The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
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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Janier, M., Hegyi, V., Dupin, N., Unemo, M., Ţiplica, G., Potočnik, M., French, P., & Patel, R. (2015) · Dermatology Review · doi:10.5114/dr.2015.55318 · Cited by 31
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“pallidum OM (73–75) and the pathogen’s ability to invade and perhaps hide in immune privileged organs, such as the central nervous system (76).”
BackgroundOcular and neurosyphilis: epidemiology and approach to management
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“Unfortunately, the long-term outcome of patients with detectable TP and normal CSF is unknown but is thought to eventually result in neurological complications [20,22].”
BackgroundMethodA case of secondary syphilis presenting as optic neuritis
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“Although it is still controversial whether ophthalmic lesions, as a sign of neurosyphilis, are typical of early or late stages of the disease [5, 6].”
BackgroundRe-evaluating the sensitivity of the rabbit infectivity test for Treponema pallidum in modern era
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“There is a 30%-40% likelihood of CSF abnormalities in primary- and secondary-stage syphilis [31].”
BackgroundA Review and Update on Adult Syphilis, with Particular Reference to its Treatment
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“pallidum has received much attention (34-37).”
BackgroundImaging of the Brain in Patients With Human Immunodeficiency Virus Infection
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Church, B., Wall, E. M., Webb, J. R., & Cameron, C. E. (2019) · PLoS ONE · doi:10.1371/journal.pone.0210902 · Cited by 28
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“pallidum was isolated from the CSF of 30% of those with primary or secondary syphilis [27].”
BackgroundAn Experimental Model of Early Central Nervous System Syphilis
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“pallidum from CSF has been documented after currently recommended doses of benzathine penicillin for early syphilis [1, 3].”
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“pallidum in the cerebrospinal fluid (CSF).(38,39) An inflammatory CSF profile, reactive Venereal Disease Research Laboratory (VDRL), or some combination of these CSF abnormalities may also be present.”
BackgroundContribution of CNS and extra-CNS infections to neurodegeneration: a narrative review
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“CNS presentation is relatively common at the early stages of syphilis [247].”
BackgroundNeurosyphilis in Africa: A systematic review
Marks, M., Jarvis, J. N., Howlett, W. P., & Mabey, D. C. W. (2017) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0005880 · Cited by 26
“pallidum may be frequently identified in the CSF of patients with early stage syphilis[7].”
Background
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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