AEGiS-11CROI: Molecular Analysis of Blood and Cerebrospinal Fluid Treponema pallidum in Neuroinvasion Compared to Neurosyphilis in HIV-infected Individuals.

11th Conference on Retroviruses and Opportunistic Infections

San Francisco, California - February 8 - 11, 2004

Molecular Analysis of Blood and Cerebrospinal Fluid Treponema pallidum in Neuroinvasion Compared to Neurosyphilis in HIV-infected Individuals.

Conf Retrovir Opportunistic Infect 2004 Feb 8-11; 11:(abstract no. 485)

Marra CM, Bashiri H, Centurion A, Mittler J, Lukehart SA; Univ. of Washington, Seattle, USA

BACKGROUND: Neuroinvasion by Treponema pallidum is common in early syphilis; neurosyphilis, with CSF abnormalities, is less common. The tprK gene in T. pallidum is a single-copy gene that is heterogeneous within and among T. pallidum strains. Organisms within a strain are polyclonal as defined by their tprK sequences, each carrying a single unique sequence.

METHODS: Blood and CSF were collected from 5 HIV-infected individuals with early syphilis. T. pallidum strains were isolated and propagated from blood and CSF by rabbit inoculation. A 630- to 660-bp portion of the tprK gene was amplified directly from blood from all and from CSF from 3 patients. A 1220- to 1260-bp region was amplified from 20 T. pallidum DNA equivalents from all 5 blood and CSF strains. Neighbor-joining clustering analysis was performed from the deduced amino acid sequences using PHYLIP version 3.2. The method of Slatkin and Maddison was used to estimate the average level of gene flow (M) between the blood and CSF compartments.

RESULTS: Based on results of CSF white blood cells and CSF-Venereal Disease Research Laboratory reactivity, 2 patients had neurosyphilis and 3 had neuroinvasion without neurosyphilis. Visual inspection of phylogenetic trees suggested that sequences from the blood and CSF compartments from the 3 patients without neurosyphilis clustered separately, while those from the 2 subjects with neurosyphilis were intermixed. Analysis of gene flow between the compartments for the T. pallidum strains was consistent with this assessment. M (95% CI) for the 3 patients with neuroinvasion: 0.5 (<0.1 to 2.25), <0.1 (0 to 0.4), <0.1 (0 to 0.4); M for the 2 patients with neurosyphilis: 10 (1.3 to 135.2), 3.5 (0.4 to 66.8). Despite the small number of subjects, M tended to be higher in the subjects with neurosyphilis (p = 0.08) and in subjects with higher CSF WBC (p = 0.09).

CONCLUSIONS: Our results suggest that T. pallidum organisms may be compartmentalized in blood and CSF in patients with neuroinvasion, but may be less compartmentalized in patients with neurosyphilis. These findings are consistent with the hypothesis that T. pallidum organisms that invade the CSF are distinct from blood organisms or that they evolve separately from blood organisms once they reach the CSF compartment. Development of an inflammatory response in the CSF may disrupt the blood-CSF barrier and allow for interchange of organisms between the CSF and blood, thus mixing populations.

Keywords: AEGIS, Treponema pallidum, Neurosyphilis, HIV, Syphilis, HIV Infections, DNA, Bacterial, Amino Acid Sequence, HIV-1, Research, Cerebrospinal Fluid Proteins, HIV Seropositivity, Sexually Transmitted Diseases, T-DNA, Human, Animal, Rabbits, blood, cerebrospinal fluid, analysis

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Copyright © 2004 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.