Assessment Report on March 31, 2014. Worrisomely, the report underscores that no person or nation will remain untouched by the climate change, highlighting the shared pressing life sciences challenges for global society. To this end, we recall that President John F. Kennedy advocated for volunteer work that has enduring, transgenerational, and global impacts. This culminated in establishment of the Peace Corps in 1961. Earlier, President Abraham Lincoln aptly observed, "nearly all men can stand adversity, but if you want to test a man's character, give him power." We therefore petition President Barack Obama, other world leaders, and international development agencies in positions of power around the globe, to consider deploying a Science Peace Corps to cultivate the essential (and presently missing) ties among life sciences, foreign policy, development, and peace agendas. A Science Peace Corps requires support by a credible and independent intergovernmental organization or development agency for funding, and arbitration in the course of volunteer work when the global versus local (glocal) value-based priorities and human rights intersect in synergy or conflict. In all, Science Peace Corps is an invitation to a new pathway for competence in 21(st) century science that is locally productive and globally competitive. It can open up scientific institutions to broader considerations and broader inputs, and thus cultivate vital translational science in a world sorely in need of solidarity and sustainable responses to the challenges of 21(st) century science and society.

Ready to put metadata on the post-2015 development agenda? Linking data publications to responsible innovation and science diplomacy.

Metadata refer to descriptions about data or as some put it, "data about data." Metadata capture what happens on the backstage of science, on the trajectory from study conception, design, funding, implementation, and analysis to reporting. Definitions of metadata vary, but they can include the context information surrounding the practice of science, or data generated as one uses a technology, including transactional information about the user. As the pursuit of knowledge broadens in the 21(st) century from traditional "science of whats" (data) to include "science of hows" (metadata), we analyze the ways in which metadata serve as a catalyst for responsible and open innovation, and by extension, science diplomacy. In 2015, the United Nations Millennium Development Goals (MDGs) will formally come to an end. Therefore, we propose that metadata, as an ingredient of responsible innovation, can help achieve the Sustainable Development Goals (SDGs) on the post-2015 agenda. Such responsible innovation, as a collective learning process, has become a key component, for example, of the European Union's 80 billion Euro Horizon 2020 R&D Program from 2014-2020. Looking ahead, OMICS: A Journal of Integrative Biology, is launching an initiative for a multi-omics metadata checklist that is flexible yet comprehensive, and will enable more complete utilization of single and multi-omics data sets through data harmonization and greater visibility and accessibility. The generation of metadata that shed light on how omics research is carried out, by whom and under what circumstances, will create an "intervention space" for integration of science with its socio-technical context. This will go a long way to addressing responsible innovation for a fairer and more transparent society. If we believe in science, then such reflexive qualities and commitments attained by availability of omics metadata are preconditions for a robust and socially attuned science, which can then remain broadly respected, independent, and responsibly innovative. "In Sierra Leone, we have not too much electricity. The lights will come on once in a week, and the rest of the month, dark[ness]. So I made my own battery to power light in people's houses." Kelvin Doe (Global Minimum, 2012) MIT Visiting Young Innovator Cambridge, USA, and Sierra Leone "An important function of the (Global) R&D Observatory will be to provide support and training to build capacity in the collection and analysis of R&D flows, and how to link them to the product pipeline." World Health Organization (2013) Draft Working Paper on a Global Health R&D Observatory.

The burden of sickle cell disease in Cape Town.

BACKGROUND: South Africa has a low incidence of sickle cell disease (SCD). However, its demographics are changing because of immigration from sub-Saharan African countries where SCD is prevalent. OBJECTIVES: We aimed to determine the frequency of SCD presenting to the Haematology/Oncology Service at Red Cross War Memorial Children's Hospital in Cape Town and to measure the associated disease burden. METHODS: This was a retrospective cross-sectional study of patients first attending the Haematology Service between January 2001 and June 2010. RESULTS: A total of 58 SCD patients were identified, with an annual frequency that increased over the study period by 300 - 400%. Up to 93.1% (n=54) were originally from other African countries, mainly the Democratic Republic of Congo (62.1%, n=36). One patient had sickle D-Punjab genotype, and all the other patients had the homozygous sickle cell anaemia genotype (Hb SS). Their haematological parameters demonstrated a normocytic anaemia with high white cell counts. The mean number of clinic visits per patient per year was 22.2 (range 0 - 64), and the mean number of hospital admissions per patient per year was 1.2 (range 0 - 5). All the patients were on antibiotic prophylaxis. The majority had at least one blood transfusion (65.5%, n=38), and a significant proportion required intravenous analgesia on admission (29.3%, n=17) and hydroxyurea treatment (36.2%, n=21). CONCLUSIONS: Over the past 10 years the frequency of SCD has increased considerably, imposing a significant burden and new challenges to the health services in Cape Town.

Report on the 6th African Society of Human Genetics (AfSHG) Meeting, March 12-15, 2009, Yaounde, Cameroon.

The African Society of Human Genetics (AfSHG), founded in 2003 with its inaugural meeting in Accra, Ghana,1 has the stated missions of (1) disseminating information about human genetics research in Africa, (2) establishing a mentorship network providing educational resources, including the development of appropriate technology transfer, (3) providing advocacy for human genetic research in Africa, and (4) encouraging collaborative research. Despite its young age, the AfSHG has developed a strong cadre of active researchers, both within and outside of Africa, with more than 400 members (from 16 countries across Africa as well as 8 other countries), and has held six successful meetings, five in Africa and one in the United States.