Tick-borne diseases are the most common vector-borne diseases in the US. North Carolina suffers from some of the highest rates of Rocky Mountain spotted fever (RMSF), which can cause severe illness and death. The first aim of this dissertation explored whether spotted fever group rickettsiae (SFGR) other than Rickettsia rickettsii are responsible for spotted fever rickettsioses in North Carolina. A retrospective seroepidemiologic study was conducted in which the reactivity of paired sera from North Carolina patients who had been tested for RMSF we evaluated against a panel of SFGR, including R. rickettsii, R. amblyommii, and R. parkeri. Of the 106 eligible pairs tested, 21 patients seroconverted to one or more antigens. Cross-reactivity was observed in ten patients and seroconversions to single antigens occurred in 11 patients, including one against R. rickettsii, four against R. parkeri, and six against R. amblyommii. These findings suggest that species other than R. rickettsii are associated with illness among North Carolina residents. The second aim of this dissertation focused on tick bite prevention among North Carolina outdoor workers. A double-blind randomized controlled trial was conducted to evaluate the protective effectiveness of long-lasting permethrin impregnated (LLPI) uniforms among workers from North Carolina State Divisions of Forestry, Parks and Recreation, and Wildlife. 159 subjects were randomized; uniforms of participants in the treatment group were factory-impregnated with long-lasting permethrin while control group uniforms received a sham treatment. Participants continued standard recommended tick-bite prevention activities and provided weekly tick bite logs during two tick seasons. 130 subjects reported 1,045 work-related tick bites over 5,251 person-weeks of follow-up. The effectiveness of LLPI uniforms for the prevention of work-related tick bites was 0.82 (95% Confidence Interval (CI): 0.66, 0.91) for the first year of follow-up and 0.34 (95% CI: -0.67, 0.74) for the second year of follow-up. These results indicate that LLPI uniforms are highly effective for at least one year against tick bites in the context of existing tick bite prevention measure usage by outdoor workers.