“Over the last 16 years this has grown to become one of the most active research programmes in Africa; the site is now a full KEMRI centre and we work not only on the coast but throughout all of Kenya with over 350 people in the Programme.”

I had always had an interest in working in developing countries, though to be honest, I was probably driven more by the wish to avoid a settled life in England rather than any specific medical or scientific interest! This was fuelled by being a medical student in Liverpool; consequently I did the Diploma in Tropical Medicine and Hygiene at the Liverpool School as soon as I could after training in internal medicine. While there, we had a series of lectures from Sir Ian McGregor on the immunology of malaria which seized my imagination. I immediately decided that this is what I wanted to work on, and within a few weeks had applied to work with Brian Greenwood in the Gambia, who agreed but suggested that I first spend a bit of time with Louis Miller at the NIH in the States. At the time, this seemed to all fall into place naturally—and it was only in retrospect that I realized how lucky I was to come under the influence of two giants in the field, and that they were prepared to give me quite so much of their time and interest.

Before going to the Gambia I had trained as an adult physician and it was suggested to me that I work on the loss of immunity in pregnant women. However, it soon became clear to me that this was going to be difficult as no one knew how to measure immunity anyway! And that drove me naturally to looking at the group who were in the process of acquiring immunity, i.e., young children. This, combined with the fact that from a clinical point of view the load of illness in children was overwhelming, meant that my interest naturally drifted from adult medicine to paediatrics. Later on when I moved to Kenya, I had not really intended to spend so much time out of the lab, but an interest in pathogenesis meant that we needed to establish a good clinical surveillance system, and this inevitably led to more and more bedside practice which turned out to be absolutely fascinating and opened up an area of research which I had not really anticipated spending so much time on.

Cerebral malaria is one of those rather emotive but imprecise terms. In a general sense it has been used to describe any degree of central nervous system involvement in malaria, ranging from patients simply behaving a bit oddly, through a range of features such as convulsions, to profound coma leading to death. The field has been a bit further confused by the fact that the clinical description sits alongside a pathological phenomenon, in which cerebral malaria is defined by the accumulation of mature parasites in the cerebral micro- vasculature. It is now clear that the clinical syndrome of cerebral malaria, even when more precisely defined, does not correspond in any exact way with the histological definition, but rather identifies a heterogeneous group of patients. Some individuals do seem to have a primary neurological condition related to sequestration of parasites in the brain, but in other cases coma seems to reflect a response to overwhelming metabolic problems such as hypovolaemia and acidosis.

If we simply take the definition of cerebral malaria as being coma caused by malarial parasitization, the epidemiology is quite interesting. Non-immune individuals, such as tourists or people living in areas of unstable endemicity, are prone to cerebral malaria at all ages, and often the epidemiology reflects occupational or travel-related exposure. But in stable endemic areas of Africa, cerebral malaria is a problem in children, though it is striking that the age of children presenting with cerebral malaria is always somewhat higher than that of those presenting with other forms of severe malaria, such as severe anaemia. The case fatality of cerebral malaria varies, depending on what other complications are involved, but is usually between 10 and 30%. A proportion of survivors have obvious neurological sequelae but one of the more important things emerging now is the fact that less obvious sequelae, such as specific cognitive deficits and an increased incidence of epilepsy, are common—and may have major implications for later life.

After leaving the Gambia I was based in the molecular parasitology group in Oxford but was planning a series of projects with the idea of going back to West Africa. On a visit to Kenya in 1987 for a meeting, I was invited by Bill Watkins, who was then heading the Wellcome-funded group in Nairobi, to come down to the coast for a weekend. The Wellcome Trust and KEMRI had previously carried out some exploratory work in Kilifi, a small rural town, on the coast, but this had come to an end and Bill was keen to see if anything more could be developed there. On visiting the hospital I felt that there were fantastic opportunities for some of the areas we were interested in. Over the next couple of years we developed with KEMRI a collaborative series of projects which were funded by the Wellcome Trust. In 1989 when we began the current phase of work in Kilifi, there were probably a dozen or so of us all together, including nurses, drivers, and fieldworkers. Over the last 16 years this has grown to become one of the most active research programmes in Africa; the site is now a full KEMRI centre and we work not only on the coast but throughout all of Kenya with over 350 people in the Programme.

Over the last 20 years the state of malaria, at least in Africa, has certainly not got better overall. A major issue has been the development chloroquine resistance. Chloroquine was an extremely effective, cheap, and safe drug, and its widespread use to some degree kept the lid on malaria in much of Africa where there were few other controls or treatment activities. Since the spread of resistance, we think mortality has probably pretty much doubled over the last 20 years.

On the other hand, there are clear and effective approaches to both prevention and cure but they are just not being applied widely enough. From a preventative point of view, insecticide-impregnated bed-nets are one of the most effective public-health interventions, leading to a reduction in all-cause childhood mortality by around 20% when introduced in an area. The challenges now are to achieve widespread access. When it comes to treatment, a previously rather dismal situation, in which there was little interest in developing antimalarial drugs, has been changed considerably by the development of a number of international public–private partnerships and now there are a number of exciting new antimalarials on the horizon. A major advance has been the development of combination therapies incorporating the rapidly acting artemesinin drugs (originally developed from Chinese traditional medicine) in combination with other new antimalarials, the idea being that each drug protects the other against the chance of resistance. Again the challenges are to achieve adequate access, and this involves both international financing but also solving the problems of raw materials supply.

Obviously malaria vaccines are an exciting and potentially important tool for malaria control. The vaccine story has gone up and down over the last 20 years, but currently there is a considerable excitement, particularly over recent developments with the RTS,S vaccine but also in relation to a number of other potential vaccines in development. However, vaccine development is a long-term process and even if things go as well as possible, vaccines are not going to play any major public health role in the next decade.