Relapsing fever spirochetosis is a neglected global disease primarily afflicting those in resource-poor countries (Fig. 9.1). Infection with the causative Borrelia spp. spirochetes can be either louse-borne (epidemic) or tick-borne (endemic). Signs and symptoms largely overlap, but vary between the two in important ways that affect their respective mortality. Where mortality with endemic RF is rare (<5 %), epidemic RF can reach up to 40 % mortality in an outbreak (Raoult and Roux 1999). The true global impact of this disease is masked by the non-specific symptoms caused by the spirochetal infection, such that it may be attributed to other pathogens that are prevalent in a population. For instance, in Sudan an outbreak of louse-borne relapsing fever affected 20,000 villagers with a 10 % mortality rate, yet was originally diagnosed as being caused by a hemorrhagic fever virus (Piesman and Schwan 2010). Further complicating our understanding of the potential significance of this disease is the geographical overlap of RF spirochetes with additional febrile episode-inducing illnesses (Fig. 9.1), with one study reporting that 18.2 % of RF borreliosis cases were misdiagnosed as malaria (Nordstrand et al. 2007).