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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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Tuddenham, S., & Ghanem, K. G. (2014) · Clinical Infectious Diseases · doi:10.1093/cid/ciu890 · Cited by 5
“Whether CSF treponemicidal concentrations of penicillin are necessary to cure neurosyphilis is not known; the decades of successful clinical experience with this regimen might argue against it.”
BackgroundInfluentialUse of Antimicrobial Agents to Treat Central Nervous System Infection
Klein, O., & Neu, H. C. (1992) · Neurosurgery Clinics of North America · doi:10.1016/s1042-3680(18)30665-x · Cited by 3
The performance of a novel diagnostic criteria for neurosyphilis in HIV-negative patients
Zhang, R., Zhang, X., Du, F., Zhou, Q.-Y., Wu, M., Ren, J.-J., Zhou, Z., Li, A.-L., Li, D., Li, H., et al. (2024) · Scientific Reports · doi:10.1038/s41598-024-82477-6 · Cited by 3
A patient with secondary syphilis following incomplete treatment of primary infection
Lorenz, Z. W., Rybolt, L. E., Ghanem, K. G., & Shiroky-Kochavi, J. (2023) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(23)00211-6 · Cited by 4
Infecciones por treponemas. Sífilis
de Suso, M. T. G., Martínez‐Sanz, J., Gi-Redondo, R., & Zapata, M. R. (2018) · Medicine - Programa de Formación Médica Continuada Acreditado · doi:10.1016/j.med.2018.06.009 · Cited by 3
Luan, X., Du, Y., & Luo, D. (2023) · International Journal of STD & AIDS · doi:10.1177/09564624231205328 · Cited by 3
“29 Conventional CSF examination is rejected in early syphilis with HIV coinfection unless there are neurological manifestations, and existing evidence indicate the correlation of HIV with neurosyphilis more in late syphilis, especially associated with blood CD4+T cell count and antiretroviral…”
Tryptophan-kynurenine metabolic pathway and daytime dysfunction in women with HIV
Shorer, E. F., Rubin, L. H., French, A. L., Weber, K. M., Daubert, E. M., Yohannes, T., Morack, R., Clish, C. B., Bullock, K. H., Gustafson, D., et al. (2024) · Journal of NeuroVirology · doi:10.1007/s13365-024-01195-x · Cited by 3
“Additionally, we did not account for specific ART regimens, or quan - tify inflammatory biomarkers, which are known to activate IDO and alter kynurenine-tryptophan ratios (Lukehart et al. 1988; Zangerle et al. 2002; Schwarcz et al. 2012; Routy et al. 2015; Spitsin et al. 2021).”
Drago, F., Ciccarese, G., Javor, S., & Parodi, A. (2015) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/jdv.13319 · Cited by 3
Pitfalls in cerebrospinal fluid test for the diagnosis of neurosyphilis
Alsemari, A., Bohlega, S., Cupler, E., McLean, D. R., & Al-Watban, J. A. (2001) · Saudi Medical Journal · doi:10.15537/1658-3175.1346 · Cited by 3
Mazaira, M., Almagro, M., & Fonseca, E. (2008) · Actas Dermo-Sifiliográficas · doi:10.1016/s0001-7310(08)76176-3 · Cited by 3
“Lo que sí es cierto es que la infección por el VIH fa-cilita la neuroinvasión por el treponema, y viceversa 17 ; esto unido a que, debido a la inmunodeficiencia, el treponema no se elimina completamente del SNC, hace que exista una mayor preocupación por descartar neurosífilis mediante el examen…”
Neurosífilis tras tratamiento de hepatitis sifilítica en un paciente inmunocompetente
Ferreira-González, L., de Celis, E. P. R., & Sesma, P. (2012) · Enfermedades Infecciosas y Microbiología Clínica · doi:10.1016/j.eimc.2012.01.015 · Cited by 3
Ein Klassiker, den auch der Hausarzt gut kennen sollte
Spornraft‐Ragaller, P. (2014) · MMW - Fortschritte der Medizin · doi:10.1007/s15006-014-2872-6 · Cited by 3
Concurrent central nervous system infective pathology in a severely immunocompromised patient
Swe, T., Laurent, B., & Shah, N. N. (2016) · Journal of Family Medicine and Primary Care · doi:10.4103/2249-4863.197304 · Cited by 3
“Although CSF‐VDRL is negative in our case, CSF WBC and protein were high enough (supported by CSF FTA test reactive test) to start treatment for neurosyphilis.[8,9]”
BackgroundEdwards, R. K. (2000) · Primary Care Update for OB/GYNS · doi:10.1016/s1068-607x(00)00044-5 · Cited by 3
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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