A Dual-Platform Point-of-Care Test for Neurosyphilis Diagnosis.
Journal
Sexually transmitted diseases
ISSN: 1537-4521
Titre abrégé: Sex Transm Dis
Pays: United States
ID NLM: 7705941
Informations de publication
Date de publication:
01 05 2021
01 05 2021
Historique:
entrez:
12
4
2021
pubmed:
13
4
2021
medline:
25
5
2021
Statut:
ppublish
Résumé
The diagnosis of neurosyphilis relies on cerebrospinal fluid (CSF) abnormalities (pleocytosis, elevated protein) and CSF-Venereal Disease Research Laboratory (VDRL) test. In resource-limited settings, the CSF-VDRL test may not be widely available. We optimized a commercial immunochromatographic strip test, the DPP Chembio syphilis assay, for performance with CSF and tested centrifuged CSF samples of 71 patients with syphilis (35 with neurosyphilis and 36 without neurosyphilis). A CSF dilution of 1:4 was chosen based on agreement with CSF pools with documented results from the CSF-VDRL test and fluorescent treponemal antibody absorption test on CSF. Using an electronic reader, we obtained unit values of treponemal and nontreponemal antibodies for all study samples and generated a receiver operating characteristic curve; using the Youden index, we established diagnostic cutoffs with optimal sensitivity and specificity. Diagnostic sensitivity of the nontreponemal test was 80% (95% confidence interval, 63%-92%) and specificity was 97% (95% confidence interval, 85%-100%) for neurosyphilis diagnosis using a reactive CSF-VDRL that improved after neurosyphilis therapy as a criterion standard. In this small study, the DPP Chembio test showed promising results for neurosyphilis diagnosis. Further studies are needed to assess its performance in resource-limited settings.
Sections du résumé
BACKGROUND
The diagnosis of neurosyphilis relies on cerebrospinal fluid (CSF) abnormalities (pleocytosis, elevated protein) and CSF-Venereal Disease Research Laboratory (VDRL) test. In resource-limited settings, the CSF-VDRL test may not be widely available.
METHODS
We optimized a commercial immunochromatographic strip test, the DPP Chembio syphilis assay, for performance with CSF and tested centrifuged CSF samples of 71 patients with syphilis (35 with neurosyphilis and 36 without neurosyphilis). A CSF dilution of 1:4 was chosen based on agreement with CSF pools with documented results from the CSF-VDRL test and fluorescent treponemal antibody absorption test on CSF. Using an electronic reader, we obtained unit values of treponemal and nontreponemal antibodies for all study samples and generated a receiver operating characteristic curve; using the Youden index, we established diagnostic cutoffs with optimal sensitivity and specificity.
RESULTS
Diagnostic sensitivity of the nontreponemal test was 80% (95% confidence interval, 63%-92%) and specificity was 97% (95% confidence interval, 85%-100%) for neurosyphilis diagnosis using a reactive CSF-VDRL that improved after neurosyphilis therapy as a criterion standard.
CONCLUSIONS
In this small study, the DPP Chembio test showed promising results for neurosyphilis diagnosis. Further studies are needed to assess its performance in resource-limited settings.
Identifiants
pubmed: 33843803
doi: 10.1097/OLQ.0000000000001308
pii: 00007435-202105000-00009
pmc: PMC8048315
mid: NIHMS1632025
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
353-356Subventions
Organisme : NINDS NIH HHS
ID : R01 NS034235
Pays : United States
Informations de copyright
Copyright © 2021 American Sexually Transmitted Diseases Association. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of Interest and Sources of Funding: H.G. has received a grant from an AIDS Clinical Trials Group Minority HIV Mentoring Program award. I.J.K. has served on an advisory board for Medimmune and received royalties from UpToDate for chapters on HIV and progressive multifocal leukoencephalopathy. G.D.H. has received institutional research grants from Gilead, Janssen, Proteus, Viiv, and BMS and has served on an advisory board for Gilead, Viiv, Janssen, and Theratechnologies. C.M.M. has received royalties from Wolters Kluwer and grants from the National Institutes of Health. L.C.T. and Z.O. have no conflicts of interest to disclose.
Références
Rowley J, Vander Hoorn S, Korenromp E, et al. Chlamydia, gonorrhoea, trichomoniasis and syphilis: Global prevalence and incidence estimates, 2016. Bull World Health Organ 2019; 97:548–62P.
Bank W. GNI per capita, Atlas method (current US$). Available at: https://data.worldbank.org/indicator/NY.GNP.PCAP.CD . Accessed April 20, 2020.
GBD 2015 HIV Collaborators. Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980–2015: The Global Burden of Disease Study 2015. Lancet HIV 2016; 3:e361–e387.
Joseph Davey DL, Shull HI, Billings JD, et al. Prevalence of curable sexually transmitted infections in pregnant women in low- and middle-income countries from 2010 to 2015: A systematic review. Sex Transm Dis 2016; 43:450–458.
Kojima N, Klausner JD. An update on the global epidemiology of syphilis. Curr Epidemiol Rep 2018; 5:24–38.
ECDPC. Syphilis. In: ECDC. Annual Epidemiological Report for 2016. Stockholm: European Centre for Disease Prevention and Control, 2018.
Taylor MM, Aynalem G, Olea LM, et al. A consequence of the syphilis epidemic among men who have sex with men (MSM): Neurosyphilis in Los Angeles, 2001–2004. Sex Transm Dis 2008; 35:430–434.
Larsen SA, Hambie EA, Wobig GH, et al. Cerebrospinal fluid serologic test for syphilis: Treponemal and nontreponemal tests. In: Morisset R, Kurstak E, eds. Advances in Sexually Transmitted Diseases. Utrecht, the Netherlands: VNU Science Press, 1986:157–162.
Shiva F, Goldmeier D, Lane P, et al. Cerebrospinal fluid TPPA titres in the diagnosis of neurosyphilis. Sex Transm Infect 2020; 96:389–390.
Marra CM, Maxwell CL, Dunaway SB, et al. Cerebrospinal fluid Treponema pallidum particle agglutination assay for neurosyphilis diagnosis. J Clin Microbiol 2017; 55:1865–1870.
Tucker JD, Bu J, Brown LB, et al. Accelerating worldwide syphilis screening through rapid testing: A systematic review. Lancet Infect Dis 2010; 10:381–386.
Ho EL, Tantalo LC, Jones T, et al. Point-of-care treponemal tests for neurosyphilis diagnosis. Sex Transm Dis 2015; 42:48–52.
DPP® Syphilis Screen & Confirm Assay (CE Marked). Available at: http://chembio.com/products/human-diagnostics/dpp-syphilis-screen-and-confirm/ . Accessed October 25, 2020.
Castro AR, Esfandiari J, Kumar S, et al. Novel point-of-care test for simultaneous detection of nontreponemal and treponemal antibodies in patients with syphilis. J Clin Microbiol 2010; 48:4615–4619.
Causer LM, Kaldor JM, Conway DP, et al. An evaluation of a novel dual treponemal/nontreponemal point-of-care test for syphilis as a tool to distinguish active from past treated infection. Clin Infect Dis 2015; 61:184–191.
Yin YP, Chen XS, Wei WH, et al. A dual point-of-care test shows good performance in simultaneously detecting nontreponemal and treponemal antibodies in patients with syphilis: A multisite evaluation study in China. Clin Infect Dis 2013; 56:659–665.
Marra CM, Maxwell CL, Smith SL, et al. Cerebrospinal fluid abnormalities in patients with syphilis: Association with clinical and laboratory features. J Infect Dis 2004; 189:369–376.
Workowski KA, Bolan GA; Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep 2015; 64:1–137.
Larsen SPV, Johnson RE, Kennedy EJ Jr. A Manual of Tests for Syphilis. 9th ed. Washington, DC: American Public Health Association, 1998:361.
Centurion-Lara A, Castro C, Shaffer JM, et al. Detection of Treponema pallidum by a sensitive reverse transcriptase PCR. J Clin Microbiol 1997; 35:1348–1352.
Castro R, Prieto ES, Aguas MJ, et al. Evaluation of the Treponema pallidum particle agglutination technique (TP.PA) in the diagnosis of neurosyphilis. J Clin Lab Anal 2006; 20:233–238.