Malaria testing at the Shoklo Malaria Research Unit on the Thai-Myanmar border — SMRU provides quality health care to refugees and migrant workers, combining research and humanitarian services: © Gerhard Jörén, MORU

Oxford Tropical Medicine: the large footprint of the Centre for Tropical Medicine and Global Health

Nick Day, Professor of Tropical Medicine, Director of the Mahidol-Oxford Tropical Medicine Research Unit, Thailand, and of the Wellcome Trust Thailand Africa and Asia Programme

A week ago you returned from a trip of a lifetime safari in Tanzania, and while initially you felt rejuvenated by the holiday, you are now shivery, ache all over, and feel truly awful. A trip to the GP, and then to your local hospital, and you have a diagnosis of malaria. You are treated with an artemisinin combination therapy, and within two to three days are completely cured. What you will probably not realize is that Oxford researchers and their local collaborators working in the tropics made major contributions to the development of this extremely efficient treatment, leading to its availability in the UK and worldwide as a first line treatment for malaria. It’s one example of the fruits of research carried out over the past 40 years by the Oxford Tropical Network.

Oxford’s network of research units in Asia and Africa is centred around three large Wellcome Trust-supported tropical medicine research programmes, based in Bangkok, Thailand, Ho Chi Minh City in Vietnam, and in Kilifi on the Kenyan coast. These enterprises are not small, employing 119 Oxford staff and over 2,000 local clinicians, scientists and support staff. Many staff are in clinical research units in other parts of their programme’s host country, and in closely linked regional research units in Laos, Indonesia, Nepal, Cambodia, Myanmar, Uganda and the Democratic Republic of Congo. Working with their many close collaborators based in governments, hospitals, and academic institutions, the programmes are currently carrying out clinical and epidemiological research in over 60 sites across Asia and Africa.

All this overseas activity is ably supported by the Nuffield Department of Medicine’s Centre for Tropical Medicine and Global Health (CTMGH), based in true Oxford fashion in a large but rather gloomy basement on the Old Road Campus in Headington. In addition CTMGH hosts an increasing number of Oxford-based academic groups whose research focus is on global health. All together CTMGH manages a funding portfolio of £310m, which supports the research of 57 principal investigators including 27 professors and 19 associate professors, — four fifths of whom live and work in the tropics. The Oxford Tropical Network hosts nearly 200 DPhil and PhD students, mainly based in the overseas units, and in Oxford CTMGH manages the internationally popular Masters in International Health and Tropical Medicine.

Mosquito feeding time at SMRU on the Thai-Myanmar border.

What is now a large and extensive network began in 1979 when, with the encouragement and support of David Weatherall, the newly appointed Nuffield Professor of Medicine, David and Mary Warrell founded the unit in Thailand as a partnership between Oxford, Thailand’s Mahidol University, and the Wellcome Trust. The initial research focus was on severe malaria, snakebite and rabies. A seminal clinical trial in cerebral malaria proved that the then widely used steroid treatment was harmful rather than beneficial, and despite heroic efforts at treatment established rabies encephalitis proved as 100% lethal as ever. In 1986 Nick (now Sir Nick) White took over as director of the Thailand Unit. He expanded the malaria research and, following a very unpleasant experience involving an escaped cobra in his Land Rover, discontinued studies on snake bite. The unit started working on malaria along the Thai-Burmese border, and in Northeast Thailand began to study melioidosis, a common, deadly and hitherto understudied bacterial infection afflicting rice farmers. A new antibiotic treatment halved the death rate from melioidosis from 80% to 40%, and incremental advances in its diagnosis and treatment have continued since.

In 1991 a new unit was started in the Hospital for Tropical Diseases, Ho Chi Minh City in Vietnam (the Oxford University Clinical Research Unit, or OUCRU), focusing on the nature and treatment of severe malaria, typhoid, dengue and tetanus. This began as a spin-off unit of the Thai unit, but has since expanded into a major separate research programme and an important public health resource for the whole country. It attained international recognition during the 2003 avian influenza epidemic, when the then OUCRU director Jeremy Farrar (now Sir Jeremy, director of the Wellcome Trust) and his colleague Prof Tran Tinh Hien described the disease and its lethality in a large series of patients. OUCRU also made significant headway on improving survival in tuberculous meningitis using steroid treatment (the same treatment which didn’t work in cerebral malaria). The young research fellow who conducted this landmark trial, Guy Thwaites, is now the director of OUCRU.

KEMRI-Wellcome research unit in Kilifi, Kenya — KWTRP aims to expand a strong, sustainable and internationally competitive multidisciplinary research on the major causes of morbidity and mortality in Africa: © Ruth Wanjala, KWTRP unit

Meanwhile Oxford was not standing still in Africa. The KEMRI-Wellcome unit in Kilifi in Kenya was founded in 1989, and under Kevin Marsh (director from 1990 until 2013 ) expanded to become one of the foremost medical research centres in Africa with state of the art laboratories and a large demographic surveillance system to track malaria and other infections in the surrounding population. Roughly 90% of malaria deaths worldwide occur in African children, and KEMRI-Wellcome’s has been working to understand the epidemiology of malaria and of the human immune system’s response to being infected, to improve the treatment of this devastating disease, and to test vaccines that might prevent infection in the first place. It is now directed by Philip Bejon, who led a large clinical trial of the RTS,S malaria vaccine, the only malaria vaccine to have been developed to the stage of pilot deployment. In KEMRI-Wellcome’s Nairobi unit Bob Snow works on mapping malaria and malaria deaths. In 2017 Bob published what he calls his life work, a paper describing the prevalence of malaria infection across the whole continent over the past 115 years. In this extraordinary paper Bob analyses 50,424 historical malaria surveys he has painstakingly collected over the past quarter century. These surveys were conducted at 36,966 geocoded locations, and the resulting space-time map showed that whereas malaria prevalence has gone up and down considerably over the twentieth century, from 2000 onwards we have witnessed a welcome but unprecedented decline. The combination of insecticide treated bed nets (also tested by KEMRI-Wellcome) and artemisinin combination therapies (rolled out since 2006) have probably contributed to this decline, but are not the whole story.

If a child does get severe malaria she can now be treated with injectable artesunate, which significantly increases survival compared with injected quinine. This artemisinin derivative was developed by Chinese scientists, but the large clinical trials in both Southeast Asia and Africa which led to it becoming the WHO recommended first line treatment for severe malaria globally were initiated and led by the Oxford Tropical Network. We estimate that this move to artesunate from quinine has already prevented at least one hundred thousand deaths in African children since 2010.

All is not rosy though, as ten years ago the Oxford Southeast Asian units detected malaria parasites resistant to the artemisinins, and there is deep concern that this resistance will spread to Africa, with potentially disastrous consequences. The Oxford Tropical Network in both Asia and Africa is currently deeply involved in collaborative research to develop tools to stop this happening, and to test new drug treatments which will both prevent and treat resistant infections.

The programmes in Asia and Africa are all collaborations with local partners, and the joint research contributes to training host country academic leaders and local research capacity. Most of each unit’s collaborations are between partners in the South, rather than the more traditional North-South interactions; and research projects are increasingly led by local academics, many trained within the programmes. As the UK faces up to the uncertain and maybe unrealistic task of being ‘Global Britain’, at least in terms of international health CTMGH is doing its bit to promote ‘Global Oxford’.

Conducting clinical trials during the West African Ebola outbreak — Donning personal protective equipment at an Ebola treatment centre, Port Loko, Sierra Leone: © Rebecca Inglis

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