Graduate Research Prize Winners 2013
I joined the KEMRI-Wellcome Trust Research programme in 2005 as a research clinician working within several clinical studies of malaria pathogenesis.
In 2006, I won a WHO/TDR career development fellowship in malaria vaccine development and spent a year at GSKBiologicals in Rixensart, Belgium and WHO/TDR head quarters in Geneva, Switzerland. I received “on-the-job” training on malaria vaccine research and development and clinical trials management. I was also involved in coordinating two malaria vaccine trials in West Africa and played a role in the development of clinical trial protocols and standard operating procedures.
When I returned to Kenya, I became a co-principal investigator in a multi-centre trial evaluating the safety and efficacy of a candidate malaria vaccine and participated in setting up a clinical trial facility which provided support to the trial. After the end of the industry-sponsored study we initiated an investigator-led extension under the supervision of Dr Philip Bejon. This extension study formed the basis of my DPhil work which started in 2010.
My main contribution has been an investigation of the long term efficacy of a candidate malaria vaccine (RTS,S) in young children living in a malaria endemic country. I also described the interaction between the vaccine efficacy and malaria exposure which has implications for where the vaccine is deployed. In addition I have studied immunological markers of vaccine efficacy and of naturally-acquired infection.
Before my DPhil I had practical experience of clinical research but no background in the rationale or underlining epidemiology. My DPhil work has given me an opportunity to develop an analytical approach and to learn to identify the important questions in clinical studies and design studies to answer. I have continued support from the Wellcome Trust for a career development year after the successful defense of my DPhil that I will use to plan the next stage of my career in clinical research.
1. Olotu A, Fegan G, Wambua J, Nyangweso G, Awuondo KO, Leach A, Lievens M, Leboulleux D, Njuguna P, Peshu N, Marsh K, Bejon P. Four-year efficacy of RTS,S/AS01E and its interaction with malaria exposure. N Engl J Med 2013 Mar 21;368(12):1111-20.
2. Olotu A, Fegan G, Wambua J, Nyangweso G, Ogada E, Drakeley C, Marsh K, Bejon P. Estimating individual exposure to malaria using local prevalence of malaria infection in the field. PLoS ONE 2012;7(3):e32929.
3. Olotu A, Fegan G, Williams TN, Sasi P, Ogada E, Bauni E, Wambua J, Marsh K, Borrmann S, Bejon P. Defining clinical malaria: the specificity and incidence of endpoints from active and passive surveillance of children in rural Kenya. PLoS ONE 2010;5(12):e15569.
4. Olotu A, Lusingu J, Leach A, Lievens M, Vekemans J, Msham S, Lang T, Gould J, Dubois MC, Jongert E, Vansadia P, Carter T, Njuguna P, Awuondo KO, Malabeja A, Abdul O, Gesase S, Mturi N, Drakeley CJ, Savarese B, Villafana T, Lapierre D, Ballou WR, Cohen J, Lemnge MM, Peshu N, Marsh K, Riley EM, von Seidlein L, Bejon P. Efficacy of RTS,S/AS01E malaria vaccine and exploratory analysis on anti-circumsporozoite antibody titres and protection in children aged 5-17 months in Kenya and Tanzania: a randomised controlled trial. Lancet Infect Dis 2011 Feb;11(2):102-9.
5. Olotu A, Moris P, Mwacharo J, Vekemans J, Kimani D, Janssens M, Kai O, Jongert E, Lievens M, Leach A, Villafana T, Savarese B, Marsh K, Cohen J, Bejon P. Circumsporozoite-specific T cell responses in children vaccinated with RTS,S/AS01E and protection against P falciparum clinical malaria. PLoS ONE 2011;6(10):e25786.
6. Olotu AI, Fegan G, Bejon P. Further analysis of correlates of protection from a phase 2a trial of the falciparum malaria vaccines RTS,S/AS01B and RTS,S/AS02A in malaria-naive adults. J Infect Dis 2010 Mar 15;201(6):970-1.
7. CTPC group. A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants. N Engl J Med 2012 Dec 13;367(24):2284-95.
8. CTPC group. First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children. N Engl J Med 2011 Nov 17;365(20):1863-75.
9. Ndungu FM, Olotu A, Mwacharo J, Nyonda M, Apfeld J, Mramba LK, Fegan GW, Bejon P, Marsh K. Memory B cells are a more reliable archive for historical antimalarial responses than plasma antibodies in no-longer exposed children. Proc Natl Acad Sci U S A 2012 May 22;109(21):8247-52.
10. Roetynck S, Olotu A, Simam J, Marsh K, Stockinger B, Urban B, Langhorne J. Phenotypic and functional profiling of CD4 T cell compartment in distinct populations of healthy adults with different antigenic exposure. PLoS ONE 2013;8(1):e55195.
11. Ibison F, Olotu A, Muema DM, Mwacharo J, Ohuma E, Kimani D, Marsh K, Bejon P, Ndungu FM. Lack of avidity maturation of merozoite antigen-specific antibodies with increasing exposure to Plasmodium falciparum amongst children and adults exposed to endemic malaria in Kenya. PLoS ONE 2012;7(12):e52939.
12. Bejon P, Cook J, Bergmann-Leitner E, Olotu A, Lusingu J, Mwacharo J, Vekemans J, Njuguna P, Leach A, Lievens M, Dutta S, von Seidlein L, Savarese B, Villafana T, Lemnge MM, Cohen J, Marsh K, Corran PH, Angov E, Riley EM, Drakeley CJ. Effect of the pre-erythrocytic candidate malaria vaccine RTS,S/AS01E on blood stage immunity in young children. J Infect Dis 2011 Jul;204(1):9-18.
13. Bejon P, Lusingu J, Olotu A, Leach A, Lievens M, Vekemans J, Mshamu S, Lang T, Gould J, Dubois MC, Demoitie MA, Stallaert JF, Vansadia P, Carter T, Njuguna P, Awuondo KO, Malabeja A, Abdul O, Gesase S, Mturi N, Drakeley CJ, Savarese B, Villafana T, Ballou WR, Cohen J, Riley EM, Lemnge MM, Marsh K, von Seidlein L. Efficacy of RTS,S/AS01E vaccine against malaria in children 5 to 17 months of age. N Engl J Med 2008 Dec 11;359(24):2521-32.
14. Bejon P, Turner L, Lavstsen T, Cham G, Olotu A, Drakeley CJ, Lievens M, Vekemans J, Savarese B, Lusingu J, von Seidlein L, Bull PC, Marsh K, Theander TG. Serological evidence of discrete spatial clusters of Plasmodium falciparum parasites. PLoS ONE 2011;6(6):e21711.
15. Bejon P, White MT, Olotu A, Bojang K, Lusingu JP, Salim N, Otsyula NN, Agnandji ST, Asante KP, Owusu-Agyei S, Abdulla S, Ghani AC. Efficacy of RTS,S malaria vaccines: individual-participant pooled analysis of phase 2 data. Lancet Infect Dis 2013 Apr;13(4):319-27.
16. Bejon P, Williams TN, Liljander A, Noor AM, Wambua J, Ogada E, Olotu A, Osier FH, Hay SI, Farnert A, Marsh K. Stable and unstable malaria hotspots in longitudinal cohort studies in Kenya. Plos Med 2010 Jul;7(7):e1000304.
17. Gikonyo C, Kamuya D, Mbete B, Njuguna P, Olotu A, Bejon P, Marsh V, Molyneux S. Feedback of research findings for vaccine trials: experiences from two Malaria vaccine trials involving healthy children on the Kenyan Coast. Dev World Bioeth 2013 Apr;13(1):48-56.
18. Kariuki SM, Ikumi M, Ojal J, Sadarangani M, Idro R, Olotu A, Bejon P, Berkley JA, Marsh K, Newton CR. Acute seizures attributable to falciparum malaria in an endemic area on the Kenyan coast. Brain 2011 May;134(Pt 5):1519-28.
19. Lusingu J, Olotu A, Leach A, Lievens M, Vekemans J, Olivier A, Benns S, Olomi R, Msham S, Lang T, Gould J, Hallez K, Guerra Y, Njuguna P, Awuondo KO, Malabeja A, Abdul O, Gesase S, Dekker D, Malle L, Ismael S, Mturi N, Drakeley CJ, Savarese B, Villafana T, Ballou WR, Cohen J, Riley EM, Lemnge MM, Marsh K, Bejon P, von Seidlein L. Safety of the malaria vaccine candidate, RTS,S/AS01E in 5 to 17 month old Kenyan and Tanzanian Children. PLoS ONE 2010;5(11):e14090.
20. Midega JT, Smith DL, Olotu A, Mwangangi JM, Nzovu JG, Wambua J, Nyangweso G, Mbogo CM, Christophides GK, Marsh K, Bejon P. Wind direction and proximity to larval sites determines malaria risk in Kilifi District in Kenya. Nat Commun 2012;3:674.
21. Ndungu FM, Mwacharo J, Kimani D, Kai O, Moris P, Jongert E, Vekemans J, Olotu A, Bejon P. A statistical interaction between circumsporozoite protein-specific T cell and antibody responses and risk of clinical malaria episodes following vaccination with RTS,S/AS01E. PLoS ONE 2012;7(12):e52870.
22. Warimwe GM, Fletcher HA, Olotu A, Agnandji ST, Hill AV, Marsh K, Bejon P. Peripheral blood monocyte-to-lymphocyte ratio at study enrollment predicts efficacy of the RTS,S malaria vaccine: analysis of pooled phase II clinical trial data. BMC Med 2013;11(1):184.
23. White MT, Bejon P, Olotu A, Griffin JT, Riley EM, Kester KE, Ockenhouse CF, Ghani AC. The Relationship between RTS,S Vaccine-Induced Antibodies, CD4(+) T Cell Responses and Protection against Plasmodium falciparum Infection. PLoS ONE 2013;8(4):e61395.