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Invasion of the Central Nervous System by Treponema pallidum: Implications for Diagnosis and Treatment
Abstract
STUDY OBJECTIVES: To determine the prevalence of Treponema pallidum in cerebrospinal fluid (CSF) of patients with syphilis, to determine the effect of concurrent HIV infection on central nervous system involvement by T. pallidum, and to examine the efficacy of conventional therapy for asymptomatic neurologic involvement. PATIENTS: Fifty-eight patients with untreated syphilis who consented to lumbar puncture, representing approximately 10% of new cases of syphilis during the study period. INTERVENTIONS: Lumbar puncture was done on all patients. Rabbit inoculation was used to test cerebrospinal fluid for viable T. pallidum. Patients with normal fluid received recommended benzathine penicillin therapy according to the stage of syphilis; patients with CSF abnormalities were offered 10-day therapy for neurosyphilis. RESULTS: Treponema pallidum was isolated from the CSF of 12 (30%) of 40 patients (95% CI, 17 to 46) with untreated primary and secondary syphilis; isolation of T. pallidum was significantly associated (P = 0.008) with the presence of two or more abnormal laboratory variables (among leukocyte count, protein concentration, and CSF-Venereal Disease Research Laboratory [VDRL] test). Two (67%) of 3 early latent (CI, 13 to 100) and 3 (20%) of 15 late latent syphilis patients (CI, 5 to 47) also had reactive CSF-VDRL tests and elevated cell and protein levels, although T. pallidum was not isolated. Concurrent infection with the human immunodeficiency virus (HIV) was not associated with isolation of T. pallidum, increased number of CSF abnormalities, or reactive CSF serologic tests for syphilis, although CSF pleocytosis was commoner in subjects infected with HIV. Treatment with conventional benzathine penicillin G (2.4 mIU) failed to cure 3 of 4 patients with secondary syphilis from whom T. pallidum was isolated before therapy; all 3 patients in whom treatment failed were HIV seropositive when treated or seroconverted during follow-up. CONCLUSIONS: Central nervous system invasion by T. pallidum is common in early syphilis, and is apparently independent of HIV infection. Examination of the CSF may be beneficial in patients with early syphilis, and therapy should be guided by knowledge of central nervous system involvement. Conventional benzathine penicillin G therapy may have reduced efficacy in patients with early syphilis who are also infected with HIV.
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“Invasion of CSF by T. pallidum accompanied by CSF laboratory abnormalities is common among adults who have primary or secondary syphilis but has unknown medical significance (585).”
From Sexually Transmitted Infections Treatment Guidelines, 2021 (2021) · cites this paper as [585]
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BackgroundHay, P., Clarke, J. R., Strugnell, R. A., TAYLOR‐ROBINSON, D., & Goldmeier, D. (1990) · FEMS Microbiology Letters · doi:10.1016/s0378-1097(05)80046-1 · Cited by 82
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Molecular Differentiation ofTreponema pallidumSubspecies
Centurion‐Lara, A., Molini, B. J., Godornes, C., Sun, E. S., Hevner, K., A, W. C. V. V., & Lukehart, S. A. (2006) · Journal of Clinical Microbiology · doi:10.1128/jcm.00784-06 · Cited by 78
Self-citationEvaluation and treatment of congenital syphilis
Ikeda, M. K., & Jenson, H. B. (1990) · The Journal of Pediatrics · doi:10.1016/s0022-3476(05)80120-9 · Cited by 76
Syphilis and HIV Infection: an Update
Stevenson, J., & Heath, M. L. (2006) · Dermatologic Clinics · doi:10.1016/j.det.2006.06.013 · Cited by 75
Castro, R., Prieto, E., & Pereira, F. (2008) · Journal of Clinical Laboratory Analysis · doi:10.1002/jcla.20254 · Cited by 75
“This may be a consequence of a possible neurological reaction in secondary syphilis, as previously stated by other authors (12), or to be in relation with the HIV infection present in these patients.”
ResultLaFond, R. E., Centurion‐Lara, A., Godornes, C., Rompalo, A. M., A, W. C. V. V., & Lukehart, S. A. (2003) · Journal of Bacteriology · doi:10.1128/jb.185.21.6262-6268.2003 · Cited by 75
“inoculation of the cerebrospinal fluid from three patients with neurosyphilis (11),”
BackgroundSelf-citationSmith, N. H., Musher, D. M., Huang, D. B., Rodriguez, P. S., Dowell, M. E., Ace, W., & White, A. C. (2004) · International Journal of STD & AIDS · doi:10.1177/095646240401500511 · Cited by 74
Horowitz, H. W., Valsamis, M. P., Wicher, V., Abbruscato, F. C., Larsen, S. A., Wormser, G. P., & Wicher, K. (1994) · New England Journal of Medicine · doi:10.1056/nejm199412013312204 · Cited by 74
Sánchez, P. J., & Wendel, G. D. (1997) · Clinics in Perinatology · doi:10.1016/s0095-5108(18)30185-4 · Cited by 74
Clinical Prediction and Diagnosis of Neurosyphilis in HIV-Infected Patients with Early Syphilis
Dumaresq, J., Langevin, S., Gagnon, S., Serhir, B., Deligne, B., Tremblay, C. L., Tsang, R. S. W., Fortin, C., Coutlée, F., & Roger, M. (2013) · Journal of Clinical Microbiology · doi:10.1128/jcm.01989-13 · Cited by 72
“pallidum in the CSF is possible using rabbit infectivity testing, but this cumbersome method requires live virulent bacteria, and even if it can detect as few as one to 10 organisms, its sensitivity and specificity for the diagnosis of NS are imperfect (17).”
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Treatment of syphilis in HIV-infected subjects: a systematic review of the literature
Blank, L. J., Rompalo, A., Erbelding, E. J., Zenilman, J. M., & Ghanem, K. G. (2010) · Sexually Transmitted Infections · doi:10.1136/sti.2010.043893 · Cited by 70
Changes in neurosyphilis presentation: a survey on 286 patients
Drago, F., Merlo, G., Ciccarese, G., Agnoletti, A. F., Cozzani, E., Rebora, A., & Parodi, A. (2016) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/jdv.13753 · Cited by 72
Clinical Spectrum of Neurosyphilis among HIV-Negative Patients in the Modern Era
Zhang, H., Lin, L., Liu, G.-L., Zeng, Y., Wu, J., Zheng, W., Tong, M.-L., Dong, J., Su, Y., Liu, L., et al. (2013) · Dermatology · doi:10.1159/000347109 · Cited by 69
Central Nervous System Infections
Archibald, L. K., & Quisling, R. G. (2013) · Springer eBooks · doi:10.1007/978-1-4471-5226-2_22 · Cited by 76
Marra, C. M. (2004) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-004-0065-x · Cited by 68
Current Controversies in the Management of Adult Syphilis
Stoner, B. P. (2007) · Clinical Infectious Diseases · doi:10.1086/511426 · Cited by 67
“On one hand, although it has long been known that treponemal invasion of the CNS occurs quite frequently in early syphilis, most patients seem to respond to standard, nonneurosyphilis treatment regimens for early syphilis [80].”
BackgroundMolecular Evolution of the tprC, D, I, K, G, and J Genes in the Pathogenic Genus Treponema
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Biological False-Positive Syphilis Test Results for Women Infected with Human Immunodeficiency Virus
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“In addition, syphilitic lesions probably facilitate the transmission of HIV [4], while the immunosuppression associated with HIV infection may alter the natural history of syphilis and its response to therapy [5-7].”
BackgroundHutchinson, C. M., & Hook, E. W. (1990) · Medical Clinics of North America · doi:10.1016/s0025-7125(16)30487-4 · Cited by 64
Self-citationSyphilis: New Diagnostic Directions
Young, H.-K. (1992) · International Journal of STD & AIDS · doi:10.1177/095646249200300601 · Cited by 63
SYPHILITIC ARTHRITIS AND OSTEITIS
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Metadata
- Authors
- Lukehart, S. A., Hook, E. W., Baker-Zander, S. A., Collier, A. C., Critchlow, C. W., & Handsfield, H. H.
- Affiliations
- University of Washington (US)
- Venue
- Annals of Internal Medicine
- Publisher
- American College of Physicians
- Published
- 1988-12-01
- Volume
- 109
- Issue
- 11
- Pages
- 855-862
- ISSN
- 0003-4819 (ISSN-L)
- 1539-3704
- OpenAlex
- W2056330847
- Cited by
- 603
- References
- 41
- Citations by year
- 2026: 14 · 2025: 13 · 2024: 16 · 2023: 16 · 2022: 16 · 2021: 8 · 2020: 24 · 2019: 14 · 2018: 22 · 2017: 21 · 2016: 18 · 2015: 22 · 2014: 22 · 2013: 19 · 2012: 21
- FWCI
- 19.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (AI-12192, AI 18988)
- National Institute of Neurological Disorders and Stroke (NS-23677)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Syphilis Diagnosis and Treatment
- Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
- Health Sciences › Medicine › Infectious Diseases › Infectious Diseases and Tuberculosis
- Keywords
- Treponema pallidum, neurosyphilis, untreated syphilis, cerebrospinal fluid, HIV coinfection, cerebrospinal fluid pleocytosis, benzathine penicillin G, treatment failure, early latent syphilis, secondary syphilis
- MeSH terms
- Adult, Aged, Animals, Cerebrospinal Fluid, Cerebrospinal Fluid Proteins, Female, HIV Seropositivity, Humans, Leukocyte Count, Male, Middle Aged, Neurosyphilis, Penicillin G Benzathine, Prospective Studies, Rabbits, Syphilis, Syphilis Serodiagnosis, Treponema pallidum
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