An Experimental Model of Early Central Nervous System Syphilis

Abstract

Although up to 40% of patients with early syphilis have evidence of central nervous system (CNS) invasion by Treponema pallidum, the pathogenesis of CNS syphilis is not understood. A rabbit model that mimics early CNS involvement in humans was developed and characterized. Mild cerebrospinal fluid pleocytosis was evident 2 weeks after intracisternal inoculation of T. pallidum and peaked at 9 weeks. The VDRL test in cerebrospinal fluid was reactive in 24% of animals, most commonly at 9 weeks after infection. T. pallidum could be isolated from the CNS of animals infected for 4, 6, or 9 weeks but not from animals infected for 12 or 20 weeks. Clinically, 6% of animals developed uveitis, similar to the frequency in patients with secondary syphilis. Thus, this model of meningeal and ocular syphilis seems to be analogous to the early CNS infection in humans and can be used for studies of pathogenesis and treatment.

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

“…Both neurosyphilis and Lyme neuroborreliosis are characterized by an early invasion of the nervous system, as shown by experimental evidence in animal models [10], [16]. This is consistent with the finding of a clinically silent CSF pleocytosis in many patients at an early stage of infection, likely representing early nervous system invasion.…”

“…Likewise, uveitis has been reported in rabbits inoculated via the intradermal route [9]. Meningeal and ocular manifestations in this model recreate the early neurosyphilis in patients [10]. NHP were infected by the intrathecal route resulting in objective neurosyphilis findings that included pleocytosis in the CSF, persistence of organisms for several weeks, and changes in cytokine profiles.…”

Biological Basis for Syphilis

“…After testicular infection of rabbits, treponemes were visible in the lymph nodes, brain, and aqueous humor, and in the CSF as early as 18 h postinoculation (73). T. pallidum RNA has also been detected by reverse transcription-PCR in the CSF of intravenously infected animals (306), and Marra et al found that 6% of rabbits inoculated by the intrathecal method developed ocular syphilis (192), demonstrating that organisms are able to travel from the CSF to the eye. Not only do treponemes disseminate to distant sites but they also can persist in distant tissues during chronic infection.…”

Treponema pallidumStrain‐Specific Differences in Neuroinvasion and Clinical Phenotype in a Rabbit Model

“…Serologic analysis and CSF RT-PCR. Serum VDRL and fluorescent treponemal antibody-absorbed (FTA-ABS) tests were performed as described elsewhere [12]. CSF-VDRL was performed using standard methods [13].…”