Screening for asymptomatic neurosyphilis in HIV patients after treatment of early syphilis: an observational study

Tomkins, Andrew; Ahmad, Shazaad; Cousins, Darren; Thng, Caroline M; Vilar, F. Javier; Higgins, Stephen P.

doi:10.1136/sextrans-2016-052938

Cited by 20 publications

(16 citation statements)

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“…Currently, despite the lack of consensus on the diagnostic criteria for ANS [7], most studies agree on the generic definition of a pathology characterized by a CSF finding compatible with a neurosyphilis diagnosis in the absence of neurological signs or symptoms. For these reasons, although the definition of ANS remains difficult to clarify and its epidemiological impact has been poorly studied, the most recent guidelines on syphilis definitively recognize this nosological entity [7,8,13]. Actually, in PLWH without neurological signs but with a significant suspicious of ANS due to low levels of CD4 (≤350 cells/mm 3 ) and/or VDRL/RPR title > 1:32, serological failure after previous adequate antibiotic treatment or the use of alternative drugs, the diagnosis of ANS is based principally on CSF abnormalities [13].…”

Section: Discussionmentioning

confidence: 99%

“…Asymptomatic neurosyphilis was defined and diagnosed by a reactive CSF RPR test (or CSF white blood cells >20/μL plus a reactive CSF TP particle agglutination ≥ 1:640.) [7,8] in PLWH asymptomatic for neurological signs or symptoms. Late syphilis was defined as syphilis acquired >2 years previously according with the World Health Organization (WHO) and European Guidelines for syphilis [7].…”

Section: Methodsmentioning

confidence: 99%

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Diagnostic Issues of Asymptomatic Neurosyphilis in HIV-Positive Patients: A Retrospective Study

et al. 2019

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Introduction: Asymptomatic neurosyphilis (ANS) is a disease that is difficult to diagnose in people living with HIV (PLWH). The European Guidelines on the management of syphilis suggest that ANS should be suspected and thus the lumbar puncture (LP) should be performed in cases of (1) late syphilis (acquired >2 years previously), (2) CD4+ cells ≤ 350/mm3 and/or a serum Venereal Disease Research Laboratory/Rapid Plasma Reagin (VDRL/RPR) title > 1:32, (3) “serological failure” after syphilis therapy, and (4) the use of alternative treatment for syphilis. In the present study, we aimed to verify the accuracy of the guideline’s criteria for the indication of LP in the suspicion of ANS in a cohort of PLWH. Methods: This retrospective study was carried out in a cohort of PLWH referred at a single medical center of a large academic hospital in Italy. Clinical and laboratory data of patients diagnosed with late syphilis were extracted from the cohort and analyzed. The European Guidelines of syphilis were adopted for patient management. Results: Out of a cohort of 713 PLWH, only 51 (7%) had a diagnosis of late syphilis and were therefore included in the study. Thirty-one subjects (61%) met one or more diagnostic criteria to perform LP: 39% (12/31) of patients undergoing LP had a diagnosis of ANS. The accuracy of predictive criteria for ANS, suggested by the guidelines, was 62% for RPR > 1:32 and 74% for CD4+ ≤ 350 cc/µL. The simultaneous occurrence of both criteria (RPR > 1:32 plus CD4+ ≤ 350 cc/µL) achieved a diagnostic accuracy of 59%. Interestingly, only 17% of patients who underwent LP for serological failure were eventually diagnosed positive for ANS. Conclusion: Asymptomatic neurosyphilis represents a challenging, but not uncommon, diagnosis. Therefore, it requires a careful investigation. Low CD4+ cell count and RPR > 1:32 remain excellent predictors of neurosyphilis, but have become the only acceptable predictors of ANS in PLWH. “Serologic failure” should be regarded with caution as a criterion to perform LP in order to investigate possible ANS in HIV-syphilis coinfected patients asymptomatic for neurological disorders. The retrospective nature of this single-site study may represent a limit to the interpretation of the data. Thus, larger clinical studies on the topic are warranted.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Diagnostic Issues of Asymptomatic Neurosyphilis in HIV-Positive Patients: A Retrospective Study

et al. 2019

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“…Given ongoing uncertainties about the significance of asymptomatic neurosyphilis, there remains debate about the need for CSF analysis to assess for neurosyphilis in all asymptomatic patients who were HIV-positive. A recent UK study found that among patients who have received treatment for early syphilis with benzathine penicillin G, the rates of asymptomatic neurosyphilis after treatment are low 29. In view of this the optimal timing and use of lumbar puncture in the management of syphilis remains uncertain 30…”

Section: Discussionmentioning

confidence: 99%

Diagnostic performance of PCR assays for the diagnosis of neurosyphilis: a systematic review

et al. 2018

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The sensitivity of PCR was low compared with CSF-serological assays but the challenges of evaluating a diagnostic test in the absence of a clear gold standard make definitive interpretation challenging. Most studies were small and not adequately powered highlighting the need for multicentre, multicountry trials to provide adequate statistical power in evaluations of new tests the diagnosis of neurosyphilis.

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“…Treatment with doxycycline (2 × 200 mg per day [200 mg every 12 h] for 28 days) can be considered as an alternative. The rationale for this treatment approach is the well-known effectiveness (and recommendation) of doxycycline therapy for systemic forms of syphilis [3,38], sufficient penetration of doxycycline into the CSF at a dose of 2 × 200 mg per day [42], and several case reports of positive treatment results with doxycycline in neurosyphilis [42][43][44]. Owing to the lack of randomized studies, however, there is no recommendation from the CDC or the European guideline for the treatment of neurosyphilis with doxycycline [3,25].…”

Section: Antibiotic Therapy Backgroundmentioning

confidence: 99%

German guidelines on the diagnosis and treatment of neurosyphilis

Klein

Angstwurm

Eßer³

et al. 2020

Neurol. Res. Pract.

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Introduction In view of the importance of neurosyphilis and the difficulties encountered in diagnosing it, the S1 guideline “Neurosyphilis” has been published by the German Society for Neurology (DGN) in accordance with the stipulations of the Association of the Scientific Medical Societies in Germany (AWMF). The present article is an abridged translation of that German guideline. Main recommendations (a) Neurosyphilis can manifest as early neurosyphilis (meningitis, meningovascular neurosyphilis or syphilitic gummas) or late neurosyphilis (tabes dorsalis, general paresis). (b) The following diagnostic criteria help to establish the presence of probable neurosyphilis (always point iv, accompanied by any two of points i to iii): (i) subacute or chronic neuro-psychiatric symptoms; (ii) increased cerebrospinal fluid (CSF) cell count or signs of blood–CSF barrier disruption; (iii) positive effect of anti-neurosyphilis antibiotic therapy on clinical course and CSF findings; (iv) positive TPHA/TPPA or FTA test in serum. (c) The diagnosis of neurosyphilis is confirmed by the subsequent detection of intrathecal production of antibodies against Treponema pallidum. (d) In neurosyphilis, treatment with intravenous penicillin or ceftriaxone for 14 days is recommended. (e) The following parameters can be used to assess a therapeutic effect: clinical findings, serum VDRL, and CSF cell count. Conclusion The German guideline on the diagnosis and treatment of neurosyphilis is a practical tool to support clinicians in diagnosing and treating patients with neurosyphilis. This article is an abridged translation of this guideline (Klein MW, J.; Angstwurm, K.; Esser, S.; Hahn, K.; Matschke, M.; Scheithauer, S.; Schoefer, H.; Sturzenegger, M.; Wildemann, B. Neurosyphilis, S1-Leitlinie. Deutsche Gesellschaft für Neurologie, Leitlinien für Diagnostik und Thearpie in der Neurologie 2020).

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Screening for asymptomatic neurosyphilis in HIV patients after treatment of early syphilis: an observational study

Abstract: Although the number of patients in our study is modest, single-dose BPG appears to be highly effective even in patients at high risk of neurosyphilis.

Cited by 20 publications

References 9 publications

Diagnostic Issues of Asymptomatic Neurosyphilis in HIV-Positive Patients: A Retrospective Study

Diagnostic Issues of Asymptomatic Neurosyphilis in HIV-Positive Patients: A Retrospective Study

Diagnostic performance of PCR assays for the diagnosis of neurosyphilis: a systematic review

German guidelines on the diagnosis and treatment of neurosyphilis

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