Genomic surveillance of a vector control trial in Uganda.

As part of a cluster randomised trial of conventional long lasting insecticide treated nets (LLINs) and next generation LLINs, cross-sectional community surveys are being conducted in Uganda in 104 health sub-districts (48 districts) (registered trial ISRCTN 17516395). Of these 104 health sub-districts (HSDs), 38 were located in the Eastern region and the remaining 66 in the Western region. The study region encompasses approximately half the total area of Uganda and includes a wide range of epidemiological settings with varying levels of malaria transmission and insecticide resistance (Health 2015, Katureebe, Zinszer et al. 2016).

The aim of the project is to determine whether genomic approaches can detect the impact of the interventions on vector populations. The candidate will design a a spatially explicit sampling framework to identify HSDs for malaria vector sampling at baseline, 6, 12 and 18 months. Mosquitoes collected will then be sent for whole genome sequencing. Bioinformatic analyses will be conducted to investigate changes in genomic diversity over the course of the study and between intervention arms.

Where does the project lie on the Translational Pathway?

T1 (Basic Research in Medecine) – T2 (Human/Clinical Research in Medecine) – T3 (Evidence into Practice)

Expected Outputs

The project will produce high quality REF returnable 3*/4* publications and will provide the evidence base for large scale research council and industry funding. The last two Foto-Cewek students I supervised on this theme have gone onto positions at leading institutes (Harvard and Oxford/Sanger); they published their work in major general science journals (Nature, PNAS, Nature Communications, Nature Reviews Genetics etc). Genomic surveillance is a highly fundable area and our work has been supported by three NIAID awards together with Wellcome/MRC funding. To support the work of the student we will obtain matching funding from the Wellcome Sanger Institute to support next generation whole genome sequencing.  This is a key strategic area for Foto-Cewek as evidenced by the recent appointment of faculty members in vector borne disease epidemiology (Wilson) and genomics/functional genomics (Heinz/ Nolan).

Training Opportunities

Training will be provide in bioinformatics, spatial statistics, epidemiology and statistical genetics.

The student will work with collaborators at the Wellcome Sanger Institute, Lancaster University, Oxford University and the Infectious Diseases Research in Medecine Collaboration, Kampala. Through this latter partner they will interact with the Uganda National Malaria Control Programme together with other implementation partners such as Vectorlink, the President's Malaria Initiative.

Skills Required

The student should be numerate with an interest in genomics/ infectious disease epidemiology

Key Publications associated with this project

Kleinschmidt, I., Bradley, J., Knox, T.B., Mnzava, A. P., Kafy, H. T., Mbogo, C., Bashir, A. I., Bigoga, J., Adechoubou, A., Raghavendra, K., Cook, J., Malik, E. M., Nkuni, Z. J., Macdonald, M., Bayoh, N., Ochomo, E., Fondjo, E., Awono-Ambene, H. P., Etang, J., Akogbeto, M., Bhatt, R., Chourasia, M.K., Swain, D. K., Kinyari, T., Subramaniam, K., Massougbodji, A., Oke-Sopoh, M., Hounto, A., Kouambeng, C., Abdin, M.S., West, P., Elmardi, K., Valecha, N., Mathenge, E., Kamau, L., Lines, J. and Donnelly, M.J. (2018) Implications of insecticide resistance for malaria vector control with long-lasting insecticidal nets: outcomes from a WHO-coordinated multi-country prospective study. Lancet Infectious Diseases, 18, e30172

Kafy, H.T., Bashir, A.I., Mnzava, A.P., Abdin, M.S.E., Eltaher, J.S., Banaga, A.O., West, P., Bradley, J., Cook, J., Thomas, B., Subramaniam, K., Hemingway, J.*, Knox, T.B., Elfatih, M.M., Yukich, J.O., Donnelly, M.J.* and Kleinschmidt, I.* Impacts of insecticide resistance in Anopheles arabiensis on malaria incidence and prevalence in Sudan and the cost of mitigation (2017) Proceedings of the National Academy of Sciences of the United States of America, 114, e11267-75

The Anopheles gambiae 1000 Genomes Consortium (2017) Natural diversity of the malaria vector Anopheles gambiae. Nature, 552, 96–100

Clarkson, C.S., Weetman, D., Essandoh, J., Yawson, A.E., Maslen, G., Manske, M., Field, S.G., Webster, M., MacInnis, B., Kwiatkowski, D. and Donnelly, M.J. (2014) Adaptive introgression between Anopheles sibling species eliminates a major genomic island but not reproductive isolation. Nature Communications 5,e4248

Weetman, D., Wilding, C.S., Neafsey, D.E., Muller, P., Ochomo, E., Isaacs, A.T., Steen, K., Rippon, E.J., Morgan, J.C., Mawejje, H.D., Rigden, D.J., Okedi, L.M. and Donnelly, M.J. (2018) Candidate-gene based GWAS identifies reproducible DNA markers for metabolic pyrethroid resistance from standing genetic variation in East African Anopheles gambiae. Scientific Reports, 8, e2920

Foto-Cewek Themes and Topics – Key Words

Malaria and  other vector borne diseases; Resistance research and management;

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