Defining hotspots of malaria transmission

Lead Research Organisation: University of Oxford
Department Name: Clinical Medicine

Abstract

Malaria transmission is patchy at a local level, with hotspots of intense transmission. This hinders control measures, but also means that targeting additional interventions on hotspots will be highly effective. At present, we do not know how best to detect these hotspots, or how to apply the interventions available. For example, we need to know how much transmission in the surrounding area results from the hotspot, and how focal the point source is.
I will analyse 19 years of historical data on malaria from coastal Kenya, supplemented by data from the Gambia in West Africa, to determine the spatial patterns of hotspots and how they might be detected. I will extend my findings by collaborations with investigators collecting spatial data on malaria cases in Gambia, Indonesia and elsewhere in Africa.
In collaboration with Dominic Kwiatkowski in the Wellcome Trust Sanger Institute, I will conduct detailed genotyping studies to assign a bar-code to malaria parasites. This will allow me to distinguish the recent origin of malaria parasites isolated in the field, in order to inform the design of targeted interventions against hotspots.

Technical Summary

Malaria transmission is spatially heterogeneous, and groups of homesteads that form hotspots or clusters of transmission can be identified. The presence of these hotspots makes malaria control measures less effective than they might be. However, adding targeted interventions to interrupt these hotspots will be highly effective. At present, we lack detailed epidemiological descriptions of the properties of hotspots and the ways in which they might be identified by malaria control programmes. Furthermore, in order to rationally design targeted interventions, we need to understand their transmission dynamics. For example, we need to know how much transmission in the surrounding area results from the hotspot, and how focal the point source is.
I will analyse 19 years of historical data on severe malaria, mild malaria and asymptomatic infection in Kilifi, Kenya. I will use datasets from cohorts under active surveillance in the field, and passive dispensary and hospital level surveillance, to describe the spatial and temporal limits of individual clusters of transmission, and the epidemiological markers of them. I will obtain external validation of my findings by collaborations with investigators collecting spatial data on malaria cases in Africa, including the Gambia and Indonesia.
In collaboration with Dominic Kwiatkowski in the Wellcome Trust Sanger Institute, I will conduct detailed genotyping studies to assign a bar-code to parasites. High resolution spatial and genotyping data will be combined to accurately identify transmission in and around hotspots, in order to predict the likely outcomes of intervening in hotspots. I will use a descriptive statistical approach for my primary analysis, but will also collaborate with Gil McVean (Oxford University), Dave Smith (Florida University) and Azra Ghani (Imperial College) to conduct post hoc analyses of the population genetic structure, potential indirect effects of interventions and Bayesian approaches to cluster determination, respectively.

Publications

10 25 50

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Afolabi MO (2016) Safety and Immunogenicity of ChAd63 and MVA ME-TRAP in West African Children and Infants. in Molecular therapy : the journal of the American Society of Gene Therapy

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Anopheles Gambiae 1000 Genomes Consortium (2017) Genetic diversity of the African malaria vector Anopheles gambiae. in Nature

 
Description Advise Technical Advisory Group to WHO
Geographic Reach Africa 
Policy Influence Type Participation in a advisory committee
 
Description Advise WHO working group on transmission dynamics of malaria
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
 
Description Transmission measures working group, Malaria Vaccine Initiative
Geographic Reach Africa 
Policy Influence Type Participation in advisory committee
 
Description Health Technology Assessment
Amount £895,946 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 08/2013 
End 12/2016
 
Description Strategic Award
Amount £4,500,000 (GBP)
Organisation Wellcome Trust 
Department Wellcome Trust Strategic Award
Sector Charity/Non Profit
Country United Kingdom
Start 11/2015 
End 11/2020
 
Description Strategic Primer Grant
Amount € 1,101,415 (EUR)
Organisation Sixth Framework Programme (FP6) 
Department European and Developing Countries Clinical Trials Partnership
Sector Public
Country European Union (EU)
Start 05/2012 
End 05/2014
 
Description Dave Smith, Janet Midega 
Organisation Johns Hopkins University
Department Department of Epidemiology
Country United States 
Sector Academic/University 
PI Contribution Analysis of spatial field entomology data
Collaborator Contribution Analytical support (Dave Smith) and entomological studies (Janet Midega)
Impact Publication in Nat. Comms, 2012, Midega et al. Ongoing field work for follow up studies.
Start Year 2012
 
Description Dave Smith, Janet Midega 
Organisation Kenyan Institute for Medical Research (KEMRI)
Department KEMRI CGMRC Programme
Country Kenya 
Sector Academic/University 
PI Contribution Analysis of spatial field entomology data
Collaborator Contribution Analytical support (Dave Smith) and entomological studies (Janet Midega)
Impact Publication in Nat. Comms, 2012, Midega et al. Ongoing field work for follow up studies.
Start Year 2012
 
Description Kwiatkowski Group 
Organisation The Wellcome Trust Sanger Institute
Department MRC Centre for Genomics and Global Health, WTCHG and WTSI
Country United Kingdom 
Sector Academic/University 
PI Contribution I will use sequence data from Ghana for spatial analyses. I will provide samples from previous field work in Kenya for genotyping
Collaborator Contribution Provision of data from previously analysed samples in Ghana. Laboratory resources and bio-informatics support to process samples from Kenya.
Impact Analyses and work still in progress.
Start Year 2012
 
Description Multi-centre hotspots 
Organisation Bernhard Nocht Institute for Tropical Medicine
Country Germany 
Sector Hospitals 
PI Contribution Analysis
Collaborator Contribution Sharing of data in order to support a pooled analysis of hotspots in multiple datasets. Submitted for publication.
Impact A pooled analysis of data has been completed and submitted for publication.
Start Year 2016
 
Description Multi-centre hotspots 
Organisation Kenyan Institute for Medical Research (KEMRI)
Department KEMRI/CDC Research and Public Health Collaboration
Country Kenya 
Sector Public 
PI Contribution Analysis
Collaborator Contribution Sharing of data in order to support a pooled analysis of hotspots in multiple datasets. Submitted for publication.
Impact A pooled analysis of data has been completed and submitted for publication.
Start Year 2016
 
Description Multi-centre hotspots 
Organisation London School of Hygiene and Tropical Medicine (LSHTM)
Country United Kingdom 
Sector Academic/University 
PI Contribution Analysis
Collaborator Contribution Sharing of data in order to support a pooled analysis of hotspots in multiple datasets. Submitted for publication.
Impact A pooled analysis of data has been completed and submitted for publication.
Start Year 2016
 
Description Multi-centre hotspots 
Organisation Medical Research Council (MRC)
Department MRC Unit, The Gambia
Country Gambia 
Sector Public 
PI Contribution Analysis
Collaborator Contribution Sharing of data in order to support a pooled analysis of hotspots in multiple datasets. Submitted for publication.
Impact A pooled analysis of data has been completed and submitted for publication.
Start Year 2016
 
Description Multi-centre hotspots 
Organisation National Centre for Research and Training on Malaria
Country Burkina Faso 
Sector Public 
PI Contribution Analysis
Collaborator Contribution Sharing of data in order to support a pooled analysis of hotspots in multiple datasets. Submitted for publication.
Impact A pooled analysis of data has been completed and submitted for publication.
Start Year 2016
 
Description Multi-centre spatial epidemiology 
Organisation London School of Hygiene and Tropical Medicine (LSHTM)
Country United Kingdom 
Sector Academic/University 
PI Contribution Assembling data for multi-centre analysis and analysis plan.
Collaborator Contribution Providing data.
Impact Publications (Omedo et al)
Start Year 2012
 
Description Community Liaison Meetings in Kenya 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact A series of meetings have been held in the research programme taking 100 community representatives at a time and describing individual research studies with a question and answer session.

Recruitment to further studies has been facilitated and communication regarding our research in the field is easier.
Year(s) Of Engagement Activity 2012,2013,2014
 
Description Radio Programme 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact I discussed malaria research in an interview and call-in radio programme.
Year(s) Of Engagement Activity 2016
URL http://barakafm.org/
 
Description Writing leaflets and material for public engagement 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Part of a local "show" including organizations based in the area.
Year(s) Of Engagement Activity 2015