Modelling the impact of a transmission blocking vaccine against leishmaniasis on sand fly vectorial capacity
Led by Dr Matthew Rogers (LSHTM, UK), with Dr Laith Yakob (LSHTM, UK), and Dr Godwin Kwayke-Nuako (University of Cape Coast, Ghana)
Transmission blocking vaccines could offer a new way of controlling Leishmania infection by preventing the parasite from establishing themselves in their sand fly vector. However, before such targets are sought the feasibility of such a strategy must first be explored using a combination of basic knowledge of the transmission dynamics between hosts and vectors, the biology of the interaction between the parasite and its vector host and mathematical modelling. By applying modelling to a limited data set from the literature we have found that a hypothetical transmision blocking vaccine (TBV), which prevents the parasites from attaching to the gut of the sand fly, could result in effective protection or, worryingly, more transmission. These drastically different scenarios were dependent on whether Leishmania influence the survival of the sand fly in the early or later stages of infection. In this study we aim to clarify this and develop an improved model of sand fly transmission to better assess the impact of TBVs in the future. To do this we propose to conduct a series of sand fly infections using variable infecting doses of parasites, under stressed and unstressed conditions to extract data to parameterize our model. In addition, we will take advantage of mutant Leishmania which fail to attach or survive beyond the infecting bloodmeal, to test which parasites stages are responsible for sand fly mortality. We will also apply our model to an emerging Leishmania-vector relationship involving a new group of pathogenic Leishmania in Ghana and midges, which can host these parasites to a mature, transmissible stage. Data from this study will enable us to develop better TBVs against leishmaniasis.
Transmission blocking vaccines could offer a new way of controlling Leishmania infection by preventing the parasite from establishing themselves in their sand fly vector. The aim of the project was to improve our understanding of this parasite-vector interaction to assess transmission blockade as a means of leishmanaisis control. Our initial modelling found that a hypothetical transmission blocking vaccine (TBV), which prevents the parasites from attaching to the gut of the sand fly, could result in effective protection or, worryingly, more transmission, depending on whether Leishmania influences the survival of the sand fly in the early or later stages of infection. Our results, over a series of sand fly infections using variable infecting doses of parasites, under stressed and unstressed conditions, demonstrated that parasite-induced mortality was determined by the density of infecting parasites. Furthermore, this was only manifest if the infected vector was subjected to other environmental stresses, including sugarmeal deprivation, induced flight and low temperatures. Experiments using mutant Leishmania which fail to attach or survive beyond the infecting bloodmeal, highlighted that sand fly mortality was associated with the early, bloodmeal, stages of the parasite. This was confirmed with wild type Leishmania infections stressed at specific times, which showed that parasite-induced mortality was restricted to the bloodmeal phase of development (days 1-4), not after, when the sand fly became infectious. These data indicate that a TBV which targets midgut attachment should work and have a proportional effect on transmission. Data acquired during these experiments are currently being used to parameterize our TBV model to confirm this.
Hall A. R., Blakeman J. T., Eissa A. M., Chapman P., Morales-García A. L., Stennett L., Martin O., Giraud E., Dockrell D. H., Cameron N. R., Wiese M., Yakob L., Rogers M. E.* and Geoghegan M. (2020). Glycan-glycan interactions determine Leishmania attachment to the midgut of permissive sand fly vectors. Chemical Science.
Research models/tools/methods created:
- New experimental model for transmission blockade evaluation
- New experimental model for testing Leishmania vectorial capacity
- New mathematical model for transmission blockade evaluation
- New mathematical model for testing Leishmania vectorial capacity