Improving design of malaria intervention programmes in East Africa

The 2024/25 application process is now closed

Visit the MRC DTP/CASE at LSTM pages for further information.

Abstract

Malaria is a major cause of mortality and morbidity in Sub-Saharan Africa (SSA) and one of the biggest impediments to the economic development. The major method for controlling these malaria-transmitting mosquitoes is through the use of chemical insecticides but resistance has emerged and is a major threat to the recent reductions in both deaths and malaria infections.

 

The PhD student will work within large vector control trials in East Africa. There is a high degree of flexibility within the project and the student may choose to:- 

 

  • apply genomic sequencing approaches to investigate the key genetic drivers of insecticide resistance
  • use CRISPR/Cas to functionally characterise resistance candidates
  • develop insecticide resistance models to quantify the impact of resistance on intervention efficacy on epidemiological indicators.

 

Work will be conducted at LSTM with an opportunity to conduct part of the research with partners in Kenya.

 

Where does the project lie on the Translational Pathway?

T1 – Basic Research          

T2 Human / Clinical Research         

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. Research costs will be partially underwritten by recent awards from BMGF and NIAID. Recent PhD graduates from our labs have published extensively in the general science journals (Nature, PNAS, Nature Communications). This is a key strategic area for LSTM and brings together research groups from across the Biological and Clinical Sciences faculty

Training Opportunities

The student will gain skills in field entomology; molecular biology; experimental design; statistical analysis; genomics; epidemiology

Skills Required

N/A

 

Key Publications associated with this project

Staedke, S.G. et al (2020) Effect of long-lasting insecticidal nets with and without piperonyl butoxide on malaria indicators in Uganda (LLINEUP): a pragmatic, cluster-randomised trial embedded in a national LLIN distribution campaign. Lancet, 395, 1292-1303

Maiteki-Sebuguzi, C., Gonahasa, S., Kamya, M.R., Katureebe, A., Lynd, A., Mutungi, P., Kigozi, S.P., Opigo, J., Hemingway, J. Dorsey, G., Donnelly, M.J. and Staedke, S.G. (2022) LLIN Evaluation in Uganda Project (LLINEUP) – Effect of long-lasting insecticidal nets with and without piperonyl butoxide on malaria indicators in Uganda 25 months after distribution: a cluster-randomised trial.  Lancet Infectious Diseases in press

Njoroge, H., van’t Hof, A., Oruni, A., Pipini, D., Nagi, S.C., Lynd, A., Lucas, E.R., Tomlinson, S., Grau-Bové, X., McDermott, D., Wat’senga, F.T., Manzambi, E.Z., Agossa, F.R., Mokuba, A., Irish, S., Kabula, B., Mbogo, C., Bargul, J., Paine, M.J.I., Weetman, D. and Donnelly, M.J. (2022) Identification of a rapidly-spreading triple mutant for high-level metabolic insecticide resistance in Anopheles gambiae provides a real-time molecular diagnostic for anti-malarial intervention deployment. Molecular Ecology 31, 4301-4318

Clarkson, C.S., Miles, A., Harding, N.J., O’Reilly, A., Weetman, D., Kwiatkowski, D., Donnelly, M.J. and the Anopheles gambiae 1000 Genomes Consortium (2021) The genetic architecture of target-site resistance to pyrethroid insecticides in the African malaria vectors Anopheles gambiae and Anopheles coluzzii. Molecular Ecology 30, 5303–5317

The Anopheles gambiae 1000 Genomes Consortium (2020) Genome variation and population structure among 1,142 mosquitoes of the African malaria vector species Anopheles gambiae and Anopheles coluzzii Genome Research, 10, 1533-1546