Neglected tropical diseases: The Wellcome connection
In the third post of our series about neglected tropical diseases, Penny Bailey explores the history of the Wellcome Trust’s consistent support for research into tropical medicine, encompassing many diseases that have been labelled ‘neglected’.
A look back over the Wellcome Trust’s history of funding research into tropical diseases suggests it’s not a career for the faint-hearted: a certain resilience to capture by bandits along with a readiness to use yourself as bait to trap disease-carrying insects seems to have been par for the course.
Thanks to that bold and pioneering spirit, early Trust-funded research into tropical diseases has developed into thriving research programmes on the African, Asian and South American continents. Rooted in long-standing partnerships with local researchers, communities and institutions, our Major Overseas Programmes (MOPs) tackle a range of health problems, including malaria, anaemia, tuberculosis, typhoid and several ‘neglected tropical diseases’ (NTDs) such as leishmaniasis and Chagas’ disease. The MOPs also help train, support and equip researchers to help them address the health challenges on their doorstep.
In the beginning…
The seeds of the Wellcome Trust’s involvement in tropical medicine began just over a century ago, when our founder Sir Henry Wellcome sailed up the Nile from Egypt to Sudan in 1901. Horrified by the disease, filth and famine he saw along the banks, he offered to donate state-of-the-art equipment for research laboratories in the grounds of Gordon Memorial College, Khartoum, provided that the Sudanese authorities would contribute to their upkeep.
Opened in 1902, these were the first Wellcome Tropical Research Laboratories. Sir Henry helped select their first director, Dr Andrew Balfour, and asked him to concentrate on eradicating malaria – a challenge that remains a key priority for the Wellcome Trust today. Balfour set up a task force to drain and clear the mosquito breeding grounds in and around the city, and created a clean water and sanitary system, cutting the death rate from malaria by 90 per cent.
Five years later, Sir Henry provided Sudan with a floating laboratory that could be towed along the Nile into inaccessible regions, allowing researchers to collect specimens and analyse them on the boat.
In 1913 he opened his UK-based tropical research laboratories, the Wellcome Bureau of Scientific Research in London, bringing Dr Balfour home to run them. This set the pattern – which the Trust continued after his death – of establishing and supporting research laboratories dedicated to tropical diseases in both the countries directly affected and the UK. Researchers at the Bureau studied sleeping sickness (human African trypanosomiasis) and other diseases, and developed a vaccine against yellow fever.
Considering Wellcome’s keen interest in tropical medicine – and malaria in particular – it is perhaps not surprising that, two years after his death in 1936, one of the newly established Wellcome Trust’s first funding decisions was to support malaria research. Henry Foy had been appointed by the League of Nations to investigate malaria and its control in Greece where, in 1932, he set up a laboratory in the grounds of Thessaloniki’s Refugee Hospital. It was Foy who was captured by bandits in a remote region while collecting mosquitoes infected with malaria parasites.
By 1937 Foy’s funds were drying up. The Wellcome Trust stepped into the breach and took over his funding, establishing the Wellcome Trust Research Laboratories in Thessaloniki. When Germany invaded Greece in April 1941, Foy and his long-term collaborator Dr Athena Kondi fled to Istanbul and from there to Africa, taking much of their equipment with them. Arriving in Nairobi, they discovered that malaria, sickle-cell anaemia, nutritional deficiencies and many NTDs (including hookworm infection and schistosomiasis) were abundant in the region, so they decided to continue their research there. The Wellcome Trust agreed to fund the unit and thus was born a sustained commitment to research in Kenya that continues today.
In 1957, a decade after India had gained independence from British rule, the Wellcome Trust established research laboratories in Vellore in southern India to study tropical sprue and nutritional anaemias. By the 1960s, other British colonies had begun to gain their independence, leading to a huge decline in opportunities for European doctors to work in the tropics where, looking after colonial expatriates and their servants, they could observe local diseases (often giving them different names in their own language).
In response, the first Wellcome Trust Policy, published in 1966, named centres and field research overseas, endemic tropical diseases, and inadequately supported subjects (including tropical medicine) as three of its seven priority funding areas. The Trust also shifted its focus from funding buildings and equipment to personal fellowships – including fellowships in tropical medicine. The following decade saw tropical medicine taking a significant 15 per cent slice of Trust awards.
An early beneficiary was parasitologist Ralph Lainson, now a Professor, FRS and OBE (and the Wellcome Trust’s longest-serving grant holder). In 1965, young Ralph set off for Brazil armed with only a three-year grant to study the parasites, insects, wild animals and people involved in cutaneous leishmaniasis. He stayed for three decades, establishing a thriving Trust-funded research unit at the Evandro Chagas Institute, Belém.
By 1979, researchers at Lainson’s unit had discovered 13 Leishmania species, which led them to propose a new classification of the parasite. They also discovered previously unknown Leishmania hosts and described four clinical types in people. Some of the research involved capturing large numbers of flies at night. The researchers used themselves, first as bait then as experimental subjects to see whether a sandfly bite would transmit leishmaniasis.
The Major Overseas Programmes
During the 1980s, the Trust extended its global reach beyond its three flourishing research units in Kenya, India and Brazil, and supported programmes in the West Indies (on leptospirosis), the Sudan (relapsing fever), Nigeria and Tanzania (trypanosomiasis) and Jamaica (sickle cell anaemia).
In Kenya, the Nairobi unit was thriving and had established a pharmacological group to develop drugs and vaccines. In 1983, the Kenya Medical Research Institute (KEMRI) invited the Wellcome Trust to set up a new research programme in Kilifi, an hour’s drive north of Mombasa on the coast. With its well-characterised rural population, Kilifi became an important centre for testing vaccines and drugs developed in Nairobi, and for studying the transmission of malaria and other diseases in the community.
Six years later, the units in Nairobi and Kilifi formally became the KEMRI-Wellcome Trust Research Programme. Researchers there work closely with the Kenyan Ministry of Health to ensure research findings inform public health policy. They have shown that mobile phone messaging to health workers increases correct case management of malaria; and prompted the Ministry of Health to prioritise routine vaccination of children with the Haemophilus influenza type b (Hib) vaccine to dramatically cut the incidence of bacterial infection.
In collaboration with Oxford University, the Trust had provided funds for David Warrell to set up a small unit in the Faculty of Tropical Medicine at Mahidol University in Bangkok in 1979 to study snake bites and severe malaria. While working at the unit, Professor Nick White and colleagues chanced upon a paper in a Chinese scientific journal detailing the antimalarial properties of a herb called artemisinin, derived from the sweet wormwood tree, and tracked down the Chinese scientists who had done the work. White’s team began conducting detailed, large-scale studies of artemisinin as a treatment for malaria – over the next 30 years, those studies would eventually prove that derivatives of artemisinin worked better than the existing treatment, quinine, to vanquish malaria.
In 1990, Professor White began to collaborate with researchers in Ho Chi Minh City, Vietnam carrying out further trials of artemisinin in this new population. That turned out to be the first step in extending the Trust-funded research programme in Thailand to Vietnam – ultimately establishing what is now the Wellcome Trust Vietnam MOP, with satellite sites in Hanoi, Burma, Cambodia, Laos and China. As a result of research by the Thailand and Vietnam MOPs, the World Health Organization now recommends a frontline treatment called artemisinin-based combination therapy (ACT) for adults with malaria in South-east Asia. The more recent AQUAMAT trial showed that artesunate should also be the preferred treatment for malaria in both children and adults in Africa.
Back at home, to provide logistical, financial and scientific support for the researchers we were supporting in our budding overseas units, the Trust established four UK-based Centres for Clinical Tropical Medicine in 1995. True to the spirit of Sir Henry Wellcome, these Centres continue to facilitate the recruitment and training of outstanding clinicians and scientists in tropical medicine.
In the same year, we established a new research programme in Malawi. Based in the national hospital in Blantyre and integrated with the University of Malawi’s College of Medicine, it developed into a Major Overseas Programme in its own right. Researchers there identified new strains of the rotavirus, leading Blantyre to become the main site of a major trial of a rotavirus vaccine.
Another collaboration – this time with the South African Medical Research Council – spawned a third African MOP in 1998: the Africa Centre for Health and Population Studies at the University of KwaZulu-Natal. Here, researchers carry out demographic and health research on a rural population with one of the highest burdens of HIV in the world. A key study showed the importance of exclusive breastfeeding in preventing transmission of HIV from mother to child, leading UNICEF, the World Health Organization and UNAIDS to revise their guidelines on the feeding of infants of HIV-infected mothers.
Tropical disease research in the 21st century
African countries suffer some of the highest rates of NTDs, and they still lack the critical mass of talented local researchers – along with supporting infrastructure and networks – necessary to address them. The Wellcome Trust is supplementing its investment in the three African MOPS by supporting research programmes elsewhere in Africa as well as international and local collaborations aiming to strengthen capacity throughout the continent.
In 2008, we made two Strategic Awards to establish new centres of excellence in Uganda and South Africa: the Uganda Virus Research Institute at Makerere University and the Centre for Clinical Infectious Diseases Research at the University of Cape Town. The following year, we launched our £30 million initiative African Institutions Initiative, which supports seven pan-African consortiums, involving 50 research institutions in 18 African countries, each focused on building a critical mass of sustainable local research capacity across Africa. The Wellcome Trust and the UK Department for International Development (DFID) committed £10m each to the Health Research Capacity Strengthening Initiative, which aims to strengthen capacity in Kenya and Malawi specifically, and to improve the use of research findings in evidence-based policy making.
Vital as capacity-building is to the future of global research, tropical diseases urgently require new tools. The Trust, together with international partners, has supported numerous initiatives in recent years to accelerate the development of new drugs and other interventions. For example, in 2005 the Trust made an award to Dundee University to support a drug discovery programme for NTDs. The aim was to translate basic research discoveries across a range of tropical diseases, including human African trypanosomiasis, Chagas’ disease and leishmaniasis, into candidate drugs ready for clinical trials. We also pledged £10m over five years – matched by the UK Government’s Department for International Development (DFID) – to support the discovery, development and registration of antimalarial drugs by the Medicines for Malaria Venture (MMV).
The £36m Joint Global Health Trials scheme, which launched in 2010, is a joint initiative with DFID and the Medical Research Council. It provides funding for late-stage clinical trials of interventions to improve health in low- and middle-income countries across the globe.
The same year, we announced a major initiative in Asia: the £45m ‘R&D for Affordable Healthcare in India’ scheme, jointly funded with India’s Department of Biotechnology. Building on the original 2007 Wellcome Trust/DBT India Alliance, the aim is to bring together researchers from both the public and private sectors, largely working in India, to develop new, cost-effective interventions that will reach the greatest numbers of beneficiaries, without compromising on quality.
Innovation is not limited to rich developed nations. In many ways, NTDs call for greater innovation because of the challenges of treating chronic endemic diseases often concentrated in rural areas of very poor countries. They require the best tools and most appropriate approaches to understanding disease and to treating it that modern research has to offer. For example, in partnership with the US National Institutes of Health, we established the Human Heredity and Health in Africa project (H3 Africa) in 2010. This US$38m (£25m) initiative supports population-wide genetic studies of diseases by African researchers on the African continent, aiming to unravel the roles of genes and environment in disease.
Continuing the genetic theme, researchers at our Vietnam programme are characterising genetic variation in the dengue virus genome as part of an international consortium. On the back of this work, the first-ever clinical trials of an antiviral treatment for dengue fever – developed in collaboration with the Novartis Institute for Tropical Diseases, Singapore – are underway. Other UK research is tackling the disease by attacking the mosquitoes that carry the virus. Oxford-based company Oxitec Ltd has developed a technique that uses advanced genetics to modify male mosquitoes to be ‘sterile’ which should reduce the male mosquito population below the threshold level required to transmit the disease. The researchers were awarded a Wellcome Trust Translation Award in 2010 to test the lead strain in Malaysia.
More than a hundred years ago, as he travelled in search of medicinal compounds and archaeological artefacts, Henry Wellcome saw the effects that tropical diseases could wreak on people around the world. His legacy ensured that research into tropical diseases has never been neglected by the Wellcome Trust.
You can find out more about the history of the Wellcome Trust on our website.