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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Citations
Cites
Johns, D. R., Tierney, M. R., & Felsenstein, D. (1987) · New England Journal of Medicine · doi:10.1056/nejm198706183162503 · Cited by 556
Berry, C., Hooton, T. M., Collier, A. C., & Lukehart, S. A. (1987) · New England Journal of Medicine · doi:10.1056/nejm198706183162507 · Cited by 340
Self-citationNeurosyphilis. A study of 241 patients
Hooshmand, H. (1972) · JAMA · doi:10.1001/jama.219.6.726 · Cited by 237
Neurosyphilis: A Study of 241 Patients
Hooshmand, H. (1972) · JAMA · doi:10.1001/jama.1972.03190320032011 · Cited by 215
Neurosyphilis and Penicillin Levels in Cerebrospinal Fluid
Mohr, J. A. (1976) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1976.03270200046031 · Cited by 178
Treatment for Early Syphilis and Reactivity of Serologic Tests
Schroeter, A. L. (1972) · JAMA · doi:10.1001/jama.1972.03200180015003 · Cited by 147
Persistence of Treponema pallidum following penicillin G therapy. Report of two cases
Tramont, E. C. (1976) · JAMA · doi:10.1001/jama.236.19.2206 · Cited by 146
Tramont, E. C. (1987) · New England Journal of Medicine · doi:10.1056/nejm198706183162510 · Cited by 132
Fluorescent Treponemal Antibody-Absorption (FTA-ABS) Test for Syphilis
Deacon, W. E. (1966) · JAMA · doi:10.1001/jama.1966.03110190106026 · Cited by 126
Lukehart, S. A., BAKER-ZANDER, S. A., Lloyd, R. M., & Sell, S. (1980) · The Journal of Immunology · doi:10.4049/jimmunol.124.1.461 · Cited by 121
Self-citation
Research works printed but not linked: 19
- 1988, MMWR., 37, 35
- Hotson J, 1981, West J Med., 135, 191
- Catterall R, 1977, Br J Hosp Med., 17, 585
- Smego R, 1984, NC Med J., 45, 253
- Izzat N, 1971, Br J Vener Dis., 47, 162
- Manual of Tests for Syphilis. Atlanta: Centers for Disease Control; 1969:15-22, 33-42.
- 1985, MMWR., 34, 1
- 1985, MMWR (Suppl)., 34, 94s
- Smith J . Spirochetes in Late Seronegative Syphilis, Penicillin Notwithstanding. Springfield,Illinois:CharlesCThomas; 1969:227-43.
- Yobs A, 1964, Arch Pathol., 77, 220
- Turner T, 1969, Br J Vener Dis., 45, 183
- Miller J . Spirochetes in Body Fluids and Tissues. Springfield, Illinois: Charles C Thomas; 1971:25-6.
- Wile U, 1914, J Cut Dis., 32, 607
- Scott V, 1944, Am J Syph Gonorrhea Vener Dis., 28, 431
- Polnikorn N, 1980, Br J Vener Dis., 56, 363
- 10.1001/jama.1976.03270200044030 · DOI
- 10.1001/archderm.1966.01600190093022 · DOI
- Gjestland T, 1955, Acta Dermato Venereol., 35, 11
- Brown S, 1976, J Am Vener Dis Assoc., 3, 136
Cited by
Sorted by citations
Items 201–300 of 601
Neurosyphilis in a tertiary care hospital in north India.
Sethi, S. K., Das, A., Kakkar, N., Banga, S. S., Prabhakar, S., & Sharma, M. (2005) · PubMed · Cited by 26
IgM Antibody to Treponema pallidum in Cerebrospinal Fluid of Infants With Congenital Syphilis
Sánchez, P. J. (1992) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/archpedi.1992.02160220057022 · Cited by 26
Interjunctional invasion of endothelial cell monolayers
Haake, D. A., & Lovett, M. (1994) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(94)36033-2 · Cited by 26
Secondary Syphilis Presenting as a Generalized Lymphadenopathy
Park, S. Y., Kang, J. H., Roh, J. H., Huh, H. J., Yeo, J. S., & Kim, D. Y. (2013) · Sexually Transmitted Diseases · doi:10.1097/olq.0b013e3182897eb0 · Cited by 25
“Traditionally, neurosyphilis has been considered a late manifestation of syphilis, but this view might be inaccurate.(13,14) Central nervous system syphilis represents a continuum encompassing early invasion, months to years of asymptomatic involvement, and, in some cases, development of early or late neurologic manif…”
BackgroundSch�fer, H. (2004) · Der Hautarzt · doi:10.1007/s00105-003-0608-0 · Cited by 25
Lyme disease concurrent with human immunodeficiency virus infection
García‐Moncó, J. C., Frey, H. M., Villar, B. F., Golightly, M. G., & Benach, J. L. (1989) · The American Journal of Medicine · doi:10.1016/0002-9343(89)90616-5 · Cited by 25
Gummatous lesions in men infected with human immunodeficiency virus and syphilis.
Hay, P., Tam, F. W. K., Kitchen, V. S., Horner, S., Bridger, J., & Weber, J. (1990) · Sexually Transmitted Infections · doi:10.1136/sti.66.5.374 · Cited by 25
Infectious Etiologies of Stroke
Shulman, J. G., & Cervantes-Arslanian, A. M. (2019) · Seminars in Neurology · doi:10.1055/s-0039-1687915 · Cited by 29
Evaluation of New Anti-Infective Drugs for the Treatment of Syphilis
Ronald, A., Silverman, M., McCutchan, J. A., Corey, L., & Handsfield, H. H. (1992) · Clinical Infectious Diseases · doi:10.1093/clind/15.supplement_1.s140 · Cited by 24
Self-citationSPIROCHETAL INFECTION OF THE NERVOUS SYSTEM
Estanislao, L., & Pachner, A. R. (1999) · Neurologic Clinics · doi:10.1016/s0733-8619(05)70166-3 · Cited by 25
HIV and the central nervous system
Bensalem‐Owen, M., & Berger, J. R. (2002) · Comprehensive Therapy · doi:10.1007/s12019-002-0039-3 · Cited by 24
STD in children: syphilis and gonorrhoea.
Rawstron, S. A., Bromberg, K., & Hammerschlag, M. R. (1993) · Sexually Transmitted Infections · doi:10.1136/sti.69.1.66 · Cited by 24
Yoon, Y. K., Kim, M. J., Chae, Y. S., & Kang, S.-H. (2013) · Journal of Korean Neurosurgical Society · doi:10.3340/jkns.2013.53.3.197 · Cited by 23
Ho, E. L., Maxwell, C. L., Dunaway, S. B., Sahi, S. K., Tantalo, L. C., Lukehart, S. A., & Marra, C. M. (2017) · Clinical Infectious Diseases · doi:10.1093/cid/cix473 · Cited by 25
Self-citationHicks, L. C. B. (1991) · Dermatologic Clinics · doi:10.1016/s0733-8635(18)30397-8 · Cited by 23
Gaspar, P. C., Bigolin, Á., Neto, J. B. A., Pereira, E. D. D. S., & Bazzo, M. L. (2021) · Epidemiologia e Serviços de Saúde · doi:10.1590/s1679-4974202100006.esp1 · Cited by 118
Houston, S., Lithgow, K., Osbak, K. K., Kenyon, C. R., & Cameron, C. E. (2018) · BMC Structural Biology · doi:10.1186/s12900-018-0086-3 · Cited by 22
“It is also one of the few pathogens capable of traversing both the placental and bloodbrain barriers [4].”
BackgroundPrevalence of Self-reported Neurologic and Ocular Symptoms in Early Syphilis Cases
Quilter, L. A. S., de Voux, A., Amiya, R. M., Davies, E. D., Hennessy, R. R., Kerani, R. P., Madera, R., Matthias, J., Pearson, V. M., Walters, J. K., et al. (2020) · Clinical Infectious Diseases · doi:10.1093/cid/ciaa180 · Cited by 22
Ray, J. G. (1995) · Obstetrical & Gynecological Survey · doi:10.1097/00006254-199512000-00003 · Cited by 22
Syphilis. A tale of twisted treponemes.
Flores, J. L. (1995) · Europe PMC (PubMed Central) · Cited by 22
Serologic Testing after Therapy for Syphilis: Is There a Test for Cure?
Lukehart, S. A. (1991) · Annals of Internal Medicine · doi:10.7326/0003-4819-114-12-1057 · Cited by 22
Self-citationMatlow, A., & Rachlis, A. (1990) · Clinical Infectious Diseases · doi:10.1093/clinids/12.4.703 · Cited by 22
Franco, M., & Nogueira, V. (2016) · Europe PMC (PubMed Central) · doi:10.3205/oc000039 · Cited by 21
“Ocular involvement may be silent or present as anterior uveitis, choroiditis, interstitial keratitis, retinal vasculitis, retinitis, optic neuritis, dacryoadenitis, or scleritis [5], [6], [7].”
BackgroundNeurosyphilis and the impact of HIV infection
Ho, E. L., & Spudich, S. (2015) · Sexual Health · doi:10.1071/sh14195 · Cited by 20
Experimental congenital syphilis: guinea pig model
Wicher, K., BAUGHN, R. E., Wicher, V., & Nakeeb, S. M. (1992) · Infection and Immunity · doi:10.1128/iai.60.1.271-277.1992 · Cited by 21
“(24) reached the same conclusion: although a rabbit infectivity test provides definite proof of the presence of viable T.”
BackgroundCongenital syphilis. Serologic diagnosis in the young infant.
Lewis, L. L. (1992) · PubMed · Cited by 21
Finding Neurosyphilis Without the Venereal Disease Research Laboratory Test
MacLEAN, S., & Luger, A. (1996) · Sexually Transmitted Diseases · doi:10.1097/00007435-199609000-00008 · Cited by 21
Contribution of Neelaredoxin to Oxygen Tolerance by Treponema pallidum
Hazlett, K. R. O., Cox, D. L., Sikkink, R. A., Auchère, F., Rusnak, F. M., & Radolf, J. D. (2002) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(02)53044-5 · Cited by 21
Epidemiology of Infectious Syphilis in Ottawa
Leber, A., MacPherson, P. A., & Lee, B. C. (2008) · Canadian Journal of Public Health · doi:10.1007/bf03405250 · Cited by 25
Brazilian Protocol for Sexually Transmitted Infections 2020: syphilis diagnostic tests
Gaspar, P. C., Bigolin, Á., Neto, J. B. A., Pereira, E. D. D. S., & Bazzo, M. L. (2021) · Revista da Sociedade Brasileira de Medicina Tropical · doi:10.1590/0037-8682-630-2020 · Cited by 23
2014 European guideline on the management of syphilis: giving evidence priority
Janier, M., Unemo, M., Dupin, N., Ţiplica, G., & Patel, R. (2015) · Journal of the European Academy of Dermatology and Venereology · doi:10.1111/jdv.13320 · Cited by 20
Medullary involvement in neurosyphilis: a report of 12 cases and a review of the literature
Elmouden, H., Louhab, N., & Kissani, N. (2019) · Spinal Cord Series and Cases · doi:10.1038/s41394-019-0185-9 · Cited by 20
Houston, S., Taylor, J. S., Denchev, Y., Hof, R., Zuerner, R. L., & Cameron, C. E. (2015) · Infection and Immunity · doi:10.1128/iai.00643-15 · Cited by 20
“pallidum is further highlighted by its ability to traverse the placental barrier to cause congenital syphilis and the blood-brain barrier to invade the central nervous system (9) and by the diverse and widespread clinical manifestations associated with secondary and tertiary syphilis (6).”
BackgroundA 50-Year-Old Man With Skin Lesions and Multiple Pulmonary Nodules
Olson, A. L., Gutman, J. A., & Welsh, C. H. (2004) · CHEST Journal · doi:10.1378/chest.125.6.2322 · Cited by 20
Sheffield, J. S., & Wendel, G. D. (1999) · Clinical Obstetrics & Gynecology · doi:10.1097/00003081-199903000-00015 · Cited by 20
NEUROLOGIC COMPLICATIONS OF LYME DISEASE
Coyle, P. K. (1993) · Rheumatic Disease Clinics of North America · doi:10.1016/s0889-857x(21)00217-9 · Cited by 20
Schmid, G. P. (1990) · Clinical Infectious Diseases · doi:10.1093/clinids/12.supplement_6.s580 · Cited by 20
Dementia due to neurosyphilis with persistently negative CSF VDRL
Lee, J. W., Wilck, M., & Venna, N. (2005) · Neurology · doi:10.1212/01.wnl.0000187082.92497.95 · Cited by 19
Target organs of infection in guinea pigs with acquired congenital syphilis
Wicher, K., Abbruscato, F. C., Wicher, V., BAUGHN, R. E., & Noordhoek, G. T. (1996) · Infection and Immunity · doi:10.1128/iai.64.8.3174-3179.1996 · Cited by 19
“Multiple blood, SP, LIV, lung (LNG), HRT, and BRN samples were collected and analyzed individually by PCR. RIT.”
BackgroundInfluentialCenters for Disease Control and Prevention guidelines for congenital syphilis
Glaser, J. H. (1996) · The Journal of Pediatrics · doi:10.1016/s0022-3476(96)70109-9 · Cited by 19
Neurocognitive Changes in Tertiary Neurosyphilis: A Retrospective Chart Review
Beauchemin, P., & Laforce, R. J. (2014) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/s0317167100018485 · Cited by 18
Levin, S. N., & Lyons, J. L. (2018) · Handbook of clinical neurology · doi:10.1016/b978-0-444-63849-6.00017-7 · Cited by 18
Serrano-Cárdenas, K. M., Sánchez‐Rodríguez, A., Pozueta, A., Pelayo‐Negro, A. L., & Riancho, J. (2017) · Neurological Sciences · doi:10.1007/s10072-017-3109-0 · Cited by 18
“Although the prevalence of neurosyphilis has significantly decreased during last decades, it is still considerable among several risky populations such as HIV-infected patients or subjects with risky sexual behaviours [4].”
BackgroundSpirochetal Infection of the Central Nervous System
Coyle, P., & Dattwyler, R. J. (1990) · Infectious Disease Clinics of North America · doi:10.1016/s0891-5520(20)30374-3 · Cited by 18
Rasoldier, V., Gueudry, J., Chapuzet, C., Bodaghi, B., Muraine, M., Tubiana, R., Paris, L., Pestel‐Caron, M., Caron, F., & Caumes, É. (2020) · Infectious Diseases Now · doi:10.1016/j.medmal.2020.10.016 · Cited by 17
“[6] Lukehart SA, Hook EW, Baker-Zander SA, Collier AC, Critchlow CW, Handsfield HH.”
BackgroundOcular vs neurosyphilis. are they the same? A guide to investigation and management
Reid, G. A., Halmagyi, G. M., Whyte, C., & McCluskey, P. J. (2024) · Eye · doi:10.1038/s41433-024-03150-w · Cited by 17
“In later stages of untreated syphilis, CSF abnormalities are much less common [38].”
BackgroundPereira, L., Katz, S. S., Sun, Y., Mills, P., Taylor, W., Atkins, P., Thurlow, C. M., Chi, K.-H., Danavall, D. C., Cook, N., et al. (2020) · PLoS ONE · doi:10.1371/journal.pone.0227769 · Cited by 17
“pallidum has been grown in rabbits using fresh blood, fresh CSF and fresh primary chancre exudate [9, 27, 31, 50] from patients diagnosed with syphilis, there have been no prior reports of adapting this method for cryopreserved lesion exudate.”
MethodA Patient with Neurosyphilis Presenting as Chorea
Jones, A. L., & Bouchier, I. A. D. (1993) · Scottish Medical Journal · doi:10.1177/003693309303800309 · Cited by 17
Optic Neuropathy From Viruses and Spirochetes
Bhatti, M. T. (2007) · International Ophthalmology Clinics · doi:10.1097/iio.0b013e318157202d · Cited by 17
“pallidum was documented in 30% of cases.(81) Acute neurosyphilis can be asymptomatic in as many as 40% of patients and in the majority of cases the infection clears spontaneously.”
BackgroundLaboratory techniques in the diagnosis of syphilis: a review.
van der Sluis, J. J. (1992) · Sexually Transmitted Infections · doi:10.1136/sti.68.6.413 · Cited by 17
“However, the results differ from the RIT results with the CSFs from patients with late syphilis in the study by Lukehart et al.58 Furthermore, the presence of treponemal DNA in CSFs from intravenously treated patients stressed the importance of simultaneous RIT studies.”
ResultMoss, G. B., & Kreiss, J. K. (1990) · Medical Clinics of North America · doi:10.1016/s0025-7125(16)30500-4 · Cited by 17
Chen, K.-H. S., Sun, H., Chen, C.-H., Chuang, Y., Huang, Y., Liu, W.-D., Hsieh, S., Sheng, W., Cheng, A., Wu, T., et al. (2023) · Clinical Infectious Diseases · doi:10.1093/cid/ciad508 · Cited by 17
Diagnosis of Neurosyphilis: New Tools
Sparling, P. F. (2010) · Sexually Transmitted Diseases · doi:10.1097/olq.0b013e3181d90445 · Cited by 16
Syphilis and HIV: Old and new foes aligned against us
Eaton, M. E. (2009) · Current Infectious Disease Reports · doi:10.1007/s11908-009-0023-5 · Cited by 16
Ishii, Y., Miyahara, M., & Watanabe, K. (2016) · Journal of Bioscience and Bioengineering · doi:10.1016/j.jbiosc.2016.07.014 · Cited by 16
Neuro-ophthalmic Manifestations of Human Immunodeficiency Virus Infection
Friedman, D. I. (1991) · Neurologic Clinics · doi:10.1016/s0733-8619(18)30303-7 · Cited by 16
Initially Unrecognized Dementia in a Young Man With Neurosyphilis
Lee, C., Lin, W.-C., Lu, C., & Liu, J.-W. (2009) · The Neurologist · doi:10.1097/nrl.0b013e31817781c9 · Cited by 16
“Treponema pallidum invades the central nervous system (CNS) of some infected people early in the course of syphilis, and those with organisms being persistently in their CNS are at risk for development symptomatic neurosyphilis.(1) Symptomatic neurosyphilis can be divided into early and late forms.”
BackgroundLewis, L. L. (1992) · Infectious Disease Clinics of North America · doi:10.1016/s0891-5520(20)30423-2 · Cited by 16
Albrecht, L. M., & Wilkes, L. (1991) · Journal of Pharmacy Practice · doi:10.1177/089719009100400403 · Cited by 16
Human immunodeficiency virus infection, Part I
Horowitz, H. W., Telzak, E. E., Sepkowitz, K. A., & Wormser, G. P. (1998) · Disease-a-Month · doi:10.1016/s0011-5029(98)90014-1 · Cited by 16
Management of syphilis in human immunodeficiency virus-infected patients
Hook, E. W. (1992) · The American Journal of Medicine · doi:10.1016/0002-9343(92)90573-t · Cited by 16
Self-citationIndicações da punção liquórica nos portadores de sífilis
Nadal, L. R. M., & Nadal, S. R. (2006) · Revista Brasileira de Coloproctologia · doi:10.1590/s0101-98802006000400015 · Cited by 15
“Então, o diagnóstico depende dos testes sorológicos e do exame do LCR.(6,7,20,22) É descrito que a análise liquórica pode ser benéfica em portadores da sífilis primária.”
BackgroundThe management of HIV-related illness in the emergency department
Talan, D. A., & Kennedy, C. A. (1991) · Annals of Emergency Medicine · doi:10.1016/s0196-0644(05)81080-7 · Cited by 15
Luo, X., Shi, H., Hou, L., Zhong, X., Chen, X., Zhang, Y., Zheng, D., Tan, Y., Hu, G., Mu, N., et al. (2015) · European Journal of Neurology · doi:10.1111/ene.12680 · Cited by 17
“pallidum is detected in 20% to more than 40% of patients with early or late stage syphilis, regardless of their treatment [2,3].”
BackgroundLi, W., Wu, W., Chang, H., Jiang, M., Gao, J., Xu, Y., Xu, D., Yin, L., & Zhang, X. (2020) · BioMed Research International · doi:10.1155/2020/3812671 · Cited by 36
“pallidum could invade the CSF early in the course of disease [5].”
BackgroundNeurosyphilis manifesting with unilateral visual loss and hyponatremia: a case report
Milger, K., Fleig, V., Kohlenberg, A., Discher, T., & Lohmeyer, J. (2011) · BMC Infectious Diseases · doi:10.1186/1471-2334-11-17 · Cited by 14
Körber, A., Dissemond, J., Lehnen, M., Franckson, T., Grabbe, S., & Eßer, S. (2004) · JDDG Journal der Deutschen Dermatologischen Gesellschaft · doi:10.1046/j.1439-0353.2004.04071.x · Cited by 15
Antibacterial Therapy of Neurosyphilis
Ali, L. K., & Roos, K. L. (2002) · CNS Drugs · doi:10.2165/00023210-200216120-00001 · Cited by 15
“[9,10] 800 Ali & Roos”
Syphilitic meningitis causing paraparesis in an HIV-negative woman
Byrne, T. N., Bose, A., Sze, G., & Waxman, S. G. (1991) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(91)90282-c · Cited by 15
Miura, H., Nakano, M., Ryu, T., Kitamura, S., & Suzaki, A. (2010) · Internal Medicine · doi:10.2169/internalmedicine.49.3414 · Cited by 14
Management of neurosyphilis: time for a new approach?
Smibert, O. C., Jenney, A. W. J., & Spelman, D. W. (2018) · Internal Medicine Journal · doi:10.1111/imj.13703 · Cited by 14
Zhang, X., Andrea, S., Yang, L., Xue, Y., Wang, L., Yang, B., Zheng, H., Chen, J. S., Radolf, J. D., & Seña, A. C. (2020) · Sexually Transmitted Diseases · doi:10.1097/olq.0000000000001321 · Cited by 14
A Disconnect between the Neurospirochetoses in Humans and Rodent Models of Disease
García‐Moncó, J. C., & Benach, J. L. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003288 · Cited by 14
“30% of patients with early syphilis, indicating that invasion of the nervous system is a common and early event [8] and can include”
BackgroundIntraoral tertiary syphilis (gumma) in a human immunodeficiency virus-positive man: A case report
Kearns, G. J., Pogrel, M. A., & Honda, G. (1993) · Journal of Oral and Maxillofacial Surgery · doi:10.1016/s0278-2391(10)80397-0 · Cited by 14
Efficacy of cefmetazole in the treatment of active syphilis in the rabbit model
BAKER-ZANDER, S. A., & Lukehart, S. A. (1989) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.33.9.1465 · Cited by 14
“It is therefore important to identify other alternative antibiotics with treponemicidal capabilities, particularly in light of the increasing reports of treatment failure in syphilis patients concurrently infected with the human immunodeficiency virus following standard benzathine penicillin therapy (2, 21).”
BackgroundSelf-citationEngelkens, H. J., van der Sluis, J. J., & Stolz, E. (1991) · International Journal of Dermatology · doi:10.1111/j.1365-4362.1991.tb04632.x · Cited by 14
Borrelia BurgdorferiInfection: Clinical Diagnostic Techniques
Coyle, P. K. (1997) · Immunological Investigations · doi:10.3109/08820139709048920 · Cited by 14
Treponemal Tests for Neurosyphilis—Less Accurate Than What We Thought?
Ho, E. L., & Marra, C. M. (2012) · Sexually Transmitted Diseases · doi:10.1097/olq.0b013e31824ee574 · Cited by 14
DIAGNOSIS AND TREATMENT OF SUBSTANCE USERS WITH HIV INFECTION
Selwyn, P. A., & O’Connor, P. G. (1992) · Primary Care Clinics in Office Practice · doi:10.1016/s0095-4543(21)00124-x · Cited by 13
Dionne‐Odom, J., Giacani, L., Tamhane, A. R., Workowski, K., Lieberman, N. A. P., Greninger, A. L., Perlowski, C., Newman, L. M., & Hook, E. W. (2023) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiad582 · Cited by 13
Self-citationTan, X., Zhang, J., Li, J., Yue, X., & Gong, X. (2020) · PLoS ONE · doi:10.1371/journal.pone.0241572 · Cited by 13
“As the most common form of neurosyphilis, the asymptomatic neurosyphilis (ANS) is characterized by the abnormality of cerebrospinal fluid (CSF) with no symptoms or signs of involvement of the central nervous system [12, 13].”
BackgroundNeurosyphilis manifesting as spinal transverse myelitis.
Matijošaitis, V., Vaitkus, A., Pauza, V., Valiukevičienė, S., & Gleiznienė, R. (2006) · PubMed · Cited by 13
Moskophidis, M., & Peters, S. (1996) · Zentralblatt für Bakteriologie · doi:10.1016/s0934-8840(96)80063-6 · Cited by 13
Neurosyphilis Is a Long-forgotten Disease but Still a Possible Etiology for Dementia
Hagiya, H., Deguchi, K., Kawada, K., & Otsuka, F. (2015) · Internal Medicine · doi:10.2169/internalmedicine.54.4956 · Cited by 13
“pallidum can latently infect the central nervous system from an early stage of the clinical course (5 to 10% of untreated patients) (12) without any apparent inflammatory reaction (3, 13), leading to asymptomatic neurosyphilis.”
BackgroundCadavid, D. (2010) · Handbook of clinical neurology · doi:10.1016/s0072-9752(09)96012-2 · Cited by 13
Analysis of lymphocyte subsets in HIV-negative neurosyphilis patients
Liu, L., Chao, P.-L., Zhang, H., Tong, M.-L., Liu, G.-L., Lin, L., Su, Y., Wu, J., Dong, J., Zheng, W., et al. (2012) · Diagnostic Microbiology and Infectious Disease · doi:10.1016/j.diagmicrobio.2012.10.007 · Cited by 13
“This process is called “neuroinvasion” (Lukehart et al., 1988).”
Response to Standard Syphilis Treatment in Patients Infected with the Human Immunodeficiency Virus
Bordón, J., Martínez-Vázquez, C., la Fuente-Aguado, J. D., SOPEÑA, B., Ocampo, A., Nuñez-Torrón, J., Rodríguez-Sousa, T., Álvarez-Fernández, M., & del Blanco, T. (1999) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/s100960050387 · Cited by 13
“The RIT was performed on CSF samples following published methodology [14, 15].”
MethodSEXUALLY TRANSMITTED DISEASES UPDATE
McDonald, L. L., Stites, P. C., & Buntin, D. M. (1997) · Dermatologic Clinics · doi:10.1016/s0733-8635(05)70431-9 · Cited by 13
Persistence of neurosyphilis despite multiple treatment regimens
Whiteside, C. (1989) · The American Journal of Medicine · doi:10.1016/0002-9343(89)90578-0 · Cited by 13
Editorial Commentary: Toward a Better Understanding of European Lyme Neuroborreliosis
Wormser, G. P., & HALPERIN, J. J. (2013) · Clinical Infectious Diseases · doi:10.1093/cid/cit322 · Cited by 13
“occur with Treponema pallidum in certain patients with early syphilis [21].”
Marra, C. M. (2025) · Brain · doi:10.1093/brain/awaf329 · Cited by 19
Koizumi, Y., Watabe, T., Ota, Y., Nakayama, S., Asai, N., Hagihara, M., Yamagishi, Y., Suematsu, H., Tsuzuki, T., Takayasu, M., et al. (2017) · Sexually Transmitted Diseases · doi:10.1097/olq.0000000000000701 · Cited by 12
“pallidum in CSF do not develop neurosyphilis even after conventional benzathine penicillin regimens which poorly penetrate blood brain barrier, those cases can cause reisolation after benzathine penicillin therapy especially in HIV positives.(11) Amoxicillin, in contrast, is an oral penicillin which can achieve trepon…”
BackgroundHouston, S., Schovanek, E., Conway, K. M. E., Mustafa, S., Gomez, A., Ramaswamy, R., Haimour, A., Boulanger, M. J., Reynolds, L. A., & Cameron, C. E. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.888525 · Cited by 12
Tertiary Syphilis in the Cervical Spine: A Case Report and Review of the Literature
Salem, K. M. I., Majeed, H., Bommireddy, R., & Klézl, Z. (2012) · Global Spine Journal · doi:10.1055/s-0032-1329887 · Cited by 12
Relevance in biology and mechanisms of immune and treatment evasion of Treponema pallidum
Drago, F., Javor, S., & Parodi, A. (2019) · Giornale Italiano di Dermatologia e Venereologia · doi:10.23736/s0392-0488.17.05830-8 · Cited by 12
Clinical features associated with neurosyphilis in people living with HIV and late latent syphilis
Martínez-Ayala, P., Quiñonez-Flores, A., González-Hernández, L. A., Ruíz-Herrera, V. V., Zúñiga-Quiñones, S., Alanis-Sánchez, G., Cabrera-Silva, R. I., Amador-Lara, F., Sánchez-Reyes, K., Álvarez-Zavala, M., et al. (2022) · International Journal of STD & AIDS · doi:10.1177/09564624211063091 · Cited by 12
“Neuroinvasion by Treponema pallidum occurs early in the course of the disease, and it can lead to asymptomatic meningitis that, if untreated, can progress to symptomatic neurosyphilis.(3,4) Early forms of symptomatic neurosyphilis include meningitis, stroke, and loss of hearing and vision, while late forms include dem…”
BackgroundSecondary Central Nervous System Demyelinating Disorders in the Elderly: A Narrative Review
Bakirtzis, C., Lima, M., Lorenzo, S. S. D., Artemiadis, A., Theotokis, P., Kesidou, E., Konstantinidou, N., Sintila, S.-A., Boziki, M. K., Parissis, D., et al. (2023) · Healthcare · doi:10.3390/healthcare11152126 · Cited by 11
“Therefore, tabes dorsalis appears later in life and can also affect elderly people [44].”
BackgroundRawstron, S. A., & Hawkes, S. (2012) · Elsevier eBooks · doi:10.1016/b978-1-4377-2702-9.00184-7 · Cited by 11
Syphilis: Far from Ancient History.
Ricco, J. A., & Westby, A. (2020) · PubMed · Cited by 11
Felman, Y. M. (1989) · Archives of Dermatology · doi:10.1001/archderm.1989.01670240098023 · Cited by 11
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review