The joint Wellcome Trust–Burroughs Wellcome Fund (WT–BWF) Initiative aims to promote collaborative research addressing major infectious diseases in developing countries – with the ‘centre of gravity’ firmly in the developing world. These collaborations between scientists in the UK, North America and developing countries create cross-fertilisation of ideas and experience, adding value as the differing expertise and strengths of diverse partners are harnessed in a common goal. The initiative ran for two years, awarding grants of some £18 million to a total of 13 projects, all of them involving institutions in at least three countries.

A key aim is to increase capacity in developing countries by training and technology transfer. Michael Chew, a Scientific Programme Officer in the Tropical Medicine Programme, points to research based in Egypt by G Thomas Stickland as an excellent example of this ‘capacity strengthening’. Dr Stickland, based in the University of Maryland, is collaborating with Professor Paul Hagan in Glasgow and Maged Al-Sherbiny, Mohamed Abdel-Hamid and others in Egypt to evaluate immunity to hepatitis C infection. "This project was in the first round of funding under the WT–BWF Initiative in 1999," says Dr Chew, "and it has involved not just Maryland and Glasgow, but a whole network of institutions across Egypt. We have Egyptian community health centres, research institutes, hospitals and universities all involved, as well as the collaboration at international level. Several Egyptian scientists will receive research training in Baltimore and Glasgow as part of this award."

Several of the awards made late in 2000 illustrate a pleasing continuity and fruition of previous and existing Trust funding. Professor Jerrold Ellner and colleagues will be working on multidrug-resistant tuberculosis with Alison Elliot, a Research Career Development Fellow in Clinical Tropical Medicine based in Uganda. "Dr Ellner is a leading specialist in the field," says Dr Chew, "and there is real added value for the Trust in enabling Dr Elliot, one of its own fellows, to work with the best specialists on this major health problem."

Multidrug-resistant tuberculosis

TB is a major global health problem, but its effects are disproportionately felt in developing countries, where 90 per cent of cases and 98 per cent of deaths occur. Professor Ellner from the University of Medicine and Dentistry of New Jersey, together with Professor Roy Mugerwa of the Makerere University Medical School in Kampala, Uganda, and Professor Peter Smith from the London School of Hygiene and Tropical Medicine, are researching treatment and prevention of multidrug-resistant TB in Uganda.

Multidrug-resistant TB – disease that is resistant to at least two of the common treatments – is emerging as a serious global threat to health. Most multidrug-resistant TB occurs in developing countries, where inadequately resourced control programmes, together with the availability of over-the-counter TB medication and patient non-compliance, all combine to promote drug resistance. Cure of multidrug-resistant TB requires expensive drugs for prolonged periods.

A particular problem is nosocomial transmission – the spread of an infection within a healthcare setting – which can occur on hospital wards where patients with TB are treated together with others susceptible to the infection, for example those with HIV infection.

In Uganda, the most recent figures suggest that 12 people in every 10 000 are infected with TB, of whom approximately 24 per cent have multidrug-resistant strains. Old Mulago Hospital in Kampala is the tertiary referral centre for TB treatment for the whole of Uganda, and currently treats more than 4000 new patients annually. The inpatient TB ward currently co-mingles ineffectively treated drug-resistant TB patients with other susceptible individuals, including patients with HIV and healthcare workers.

The collaboration will assess the incidence of nosocomial TB transmission in Old Mulago Hospital, with a view to developing inexpensive means of reducing its spread. The researchers will be working to identify the host and microbial factors that predict transmission. They will also be evaluating new ways to reduce transmission, including rapid diagnostics, new approaches to monitoring therapies and modified lower cost treatment regimes.

Old Mulago Hospital has long been at the forefront of treatment and prevention studies, and the TB treatment centre is an ideal site for identifying key transmission factors and testing prevention measures. Perhaps most significantly, interventions shown to be cost-effective in Uganda could be adapted in many developing country settings – helping to reduce at least one way in which this dangerous and disabling pathogen is transmitted.

Oral rehydration for diarrhoea

Between 1957 and 1990, the Trust funded an overseas unit based at the Christian Medical College and Hospital in Vellore, India. One of its staff, Professor B S Ramakrishna, is now principal applicant on a trilateral programme to improve oral rehydration therapy for diarrhoea.

Diarrhoea is a major cause of mortality in developing countries. The main treatment is oral rehydration therapy, the administration of a controlled glucose-based solution. This simple but effective treatment has saved many lives, and been hailed as one of the great medical advances of the twentieth century. However, while oral rehydration solution corrects dehydration, it does not reduce the diarrhoea itself. It has therefore been assumed in some communities to be ineffective, which militates against its widespread use.

Professor B S Ramakrishna of the Christian Medical College and Hospital in Vellore, India, Professor Henry Binder of Yale University School of Medicine and Professor Michael Farthing of the University of Glasgow Faculty of Medicine are taking advantage of recent scientific advances in the physiology of the intestine to try and overcome the perceived limitations of oral rehydration therapy.

Professors Binder and Ramakrishna have discovered that short chain fatty acids stimulate fluid absorption from parts of the colon, and that resistant starch, a substrate for short chain fatty acids, reduces diarrhoea and shortens illness in cholera. In addition, Professor Farthing has shown that very dilute (hypo-osmolar) oral rehydration solutions are particularly effective in non-cholera diarrhoea in children.

The researchers will combine these two advances to create a new oral rehydration solution that both rehydrates and reduces diarrhoea. Initial animal tests will establish the best composition of a solution that is both hypo-osmolar and contains resistant starch, which will be followed by randomised controlled trials in both adults and children with acute diarrhoea.

Many factors contribute to whether treatments for a disease are adopted by any particular community. In the case of diarrhoea, a study from a village in Vellore in India showed that less than half the villagers were willing to use rehydration therapy if their children had diarrhoea. There were a number of reasons. First, diarrhoea is such a frequent occurrence that it is not seen as requiring treatment. Also, the oral rehydration solution, being in effect a mixture of sugar, salt and water, was not seen as a proper ‘drug’. Finally, the inability of the solution to reduce diarrhoea meant that some people who had used the solution were not willing to use it again.

The researchers will investigate the current use of oral rehydration therapy in a number of south Indian villages, looking particularly at the role of health education in the improvement of uptake. The researchers will then introduce community trials of the new, hypo-osmolar, resistant starch solution instead of the traditional glucose-based solution. It is hoped that the enhanced anti-diarrhoea action of the new solution will produce a more directly tangible effect for patients and their carers, and thus provide both a more effective – and a more acceptable – version of this life-saving treatment.

The project is a good example of how basic laboratory science may be linked tangibly to clinical interventions and public acceptance – ultimately leading to improvements in health within a population.

External links

• Makerere University, Kampala, Uganda
• University of Medicine and Dentistry of New Jersey, Newark, USA
• Professor Peter Smith at the London School of Hygiene and Tropical Medicine
• Christian Medical College and Hospital Vellore, India
• Professor Henry Binder at Yale University School of Medicine
• University of Glasgow: Faculty of Medicine
• BWF: Burroughs Wellcome Fund