African trypanosomiasis or sleeping sickness — caused when the parasite is transmitted between livestock and humans via tsetse fly bites — infects 30,000 people, and causes losses of US$1 billion from livestock production a year in Sub-Saharan Africa, according to the study published in PLOS Neglected Tropical Diseases last month (15 August).
Researchers have been considering genetically modifying bacteria that live inside tsetse flies, to try to eliminate the disease in the wild, a strategy called paratransgenesis.
A group of researchers in the United States modelled the spread of a bacteria (Wolbachia) to see if it could help drive another bacteria (Sodalis) carrying the resistance gene into the wild tsetse population.
"Sodalis lives in the gut and Wolbachia lives in the reproductive organs [of tsetse flies]. But they are transmitted together to the tsetse progeny," Serap Aksoy, co-author of the study and a researcher at the Yale School of Public Health, tells SciDev.Net.
Wolbachia gives the female tsetse flies in which it resides a reproductive advantage over female flies in which it does not, therefore becoming more common over time in the tsetse population. (But its presence in the population of flies also depends on different factors.)
It is this well-known feature of Wolbachia that made researchers think of it as a way to spread the resistance gene inserted into Sodalis, as the link in transmission between the two bacteria species had been shown to work in the laboratory in previous studies.
Sodalis is an ideal carrier of the resistance gene as it resides in the gut, which is where the sleeping sickness parasite first multiplies following infection, researchers say.
The study used data from Sub-Saharan Africa on the transmission of sleeping sickness among tsetse flies, humans and livestock, alongside data from Uganda on the number of wild tsetse flies carrying Wolbachia, to show that paratransgenesis is a promising technique for eliminating the disease.
It shows that a single release of tsetse flies, carrying both Wolbachia and genetically-modified Sodalis, could potentially eliminate sleeping sickness in between one-to-ten years, depending on the exact numbers of flies released.
“If this technique of paratransgenesis is applicable on a large-scale while using limited resources, it may prove to be a very useful control method.”
François Chappuis, Médecins Sans Frontières
But because several tsetse fly species exist in the wild, this can only be achieved if the species released comprises at least 85 per cent of the total population in the area of release.
Aksoy also warns that the model works under the assumptions that the anti-parasite gene is not lost from the tsetse population, the parasite does not gain resistance to it and the link between Sodalis and Wolbachia does not break.
François Chappuis, a medical advisor for Médecins Sans Frontières, an NGO involved in the fight against sleeping sickness, says: "Every new control method that is developed can be used alongside existing methods ... If this technique of paratransgenesis is applicable on a large-scale while using limited resources, it may prove to be a very useful control method.
"But going from a mathematical model to a pilot study in infected areas and then applications in large, remote areas seems a long way off."
Aksoy's lab is now planning to insert the resistance gene into Sodalis, a feat that has been independently achieved by Jan Van Den Abbeele, a senior researcher at the Institute of Tropical Medicine in Antwerp, Belgium.
Van Den Abbeele plans to take the technique a step further by recolonising tsetse flies with genetically modified Sodalis to see if it protects flies from carrying the sleeping sickness parasite.
"So far, we were successful in genetically-modifying Sodalis to express an [anti-parasite gene] that specifically targets bloodstream [parasites]. With this we showed the proof-of-concept that indeed the Sodalis bacterium is able to express and release a sufficient amount of active, functional, parasite-targeting [compound]," Van Den Abbeele tells SciDev.Net.
His team is continuing to identify genes coding for proteins that target the parasite in the tsetse fly gut, and studying the inheritance of the genetically modified bacteria.
"We are now doing more basic research to understand better the mechanism of Sodalis mother-to-offspring transfer in order to use that knowledge to improve [its] transfer to the [tsetse] offspring," he says.
The aim is to produce tsetse flies that are resistant to human and animal sleeping sickness , says Van Den Abbeele, but a similar approach is also being explored for malaria and Chagas disease, which are transmitted by mosquitoes and Triatoma bugs respectively.
>Link to full study
>Link to full study by Van Den Abbeele