A Disconnect between the Neurospirochetoses in Humans and Rodent Models of Disease

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The human spirochetal diseases share many clinical similarities despite their diverse epidemiology. Syphilis is a sexually transmitted infection, whereas the leptospiroses and the borrelioses are zoonoses. The clinical similarities among the spirochetoses include a relapsing-remitting course of infection. The recurrent pattern of illness has three invariant features that are shared by all human spirochetoses. Entry of spirochetes is achieved through breaks in the skin or through mucous membranes. Cutaneous lesions such as the syphilitic chancre or the erythema migrans of Lyme disease constitute the earliest manifestations of these two diseases. In all three spirochetoses, there is dissemination to distant organs through tissues, blood, and other fluids. Late disease, often with intervening relapses and latent periods, can involve one or more organ systems. The spirochetal diseases also share tropisms for skin, nervous system, and heart and arteries. The neurotropism of spirochetes is evident in syphilis, the human borrelioses (Lyme disease and relapsing fevers), and in leptospirosis. Spirochetes enter the central nervous system (CNS) very quickly. Their ability to cause neurological disease may be dependent on the virulence of the infecting strains and on the development of an inflammatory response. Yet, most of the current animal models for the spirochetoses either do not recreate the manifestations of the neurological spectrum or require special manipulations to establish infection (Figure 1). Thus, a major challenge for experimental approaches to the human neurological manifestations of the spirochetoses has been an inability or difficulties in reproducing all or some aspects of the human disease in animal models. Figure 1 Summary of animal models for the neurospirochetoses.