Submission note: A thesis submitted in total fulfilment of the requirements for the degree of Doctor of Philosophy [to the] School of Life Sciences, College of Science, Health and Engineering, La Trobe University, Victoria, Australia.
The filarial parasitic nematode Onchocerca volvulus causes the disease onchocerciasis, with 204 million people at risk of infection, mainly in Africa. Mass drug administration with ivermectin has been implemented for up to 30 years in some communities with an aim of elimination. Before stopping treatment, elimination thresholds within a transmission zone need to be met; thus, defining transmission zone boundaries is integral to stop-treatment decisions. However, current transmission zone definitions do not incorporate possible parasite migration. Furthermore, once treatment has been stopped, distinguishing between new and on-going infection by reproductively active females indicates whether transmission has ceased, yet there is no current method for detecting new infections. Population genetics is a tool for genetic epidemiology that could answer these questions, but no studies have done so in O. volvulus. I tested the hypothesis that O. volvulus has geographically large transmission zones. The mitochondrial genomes of 189 adult O. volvulus samples from West Africa were sequenced and analysed. Population structure indicates that transmission zones are geographically large ( greater than 100-200km) which may compromise the long-term sustainability of elimination if treatment ceases prematurely. Microfilariae are routinely collected during onchocerciasis elimination surveillance, and so a similar approach was adapted for this more epidemiologically practical life stage. Analysing sequence data from microfilariae from 48 individual patients from Central Africa indicated that transmission zone size is similar to those in West Africa. The use of microfilariae also enabled the estimation of the number of actively reproducing female worms per patient (average 3.19). Estimates of the active female worm population size could be a valuable adjunct to current disease surveillance methods tracking the success of elimination. Finally, analysis of all available O. volvulus mitochondrial genome data across Africa indicated the parasite meta-population fits an isolation-by-distance migration pattern, suggesting that transmission zones are large but with cross-continental migration unlikely
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