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Dr Colin Sutherland

BSc PhD MPH

Professor
of Parasitology

Room
Room 315

LSHTM
Keppel Street
London
WC1E 7HT
United Kingdom

Tel.
020 7927 2338

Colin is a biologist and parasitologist who joined the School in January 1998 to work as a Post-Doc with Professor Geoffrey Targett on the gametocytes of Plasmodium falciparum. Colin began working on parasite drug resistance in the context of the team's clinical studies in The Gambia from 1998 - 2002. From 2004 - 2011, while continuing his studies of parasite drug susceptibility, Colin developed new projects on molecular diagnostics for parasitology with Peter Chiodini and Spencer Polley in the Department of Clinical Parasitology at the Hospital for Tropical Diseases, and continues to work closely with Public Health England in the PHE Malaria Reference Laboratory, LSHTM as HCPC-registered Clinical Scientist.

Understandng of the evolutionary biology of parasitism remains the context underpinning all Colin's studies, and the tools of molecular genetics and genomics are the means used to address this goal. Parasite adaptation to the two great selective forces of host immunity and antimicrobial chemotherapy has been of particular interest. 

Among Colin's current roles are:

  • Editorial Board Member for the Journal of Antimicrobial Chemotherapy
  • Member of the Grants Committee for the British Society for Antimicrobial Chemotherapy
  • Scientific Advisory Group Member, PRISM International Center of Excellence for Malaria Research, Uganda (NIH / NIAID-funded project)

Affiliations

Faculty of Infectious and Tropical Diseases
Immunology and Infection Department

Centres

Malaria Centre
Antimicrobial Resistance Centre

Teaching

Colin contributes lectures to students studying for MSc degrees and the DTM&H. He has supervised more than 30 MSc summer research projects in the laboratory.

Colin's lab group has been involved in training researchers from a number of malaria endemic countries in techniques for molecular genotyping of malaria parasites. Trainees and students have hailed from Burkina Faso, Chad, China, Guinea-Conakry, Indonesia, Kenya, Mali, Niger, Nigeria, Pakistan, The Philippines, Senegal, Sudan, Tanzania, Thailand and The Gambia, and include scientists, clinicians, doctoral students and research assistants. 

Colin also contributes to a number of PhD examinations each year. Recent candidates have included students from the Universities of Keele, Oxford and Liverpool.

Recently completed doctoral students in the lab include:

Nazma Habib Khan (Pakistan) - "Population genetics of Leishmania causing cutaneous leishmaniasis in north-western Pakistan."
Completed: April 2013

Bismarck Dinko (Ghana) - "Longitudinal studies of anti-gametocyte antibodies in Ghanaian school children."
Completed: June 2013

Ifeyinwa Chijioke-Nwauche (Nigeria) - "Efficacy of artemether-lumefantrine and resistance marker selection in HIV positive and negative adults in southern Nigeria."
Completed: January 2014

Gisela Henriques (Portugal) - "New genetic markers of artemisinin resistance in human malaria parasites."
Completed: June 2015

Mary Grace Dacuma (The Philippines) - "Epidemiology of malaria in the provinces of Sarangani, South Cotabato and Tawi-Tawi in Mindanao, The Philippines "
Completed: June 2015

Current doctoral candidates:

Ifeyinwa Aniebo (Nigeria) - "Genomic approaches to understanding drug resistant phenotypes in Plasmodium falciparum "      
Submitted: Jan 2017 (viva pending)

Inke Nadia Lubis (Indonesia) - "Clinical efficacy of artemisinin-based combination therapy for uncomplicated Plasmodium falciparum malaria in North Sumatera, Indonesia, and the association of molecular markers with treatment outcomes"
Expected completion: 2017
 
Ryan Henrici (USA) - "Manipulation of artemisinin susceptibility in African malaria parasites by genome editing"
Expected comlpetion: 2018

Research

Colin's research falls into 3 main areas: Plasmodium falciparum gametocyte biology, malaria drug resistance and molecular diagnostics for malaria infections. The following projects are currently active in the lab:

1) Drug resistant genotypes associated with reduced susceptibility of African P. falciparum

Earlier work with Teun Bousema evaluated combination antimalarials containing artemisinin compounds, and the genetic determinants of susceptibility to these regimens in malaria parasites. This work was funded by the EU-FP7 MALACTRES consortium from 2008 until June 2013. The lab continues to work with collaborators running a number of trials and studies throughout Africa in which ACT efficacy is tested.

Through the work with Dr Bousema in western Kenya, we have identified mutations in the  P. falciparum genes, pfubp1 and pfap2mu that are associated with reduced susceptibility to ACT in vivo. We have expanded these studies to include a small focus of ACT treatment failures in Masaiti Disctrict, Zambia. Our data from both sites clearly show that determinants of susceptibility in Africa differ from those recently described in Cambodia.

With funding from the British Society for Antimicrobial Chemotherapy, we have generated transgenic P. falciparum to examine the role of polymorphisms in the pfap2mu locus in modulating parasite response to antimalarial drugs in vitro.

2) New molecular tools for diagnosis of parasitic infections

Public Health England is supporting the development of new DNA amplification assays both in the Malaria Reference Laboratory at LSHTM, with Dr Debbie Nolder and Paul Lansdell, and  with Dr Spencer Polley and Prof. Peter Chiodini at the Hospital for Tropical Diseases (HTD). New real-time qPCR assays for Plasmodium falciparum, P. vivax and P. ovale spp. have been developed and have entered routine diagnostic use. These quantitative assays are also being used to monitor parasite clearance times in patients under treatment in HTD.

In addition, clinical evaluation of LAMP technology for malaria diagnosis developed with Spencer Polley at the Clinical Parasitology Dept at HTD with funding support from FIND, Geneva were described in the Journal of Infectious Diseases in June 2013. A MESA-funded project with Dr Mary Grace Dacuma supported us to take this technology to South Cotabato Province, Mindanao, The Philippines in 2015 and demonstrated its utility in remote field settings.

3) Population biology of P. ovale curtisi and P. ovale wallikeri 

Dr Mary Oguike is leading work on these two distinct forms of malaria parasite, first described in 2010 as part of Colin's work in the UK Malaria Reference Laboratory, and has successfully generated Ilumina paired-end genome seq data direct from blood samples from patients with ovale malaria. Together with Prof Abdoulaye Djimde, University of Bamako, Mali we have been pursuing new genomic analyses, and studies of the liver-stage biology of these two species with Medical Research Council funding. With the assistance of Mojca Kristan and Dr Don van Schalkwyk we have developed a mosquito transmission pipeline, and in 2016 successfully infected cultured human hepatocytes with sporozoites from P. ovale spp.

4) In vitro drug responses of parasites isolated from UK malaria patients

As Clinical Scientist at HTD, Colin has direct contact with malaria patients who have returned to or visited the UK from malaria-endemic countries. Dr Don van Schalkwyk and Rebekah Burrow successfully adapted more than 10 P. falciparum isolates from across Africa to long-term in vitro growth since 2012, and we are now using these for further dissection of parasite susceptibility to a variety of antimalarial drugs in vitro. Ifeyinwa Aniebo has generated full genome sequence in-house (on the Illumina Mi-Seq platform at LSHTM) for some of these isolates, and is examining polymrphisms in a long list of candidate genes in each isolate.

This project has developed a novel in vitro assay for artemisinin susceptibility in P. falciparum, which we are writing-up for publication in 2017.

In January 2017 we published a case series of four malaria patients that experienced recurrent malaria symptoms 3-7 weeks after treatment with artemether-lumefantrine, the front-line antimalarial in the UK. This report, which inlcuded genetic analysis of several candidate resistance loci, generated significant media interest at the time of publication.

5) In vitro drug suscetibility of P. knowlesi 

The Medicines for Malaria Venture (MMV) are supporting a project with Don van Schalkwyk, together with the lab of LSHTM colleague Dr Robert Moon, in whcih we have successfully established robust in vitro susceptibility assays for the zoonotic parasite P. knowlesi. We have used this to screen investigational lead compounds for activity against non-falciparum malaria, and to identify differences in the drug susceptibility of this species compared to the more familiar P. falciparum.

6) EDCTP-funded studies of ACT therapy for children with malaria in West Africa

This project, coordinated by Prof Djimde in Bamako, brought a number of European and African project partners together to design. implement and evaluate Phase III trials of ACT therapies in Mali, Burkina Faso and Guinea-Conakry. Particularly exciting is the opportunity to be involved in the first large-scale trials of artesunate-pyronaridine for treating malaria in African malaria patients. Khalid Beshir developed a novel qPCR method for evaluating parasite clearance in malaria patients to be deployed across this project. Colin is involved in preparation of several manuscripts from this work for submission in 2017.

7) ACCESS-SMC - monitoring and evaluation of parasite drug resistance

As part of this UNITAID implementation project, being carried out on a vast scale across 7 Sahel countries in the seasonal malaria belt in Africa, Khalid Beshir and Julian Muwanguzi are performing high-throughput parasite detection and assessment of resistance markers for the combination of drugs used for seaonal malaria chemoprevention (SMC) in young children - sulphadoxine-pyrimethamine plus amodiaquine. The team have established an ingenious analysis pipeline, starting with the collection of bar-coded filter-paper blood-spots from ~4000 children in each participating country, followed by robotic DNA extraction of DNA at LSHTM, qPCR to test for parasites and finally sequencing of key parasite resistance loci in parasite positive samples.

Research Area
Clinical guidelines
Clinical trials
Diagnostics
Drug discovery and development
Drug resistance
Parasites
Public health
Vaccines
Chemotherapy
Protozoa
Randomised controlled trials
Discipline
Genomics
Immunoepidemiology
Molecular epidemiology
Epidemiology
Genetics
Molecular biology
Parasitology
Disease and Health Conditions
HIV/AIDS
Infectious disease
Malaria
Emerging Infectious Disease
Neglected Tropical Diseases (NTDs)
Schistosomiasis
Tropical diseases
Zoonotic disease
Country
Angola
Burkina Faso
Bangladesh
United Kingdom
Ghana
Guinea
Gambia, The
Equatorial Guinea
Haiti
Indonesia
India
Kenya
Cambodia
Mali
Myanmar
Mozambique
Nigeria
Pakistan
Philippines
Papua New Guinea
Sudan
Senegal
Swaziland
Togo
Tanzania
Uganda
Zambia
Region
East Asia & Pacific (all income levels)
Euro area
European Union
Middle East & North Africa (all income levels)
South Asia
Sub-Saharan Africa (all income levels)

Selected Publications

Pfk13-independent treatment failure in four imported cases of Plasmodium falciparum malaria given artemether-lumefantrine in the UK.
Sutherland, C.J. ; Lansdell, P. ; Sanders, M. ; Muwanguzi, J. ; van Schalkwyk, D.A. ; Kaur, H. ; Nolder, D. ; Tucker, J. ; Bennett, H.M. ; Otto, T.D. ; Berriman, M. ; Patel, T.A. ; Lynn, R. ; Gkrania-Klotsas, E. ; Chiodini, P.L. ;
Antimicrob Agents Chemother
Contribution of Plasmodium knowlesi to multi-species human malaria infections in North Sumatera, Indonesia.
Lubis, I.N. ; Wijaya, H. ; Lubis, M. ; Lubis, C.P. ; Divis, P.C. ; Beshir, K.B. ; Sutherland, C.J. ;
J Infect Dis
Lack of K13 mutations in Plasmodium falciparum persisting after artemisinin combination therapy treatment of Kenyan children.
Muwanguzi, J. ; Henriques, G. ; Sawa, P. ; Bousema, T. ; Sutherland, C.J. ; Beshir, K.B. ;
Malar J
Genome-scale comparison of expanded gene families in Plasmodium ovale wallikeri and Plasmodium ovale curtisi with Plasmodium malariae and with other Plasmodium species.
Ansari, H.R.; Templeton, T.J.; Subudhi, A.K.; Ramaprasad, A.; Tang, J.; Lu, F.; Naeem, R.; Hashish, Y.; Oguike, M.C.; Benavente, E.D.; Clark, T.G.; Sutherland, C.J.; Barnwell, J.W.; Culleton, R.; Cao, J.; Pain, A.;
Int J Parasitol
Rescuing artemisinin combination therapy in Africa.
Sutherland, C.J. ;
Lancet Glob Health
Directional selection at the pfmdr1, pfcrt, pfubp1 and pfap2mu loci of Plasmodium falciparum in Kenyan children treated with ACT.
Henriques, G.; Hallett, R.L.; Beshir, K.B.; Gadalla, N.B.; Johnson, R.E.; Burrow, R.; van Schalkwyk, D.A.; Sawa, P.; Omar, S.A.; Clark, T.G.; Bousema, T.; Sutherland, C.J.;
J Infect Dis
Two nonrecombining sympatric forms of the human malaria parasite Plasmodium ovale occur globally.
Sutherland, C.J. ; Tanomsing, N. ; Nolder, D. ; Oguike, M. ; Jennison, C. ; Pukrittayakamee, S. ; Dolecek, C. ; Hien, T.T. ; do Rosário, V.E. ; Arez, A.P. ; Pinto, J. ; Michon, P. ; Escalante, A.A. ; Nosten, F. ; Burke, M. ; Lee, R. ; Blaze, M. ; Otto, T.D. ; Barnwell, J.W. ; Pain, A. ; Williams, J. ; White, N.J. ; Day, N.P. ; Snounou, G. ; Lockhart, P.J. ; Chiodini, P.L. ; Imwong, M. ; Polley, S.D. ;
J Infect Dis
See all Dr Colin Sutherland's Publications