A Dual-Platform Point-of-Care Test for Neurosyphilis Diagnosis

Abstract

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.

Performance of the nontreponemal tests and treponemal tests on cerebrospinal fluid for the diagnosis of neurosyphilis: A meta-analysis

“…A total of 1,140 full-text publications were evaluated for eligibility, 489 were deemed irrelevant to the objective, and 622 lacked sufficient data therefore they were excluded. Ultimately, our meta-analysis was limited to 29 publications ( 2 , 4 , 7 – 33 ) to perform the quantitative synthesis.…”

“…For diagnostic purposes, Gonzalez et al found that comparing the false-negative results of both the Treponemal test and the Nontreponemal test with the true-positive results, the false-negative results had lower CSF-VDRL titers and fewer cerebrospinal fluid white blood cells, which may be related to cerebrospinal fluid dilution ( 33 ).…”

An Updated Review of Recent Advances in Neurosyphilis

“…The epidemic of syphilis and neurosyphilis in low- and middle- income countries is difficult to control due to the resource-limited settings there. However, point-of-care syphilis tests developed in recent years may relieve the pressure of disease control for its feasibility and inexpensiveness ( 56 ). JHR has also been reported in almost all types of commonly used antibiotics for syphilis, especially in the treatment of PLWH ( 68 ).…”

“…Low-and middle-income countries also showed high prevalence rates, long diagnostic delays, low follow-up rates, and inaccessibility to trained clinicians and necessary facilities ( 54 ). Optimized commercial immunochromatographic strip tests, such as the CSF-Syphicheck and the DPP Chembio syphilis assay, showed satisfying diagnostic specificity and sensitivity compared to CSF-VDRL (62–64% sensitivity, 79–81% specificity in CSF-Syphicheck; 63–92% sensitivity, 85–100% specificity in DPP Chembio syphilis assay) ( 55 , 56 ). Though further evaluation is needed, point-of-care tests may be widely applied in resource-limited regions and contribute to the control of sexually transmitted diseases, especially for neurosyphilis and congenital syphilis.…”

Comparison of Electroencephalography in Patients With Seizures Caused by Neurosyphilis and Viral Encephalitis

“…At present, there is no gold standard for the diagnosis of neurosyphilis, and the diagnosis depends on the comprehensive analysis of clinical manifestations, serological tests and cerebrospinal fluid tests ( 25 ). Therefore, it is urgent to find additional supportive criteria with differential significance for the diagnosis of neurosyphilis and viral encephalitis.…”