Browsing by Author "Evans, J."
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Item Genomics and Epigenomics of Congenital Heart Defects: Expert Review and Lessons Learned in Africa(Mary Ann Liebert Inc, 2018-05) Thomford, N.E.; Dzobo, K.; Yao, N.A.; Chimusa, E.; Evans, J.; Okai, E.; Kruszka, P.; Muenke, M.; Awandare, G.; Wonkam, A.; Dandara, C.Congenital heart defects (CHD) are structural malformations found at birth with a prevalence of 1%. The clinical trajectory of CHD is highly variable and thus in need of robust diagnostics and therapeutics. Major surgical interventions are often required for most CHDs. In Africa, despite advances in life sciences infrastructure and improving education of medical scholars, the limited clinical data suggest that CHD detection and correction are still not at par with the rest of the world. But the toll and genetics of CHDs in Africa has seldom been systematically investigated. We present an expert review on CHD with lessons learned on Africa. We found variable CHD phenotype prevalence in Africa across countries and populations. There are important gaps and paucity in genomic studies of CHD in African populations. Among the available genomic studies, the key findings in Africa were variants in GATA4 (P193H), MTHFR 677TT, and MTHFR 1298CC that were associated with atrial septal defect, ventricular septal defect (VSD), Tetralogy of Fallot (TOF), and patent ductus arteriosus phenotypes and 22q.11 deletion, which is associated with TOF. There were no data on epigenomic association of CHD in Africa, however, other studies have shown an altered expression of miR-421 and miR-1233-3p to be associated with TOF and hypermethylation of CpG islands in the promoter of SCO2 gene also been associated with TOF and VSD in children with non-syndromic CHD. These findings signal the urgent need to develop and implement genetic and genomic research on CHD to identify the hereditary and genome-environment interactions contributing to CHD. These projected studies would also offer comparisons on CHD pathophysiology between African and other populations worldwide. Genomic research on CHD in Africa should be developed in parallel with next generation technology policy research and responsible innovation frameworks that examine the social and political factors that shape the emergence and societal embedding of new technologies. © 2018, Mary Ann Liebert, Inc.Item The Malaria Genomic Epidemiology Network. A global network for investigating the genomic epidemiology of malaria(Nature 456(7223): 732-7, 2008) Achidi, E.A.; Agbenyega, T.; Allen, S.; Amodu, O.; Bojang, K.; Conway, D.; Corran, P.; Deloukas, P.; Djimde, A.; Dolo, A.; Doumbo, O.; Drakeley, C.; Duffy, P.; Dunstan, S.; Evans, J.; Farrar, J.; Fernando, D.; Tran, T.H.; Horstmann, R.; Ibrahim, M.; Karunaweera, N.; Kokwaro, G.; Koram, K.; Kwiatkowski, D.; Lemnge, M.; Makani, J.; Marsh, K.; Michon, P.; Modiano, D.; Molyneux, M.E.; Mueller, I.; Mutabingwa, T.; Parker, M.; Peshu, N.; Plowe, C.; Puijalon, O.; Ragoussis, J.; Reeder, J.; Reyburn, H.; Riley, E.; Rogers, J.; Wilson, M.; Ghansah, A.Large-scale studies of genomic variation could assist efforts to eliminate malaria. But there are scientific, ethical and practical challenges to carrying out such studies in developing countries, where the burden of disease is greatest. The Malaria Genomic Epidemiology Network (MalariaGEN) is now working to overcome these obstacles, using a consortial approach that brings together researchers from 21 countries.Item Randomized controlled trial of RTS,S/AS02D and RTS,S/AS01E malaria candidate vaccines given according to different schedules in Ghanaian children(PLoS ONE, 2009) Owusu-Agyei, S.; Ansong, D.; Asante, K.; Kwarteng Owusu, S.; Owusu, R.; Wireko Brobby, N.A.; Dosoo, D.; Osei Akoto, A.; Osei-Kwakye, K.; Adjei, E.A.; Boahen, K.O.; Sylverken, J.; Adjei, G.; Sambian, D.; Apanga, S.; Kayan, K.; Vekemans, J.; Ofori-Anyinam, O.; Leach, A.; Lievens, M.; Demoitie, M.A.; Dubois, M.C.; Cohen, J.; Ballou, W.R.; Savarese, B.; Chandramohan, D.; Gyapong, J.O.; Milligan, P.; Antwi, S.; Agbenyega, T.; Greenwood, B.; Evans, J.Background: The target delivery channel of RTS,S candidate malaria vaccines in malaria-endemic countries in Africa is the World Health Organisation Expanded Program on Immunization. As an Adjuvant System, age de-escalation and schedule selection step, this study assessed 3 schedules of RTS,S/AS01E and RTS,S/AS02D in infants and young children 5–17 months of age in Ghana. Methodology: A Phase II, partially-blind randomized controlled study (blind to vaccine, not to schedule), of 19 months duration was conducted in two (2) centres in Ghana between August 2006 and May 2008. Subjects were allocated randomly (1:1:1:1:1:1) to one of six study groups at each study site, each defining which vaccine should be given and by which schedule (0,1-, 0,1,2- or 0,1,7-months). For the 0,1,2-month schedule participants received RTS,S/AS01E or rabies vaccine at one center and RTS,S/AS01E or RTS,S/AS02D at the other. For the other schedules at both study sites, they received RTS,S/AS01E or RTS,S/AS02D. The primary outcome measure was the occurrence of serious adverse events until 10 months post dose 1. Results: The number of serious adverse events reported across groups was balanced. One child had a simple febrile convulsion, which evolved favourably without sequelae, considered to be related to RTS,S/AS01E vaccination. Low grade reactions occurred slightly more frequently in recipients of RTS,S/AS than rabies vaccines; grade 3 reactions were infrequent. Less local reactogenicity occurred with RTS,S/AS01E than RTS,S/AS02D. Both candidate vaccines were highly immunogenic for anti-circumsporozoite and anti-Hepatitis B Virus surface antigen antibodies. Recipients of RTS,S/AS01E compared to RTS,S/AS02D had higher peak anti-circumsporozoite antibody responses for all 3 schedules. Three dose schedules were more immunogenic than 2 dose schedules. Area under the curve analyses for anti-circumsporozoite antibodies were comparable between the 0,1,2- and 0,1,7-month RTS,S/AS01E schedules. Conclusions: Both candidate malaria vaccines were well tolerated. Anti-circumsporozoite responses were greater with RTS,S/AS01E than RTS,S/AS02D and when 3 rather than 2 doses were given. This study supports the selection of RTS,S/AS01E and a 3 dose schedule for further development in children and infants.