Life at the sharp end - fighting malaria on its own turf

Malaria researcher Dr Abdoulaye Djimdé, Wellcome Trust Sanger Institute International Fellow, is combining his first-hand experience of living and working in Mali with the genomic expertise of the Sanger Institute to explore this fatal disease. This collaboration will also provide unique opportunities to research other tropical infectious diseases and understand how an increasingly westernised lifestyle is contributing to the rise of health problems such as diabetes and cancer in developing countries.

Infectious disease causes major health problems in Mali: its population of 15 million has a life expectancy of only 50 years. However a shortened lifespan is not the only problem, recurring bouts of infection also have a critical economic impact. One of the greatest concerns is malaria, which is the leading cause of death. It is a disease that Djimdé, along with almost the entire nation, has personal experience of: he lost his brother to malaria when he was a child. From that moment he committed his life to fighting the disease through science.

Dr Djimde (seated on chair, far right) meeting with Malian village leaders to obtain permission to collect blood samples from villagers.

Dr Djimde (seated on chair, far right) meeting with Malian village leaders to obtain permission to collect blood samples from villagers. [Dr Abdoulaye Djimde]

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"I wanted to become a medical doctor so that I could work on malaria and treat patients," Djimdé says. "But, with limited opportunities and the way that the Malian school system works, I ended up training to be a pharmacist. The closest thing I could do to pursue my interest in malaria was to carry out research, so I started my own pharmacy in Bamako, the Capital city of Mali, in order to raise enough money to do a PhD."

It wasn't long before Djimdé was able to realise his ambition. While he was running his pharmacy, Djimdé started attending the research journal club of a research group run by Professor Doumbo at the University of Bamako every Thursday. Soon he was working in the laboratory as a volunteer investigating the Plasmodium parasites that cause malaria and, within a year, the research centre wanted to send him to learn new techniques in the United States. Only there was a problem: Djimdé didn't hold an official position and the research centre could only send contracted researchers. "So they had to give me a contract," Djimdé smiles.

This was the opportunity he had been waiting for. While he was in America, Djimdé worked under the guidance of two renowned malaria researchers, Professor Christopher V Plowe and Dr Thomas E Wellems at the National Institutes of Health. During this time, he carried out a number of studies that were published in the New England Journal of Medicine and The Lancet. But while the opportunities to continue his research in the US were tempting, after completing his PhD Djimdé returned to Mali to work in the field, where he believes he can have the most impact.

"I have a vested interested in keeping the work going and helping to understand the disease. When you live in an area where your friends and relatives regularly get sick, then no matter how daunting it is, you do whatever you can to try to improve that situation," Djimdé explains. "In fact, a few days before I came to visit the Sanger Institute, my mother contracted malaria. It almost stopped me getting on the plane to come to the UK."

Djimdé's mother is recovering well because there are drugs that currently are effective in this region. But there is worrying evidence that certain strains of the Plasmodium parasites in other parts of the world are rapidly developing resistance to these medicines, rendering the treatments ineffective. The greatest fear is that these resistant strains will spread round the globe. Resistance to chloroquine is already widely reported and now resistance is starting to spread for the only other front-line drug, artemisinin.

Djimdé and many of his fellow malaria researchers are convinced that coordinated action is needed to control the spread of resistant strains, to investigate potential new drugs and to develop effective vaccines.

Researcher looking at blood smears in a village field laboratory.

Researcher looking at blood smears in a village field laboratory. [Dr Abdoulaye Djimde]

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"I think we are now at such a level of emergency with the development of malarial artemisinin resistance in south-east Asia that there needs to be a truly global response to limit its spread. The response to malaria needs to be a concerted one, whether that is studying drug activity, rolling out of bed nets, vaccine research, or looking at the DNA sequence and genome diversity of the parasite," Djimdé explains. "By looking at the DNA of a large number of parasite samples from different places we are now starting to gather the evidence to show that genetic traits which allow the parasites to be more virulent and survive in their host, that have arisen locally, are spreading. You cannot get this type of understanding from just one place, you have to compare multiple genomes across time and geographic regions and to do this at sufficient scale needs effective collaboration and strong partnerships."

Strong partnerships across connected regions are vital, because of the way that malaria is transmitted. The parasites are carried by mosquitoes and are transferred from one person to another through the mosquito's bite. The mosquito acts like a flying syringe, sucking up parasites from an infected person and then injecting them into next person they bite. Therefore the control measures that are put in place need to tackle not only the movement of infected people but also the movement of infected mosquitoes too.

"Mosquitoes don't recognise man-made borders, so it doesn't matter what you do - if you don't do it in collaboration with neighbouring countries - any approach is bound to fail. We've seen that with polio and with meningitis. That's why we have regional health organisations trying to coordinate these activities," Djimdé says.

Djimdé has been instrumental in developing and contributing to a number of malaria networks. Currently he serves on the Scientific Advisory Board of Worldwide Antimalarial Drug Resistance Network and is Coordinator of the West African Network for Clinical Trials of Antimalarial Drugs. A champion of good citizenship in the African research community, Djimdé will be using his International Fellowship position to form new partnerships and initiate new projects across the region.

"The International Fellowship at the Sanger Institute will allow me to engage with colleagues from different disciplines and promote collaborative work between the Sanger Institute and West-African researchers. The Institute is full of brilliant people with expertise and being able to visit and discuss ideas will help to develop our scientific thinking. This will enable us to work together to carry out more research on areas of common interest."

In one such project, Djimdé is exploring the genetic diversity of malarial parasites to discover hotspots of evolution where drug resistance is likely to arise and to track the spread of this resistance. Djimdé has just started a large-scale clinical trial for malaria drugs in Mali, Burkina Faso and Guinea and will use this opportunity to also look at parasite diversity using the Sanger Institute's sequencing platforms. He hopes that this work will ultimately help to improve vaccine design and provide evidence to reinforce the need for a coordinated response.

"The Sanger Institute has the resources to carry out research quickly that would take my lab six months to achieve and would cost four or five times more to do," Djimdé notes. "As an International Fellow, I will be able to access these facilities and this is a very important benefit as we have lots of ideas for future studies that will require sequencing parasite samples."

The benefits from the partnership will flow deeply in both directions. The Institute's Faculty and students will gain invaluable insights and knowledge from Djimdé's experience of conducting research in the field. In addition both the Institute and Djimdé are keen to create further training and research opportunities for mutual benefit.

Researcher takes a blood sample from a villager to collect malaria parasites for analysis.

Researcher takes a blood sample from a villager to collect malaria parasites for analysis. [Dr Abdoulaye Djimde]

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"Our students will have the opportunity to come to the Sanger Institute for a defined period as part of their studies to work on a collaborative project. They will be doing their lab work at the Institute and their field work in Africa," says Djimdé. "We hope that our most promising students may go on to study for a PhD with the Institute's Graduate Programme [in association with Cambridge University]. On the flip side, Sanger Institute staff and students will be able to visit us in Mali to get involved with our work in the field and gain experience of research in developing countries."

The International Fellowship will also allow Djimdé to develop new collaborative research projects, not only focussing on malaria, but also broadening the scope to other diseases of major importance in sub-Saharan Africa. This includes diseases such as cancer, high blood pressure, heart disease, stroke, diabetes and obesity that are becoming more common as the population adopts increasingly westernised, sedentary lifestyles.

"The five-year tenure of being an International Fellow is a good length of time. It will allow us to plan larger studies and strengthen relationships. I grew up in an under-funded research environment where the competition for funding is intense. The support that the Sanger Institute is giving me will also give me leverage to help obtain grants where there may not be funding attached. This will allow us to conduct more research and it gives me peace of mind."

"The first area that we will be working with the Sanger Institute on is the genetic diversity of malarial parasites. This is something we have been discussing with Dominic Kwiatkowski [who leads the Malaria Programme at the Institute]. My dream is to come up with technology that allows me to distinguish between a parasite from village A and a parasite from village B. When we can do this, I think we will then start to get a detailed understanding of how genes flow and how resistance spreads. We have started to draw together a core group of people from across the world and this small nucleus will start to work on this."

"We also have an interest in neglected tropical diseases, such as Leishmania. We will be working with Matt Berriman and Dominic Kwiatkowski to take the research forward with the help of the sequencing facilities at the Institute, and I hope that we will be able to find ways to raise funds to do the field work and sample collection."

Through building successful collaborative research partnerships between researchers in the developed and developing world, Djimide's Sanger Institute International Fellowship is providing an exciting opportunity to drive forward efforts to understand and combat disease in developing countries.

* quick link - http://q.sanger.ac.uk/v3vl3ebk