ABSTRACT Schistosomiasis, a neglected tropical disease also known as Bilharzia or snail fever caused by Schistosoma trematodes, is reported in 78 tropical and subtropical countries across five of the seven continents. However, most of the global burden of this water-borne disease is predominantly found in sub-Saharan Africa (SSA), a region where the need for a One Health approach with anew focus on relevant animal reservoirs has recently been recognised. The existence of ecological settings with a multi-host, multi-parasite biological system is further emphasized by the increasing recovery of hybrids between livestock-specific (such as S. bovis) and human-specific schistosomes (with S. haematobium) from people across SSA. Amongst such settings is the Senegal River Basin (SRB), a schistosomiasis endemic area with year-round and seasonal transmission locations where both humans and their livestock—in particular domestic ruminants that can act as schistosome reservoirs—are affected. While a lack of structured control programs targeting animals remains in SSA, attempts by SRB farmers to decrease the disease impact on livestock productivity have been reported, albeit using inappropriate praziquantel (PZQ) dosages. This doctoral thesis explored a potential transmission control strategy for livestock schistosomiasis by focusing on domestic ruminants of the SRB. Three interconnected lines of enquiry were investigated. Firstly, an illustrative herd-level mathematical model of transmission and control based on baseline 2017 prevalence estimates from 200 sympatric bovines, found that the impact of a test-and-treat intervention targeted at SRB cattle is likely to be significant. Secondly, statistical analyses of 2018 data from a small PZQ drug efficacy trial (59 bovines, 22 goats and 22 sheep, naturally infected by schistosomes) used to derive preliminary drug efficacy estimates for a single 25 mg/kg PZQ dose, highlighted variation in treatment response by animal species and village. Thirdly, optimisation of microsatellite molecular markers to evaluate miracidia recovered from bovines with population genetics methods (175 pre- and 25 post-PZQ miracidia genotyped), uncovered a greater level of differentiation between pre- and post-PZQ samples than between villages during the 2018 trial. Interestingly, genetic signatures of parasite inbreeding were found in the village in which treatment was particularly ineffective. The optimal livestock schistosomiasis PZQ dosage and treatment regimen for SSA domestic ruminants are yet to be determined. This thesis underscores the need for structured control interventions targeted at ruminants within the transmission hotspot of the SRB. Findings represent a contribution towards the design of a One Health strategy to control livestock schistosomiasis in SSA. Such strategy would minimise the risk of PZQ resistance, safeguarding the efficacy of this essential medicine while helping to limit the spread of zoonotic schistosomes and the emergence of hybrids in the region.