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Tsetse genome helping find sleeping sickness cure – Prof. Jan Van Den Abbeele

The tsetse fly is the carrier of trypanosomiasis, or sleeping sickness. ©Institute of Tropical Medicine
The tsetse fly is the carrier of trypanosomiasis, or sleeping sickness. ©Institute of Tropical Medicine

The genome of the tsetse fly was sequenced in April, and it means scientists are closing in on a way to fight diseases caused by the pathogen it carries, according to Professor Jan Van Den Abbeele at the Institute of Tropical Medicine in Antwerp, who helped generate the data along with his team of researchers. 

Which aspects of the genome sequencing were you working on and why is it important? 

‘We were part of a collaboration of more than 140 experts around the world working on the tsetse genome and we were working on the saliva glands. This is important because the pathogen, a protozoa (single-celled organism) from the genus Trypanosoma, cycles within the tsetse fly and interacts within the saliva to turn into the dangerous infective form which can be spread to farm animals and humans.’

What are the illnesses associated with it?

Professor Jan Van Den Abbeele, the principal investigator of the NANOSYM project, is looking for a way to fight the drug-resistant parasite that causes sleeping sickness.Professor Jan Van Den Abbeele, the principal investigator of the NANOSYM project, is looking for a way to fight the drug-resistant parasite that causes sleeping sickness.

‘African trypanosomiasis is called sleeping sickness in humans and affects farm animals in a disease called nagana. Without treatment, sleeping sickness is 100 % fatal in humans. However the number of cases have reduced due to surveys of local areas, treatment and tsetse fly traps in areas where the flies are found such as beside rivers. In animals the disease is spread much more widely and has led to large areas which cannot be cultivated. In addition, the pathogen has been able to develop resistance to the only two veterinary drugs which are available.’

You are also leading the EU-funded NANOSYM project. What is the project trying to achieve?

‘NANOSYM is a five-year European Research Council-funded project which is looking at modifying beneficial symbiotic bacteria (that live alongside dangerous parasites) in the tsetse fly. The Trypanosoma infects less than 1 % of all tsetse flies and has a complicated life cycle within the insect. It only reaches full cycle two weeks after the tsetse fly has taken blood from an infected farm animal, then it reaches the saliva gland and can spread to other animals that the insect bites.

‘The idea is to genetically modify the bacteria to release nanobodies (ultra small antibodies) which block transmission of the pathogen by the tsetse fly. We have been able to grow the modified bacteria in the laboratory, so the next stage is to see if they will survive inside the tsetse fly and produce the nanobodies to stop the pathogen.

‘With the full genome of the tsetse fly, we can pinpoint the pathways for disease transmission.’

Professor Jan Van Den Abbeele, principal investigator of the NANOSYM project

‘Currently, the tsetse fly is targeted via an International Atomic Energy Agency (IAEA) sterile insect programme which uses gamma radiation to make male insects infertile (before releasing them into the wild in huge numbers). As the female tsetse fly mates only once and produces live larvae, this can have an effect on the total tsetse fly population. However, the tsetse fly can still spread the Trypanosoma pathogen and so a large influx of insects from the sterile insect programme can temporarily increase the rates of disease. If sterile insects could be produced which also included the bacteria which had been modified this would prevent the disease from being spread.’

How will the genetic breakthrough help fight the spread of sleeping sickness and nagana?

‘With the full genome of the tsetse fly, we can pinpoint the pathways for disease transmission and develop new technologies to prevent the pathogen from being spread. In other insects we know that components in the saliva are essential for the transmission of pathogens and we think that, in the tsetse fly, the pathogen is making use of proteins in the saliva to survive in the animal hosts it infects.’

What is the wider importance of studying the tsetse fly?

‘This is a novel approach to tackling the Trypanosoma pathogen but it is important to understand the biology behind parasitic diseases carried by other insects.

‘In Europe, people and animals are not infected by tsetse flies, however in the future we may need to be able to treat pathogens carried by other insects – as they move north with the change in climate and from accidental infections caused by larvae being imported with goods. 

‘In Africa, the total eradication of the tsetse fly is not possible and not ecologically pertinent as it has an important role in the ecosystem (preventing farmers from cultivating wild land). It is important to continue with activities such as treatment, education and the IAEA sterile insect programme alongside more research to ensure that sleeping sickness does not come back and that African livestock farmers can be more effective in specific parts of Africa.’

Sleeping sickness

In total, 70 million people are at risk of contracting human African trypanosomiasis, or sleeping sickness, with an estimated 50 000 people infected. In addition, 50 million animals are at risk of nagana, the animal version of the disease, with annual deaths of 3 million animals across 37 African countries.

The International Atomic Energy Agency (IAEA) supports Sterile Insect Technique programmes combating tsetse flies in 14 countries. The Southern Tsetse Eradication Project in Ethiopia started in 2009 and involved the weekly release of between 30 000 and 60 000 sterile male tsetse flies which has reduced the local population of tsetse flies by 90 %.

The EU has pledged almost EUR 24 million to help fund four projects that have recently started looking for new drugs to tackle parasitic diseases in developing countries, including sleeping sickness. This follows on from two additional projects funded at the start of 2007.

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