Page 1 IAEA-314-D42015-CR-.2 LIMITED DISTRIBUTION WORKING MATERIAL ENHANCING VECTOR REFRACTORINESS TO TRYPANOSOME INFECTION SECOND RESEARCH COORDINATION MEETING ORGANIZED BY THE JOINT FAO/IAEA DIVISION OF NUCLEAR TECHNIQUES IN FOOD AND AGRICULTURE Dec 1-5, 2014 Addis Ababa, Ethiopia NOTE The material in this document has been supplied by the authors and has not been edited by the IAEA. The views expressed remain the responsibility of the named authors and do not necessarily reflect those of the government of the designating Member State(s). In particular, neither the IAEAA nor any other organization or body sponsoring the meeting can be held responsible for any material reproduced in this document. Page 3 Table of Contents 1. INTRODUCTION AND CURRENT STATUS ........................................................................... 5 2. REVISED LOGICAL FRAME WORK ..................................................................................... 11 3. INDIVIDUAL WORK PLANS FOR THE NEXT 18 MONTHS .............................................. 18 4. Recommendations ....................................................................................................................... 29 5. AGENDA ................................................................................................................................... 30 Monday, 1 st December, 2014 ............................................................................................................. 30 SESSION 1 .................................................................................................................................... 30 SESSION 2 .................................................................................................................................... 30 LUNCH .............................................................................................................................................. 31 COFFEE ............................................................................................................................................. 31 Martin Kaltenpoth, Tobias Engl, Veronika Michalkova, Brian Weiss, Daniela Schneider, Wolfgang Miller, Serap Aksoy: Influence of symbiotic bacteria on cuticular hydrocarbon profiles in tsetse flies ( Glossina m. morsitans ) ............................................................................................................. 31 Wolfgang J. Miller and Daniela Schneider: Symbiont-triggered Speciation - Lessons from Tsetse Fly Hybrids ........................................................................................................................................ 32 Wednesday 3 rd December, 2014 .................................................................................................... 34 SESSION 9 .................................................................................................................................... 34 General Discussion of the Logical Framework and CRP evaluation documents .............................. 34 COFFEE ............................................................................................................................................. 34 Working Group Discussions .............................................................................................................. 34 LUNCH .............................................................................................................................................. 34 Excursion to STEP project tsetse mass rearing facility ..................................................................... 34 Group Dinner ..................................................................................................................................... 34 Thursday 4 th December, 2014 ........................................................................................................ 35 SESSION 10 .................................................................................................................................. 35 Working Group Discussions .............................................................................................................. 35 Working Group Discussions .............................................................................................................. 35 LUNCH .............................................................................................................................................. 35 Drafting Report .................................................................................................................................. 35 Drafting Report .................................................................................................................................. 35 Friday 5 th December, 2014 ................................................................................................................. 36 SESSION 11 .................................................................................................................................. 36 6. LIST OF PARTICIPANTS......................................................................................................... 37 7. NEXT MEETING ....................................................................................................................... 41 8. WORKSHOP .............................................................................................................................. 41 ANNEX I: WORKING PAPERS ...................................................................................................... 43 Page 4 Page 5 1. INTRODUCTION AND CURRENT STATUS Tsetse and African trypanosomosis . 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) in domesticated animals. HAT is endemic to 36 countries in sub-Saharan Africa with about 70 million of the 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 US$ 4,5 billion per year and has a profound effect on 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. Following the success of the SIT programme in Zanzibar and the PATTEC initiative of the AU, there interest in the use of SIT for tsetse and trypanosomosis control is increasing. To date, the IAEA supported SIT projects have been in areas without human sleeping sickness, but future projects could include areas of actual or potential human disease transmission. In such projects it would be ethically unacceptable to release flies capable of transmitting the infection to humans and so it is essential to understand the mechanisms that limit the development of infections in tsetse and how these may be enhanced. This CRP proposal addresses this issue, in particular through the interaction of the fly, its immune system, the trypanosomes and the other microorganisms associated with tsetse. Tsetse-trypanosome interactions . The transmission cycle starts when a tsetse fly feeds on an infected host. Here, the various trypanosome species have a different developmental cycle in various tissues/ organs of the tsetse fly vector. T. vivax has the simplest life cycle with a development exclusively in the mouthparts. So far, only limited information is available on factors that affect T. vivax development in the tsetse fly. For T. congolense and T. brucei initial establishment of infection occurs in the fly midgut with a subsequent maturation in the tsetse fly proboscis and salivary gland respectively. During this journey, these parasites undergo several rounds of differentiation and proliferation, finally ending in the metacyclic form that is the end-stage infective to the mammalian host. The success rate of trypanosome colonization in the tsetse fly is low and often fails during initial establishment in the vector midgut. Tsetse flies mount innate immune responses and down regulation of the Imd pathway increases the efficiency of midgut colonization. Similarly, RNAi silencing of a tsetse fly immune-responsive glutamine/proline-rich (EP) protein promotes trypanosome establishment. Reactive oxygen species are important determinants of resistance. From the midgut, trypanosome differentiation and migration to the salivary glands represents a significant bottleneck that remains to be fully understood. The proventriculus, which is an immune-active tissue, transcribes nitric oxide synthase and contains increased levels of nitric oxide, reactive oxygen intermediates and hydrogen peroxide (H 2O2). From the proventriculus, only a few trypanosomes will achieve an elusive journey to the salivary glands. The tsetse fly salivary gland plays a key role as a biotope where the parasites adhere, multiply and undergo the final re-programming into the infectious metacyclic forms. Information on the saliva composition is scanty and mainly based on in silico interpretation of the salivary