Enhancing Vector Refractoriness to Trypanosome Infection

Objective:

Four main research questions will be addressed by the CRP:

  • Can the elucidation of tsetse-trypanosomes molecular interactions help to reduce or eliminate the transmission of trypanosomosis?
  • Can the characterization and harnessing of the tsetse symbiome and pathogens help to improve the SIT?
  • How are tsetse symbionts affected by radiation?
  • Can tsetse symbionts be used to develop novel vector and disease control tools, complementary to the SIT?

Activities:

The SIT relies on the release of sterilized male insects to mate with virgin wild female insects. In the case of disease vectors, such as tsetse, the sterilising dose that the insects receive does not reduce their vectorial capacity. It is therefore critical when large numbers of sterile male vectors are released, that the risk of transmission of the disease is minimized or eliminated. In the case of tsetse flies, disease transmission has in the past been minimized by holding sterile males after emergence and adding trypanocidal drugs to the blood meal when feeding them before release.

The development of strains that would be refractory to the transmission of trypanosomes would however be a much simpler and hopefully more effective method of ensuring that released sterile flies do not transmit the disease. In that way, the SIT for tsetse and other trypanosome vectors could be significantly improved.

Tsetse flies (Diptera: Glossinidae) are the only cyclical vectors of African trypanosomes, protozoan parasites that cause sleeping sickness in humans (HAT) and animal African trypanosomosis (AAT). HAT is endemic to 36 countries in sub-Saharan Africa with about 70 million inhabitants at risk. In 2009, the number of new cases of HAT reported to WHO dropped below the symbolic number of 10 000. However, given that the disease affects hard to reach rural populations, and that active surveillance in war-torn areas is non-existent, the disease prevalence numbers are undoubtedly a gross underestimation. The related disease AAT, causes estimated losses to African agriculture of at least US $4.5 billion per year and has a profound effect on the development of the continent.

Most economically important African trypanosomes are transmitted during the bite of the tsetse fly. Humans are only infected by Trypanosoma brucei rhodesiense and T. b. gambiense. The 'nagana' causing related trypanosomatids T. vivax, T. congolense and T. brucei brucei are major pathogens of livestock. The natural transmission of the major medically and veterinary important trypanosome species (T. brucei ssp., T. congolense and T. vivax) relies on the specific biological relationship between the parasites and the blood feeding insect vector, the tsetse fly. Indeed, depending on the trypanosome species, the parasite has to go through an obligatory developmental cycle that varies from a short cycle in the mouthparts of the fly (T. vivax) to a longer, more complex life cycle in the tsetse fly midgut and mouthparts (T. congolense) or the midgut, mouthparts and salivary glands for the T. brucei subspecies. For both T. congolense and T. brucei, the molecular interplay at different stages of development will determine the success of parasite development in the fly to the final infective stage. A better understanding of the vector-trypanosomes-symbiont tripartite association is essential to develop methodologies that could result in the enhancement of refractoriness of the vectors to trypanosome infection.

Tsetse flies also harbour three maternally transmitted bacterial endosymbionts that presumably assume different roles with respect to their host's biology. Wigglesworthia, an obligate mutualist, is found in all tsetse flies examined to date. Tsetse's second symbiont, Sodalis, is a commensal bacterium found in all lab-colonized tsetse lines and some natural populations. Finally, some tsetse populations are colonized with Wolbachia. This bacterium is restricted to tsetse's germ line, and exhibits a parasitic phenotype in its host. All three of these symbionts are potentially exploitable for the purpose of reducing trypanosome transmission through tsetse. Interestingly, while only these three bacteria are found in laboratory colonies of tsetse, field caught flies house a taxonomically diverse bacterial population that further manipulates their host's biology.

The elucidation of these interactions is essential to understand the determinants of tsetse vector competence for a given trypanosome population and how they can be affected. This knowledge will help to develop tools to enhance refractoriness to trypanosome infection. In this context this CRP will focus on various aspects of this tripartite association. It will offer a unique opportunity to bring together different research groups working on tsetse and other vectors of trypanosomes from different regions in the world that are active in this scientific field stimulating inter-disciplinary discussions and collaborative work.

Participants:

Eighteen participating countries: Australia, Austria, Belgium, Burkina Faso, Cameroon, Ethiopia, France, Germany, Greece, Italy, Kenya, Netherlands, South Africa, Slovakia, Tanzania, Turkey, UK, and USA.

Reports:


Project Officer:

Andrew Parker and Abd Alla Adly Mohamed Mohamed